WO2018111104A1 - Use of human crispr sequences in diagnostics - Google Patents

Use of human crispr sequences in diagnostics Download PDF

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WO2018111104A1
WO2018111104A1 PCT/NL2017/050839 NL2017050839W WO2018111104A1 WO 2018111104 A1 WO2018111104 A1 WO 2018111104A1 NL 2017050839 W NL2017050839 W NL 2017050839W WO 2018111104 A1 WO2018111104 A1 WO 2018111104A1
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syndrome
disease
crispr
seq
sequences
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PCT/NL2017/050839
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French (fr)
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Rogier Petrus Leonardus LOUWEN
Petrus Johannes Van Der Spek
Chinmoy SAHA
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Erasmus University Medical Center Rotterdam
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

Definitions

  • the invention relates to the field of genetics, more articular human genetics, more especially the use of eukaryotic CRISPR sequences in diagnostic assays.
  • CRISPR sequences are Clustered Regularly Interspaced Short Palindromic Repeat sequences that are present in bacteria and archaea. Initially these kind of sequences have been indicated as Short Regularly Spaced Repeats (SRSRs) (Mojica, F.J. et al., 2000, Mol.
  • the present invention comprises a diagnostic assay in which eukaryotic CRISPR sequences are used.
  • the CRISPR sequences used in said assay are chosen from the human CRISPR sequences of SEQ ID NO: 1 - SEQ ID NO: 10141 or any of the non-human CRISPR sequences of SEQ ID NO: 10142 - 11297.
  • said diagnostic assay can be based on both the Affymetrix CRISPR sequences and the non-Affymetrix CRISPR sequences, as herein defined.
  • the invention comprises a method for diagnosing a disease or condition comprising the steps of:
  • the sample is preferably chosen from blood, serum, saliva, hair, urine, lymph fluid, CSF, cells and tissue.
  • the step of determining the expression profile is accomplished by probing the sample with an array of probes specific for the at least one human CRISPR nucleotide sequence, preferably wherein the sample comprises mRNA extracted from cells or tissue to be investigated, preferably wherein said array of probes comprises at least one probe that is targeting a human CRISPR sequence that is not represented on the Affymetrix U133 Plus 2GeneChip®.
  • multiple probes are available for different spacer sequences of the same CRISPR nucleotide sequence.
  • the array comprises more then 50, preferably more than 100, more preferably more than 500 and more preferably more than 1000 probes.
  • said CRISPR nucleotide sequences are selected from SEQ ID NO: 1 - 10141, more preferably comprising at least one sequence defined herein as non- Affymetrix human CRISPR sequences.
  • Another part of the invention is an array spotted with probes targeting one or more of the nucleotide sequences of SEQ ID NO: 1 - 11297, more preferably the nucleotide sequences of SEQ ID NO: 1 - 10141, wherein said probes are short nucleotide sequences.
  • said probes are DNA sequences with a length of 15 - 100 nucleotides, preferably of 20 - 75 nucleotide, more preferably of 22 - 50 nucleotides, more preferably of 23 - 40 nucleotides, more preferably 24 - 35 nucleotides, most preferably of 25 - 30 nucleotides, optionally provided with a label. It is further preferred that said nucleotide probes are spotted on a carrier.
  • At least one of said sequences of SEQ ID NO: 1 - 11297 does not possess any sequences that occur on an Affymetrix U- 133 Plus 2.0 GeneChip®.
  • the invention is further directed to the use of such an array in a method for diagnosing a disease or condition.
  • the invention comprises a method for the diagnosis of chronic B- lymphocytic leukemia by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 9342, and diagnosing that chronic B-lymphocytic leukemia is present when SEQ ID NO: 9342 is overexpressed.
  • the invention comprises a method for the diagnosis of Francisella infection by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8709, and diagnosing that Francisella infection is present when SEQ ID NO: 8709 is under-expressed.
  • the invention comprises a method for the diagnosis of hepatocellular carcinoma by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 7930, and diagnosing that hepatocellular carcinoma is present when SEQ ID NO: 7930 is
  • the invention comprises a method for the diagnosis of high-grade prostate cancer by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8566, and diagnosing that high-grade prostate cancer is present when SEQ ID NO: 8566 is under-expressed.
  • the invention comprises a method for the diagnosis of chronic pediatric immune thrombocytopenia by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8757, and diagnosing that chronic pediatric immune thrombocytopenia is present when SEQ ID NO: 8757 is overexpressed.
  • the invention comprises a method for the diagnosis of prostate cancer progression by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 9471, and diagnosing that prostate cancer progression is present when SEQ ID NO: 9471 is overexpressed.
  • the invention comprises a method for the diagnosis of fertility based on sperm health by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8713, and diagnosing that fertility based on sperm health is present when SEQ ID NO: 8713 is overexpressed.
  • the invention comprises a method to distinguish between acute and latent tuberculosis by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8190, and diagnosing that acute tuberculosis is present when SEQ ID NO: 8190 is under-expressed.
  • the invention comprises a method for the diagnosis of tibial muscular dystrophy by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 6939, and diagnosing that tibial muscular dystrophy is present when SEQ ID NO: 6939 is under-expressed.
  • the invention comprises a method to distinguish between differentiated and undifferentiated embryonic stem cells by assaying the under- or overexpression of CRISPR sequences SEQ ID NO: 5465, 1423, 68, 7865, 7648, 6872, 8273, 8190, 8678, and 3215, and diagnosing that the cells are undifferentiated if at least one of SEQ ID NO: 5465 and 68 is under-expressed and at least two of SEQ ID NO: 1423, 7865, 7648, 6872, 8273, 8190, 8678, and 3215 are overexpressed.
  • the invention comprises a method to distinguish between H1N1 infected and uninfected bronchial epithelial cells by assaying the under- or overexpression of CRISPR sequences 5465, 7873, 998, 1515, 9358, 8407, 8190, and 8861 and diagnosing that the cells are uninfected if at least two of SEQ ID NO: 5465, 8190 and 8861 are under- expressed and at least two of SEQ ID NO: 7873, 998, 1515, 9358 and 8407 are overexpressed.
  • the invention comprises a method for the detection of an infectious disease in a human by assaying the under- of overexpression of one or more of the CRISPR sequences provided in Table 23.
  • the invention comprises a method for the detection of cancer in a human by assaying the under- of overexpression of one or more of the CRISPR sequences provided in Table 17. More specifically, the invention comprises a method for the detection of a specific cancer, selected from the group of Bladder urothelial carcinoma, Breast carcinoma, Gastric carcinoma, Head neck squamous cell carcinoma, Kidney carcinoma, Kidney
  • chromophobe Liver hepatocellular carcinoma, Lung adenocarcinoma, Lung squamous cell carcinoma, Lung squamous cell carcinoma and Thyroid carcinoma
  • the invention further comprises the diagnostic use of one or more of the CRISPR sequences that reside in a transcription factor binding site as provided in Table 21 or that reside in a DNasel hypersensitive site as provided in Table 22.
  • FIG. 1 shows an example of a pure eukaryotic CRISPR on the human genome in chromosome 17 (chrl7:261087-261183;GRCh37 Hgl9 genome position).
  • the RNA-seq exon coverage data reveals the transcription of a spacer (20 out of the 35 nucleotides) and repeat (30 out of 31 nucleotides) as depicted by the red markers 1 and 2 (spacer) and red marker 2 and green marker 3 (repeat).
  • the blue block shows the transcript as detected with RNA sequencing.
  • the spacer is found to target the human genome only by showing 100% identity against open reading frame C17orf97.
  • Fig. 2 shows in A) a Heatmap and in B) a scattergram for probe 233266_at resembling a none annotated region of which the probe region overlapped with a human CRISPR (Patent SEQ ID: 6326).
  • the probe resembling a human CRISPR harbors the potential to function as a diagnostic marker to distinguish between acute asthma and convalescence patients when the RNA expression value of probe 233266_at is 28.0658 or lower (acute) or 30.2696 and higher (convalescence) (Table 4).
  • a two-tailed unpaired T-test value with p ⁇ 0.05 indicated statistical significance (* p 0.0002).
  • FIG. 3 shows in A) a Heatmap and in B) a scattergram for probe 242924_at resembling a none annotated region of which the probe region overlapped with a human CRISPR (Patent SEQ ID: 9342) the RNA expression of this region detected by the probe was found to be
  • RNA expression value is 0.0429552 or lower (Healthy control) or 0.0698454 and higher (CELL) (Table 5).
  • a two-tailed unpaired T-test value with p ⁇ 0.05 indicated statistical significance (* p 0.0043).
  • Fig. 4 shows in A) a Heatmap and in B) a scattergram for probe 234574_at resembling a none annotated region of which the probe region overlapped with human CRISPRs (Patent SEQ ID: 8709; 8713: 3664; 8711; 8712; 8714).
  • the RNA expression of this region detected by the probe was found to be upregulated in the untreated blood monocytes compared to the Francisella species infected blood monocytes. This probe harbors diagnostic potential when the RNA expression value is 5.16552 or higher (untreated blood monocytes) compared to 4.60217 or lower (Table 6).
  • Fig. 5 shows in A) a Heatmap and in B) a scattergram for probe 234643_x_at resembling a none annotated region of which the probe region overlapped with human CRISPRs (Patent SEQ ID: 7929; 7930; 7931; 7932; 7933; 7934; 7935; 7936).
  • the RNA expression of this region detected by the probe was found to be upregulated in the blood monocytes obtained from healthy controls compared to blood monocytes obtained from hepatocellular carcinoma (HCC) patients.
  • HCC hepatocellular carcinoma
  • This probe harbors diagnostic potential when the RNA expression value is 4.86397 or lower in HCC blood monocytes compared to 4.95324 or higher in blood monocytes obtained from healthy controls (Table 7).
  • a two-tailed unpaired T-test value with p ⁇ 0.05 indicated statistical significance (* p ⁇ 0.0001).
  • Fig. 6 shows a Heatmap for probe 234095_at resembling a none annotated region of which the probe region overlapped with a human CRISPR (Patent ID: 8566).
  • the RNA expression of this region detected by the probe was found to be upregulated in normal prostate tissue obtained from a prostate cancer free patient compared to prostate tissue obtained from prostate cancer patients with a high Gleason score 8 or higher.
  • This probe harbors diagnostic potential when the RNA expression value is 478.4 or higher in prostate tissue from a prostate cancer free patient compared 163.8 or lower in prostate tissue obtained from prostate cancer patients with a high Gleason score (Table 8).
  • Fig. 6 shows a Heatmap for probe 234095_at resembling a none annotated region of which the probe region overlapped with a human CRISPR (Patent ID: 8566).
  • the RNA expression of this region detected by the probe was found to be upregulated in normal prostate tissue obtained from a prostate cancer free patient compared to prostate tissue obtained from
  • RNA expression of this region detected by the probe was found to be upregulated in peripheral blood T-cells obtained from children with chronic ITP compared to peripheral blood T-cells obtained from children with newly diagnosed ITP.
  • This probe harbors diagnostic potential when the RNA expression value is 737 or higher in peripheral blood T- cells obtained from children with chronic ITP compared to 717 or lower in peripheral blood T- cells obtained from children with newly diagnosed ITP (Table 9).
  • a two-tailed unpaired T-test value with p ⁇ 0.05 indicated statistical significance (* p 0.0003).
  • Fig. 8 shows in A) a Heatmap and in B) a scattergram for probe 1566549_at resembling a none annotated region of which the probe region overlapped with a human CRISPR (Patent SEQ ID: 9471). The RNA expression of this region detected by the probe was found to be
  • RNA expression value is 338 or higher in prostate cancer tissue that is metastatic compared to 308 or lower in prostate tumor tissue that was primary or benign (Table 10).
  • Fig. 9 shows in A) a Heatmap and in B) a scattergram for probe 234490_at resembling a none annotated region of which the probe region overlapped with human CRISPRs (Patent SEQ ID: 3664; 8711; 8712; 8713; 8714).
  • the RNA expression of this region detected by the probe was found to be upregulated in teratozoospermia sperm cells compared to normal sperm cells.
  • This probe harbors diagnostic potential when the RNA expression value is 93.5249 or higher in teratozoospermia compared to 63.4615 or lower in normal sperm cells (Table 11).
  • a two-tailed unpaired T-test value with p ⁇ 0.05 indicated statistical significance (* p ⁇ 0.0001).
  • Fig. 10 shows in A) a Heatmap and in B) a scattergram for probe 217152_at resembling a none annotated region of which the probe region overlapped with human CRISPRs (Patent SEQ ID: 8179; 8190; 8191).
  • the RNA expression of this region detected by the probe was found to be upregulated in healthy controls and latent TB infected patients compared to active
  • RNA expression value 8.33663 or higher in healthy controls and latent TB infected patients compared to 8.16569 or lower in active tuberculosis patients (Table 12).
  • Fig. 11 shows in A) a Heatmap and in B) a scattergram for probe 1557539_at resembling a none annotated region of which the probe region overlapped with a human CRISPR (Patent SEQ ID: 6939). The RNA expression of this region detected by the probe was found to be upregulated in healthy controls compared to tibial muscular dystrophy patients.
  • RNA expression value 0.546921 or higher in healthy controls compared to 0.00589085 or lower in tibial muscular dystrophy patients (Table 13).
  • Fig. 12 shows a Heatmap for affymetrix U133 plus 2 probes resembling human CRISPRs. The RNA expression of these probes reveals that a large number allows to distinguish between undifferentiated and differentiated embryonic stem cells. These probes thus indicate that human CRISPRs might play a role in embryonic stem cell differentiation (Table 14).
  • Fig. 13 shows a Heatmap for affymetrix U133 plus 2 probes resembling human CRISPRs.
  • the RNA expression of these probes reveals that a large number allows to distinguish between H1N1 influenza virus infected and uninfected bronchial epithelial cells and even between H1N1 variants.
  • These probes thus indicate that human CRISPRs might play a role in the cellular defense against influenza viruses (Table 15).
  • logFC Positive log fold-change
  • logFC Positive log fold- change
  • Fig. 16 shows that the human CRISPRs (e.g. a CRISPR marked in red at position chrl2: 6201657-6201737 and patent ID 6498) overlap with regions that are known to be transcription factor binding sites, e.g., pol2 (Table 21), and/or reside in Dnasel hypersensitive sites (Table 22) (Dnasel cluster 6 in blue) indicative that this region is accessible for transcription activity.
  • pol2 e.g., pol2 (Table 21)
  • Dnasel hypersensitive sites Table 22
  • microarray refers to a collection of microscopic DNA spots aggregated and attached to a solid surface. Each DNA spot contains a small amount of a specific DNA sequence, known as a probe. These can be a short section of a nucleotide sequence that is hybridized with a cDNA or cRNA (also called anti-sense RNA) in the specimen (called target) sample under high- stringency conditions.
  • cDNA or cRNA also called anti-sense RNA
  • stringency refers to the extent to which hybridization may occur between nucleic acids with mismatched sequences. High-stringency conditions require absolute complementarity between the molecules, while low-stringency conditions permit hybridization when there are some mismatched bases. Typically, high-stringency conditions are achieved either by reducing NaCl concentration or increasing temperature up to approaching the melt temperature (Tm) of the molecules involved.
  • Tm melt temperature
  • An example of high- stringency conditions is hybridization at 50°C or higher (e.g. 55°C) and at 0.1 SSC (0.15M NaCl and 0.015M sodium citrate).
  • a nucleic acid or fragment thereof is “substantially homologous" ("or substantially similar") to another if, when optimally aligned (with appropriate nucleotide insertions or deletions) with the other nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least about 60% of the nucleotide bases, usually at least about 70%, more usually at least about 80%, preferably at least about 90%, and more preferably at least about 95, 96, 97 or 98% of the nucleotide bases.
  • nucleic acid or fragment thereof will hybridize to another nucleic acid (or a complementary strand thereof) under selective hybridization conditions, to a strand, or to its complement.
  • Selectivity of hybridization exists when hybridization that is substantially more selective than total lack of specificity occurs.
  • selective hybridization will occur when there is at least about 55% identity over a stretch of at least about 14 nucleotides, preferably at least about 65%, more preferably at least about 75%, and most preferably at least about 90%.
  • the length of homology comparison, as described, may be over longer stretches, and in certain embodiments will often be over a stretch of at least about nine nucleotides, usually at least about 20 nucleotides, more usually at least about 22 nucleotides, typically at least about 23 nucleotides, more typically at least about 24 nucleotides, and preferably at least about 25 or more nucleotides.
  • the probes to be used in the array of the invention preferably have at least 75%, more preferably at least 85%, more preferably at least 90% homology to the sequences shown in SEQ ID NO: 1 - 11297. More preferably there is at least 95%), more preferably at least 98%, homology.
  • Percentage (%) homology may be calculated over contiguous sequences, i.e. one sequence is aligned with the other sequence and each nucleotide in one sequence directly compared with the corresponding nucleotide in the other sequence, one residue at a time. This is called an "ungapped" alignment. Typically, such ungapped alignments are performed only over a relatively short number of residues (for example less than 50 contiguous nucleotides). Although this is a very simple and consistent method, it fails to take into consideration that, for example, in an otherwise identical pair of sequences, one insertion or deletion will cause the following residues to be put out of alignment, thus potentially resulting in a large reduction in % homology when a global alignment is performed.
  • GCG Bestfit program Although the final % homology can be measured in terms of identity, the alignment process itself is typically not based on an all-or-nothing pair comparison. Instead, a scaled similarity score matrix is generally used that assigns scores to each pair-wise comparison based on chemical similarity or evolutionary distance.
  • An example of such a matrix commonly used is the BLOSUM62 matrix - the default matrix for the BLAST suite of programs.
  • GCG Wisconsin programs generally use either the public default values or a custom symbol comparison table if supplied (see user manual for further details). It is preferred to use the public default values for the GCG package, or in the case of other software, the default matrix, such as BLOSUM62.
  • % homology preferably % sequence identity.
  • the software typically does this as part of the sequence comparison and generates a numerical result.
  • Nucleotide homology comparisons may be conducted, e.g. through a preferred sequence comparison program such as the GCG Wisconsin Best fit program.
  • the default scoring matrix has a match value of 10 for each identical nucleotide and -9 for each mismatch.
  • the default gap creation penalty is -50 and the default gap extension penalty is -3 for each nucleotide.
  • a homologue or homologous sequence is taken to include a nucleotide sequence which is at least 60, 70, 80 or 90% identical, preferably at least 95 or 98%. identical at the nucleotide level over at least 20, 50, 100, 200, 300, 500 or 1000 nucleotides with the nucleotides sequences of SEQ ID NO: 1 - 11297, more preferably of SEQ ID NO: 1 - 10141.
  • Nucleotide sequences of the probes used in the present invention are preferably at least 15 nucleotides in length, preferably from 20 - 75 nucleotides, more preferably from 22 - 50 nucleotides, more preferably from 23 - 40 nucleotides, more preferably from 24 - 35 nucleotides, most preferably from 25 - 30 nucleotides.
  • the shorter the length of the polynucleotide the greater the homology required to obtain selective hybridization. Consequently, where a probe sequence of the invention consists of less than about 30 nucleotides, it is preferred that the % identity is greater than 75%, preferably greater than 90% or 95% compared with the nucleotide sequences of SEQ ID NO: 1 - 11297, more preferably of SEQ ID NO: 1 - 10141.
  • a polynucleotide of the invention consists of, for example, more than 50 or 100 nucleotides
  • the % identity compared with the sequences of SEQ ID NO: 1 - 11297, more preferably of SEQ ID NO: 1 - 10141 may be lower, for example greater than 50%, preferably greater than 60 or 75%.
  • compositions of this invention comprising the sequences of
  • SEQ ID NO: 1 - 11297 examples include RNA, cDNA, genomic DNA, synthetic forms, and mixed polymers, both sense and antisense strands, and may be chemically or biochemically modified or may contain non- natural or derivatized nucleotide bases, as will be readily appreciated by those skilled in the art.
  • Such chemical or biochemical modifications include, for example, labels, methylation, substitution of one or more of the naturally occurring nucleotides with an analog,
  • internucleotide modifications such as uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoamidates, carbamates, etc.), charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), pendent moieties (e.g., polypeptides), intercalators (e.g., acridine, psoralen, etc.), chelators, alkylators, and modified linkages (e.g., alpha anomeric nucleic acids, etc.).
  • synthetic molecules that mimic polynucleotides in their ability to bind to a designated sequence via hydrogen bonding and other chemical interactions. Such molecules are known in the art and include, for example, those in which peptide linkages substitute for phosphate linkages in the backbone of the molecule.
  • the structure of a prokaryotic CRISPR array includes a number of short repeating sequences referred to as "repeats.”
  • the repeats occur in clusters and up to 249 repeats have been identified in a single CRISPR array and are usually regidarly spaced by unique intervening sequences referred to as "spacers.”
  • spacers unique intervening sequences referred to as "spacers.”
  • CRISPR repeats vary from about 24 to 47 base pairs in length and are often palindromic.
  • the repeats are generally arranged in clusters (up to about 20 or more per genome) of repeated units.
  • the spacers are located between two repeats and typically each spacer has a unique sequence of about 21-72 base pairs in length. Many spacers are identical to or have high similarity with known phage sequences. It has been shown that the insertion of a spacer sequence from a specific phage into a bacterial CRISPR can confer resistance to that phage (see e.g., Barrangou, R. et al., 2007, Science 315: 1709- 1712).
  • a CRISPR array may also include a leader sequence and often a set of two to six associated cas genes.
  • the leader sequence is an AT-rich sequence of up to 550 base pairs directly adjoining the 5' end of the first repeat. New repeat- spacer units are almost always added to the CRISPR array between the leader and the first repeat.
  • CRISPR sequences follow a similar genetic make-up as the prokaryotic CRISPRs: short repeating, often palindromic sequences of 24 - 47 base pairs separated by spacers of - generally - 21-72 base pairs.
  • a number of such eukaryotic CRISPR sequences that occur in humans is depicted in Table IA - IX of the (priority) document PCT/NL2015/050438, herein presented as SEQ ID NO: 1 - 10000, (Table 1A covers chromosome 1, table IB covers chromosome 2, etc.) or in Table IIA - IIM of said priority document, herein presented as SEQ ID NO: 10142- 11297 in which non-human eukaryotic CRISPRs are depicted.
  • Table IA - IX of the (priority) document PCT/NL2015/050438, herein presented as SEQ ID NO: 1 - 10000, (Table 1A covers chromosome 1, table IB covers chromosome
  • CRISPR sequences of SEQ ID NO: 146 - 149, 545 - 554 and 10001-10141. These CRISPRs occasionally are found to be accompanied by a Cas gene, sometimes even more than one Cas gene.
  • a eukaryotic CRISPR sequence is defined as a sequence that comprises at least two partly or complete palindromic repeats of 24 - 47 base pairs and at least one spacer of about 21 - 72 base pairs, wherein the spacer is derived from a eukaryotic sequence, especially a spacer sequence that is derived from the same organism as from which the CRISPR sequence is derived.
  • the spacer may originally be derived from a non-eukaryotic pathogen, but it will be different from the non-eukaryotic sequence because of the connection with the repeat sequences which are of eukaryotic origin.
  • a human CRISPR sequence would be a CRISPR sequence in which the spacer contains a human sequence or a sequence of a human pathogen (such as a retrovirus (HERV)), but of which the repeat sequences are of human origin.
  • HERV retrovirus
  • a specific group of eukaryotic CRISPRs are those CRISPRS that comprise spacer sequences that are only consisting of sequences that are derived from the same organisms as from which the repeat sequences are derived (see also Figure 1 of PCT NL2016/050422). These are indicated in the present application as “pure eukaryotic" CRISPR sequences. Accordingly a "pure human CRISPR sequence” is a pure eukaryotic sequence that is derived from a human being.
  • the spacer of such a pure eukaryotic CRISPR generally is directed against a eukaryotic target sequence in such a sense that it will be capable of binding to such a sequence. It should further be mentioned that the spacer sequence does not need to be completely identical to the (eukaryotic) target. As has been proven in the work on RNAi (see below), which has been confirmed in the recent research on the CRISPR-Cas gene-editing system, inhibition of expression can also be accomplished with sequences that are less than 100% complementary to their target sequence. Because of the occurrence of mutations within the spacer sequences, which are more vulnerable to mutations than sequences coding for functional proteins, it could be that the original 100%
  • sequences provided in SEQ ID NO:l - 11297 are comprised in the definition of eukaryotic CRISPR sequences.
  • human CRISPR sequences are defined as any of the sequences SEQ ID NO: 1 - 10141.
  • CRISPRFinder a web tool to identify clustered regularly interspaced short palindromic repeats. Nucleic Acids Res. 2007 May 31).
  • the program for this should be run with the following standard default parameters: a repeat length of 23 to 55 bp, a gap size between repeats of 25 to 60 bp, one nucleotide mismatch between repeats, but these parameters may be varied in an advanced search to obtain additional CRISPRs. Further criteria a CRISPR should fit to are the following:
  • the spacer size compared to the DR size is mainly added to eliminate structures having for example a 45 bp DR and a 20 bp spacer.
  • the spacer size should be from 0,6* to 2,5* the DR size.
  • This filter is set to eliminate tandem repeats.
  • the spacers' comparison is made by aligning them (using default parameters of the ClustalW program).
  • Spacers' similarity percentage is calculated with the function percentage_identity() of the (Bio)perl interface (AlignIO methods, ClustalW interface; Larkin, M.A. et al., 2007,
  • the direct repeat should be well conserved.
  • the DR scan is done using the fuzznuc program of the EMBOSS package (Rice, P. et al. 2000, Trends in Genetics 16:276-277).
  • the allowed mismatch is equal to one-third of the DR size (default- parameters) to take into account the degenerated DR (one of the flanking DRs).
  • a global mismatch score is computed as the average of mismatches (not including the degenerated DR) and this score should not exceed a threshold of 20% of the DR size(by default).
  • the sequences covered in SEQ ID NO: 1 - 10141 are the total of sequences that may be discovered by screening the genome that is contained in the database.
  • the genomes of Homo sapiens present in the Bioconductor packages was used comprising data of about 1000 human genomes that can be retrieved from
  • CRISPR Finder software recognizes that are identical or very similar to repeat sequences that also occur in bacteria or archaea (see Table 1), but in most cases the repeat sequences, although fulfilling the criteria set for the detection of CRISPR repeat sequences, seem to be unique.
  • eukaryotic CRISPRs appear to have spacer sequences that are derived from viruses or other pathogens that are known to infect eukaryotic cells. In this respect it thus appears that these CRISPRs have been established through a similar mechanism as is described for bacteria and archaea. However, in the majority of the cases, the spacers are derived from sequences that are endogenous to the organism in which the CRISPR sequence is found or has been obtained from through horizontal gene transfer.
  • sequences of SEQ ID NO: 1 - 10142 can be divided in two subsets, one subset for which probes can be used on the Affimetrix GeneChipS U133 Plus 2.0 (the SEQ ID Nos mentioned in Tables 2 and 3) and a larger subset of the SEQ ID Nos that have not been mentioned in Table 2 or 3.
  • This last subset are herein designated as the "non-Affymetrix CRISPR sequences", while the first subset is indicated as the "Affymetrix CRISPR sequences”.
  • the present invention therefore is comprising a method for diagnosing a disease or condition by assessing the expression data of one or more of the CRISPR sequences from SEQ ID NO: 1 - 10141.
  • many diseases or conditions are accompanied by (or caused by?) an under- or overexpression of a (sub)set of CRISPR sequences.
  • the data that are obtained in the present application are based on the expression data of the Affymetrix CRISPR sequences (as derived from the Affymetrix GeneChip® U133 Plus 2.0), but it is believed that also numerous CRISPR sequences from the non-Affymetrix CRISPR sequences will be equally characterized by under- or overexpression in specific diseases or conditions.
  • the present invention also comprises an assay using an array of probes, which array comprises at least one probe that is suited to hybridise under stringent conditions with a non-Affymetrix CRISPR sequence.
  • arrays will contain at least one CRISPR sequence, but preferably more and may further contain both non-Affymetrix CRISPR sequences and Affymetrix CRISPR sequences.
  • the size of the assay can vary, depending on the number of CRISPR sequences that is needed to provide a reliable diagnosis for a certain disease or condition and whether or not the array will be used for diagnosing more than one disease or condition. It is envisaged that an array may be constructed comprising probes for each and every CRISPR sequence from both the Affymetrix and non- Affymetrix CRISPR sequences.
  • such an array may also comprise multiple probes for one and the same CRISPR sequence, since there are indications that some of the CRISPR sequences that comprise more than one spacer sequence would be applicable in more than one way, because the various spacer sequences contained in one and the same CRISPR sequence could be used as a diagnostic for more than one disease or condition.
  • such an array would comprise probes that would be specific for each of the spacer sequences that are contained in the CRISPR sequences.
  • an array having at least one probe able to specifically bind to a spacer sequence of any of the non-Affymetrix CRISPR sequences. Said array could further contain probes targeting both Affymetrix
  • the disease or condition that may be diagnosed may be any disease or condition that is known. In the experimental part it is shown that many diseases cause over- or underexpression of one or more CRISPR sequences.
  • the word 'condition' is herein to be understood as a state of health, which can be represented by any physiologic signal (such as fever is represented by an elevated body temperature), but which state of health can also apply to a part of the body.
  • a physiologic signal such as fever is represented by an elevated body temperature
  • an increased level of atherosclerosis in the blood vessels may is a condition which may lead to a disease (e.g. stroke or coronary ischemia) but this condition is confined to the blood vessels. It may be represented by an increased blood pressure or by a stiffening of the walls of the blood vessels and the like.
  • a 'disease' is - of course - related to the definition of a condition, and a disease my be characterized as " a definite pathological process having a characteristic set of signs and symptoms". It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown (definition from Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. ⁇ 2003 by Saunders).
  • Conditions and diseases that may be diagnosed in this way are: asthma, chronic B- cell leukemia, hepatocellular carcinoma, Francisella infection, high grade prostate cancer, pediatric immune thrombocytopenia, tuberculosis, tibial muscular dystrophy,
  • teratozoospermia Influenza infection, stem cell differentiation, for which examples are given in the present application (see experimental part).
  • Many other diseases and (medical) conditions may also be diagnosed with the sequences of the present invention. In principle any condition or disease which has an effect on expression of genes would be amenable to be diagnosed with one or a subset of the probes that would be present on the presently defined arrays.
  • Such diseases may e.g. be Abdominal Aortic Aneurysm, Acanthamoeba Infection, ACE (Adverse Childhood Experiences), Acinetobacter Infection, Acquired Immune Deficiency Syndrome (AIDS), Adenovirus Infection, ADHD (Attention Deficit/Hyperactivity Disorder),
  • AFib AF (Atrial fibrillation), AHF (Alkhurma hemorrhagic fever), ALS (Amyotrophic Lateral Sclerosis), Alzheimer's Disease, Amebiasis, Anaplasmosis, Ancylostoma duodenale Infection, Angiostrongylus Infection, Animal-Related Diseases, Anisakiasis Infection, Anthrax [Bacillus anthracis Infection], Aortic Aneurysm, Arenavirus Infection,, Ascaris Infection (Ascariasis), Aspergillus Infection (Aspergillosis), Asthma, Autism, Avian Influenza, Burkholderia cepacia Infection, Babesiosis (Babesia Infection), Bacterial Meningitis, Bacterial Vaginosis (BV), Balamuthia Infection (Balamuthia mandrillaris Infection, Balantidiasis (Balantidium
  • BSE Brainerd Diarrhea
  • Breast Cancer Bronchiolitis
  • Bronchitis Bronchitis
  • Brucellosis (Brucella Infection), Burkholderia cepacia Infection (B. cepacia infection), C. gattii cryptococcosis, C. neoformans cryptococcosis, Campylobacteriosis (Campylobacter Infection), Candida Infection (Candidiasis), Canine Flu, Capillariasis (Capillaria Infection), Carpal Tunnel Syndrome, Carrion's disease (Bartonella bacilliformis Infection), CCHF (Crimean- Congo hemorrhagic fever), Cerebral Palsy, Cervical Cancer, CFS (Chronic Fatigue Syndrome), Chagas Disease (Trypanosoma cruzi Infection), Chapare Hemorrhagic Fever (CHHF),
  • Chickenpox (Varicella Disease), CHIKV (Chikungunya Fever), Chlamydia (Chlamydia trachomatis Disease), Chlamydia trachomatis Disease, Chlamydophila (Chlamydia) pneumoniae Infection, Cholera (Vibrio cholerae Infection), Chronic Kidney Disease (CKD), Chronic Wasting Disease (CWD), Ciguatera Fish Poisoning, Classic Creutzfeldt-Jakob
  • Clonorchiasis Clonorchiasis (Clonorchis Infection), Clostridium difficile Infection, Clostridium perfringens infection, Coccidioidomycosis, common cold, Colorado Tick Fever (CTF), Colorectal (Colon) Cancer, Concussion, Congenital Hearing Loss, Congenital Heart Defects,
  • CMV Cytomegalovirus Infection
  • DVT Deep Vein Thrombosis
  • DF Dengue Fever
  • Gnathostomiasis Gonorrhea (Neisseria gonorrhoeae Infection), Gout, Granulomatous Amoebic Encephalitis (Acanthamoeba) (GAE (Acanthamoeba)), Group A Strep Infection (GAS), Group B Strep Infection (GBS), H3N2v influenza, H5N1 Influenza, HAB (Harmful Algal Bloom (HAB)-Associated Illness), Haemophilus influenzae Infection (including Hib
  • HMD Hand, Foot, and Mouth Disease
  • HPS Hantavirus Pulmonary Syndrome
  • HAB Harmful Algal Bloom
  • HAB Harmful Algal Bloom
  • HAB -Associated Illness
  • Diarrhea-predominant IBS Post-infectious IBS, Amyloidosis VI, ICF syndrome, Ichthyocrino toxic ation, Ichthyohepatotoxication, Ichthyosarcotoxism, Ichthyosiform Erythroderma, Ichthyosis, Ichthyosis bullosa of Siemens, Ichthyosis congenita biliary atresia, Ichthyosis congenita, Harlequin fetus type, Ichthyosis follicularis-atrichia- photophobia syndrome, Ichthyosis hystrix, Ichthyosis hystrix gravior, Ichthyosis hystrix, Curth Macklin type , Ichthyosis male hypogonadism, Ichthyosis mental retardation
  • Ichthyosis microphthalmos Ichthyosis prematurity syndrome, Ichthyosis Vulgaris, Ichthyosis- cheek-eyebrow syndrome, Dykes-Markes-Harper syndrome, IBIDS syndrome, Cholestasis, Idaho syndrome, Apraxia, Idiopathic acute eosinophilic pneumonia, Idiopathic adolescent scoliosis, Idiopathic adult neutropenia, Idiopathic alveolar hypoventilation syndrome,
  • Idiopathic calcinosis cutis Calciphylaxis, Idiopathic chronic severe neutropenia, Cyclical edema syndrome, Atypical hemolytic uremic syndrome, Idiopathic diffuse interstitial fibrosis, Idiopathic dilatation of the pulmonary artery, Idiopathic dilation cardiomyopathy, Idiopathic double athetosis, Idiopathic dystonia DYT1, Idiopathic edema, Idiopathic eosinophilic chronic pneumopathy, Eosinophilic synovitis, Erythema nodosum, Diamond-Blackfan anemia, Biliary Atresia, Idiopathic facial palsy, Idiopathic gastroparesis, Giant cell myocarditis, Hydrops fetalis, Idiopathic hypereosinophilic syndrome, Idiopathic hypersomnia, Hypersomnolence,
  • Hypertrophic cardiomyopathy Asbestosis, Idiopathic intestinal pseudoobstruction, Idiopathic liver cirrhosis, Gorham's syndrome, Idiopathic minimal change nephrotic syndrome,
  • Parkinson's disease Dermatomyositis, Banti's syndrome, Idiopathic Pulmonary Fibrosis, Idiopathic pulmonary hemosiderosis, Idiopathic pulmonary hypertension, Idiopathic sclerosing mesenteritis, Idiopathic subglottic tracheal stenosis, Idiopathic Synesthesia, Idiopathic Thymus Hyperplasia, Idiopathic, hypertrophic, subaortic stenosis, Idrophrodisia, IgA nephropathy, IgA Pemphigus, IgE mediated gastrointestinal food allergy, IGF- 1 deficiency, IgG Deficiency, Hyper-IgM Syndrome, Iida-Kannari syndrome, Ileitis, Iliotibial Band Syndrome, Ilium syndrome, Capgras' syndrome, IMAGe syndrome, Imaizumi Kuroki syndrome, Hyper-IgM Syndrome, Imersluasbeck Syndrome, Imerslund's Anemia
  • Thrombocytopenic Purpura Acute Disseminated Encephalomyelitis, Good syndrome, Hyper- IgM Syndrome, Immunoglobulinic amyloidosis, Immunologic Deficiency Syndromes,
  • Facial Syndrome Impetigo, Impingement syndrome, Impossible syndrome, Inborn amino acid metabolism disorder, Inborn branched chain aminoaciduria, Dicarboxylicaminoaciduria, Argininosuccinic aciduria, Baber's syndrome, Inborn renal aminoaciduria, Inborn urea cycle disorder, Inclusion body myopathy, Inclusion Body Myositis, Inclusion conjunctivitis,
  • Bisalbuminemia Homozygotic Alpha 1 antitrypsin Defeciency, Inherited Hemolytic-Uremic Syndrome, Inherited spherocytic anemia, Iniencephaly, Insomnia, Dysentery, Insulin
  • Dermatitis Syndrome Dejerine-Sottas disease, Interstitial lung disease, Interstitial nephritis, Interstitial pneumonia, Intertrigo, Intervertebral disc disease, Amebiasis, Familial intestinal polyatresia syndrome, Bowel bypass syndrome, Intestinal capillariasis, Intestinal epithelial dysplasia, Helminthiasis, Intestinal Lymphangiectasia, Gardner syndrome, Ascariasis, Atrial myxoma, familial , Heart cancer, Benign astrocytoma, Bowen's disease, Intrahepatic cholangiocarcinoma, Goldenhar disease, Asherman's syndrome, Intussusception, Bladder Cancer, Genital psoriasis, Inversion 9 syndrome, Ankle sprain, IPEX syndrome, Aniridia, Iridocorneal dysgenesis, Iridocyclitis, Iridodialysis, Iridogoniodysgenesis typel, Chandler'
  • Adriaenssens syndrome Cogan-Reese syndrome, Iritis, Hemochromatosis, Bantu siderosis, Irons-Bhan syndrome, Irritable bowel syndrome, Irritant contact eczema, Isaacs syndrome, Ischemia, Avascular necrosis, Cardiomyopathy, Ischemic heart disease, Bywaters' syndrome, Calciphylaxis, Binswanger's Disease, Ischio-spinal dysostosis, Ischiogluteal Bursitis,
  • Isobutyric aciduria Isobutyryl-coenzyme A dehydrogenase deficiency, Ectopia lentis, Follicle- stimulating hormone deficiency, Fleisher syndrome, Calvarial hyperostosis, Isopsoriasis, Isosporiasis, Isosporosiasis, Isovaleric academia, Israeli spotted fever, Isthmus coarctation, Hypomelanosis of Ito, Ivemark Syndrome, Ives-Houston syndrome, Ivic Syndrome, Ivory Epiphyses , Jackson-Barr syndrome, Jackson-Weiss Syndrome, Jacobs syndrome, Jacobsen syndrome, Jadassohn-Lewandowsky syndrome, Jaffe-Lichtenstein syndrome, Jaffer-Beighton syndrome, Amaurosis hypertrichosis, Creutzfeldt-Jakob Disease, Amaurosis hypertrichosis, Janbon syndrome, Jankovic-Rivera syndrome, Jansen type metaphyseal chondrodys
  • Kantaputra-Gorlin syndrome Kanzaki disease
  • Kaolin pneumoconiosis Kaolin pneumoconiosis
  • Kleptolagnia Klinefelter syndrome, Klippel Feil Syndrome, Klippel-Trenaunay Syndrome, Klotz syndrome, Dejerine-Klumpke syndrome, Kluver-Bucy Syndrome, Kniest dysplasia, Knismolagnia, Knobloch syndrome, Kocher-Debre-Semelaigne syndrome, Kohler, disease, Kohler syndrome, Freiberg disease, Degos Disease, Kohlschutter-Tonz syndrome, Roller syndrome, Konigsmark-KnoxJ iussels syndrome, Koone-Rizzo-Elias syndrome, Koro syndrome, Korovnikov syndrome, Koroxenidis Syndrome, Korsakoff's psychosis, Korula- Wilson-Salomonson syndrome, Kostmann syndrome, Kosztolanyi syndrome, Kote-Katsantoni Syndrome, Kotzot -Richter syndrome, Koussef Nichols syndrome, Kowarski syndrome, Kozlowski Celermajer Tink syndrome, Koz
  • Laryngomalacia Larynx atresia, Larynx Cancer, Lassa fever, Lasseur-Graham-Little syndrome, Bessman-Baldwin syndrome, Common Variable Immunodeficiency, Latent tuberculosis, Lateral body wall complex, Goldenhar disease, Latham-Munro syndrome, Lathosterolosis, Lathyrism, Biber-Haab-Dimmer dystrophy, Lattice corneal dystrophy, Laugier-Hunziker syndrome, Launois syndrome, Launois-Bensaude adenolipomatosis, Froelich's syndrome, Laurence -Moon Syndrome, Laurence-Prosser-Rocker syndrome,
  • Marec-Bracq-Picaud syndrome Coffin syndrome 1, Leber hereditary optic neuropathy, Leber miliary aneurysm, Leber optic atrophy, Ledderhose disease, Lederer's anemia, Legg-Calve- Perthes disease, Legionella infection, Legionnaires' disease, Camurati-Engelmann Disease, Delleman-Oorthuys syndrome, Leigh syndrome, Leiner Disease, Leiomyoma, Leiomyomatosis, Leiomyosarcoma, Leishmaniasis , Lele syndrome, Lemierre's syndrome, Lenegre disease, Lennox- Gastaut Syndrome, Lentigo maligna, Lenz Majewski hyperostotic dwarfism,
  • Leptosadism Leptospirosis, Leri Pleonosteosis, Leri-Weil syndrome, Leriche syndrome, Lesch- Nyhan syndrome, Leschke syndrome, Bell mania, Letterer-Siwe disease, Leucinosis,
  • Leukemia Leukocyte Adhesion deficiency (LAD), Leukocytoclastic angiitis, Halo nevi,
  • Limb -mammary syndrome Limbic encephalitis, Limited cutaneous systemic sclerosis, CREST syndrome, Lindsay-Burn syndrome, Lindstrom syndrome, Linear IgA dermatosis, Linear porokeratosis, Hairy tongue, Linguatula serrata infection, Brinton disease, Lip cancer, Cheilitis, Lipedema, Lipid storage myopathy, Lipoamide dehydrogenase deficiency,
  • Lipoatrophic diabetes Lipodermatosclerosis, Lipodystrophy, Dunnigan syndrome, Lipoedema, Ceroid storage disease, Lipogranulomatosis, Lipoid proteinosis of Urbach and Wiethe, Lipoma, Lipomyelomeningocele, Lipoprotein glomerulopathy, Lipoproteine lipase deficiency,
  • Lipoproteinemia Liposarcoma, Lissauer paralysis, Lissencephaly, Listeriosis, Littoral cell angioma, Liver abscess, Liver cancer, Liver cirrhosis, Liver fibrosis, Budd-Chiari syndrome, Lobstein disease, Lobular carcinoma, Dysautonomia, Localized epiphyseal dysplasia,
  • dysfibrinogenemia Louse-borne diseases, Hypokalemia, Hyperacusis, Lowe oculocerebrorenal syndrome, Dejerine-Klumpke syndrome, Lower esophageal ulcer, Lowry syndrome, Lowry- Maclean syndrome, Lowry-Wood syndrome, Lubarsch-Pick syndrome, Lubinsky syndrome, Lubs syndrome, Lucey Driscoll syndrome, Lujan-Fryns syndrome, Lumbago, Lumbar Spondylosis, Lundberg syndrome, Lung cancer, Lupus, Lurie-Kletsky syndrome, Lutz- Lewandowsky epidermodysplasia verruciformis, Lutz-Miescher Disease, Lutz-Richner-Landolt syndrome, Lygerastia, Lyme disease, Lymph node neoplasm, Lymphadenitis, Bafverstedt syndrome, Lymphangiectasis, Lymphangioleiomyomatosis, Lymphangiomas, Lymphangitis, Ly
  • Lymphogranuloma venereum Lymphoid interstitial pneumonia, Lymphoma, Lymphomatoid Granulomatosis, Lymphomatoid papulosis, Lymphomatous thyroiditis, Lymphopenia, Lynch Syndrome, Lysinuric protein intolerance, Lysteria monocytoigeneses meningitis, M/SCHAD deficiency, Mac Duffie's syndrome, MacDermot-Winter syndrome, Machado-Joseph Disease, Machinery accidents, Atrophoderma vermiculata, Macleod-Fraser syndrome, Macrocephaly, Macrocytic anemia, Macrocytic Hyperchromic Anemia, Macrocytosis, Macrodactyly,
  • myofasciitis Macrophilia, Macrosomia, Macrostomia, ,Macrothrombocytopenia, Macula halo syndrome, Macular amyloidosis, Macular degeneration, Macular dystrophy, Macules, hereditary, Madelung deformity, Madokoro-Ohdo-Sonoda syndrome, MADSAM, Maffucci Syndrome, Maghazaji syndrome, Magnesium deficiency, Magnetic gait, Magrassi-Leonardi syndrome, Majeed syndrome, Majocchi disease, Major affective disorder, Major depressive disorder, Major depressive disorder related fibromyalgia, Major histocompatibility complex class I deficiency, Major histocompatibility complex class II deficiency, Major Ulcerative Stomatitis, Mai de debarquement, Malakoplakia, Malaria, Male Breast Cancer, Male infertility, Malignant astrocytoma, Malignant brain tumors ...
  • Brain cancer Malignant Buotonneuse fever, Malignant fibrous histiocytoma, Malignant germ cell tumor, Malingering, Malonic aciduria, Malouf syndrome, Malt Worker's disease, Mammary polyadenomatosis, Mania, Mann syndrome, Man refineer syndrome, Mansonelliasis, Mantle cell lymphoma, Manz syndrome, Map-dot-fingerprint dystrophy, Maple syrup urine disease, Marasmus, Marburg disease, Marchiafava-Bignami disease, Marchiafava-Micheli disease, Marcus-Gunn
  • heterotopia Marie type ataxia, Marie Unna congenital hypotrichosis, Marie-Bamberg syndrome, Marie-Sainton syndrome, Marie-See Syndrome, Marie-Strumpell disease,
  • Marinesco-Sjogren syndrome Maroteaux-Fonfria syndrome, Maroteaux-Stanescu-Cousin syndrome, Maroteaux-Verloes-Stanescu syndrome, Marsden syndrome, Marsden-Nyhan- Sakati syndrome, Marseilles fever, Marshall syndrome, Marshall-Smith Syndrome, Martsolf syndrome, MASA Syndrome, MASS syndrome, Massa-Casaer-Ceulemans syndrome, Mast cell sarcoma, Mastalgia, Mastitis, Mastix, Mastocytosis, Mastofact, Mastoiditis, Matsoukas syndrome, Matsoukas-Liarikos-Giannika syndrome, Maumenee syndrome, Mauriac syndrome, May-Hegglin thrombocytopenia, May- White syndrome, Mayaro fever, Mayer-Rokitansky- Kuster-Hauser, syndrome, Mazabraud syndrome, Mazoperosis, Mc Leod neuroacanthocytosis syndrome, MC
  • McDonough syndrome McDowall syndrome, McGillivray syndrome, McGrath Syndrome, McKusick-Kaufman syndrome, McLain-Dekaban syndrome, McLetchie-Aikens syndrome, McMurray's sign, Meadows syndrome, Measles, Meckel Syndrome, Medial Medullary
  • dehydrogenase deficiency Medium and short chain 3-hydroxyacyl-CoA dehydrogenase deficiency, Medium-Chain Acyl-CoA Dehydrogenase Deficiency, Medullary carcionoma, Medullary cystic kidney disease, Medulloblastoma, Megacolon, Megaduodenum ,
  • Membranoproliferative glomerulonephritis Mende syndrome, Mendelson syndrome, Meninges cancer, Meningioma, Meningitis, Meningocele, Meningococcal disease, Meningoencephalocele, Meningomyelocele, Menkes Disease, Menorrhagia, Meralgia paresthetica, Meretoja syndrome, Merkel cell cancer, Mesangial proliferative glomerulonephritis, Mesangial sclerosis, diffuse, Mesangiocapillary glomerulonephritis type , Mesenteric Adenitis, Mesenteric artery syndrome, Mesomelia, Mesothelioma, Metabolic Acidosis, Metabolic Syndrome,
  • Metachondromatosis Metachromatic Leukodystrophy, Metagonimiasis, Metaphyseal acroscyphodysplasia, Metapneumoviral infection, Metatarsus adductus, Metatrophic dysplasia, Metatropic dwarfism, Methaemoglobinaemia, Methimazole -- Teratogenic Agent, Methylcobalamin deficiency, Methylene tetrahydrofolate reductase deficiency,
  • Methylmalonate Semialdehyde Dehydrogenase Deficiency, Methylmalonic acidemia
  • Metrorrhagia Metz dysfibrinogenemia, Mevalonic aciduria, Meyenburg-Altherr-Uehlinger syndrome, Michelin Tire Baby Syndrome, Michels-Caskey syndrome, Mickleson syndrome, Mickulicz disease, Microcephaly-oculo-digito-esophageal-duodenal syndrome, Microcoria, congenital, Microcornea , Microcytic Anemia, Microcytosis, Microdontia -- hypodontia -- short stature, Micrencephaly, Microlissencephaly, Microsomia -- hemifacial -- radial defects, Microspherophakia with hernia, Microsporidiosis, Microtia type I , Microvascular angina, Microvillus Inclusion Disease, Middle ear infection, Midline lethal granuloma, Miescher Elastoma, Miescher's granuloma, Miescher's syndrome, Miescher's trichofolliculo
  • Monoamine oxidase A deficiency Monogenic obesity, Monomelic Amyotrophy, Mononen- Karnes-Senac syndrome, Mononeuritis multiplex, Mononucleosis, Monster cell malignant melanoma, Montefiore syndrome, Moore Smith Weaver syndrome, Morava-Mehes syndrome, Morel-Wildi syndrome, Morgellons Disease, Moriaphilia, MORM syndrome, Morning sickness, Morphea, Morphoeic basal cell carcinoma, Morquio syndrome, Morse-Rawnsley-Sargent syndrome, Mortimer's disease, Morton's Neuroma, Motion sickness, Motor neuropathy, Mottled cyanosis , Mouldy shower curtain hypersensitivity pneumonitis, Mounier-Kuhn syndrome, Mount Reback syndrome, Mountain fever, Mousa-Al Din-Al Nassar syndrome, Mouth cancer, Mouth ulcers, Mowat- Wilson syndrome, Moyamoya Disease, Moynahan syndrome, MPS 3
  • Mucormycosis Mucosal leishmaniasis (espundia), Mucositis, Muenke Syndrome, Mulibrey Nanism syndrome, Muller-Barth-Menger syndrome, Mullerian aplasia, Multicentric reticulohistiocytosis, Multiple Myeloma, Multiple Sclerosis, Multiple Sulfatase Deficiency, Multiple synostoses syndrome 1, Mumps, Mungan syndrome, Munk disease, MURCS
  • Myasthenia Gravis Mycetoma, Mycobacterial infections, Mycoplasma pneumoniae, Mydriasis, Myelinopathies, Myelitis, Myelocerebellar disorder, Myelocytic leukemia-like syndrome, familial, chronic , Myelodysplastic/myeloproliferative disease, Myelofibrosis, Myelofibrosis- osteosclerosis, Myelogenous leukemia, Myeloid Sarcoma, Myeloid splenomegaly,
  • Myelokathexis syndrome Myeloma, Myelopathy, Myeloperoxidase deficiency, Myelpathic anemia, Myhre Syndrome, Myiasis, Myocarditis, Myoclonic dystonia, Myoclonus ,
  • Myoglobinuria Myokymia, Myoma (fibroid), Myopathy, Myopia , Myosarcoma , Myositis, Myotonic Dystrophy, Myxedema, Myxoid liposarcoma, Myxoid melanoma, Meniere's disease, Menetrier's disease, N syndrome , N-acetyl glutamate synthetase deficiency, N- acetyl- alpha- glucosaminidase sulfamidase deficiency, Nablus mask-like facial syndrome, Nacrochlesis , NADH cytochrome B5 reductase deficiency , Naegleria, Nager Syndrome, Naguib syndrome, Nakajo syndrome, NAME syndrome, Nance-Horan Syndrome, Nancy dysfibrinogenemia, Nanophthalmia, Nanukayami, Narcolepsy, Nathalie syndrome, Native American myopathy, Navajo
  • Nephrocalcinosis Nephrolithiasis type 1, Nephronophthisis , Nephropathy, Nephrosclerosis, Nephrosis , Nerve cancer , Nesidioblastosis of pancreas , Netherton syndrome ichthyosis , Neu-Laxova Syndrome , Neuhauser-Daly-Magnelli syndrome, Neuhauser-Eichner-Opitz syndrome, Neuralgia, Neuraminidase deficiency, Neuritis, Neuroacanthocytosis,
  • Neuroblastoma Neurocutaneous melanosis, Neurocysticercosis, Neurodermatitis, and
  • Neuroepithelioma Neurofibromatosis, Neurofibrosarcoma, Neuroma , Neuromyelitis Optica, Neuromyotonia , Neuropathy , Neurosis, Neurosyphilis , Neutropenia, Nevo syndrome, Nevoid melanoma, Newcastle Disease, Nezelof Syndrome, Nguyen syndrome, Nicolaides- Baraitser syndrome, Nicolau syndrome, Nielsen-Jacobs syndrome, Niemann-Pick disease, Nierhoff-Hubner syndrome, Nievergelt syndrome, Nijmegen Breakage Syndrome, Nipah virus encephalitis, NISCH syndrome, NISH Syndrome , Nivelon-Nivelon-Mabille syndrome, Noble- Bass-Sherman syndrome, Nocardiosis, Nocturia, Nodular basal cell carcinoma, Nodular goiter , Nodular Prurigo, NOMID syndrome, Non cardiogenic pulmonary oedema, Non- alcoholic steatohepatitis (NASH), Non-allergic asthma,
  • Osteoradionecrosis Osteosarcoma, Osuntokun syndrome, Otitis, Oto-facio-osseous-gonadal syndrome, Otocephaly syndrome, Otodental dysplasia, Otoony chop er one al syndrome,
  • Ovarioleukodystrophy Owren Parahemophilia, Oxalosis, Ozolagnia, Pachydermoperiostosis , Pachygyria , Pachyonychia congenital syndrome, Paget's Disease, Palate cancer,
  • Palindromic rheumatism Pallidopyramidal syndrome, Pallister Killian Mosaic Syndrome , Pallister-Hall Syndrome, Pallister-Killian Syndrome, Pallister-Ulnar mammary syndrome, Palmer-Pagon syndrome, Panacinar Emphysema, Pancoast's syndrome, Pancolitis,
  • Pancreatic cancer Pancreatitis, Pancreatoblastoma, Pancytopenia, Panhypopituitarism, Panniculitis, Panophthalmitis, Panostotic fibrous dysplasia, Panuveitis, Papillary renal cell carcinoma, Papillitis, Papilledema, Papilloma, Paprika splitter's lung, Paprika splitter's lung -- Mucor Stolonifer, Papular mucinosis, Papular urticaria, Paracoccidioidomycosis, Paracusia, Paraganglioma, Paragonimiasis, Parainfluenza, Paralysis, Paraomphalocele, Paraphilias, Paraphimosis , Parapsoriasis , Parasomnia, Paresis, Paresthesia, Parkinson's Disease, Paronychia, Parotid gland cancer, Parotitis, Paroxysmal atrial tachycardia,
  • Paroxysmal kinesigenic choreoathetosis Paroxysmal ventricular fibrillation, Parry Romberg Syndrome, Pars Planitis, Parsonage Turner syndrome , Partington X-linked mental retardation syndrome, Pashayan syndrome, Passos-Bueno syndrome, Patau syndrome , Patel- Bixler syndrome, Patterson-Stevenson syndrome, Pauciarticular chronic arthritis,
  • Paucigranulocytic asthma PCBD, Pearson's anemia, Peeling skin syndrome, PEHO-like syndrome, Pelger-Huet anomaly, Pelizaeus-Merzbacher Disease, Pellagra, Pelvic Cancer, Pemphigus, Pendred syndrome, Penis Cancer, Pentalogy of Cantrell, Pentosuria, PEPCK Deficiency, Peptic Ulcer, Perennial rhinitis, Pericardial Mesothelioma, Pericarditis,
  • Phosphoenolpyruvate carboxykinase (PEPCK) deficiency Phocomelia syndrome , Phosphoenolpyruvate carboxykinase (PEPCK) deficiency
  • Phosphoribosylpyrophosphate synthetase deficiency Phosphoserine aminotransferase deficiency, Photosensitivity , Phrynoderma, Phyllodes tumor, PIBIDS syndrome, Picardi- Lassueur-Little syndrome, Pick's Disease, Pickwickian syndrome, PID-like dyspareunia, Pierre Robin's sequence, Pierson Syndome, Pigeon Breeder's disease, Pigment-dispersion syndrome, Pigmentary retinopathy, Pigmented basal cell carcinoma, Pili annulati, Pili multigemini, Pili torti, Pillay syndrome, Pilomatrixoma , Pilonidal disease, Pilotto syndrome, Acne, Pindborg Tumor, Pineal Teratoma, Piriformis Syndrome, Pitt-Hopkins syndrome , Pitt-Rogers-Danks syndrome, Pituitary Cancer, Pityriasis, Piussan-Lenaert- Mathieu
  • Pneumonitis Pneumothorax, Podder-Tolmie syndrome, POEMS syndrome, Poikilocytic anemia, Poikiloderma of Kindler, Poikiloderma of Rothmund-Thomson, Pointer syndrome, Tru Syndrome, Polio, Pollitt syndrome, Polyarteritis, Polyarthritis, Polycystic kidney disease, Polycystic liver disease, Polycythemia, Polydactyly, Polyembryoma ,Polyendocrine deficiency syndrome, Polymer Fume Fever, Polymicrogyria , Polymyalgia rheumatica, Polymyocytis, Polyneuritis, Polyomavirus Infections, Polyp, Polytopic Dystelephalangy, Pompe disease, Poncet-Spiegler's cylindroma, Pontiac fever, Porencephaly, Porphyria, Port- wine stain, Portal thrombosis, Portsmouth syndrome, Portuguese type amyloidosis,
  • Postperfusion syndrome Potassium deficiency
  • Potocki-Lupski syndrome Potter syndrome
  • Powell-Buist-Stenzel syndrome Powell-Chandra-Saal syndrome
  • Powell-Venencie-Gordon syndrome Prader-Willi syndrome
  • Pratesi syndrome Pre-invasive breast cancer
  • Pregnancy-related conditions Prehypertension , Premature aging , Premenstrual syndrome, Presbycusis, Presbylarynx, Presbyopia, Pretibial Myxedema , Priapism, Primary
  • agammaglobulinemia Primerose syndrome, Primrose Syndrome, Prinzmetal's variant angina, Prion disease, Proctalgia , Proctitis, Progeria, Prolactinoma, Prolapse,
  • Prolymphocyte leukemia Prostate Cancer, Prostatitis , Protanopia , Protein C deficiency, Protein S deficiency, Proteinuria, Proteus Syndrome, Protoporphyria, Protozoan infections , Proud-Le vine- Carpenter syndrome, Prurigo, Pseudo-torch syndrome, Pseudoachondroplasia, Pseudoaldosteronism, Pseudogout , Pseudohypoaldosteronism , Pseudomonas infections, Pseudopolycythaemia, Psittacosis , Psoriasis, Psychoneurosis, Psychosis, Ptosis , Pulmonary alveolar microlithiasis , Pulmonary edema, Pulmonary fibrosis, Pulmonary hemangiomatosis, Pulmonary hypertension, Pulmonary valve disease , Pulp Worker's
  • Pycnodysostosis Pyelonephritis , Pyle disease, Pylephlebitis , Pyloric stenosis, Pyomyositis , Pyridoxine deficiency , Pyrolagnia , Pyrosis , Pyruvate carboxylase deficiency , Pyruvate decarboxylase deficiency , Pyruvate dehydrogenase deficiency , Pyruvate dehydrogenase phosphatase deficiency , Pyruvate Kinase Deficiency, Q fever, Quadriplegia, Quattrin mcpherson syndrome, Quebec platelet disorder, Queensland tick typhus, Quinsy, Rabies, Rabson-Mendenhall syndrome, Raderaum disease, Radial Hemimelia, Radial Ray
  • Retinohepatoendocrinologic syndrome Retinopathy, Rett's syndrome, Revesz Debuse syndrome, Reye's Syndrome, Reynolds syndrome, Rh Disease, Rhabditida Infections,
  • Rhabdoid tumor Rhabdomyolysis, Rhabdomyosarcoma, Rheumatism, Rheumatoid arthritis, Rhinitis, Rhino-orbito-cerebral phycomycosis, Rhinophyma, Rhinosporidiosis,Rhinovirus infection, Rhnull syndrome, Rhombencephalosynapsis, Rhonchi, RHYNS syndrome, Ribbing syndrome, Rice millers' syndrome, Richards-Rundle syndrome, Richieri Costa Guion Almeida Cohen syndrome, Richter syndrome, Rickettsial disease, Riddle syndrome, Riedel syndrome, Rieger Syndrome, Rietti-Greppi-Micheli syndrome, Rift Valley Fever, Right hemisphere syndrome, Right pneumonectomy syndrome, Riley Shwachman syndrome, Rimbaud- Passouant-Vallat syndrome, Rippling muscle disease, Ritter syndrome, River Blindness,
  • Roberts Pseudothalidomide Syndrome Robinow Soriller syndrome, Robinow-Unger syndrome, Robinson syndrome, Roch-Leri mesosomatous lipomatosis, Rocio encephalitis, Rocky Mountain spotted fever,
  • Schneckenbecken dysplasia Schnitzler syndrome, Schofer beetz bohl syndrome, Scholte syndrome, Schopf-Schulz-Passarge syndrome, Schrander-Stumpel, Theunissen, Hulsmans syndrome, Schridde syndrome, Schroder syndrome, Schroer-Hammer-Mauldin syndrome, Schwannoma, Schwannomatosis, Schwartz newark syndrome, Schwartz, Cohen- Addad, Lambert syndrome, Schwartz-Jampel Syndrome, Schwartz- Lelek syndrome, Schweitzer kemink malcolm syndrome, Sciatica, SCID, Scissor gait, Scleredema adultorum, Scleritis, Scleroderma, Sclerosing Cholangitis, Sclerosing Lymphocytic Lobulitis, Sclerosis,
  • Extramedullary Plasmacytoma Somatostatinoma, Sommer-Hines syndrome, Sonoda syndrome, Sopite syndrome, Soto's Syndrome, Southworth symptom complex, Spanlang- Tappeiner syndrome, Spasmodic dysphonia, Spasmodic Torticollis, Sphenoid Sinusitis, Spherocytic anemia, Spherocytosis, Sphingolipidosis, Spina bifida, Spinal stenosis,
  • Taeniasis Taijin-KyofuSho syndrome, Takahara syndrome , Takayasu arteritis , Tako- Tsubo syndrome , Tangier disease , TAR syndrome, Tardive Dyskinesia , Tarsal Synostosis .Tarsal tunnel syndrome , TAU syndrome , Taussig Bing syndrome , Tay-Sachs disease , Teebi-Kaurah syndrome , Teebi-Shaltout syndrome , Tel-Hashomer camptodactyly syndrome , Telangiectasia , Telfer-Sugar-Jaeger syndrome , Temtamy syndrome , Tendinitis ,
  • Thyrotoxicosis factitia Tic disorders, Tietz Albinism-Deafness Syndrome, Tiglic acidemia, Timme syndrome, Timothy syndrome, Tinea, Tinnitus, Tollner-Horst-Manzke syndrome, Tolosa-Hunt Syndrome, Tome-Brune-Fardeau syndrome, Tongue Cancer, Toni-Fanconi syndrome, Tonsilitis, TORCH Syndrome, Toriello syndrome, Toriello-Higgins-Miller syndrome, Torticollis, Torulopsis, Touraine-Solente-Gole syndrome, Tourette Syndrome, Townes-Brocks Syndrome, Toxemia, Toxocariasis, Toxoplasmosis, Tracheal cancer, Tracheal stenosis syndrome, Tracheitis, Trachoma, Transthyretin amyloidosis, TRAPS (TNF- receptor-associated periodic syndrome), Treacher-Collins Syndrome, Treft-Sanborn-Carey syndrome, Tremor
  • Trichofolliculoma Trichomoniasis, Trichorhinophalangeal syndrome , Trichorrhexis nodosa syndrome, Trichoscyphodysplasia, Trichosporin infection, Trimethylaminuria , Triopia, Triose phosphate-isomerase deficiency, Triple-X syndrome, Tripsolagnia, Trochanteric bursitis, Troell- Junet syndrome, Troilism, Trophoblastic Cancer, Tropical sprue , Troyes dysfibrinogenemia, Trueb-Burg-Bottani syndrome, Trypanosomiasis, Tsukuhara syndrome, Tuberculosis, Tubular carcinoma, Tungiasis, Turcot syndrome, Turner Syndrome, Turpin syndrome, Tylosis, Type 1 diabetes, Type 2 diabetes, Type A Influenza, Type B Influenza, Type C Influenza, UDP-Galactose-4-epimerase deficiency, Uhl anomaly, Uhthoff syndrome
  • Urethral syndrome Urethritis, Urofacial syndrome, Urticaria, Usher Syndrome, Uveitis, Vacuolar myopathy, Vagina cancer, Vaginal candidiasis, Vaginosis (bacterial vaginosis), Vail syndrome, Valinemia, Van Allen Myhre syndrome, Van Bogaert disease, Van Bogaert- Hozay syndrome, Van Bogaert-Scherer-Epstein Disease, Van Buchem disease, Van De Berghe Dequeker syndrome, Van den Bosch syndrome, Van der Woude syndrome, Van Goethem syndrome, Van Maldergem Wetzburger Verloes syndrome, Van Regemorter
  • the disease is an auto- immune disease selected from the group consisting of Achlorhydra Autoimmune Active Chronic Hepatitis; Acute Disseminated Encephalomyelitis; Acute hemorrhagic
  • Demyelinating Diseases Idiopathic pulmonary fibrosis; Idiopathic thrombocytopenic purpura; IgA nephropathy; Inclusion body myositis; Inflammatory demyelinating polyneuopathy;
  • Interstitial cystitis Irritable Bowel Syndrome (IBS); Juvenile idiopathic arthritis; Juvenile rheumatoid arthritis; Kawasaki's Disease; Lambert-Eaton myasthenic syndrome;
  • Leukocytoclastic vasculitis Lichen planus; Lichen sclerosus; Linear IgA disease; Lou Gehrig's Disease; Lupoid hepatitis; Lupus erythematosus; Majeed syndrome; Meniere's disease;
  • mice Microscopic polyangiitis; Miller-Fisher syndrome; Mixed Connective Tissue Disease; Morphea; Mucha-Habermann disease; Muckle-Wells syndrome; Multiple Myeloma; Multiple Sclerosis; Myasthenia gravis; Myositis; Narcolepsy; Neuromyelitis optica; Neuromyotonia; Occular cicatricial pemphigoid; Opsoclonus myoclonus syndrome; Ord thyroiditis; Palindromic rheumatism; PANDAS; Paraneoplastic cerebellar degeneration; Paroxysmal nocturnal hemoglobinuria; Parry Romberg syndrome; Parsonnage-Turner syndrome; Pars planitis;
  • Spondyloarthropathy Spondyloarthropathy; Sticky blood syndrome; Still's Disease; Stiff person syndrome; Subacute bacterial endocarditis (SBE); Susac's syndrome; Sweet syndrome; Sydenham Chorea;
  • Sympathetic ophthalmia Takayasu's arteritis; Temporal arteritis; Tolosa-Hunt syndrome; Transverse Myelitis; Ulcerative Colitis; Undifferentiated connective tissue disease;
  • Undifferentiated spondyloarthropathy Undifferentiated spondyloarthropathy; Vasculitis; Vitiligo; Wegener's granulomatosis;
  • said disease is a skin disease selected from the group consisting of Acneiform eruptions; Autoinflammatory syndromes; Chronic blistering; Conditions of the mucous membranes; Conditions of the skin appendages; Conditions of the subcutaneous fat; Congenital anomalies; Connective tissue diseases (such as Abnormalities of dermal fibrous and elastic tissue); Dermal and subcutaneous growths; Dermatitis (including Atopic Dermatitis, Contact Dermatitis, Eczema, Pustular Dermatitis, and Seborrheic
  • Dermatitis Dermatitis); Disturbances of pigmentation; Drug eruptions; Endocrine -related skin disease; Eosinophilic; Epidermal nevi, neoplasms, cysts; Erythemas; Genodermatoses; Infection- related skin disease; Lichenoid eruptions; Lymphoid-related skin disease; Melanocytic nevi and neoplasms (including Melanoma); Monocyte- and macrophage-related skin disease;
  • keratodermas Pregnancy-related skin disease; Pruritic; Psoriasis; Reactive neutrophilic; Recalcitrant palmoplantar eruptions; Resulting from errors in metabolism; Resulting from physical factors (including Ionizing radiation-induced); Urticaria and angioedema; Vascular- related skin disease.
  • the disease is an endocrine disease selected from the group consisting of Adrenal disorders; Glucose homeostasis disorders; Thyroid disorders; Calcium homeostasis disorders and Metabolic bone disease; Pituitary gland disorders ; and Sex hormone disorders.
  • the disease is an eye disease selected from the group consisting of Disorders of eyelid, lacrimal system and orbit; Disorders of conjunctiva; Disorders of sclera, cornea, iris and ciliary body; Disorders of lens; Disorders of choroid and retina (including Chorioretinal inflammation, Other disorders of choroid, Chorioretinal disorders in diseases classified elsewhere, Retinal detachments and breaks, Retinal vascular occlusions, Gther retinal disorders, Glaucoma; Disorders of vitreous body and globe; Disorders of optic nerve and visual pathways; Disorders of ocular muscles, binocular movement, accommodation and refraction; Visual disturbances and blindness; and Other disorders of eye and adnexa.
  • the disease is a neurological disorder selected from the group consisting of Abarognosis; Acquired Epileptiform Aphasia; Acute disseminated encephalomyelitis; Adrenoleukodystrophy; Agenesis of the corpus callosum; Agnosia; Aicardi syndrome; Alexander disease; Alien hand syndrome; Allochiria; Alpers' disease; Alternating hemiplegia; Alzheimer's disease; Amyotrophic lateral sclerosis (see Motor Neurone Disease); Anencephaly; Angelman syndrome; Angiomatosis; Anoxia; Aphasia; Apraxia; Arachnoid cysts; Arachnoiditis; Arnold-Chiari malformation; Arteriovenous malformation; Ataxia
  • a neurological disorder selected from the group consisting of Abarognosis; Acquired Epileptiform Aphasia; Acute disseminated encephalomyelitis; Adrenoleukodystrophy; Agenesis of the corpus callosum;
  • Dysautonomia Dyscalculia; Dysgraphia; Dyslexia; Dystonia; Empty sella syndrome
  • Fibromyalgia Gaucher's disease; Gerstmann's syndrome; Giant cell arteritis; Giant cell inclusion disease; Globoid Cell Leukodystrophy; Gray matter heterotopia; Guillain-Barre syndrome; HTLV- 1 associated myelopathy; Hallervorden-Spatz disease; Head injury;
  • Headache Hemifacial Spasm; Hereditary Spastic Paraplegia; Heredopathia atactica polyneuritiformis; Herpes zoster oticus; Herpes zoster; Hirayama syndrome;
  • Hypercortisolism Hypoxia; Immune -Mediated encephalomyelitis; Inclusion body myositis; Incontinentia pigmenti; Infantile phytanic acid storage disease; Infantile Refsum disease; Infantile spasms; Inflammatory myopathy; Intracranial cyst; Intracranial hypertension; Joubert syndrome; Karak syndrome; Kearns-Sayre syndrome; Kennedy disease; Kinsbourne syndrome; Klippel Feil syndrome; Krabbe disease; Kugelberg-Welander disease; Kuru; Lafora disease; Lambert-Eaton myasthenic syndrome; Landau- Kleffner syndrome; Lateral medullary (Wallenberg) syndrome; Learning disabilities; Leigh's disease; Lennox-Gastaut syndrome; Lesch-Nyhan syndrome; Leukodystrophy; Lewy body dementia; Lissencephaly; Locked-In syndrome; Lou Gehrig's disease (See Motor Neurone Disease); Lumbar disc disease; Lumbar spinal stenosis
  • Mucopolysaccharidoses Multi-infarct dementia; Multifocal motor neuropathy; Multiple sclerosis; Multiple system atrophy; Muscular dystrophy; Myalgic encephalomyelitis;
  • Myasthenia gravis Myelinoclastic diffuse sclerosis; Myoclonic Encephalopathy of infants; Myoclonus; Myopathy; Myotubular myopathy; Myotonia congenita; Narcolepsy;
  • Neurofibromatosis Neuroleptic malignant syndrome; Neurological manifestations of AIDS; Neurological sequelae of lupus; Neuromyotonia; Neuronal ceroid lipofuscinosis; Neuronal migration disorders; Niemann-Pick disease; Non 24-hour sleep-wake syndrome; Nonverbal learning disorder; O'Sullivan-McLeod syndrome; Occipital Neuralgia; Occult Spinal
  • Dysraphism Sequence Ohtahara syndrome; Olivopontocerebellar atrophy; Opsoclonus myoclonus syndrome; Optic neuritis; Orthostatic Hypotension; Overuse syndrome; Palinopsia; Paresthesia; Parkinson's disease; Paramyotonia Congenita; Paraneoplastic diseases;
  • Paroxysmal attacks Parry-Romberg syndrome; Pelizaeus-Merzbacher disease; Periodic Paralyses; Peripheral neuropathy; Persistent Vegetative State; Pervasive developmental disorders; Photic sneeze reflex; Phytanic acid storage disease; Pick's disease; Pinched nerve; Pituitary tumors; PMG; Polio; Polymicrogyria; Polymyositis; Porencephaly; Post-Polio syndrome; Postherpetic Neuralgia (PHN); Postinfectious Encephalomyelitis; Postural
  • Rasmussen's encephalitis Reflex neurovascular dystrophy; Refsum disease; Repetitive motion disorders; Repetitive stress injury; Restless legs syndrome; Retrovirus-associated myelopathy; Rett syndrome; Reye's syndrome; Rhythmic Movement Disorder; Romberg syndrome; Saint Vitus dance; Sandhoff disease; Schizophrenia; Schilder's disease; Schizencephaly; Sensory integration dysfunction; Septo-optic dysplasia; Shaken baby syndrome; Shingles; Shy-Drager syndrome; Sjogren's syndrome; Sleep apnea; Sleeping sickness; Snatiation; Sotos syndrome; Spasticity; Spina bifida; Spinal cord injury; Spinal cord tumors; Spinal muscular atrophy; Spinocerebellar ataxia; Steele-Richardson-Olszewski syndrome; Stiff-person syndrome;
  • Transverse myelitis Traumatic brain injury; Tremor; Trigeminal neuralgia; Tropical spastic paraparesis; Trypanosomiasis; Tuberous sclerosis; Von Hippel-Lindau disease; Viliuisk Encephalomyelitis ; Wallenberg's syndrome; Werdnig-Hoffman disease; West syndrome;
  • the disease is a cardiovascular disease selected from the group consisting of Angina; Atherosclerosis ; Cerebrovascular Accident (Stroke) ;
  • Cerebrovascular disease Cerebrovascular disease; Congestive Heart Failure; Coronary Artery Disease; Myocardial infarction (Heart Attack); and Peripheral vascular disease.
  • the CRISPR sequence relates to a pleiotropic effect, it will not be able to specifically diagnose for one disease or condition, and an assay with a multiplicity of CRISPR sequences is advisable. .
  • a set of CRISPR sequences suitable for diagnosing a specific condition or disease may comprise 2 (probes specific for 2) CRISPR sequences, but may also comprise 3 probes/sequences, where the third marker is chosen from any of the sequences indicated further in the set and/or one or more of the non-Affymetrix CRISPR sequences that is under- or overexpressed in said specific condition or disease.
  • it may comprise 4 sequences, 5 sequences, 6 sequences and more. It is emphasized that the more (specific) sequences are assayed, the more reliable the diagnosis will be.
  • a set of sequences which are applicable for the current invention may consist of a combination of the Affymetrix CRISPR sequences mentioned in the Examples and non-Affymetrix CRISPR sequences that are also specific for the same condition or disease.
  • transcription factor binding motifs such as the transcription factor motifs CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 and the transcription factor motifs PAX5, EGRl, XBP1, SREBP1, OLF1, MZFl, NFY, NFKAPPAB, MYCMAX, NFE2, and RP58 were each up-regulated (sometimes more than twofold) in Down syndrome samples compared to normal samples (Kong et al., Braz. J. Med. Biol. Res. 2014, 834-841).
  • protospacer target sequences may be available in more than one micro- organism(some are present in several, even more than 20 different species of microorganisms), it was also found that these protospacer sequences were accompanied by PAM sequences, which would indicate that indeed these protospacers would be targets for a Cas9-like nuclease activity for which the (eukaryotic) spacer can act as a guide RNA.
  • the EPCAT sequences as provided in Table 24 have been found to be differently expressed in patients suffering from prostate cancer and thus would be useful as a diagnostic tool for detecting the presence of cancer tissue or the predisposition for prostate cancer. Accordingly, the group of CRISPR sequences mentioned in Table 24 can be characterized as a separate group of CRISPR sequences.
  • the CRISPR sequences can be grouped in many different groups. As already has been indicated above, the sequences SEQ ID NO: 1 - 10141 can be considered to be human CRISPR sequences. A further group as indicated above are the human non-Affymetrix CRISPR sequences. Now a further category can be indicated: human non-Affymetrix non-EPCAT sequences, which group consists of all human CRISPR sequences except for the sequences provided in Tables 2, 3 and 24.
  • human non-Affymetrix non-EPCAT sequences can further be divided into several groupings.
  • the groupings can for instance be indicated per (human) chromosome.
  • Chromosome 1 SEQ ID NO: 1
  • Chromosome 2 SEQ ID NO:
  • Chromosome 3 SEQ ID NO:
  • Chromosome 4 SEQ ID NO:
  • Chromosome 5 SEQ ID NO:
  • Chromosome 7 SEQ ID NO:
  • Chromosome 8 SEQ ID NO:
  • Chromosome 9 SEQ ID NO:
  • Chromosome 10 SEQ ID NO: 1
  • Chromosome 11 SEQ ID NO:
  • Chromosome 12 SEQ ID NO:
  • Chromosome 13 SEQ ID NO:
  • Chromosome 14 SEQ ID NO:
  • Chromosome 15 SEQ ID NO: 7773, 7819, 7820, 7821, 7822, 7823, 7824, 7825, 7827, 7828, 7829, 7830, 7831, 7832, 7833, 10 021,7590,7593,7594,7591,7595,7596,7589,7597,7598, 10016, 10017, 10018, 10019, 10020,7595,76 09, 7610, 7611, 7612, 7613, 7614, 7592, 7615, 7616, 7617, 7618, 7619, 7620, 7621, 7622, 7623, 7624, 7602 , 7603, 7604, 7605, 7629, 7630, 7631, 7632, 7633, 7634, 7635, 7636, 7637, 7638, 7639, 7640, 7641, 7642, 7 643,
  • Chromosome 16 SEQ ID NO: 1
  • Chromosome 17 SEQ ID NO:
  • Chromosome 18 SEQ ID NO:
  • Chromosome 19 SEQ ID NO:
  • Chromosome 20 SEQ ID NO: 1
  • Chromosome 21 SEQ ID NO: 1
  • Chromosome 22 SEQ ID NO:
  • a further grouping of human, non-Affymetrix, non-EPSCAT sequences can be provided by the sequences as provided in Table 21 (CRISPR sequences related to transcription factor binding sites), Table 22 (CRISPR sequences related to DNAse 1 binding sites) and Table 23 (CRISPR sequences harbouring spacer sequences that target to protospacer sequences of viruses or bacteria).
  • Table 21 CRISPR sequences related to transcription factor binding sites
  • Table 22 CRISPR sequences related to DNAse 1 binding sites
  • Table 23 CRISPR sequences harbouring spacer sequences that target to protospacer sequences of viruses or bacteria.
  • sequences that are provided in Table 2 3 and/or 24 can be distracted from these groupings, thereby providing novel sets of CRISPR sequences.
  • CRISPR sequences can be distinguished with respect to the function of the CRISPR sequences.
  • Examples 15 and 16 a group of CRISPR sequences that is differently expressed in cancer tissues can be distinguished (the CRISPR sequences listed in Table 17), where this group can be further distinguished in CRISPR sequences that are differently expressed with respect to one particular type of cancer (as indicated in Fig. 15 and Table 19).
  • CRISPR sequences form part of the group of Affymetrix sequences
  • the sequences that are specified in each of the Examples 3 - 14 which may be used as diagnostic tools according to the specific condition or disease exemplified in these examples can each be seen as a grouping of CRISPR sequences according to the invention.
  • each individual CRISPR sequence may already be known, the fact that such a sequence can be advantageously used as a diagnostic tool and especially a group of CRISPR sequences as specified in each and every example of Examples 3 - 14 for such a diagnostic purpose may be considered as novel and inventive over the prior art.
  • the assays that are useful in the present invention are preferably quantitative assays, in which the quantity of expression in the sample can be determined. This can - in principle - be achieved with all kinds of detection methods as exemplified below. While interpreting the results of such an assay, various other health determinants such as sex, age, smoking status, urbanicity, food and alcohol intake may be taken into account.
  • CRISPR sequence can related to other factors such as sex, where in males a higher expression may be found than in females, or to a factor such as age, where in elderly persons a higher level of expression may be found than in younger persons.
  • the measured values should of course be interpreted in the light of these correlations, which would be known to the skilled person, or which would be easily discernible on basis of control sample assays. .
  • kits for diagnosing or monitoring a disease or condition may contain an array according to the invention and one or more reagents and one or more consumables; optionally together with instructions for use of the kit in accordance with any of the methods defined herein.
  • the diagnosis of a disease or condition permits integration of diagnostic procedures and therapeutic regimes.
  • effectiveness of medical treatment may be difficult to test (e.g. in cases of little physiologic effects, such as mood diseases), and it has thus far not been possible in many cases to perform rapid assessment of therapy response.
  • many disease therapies require treatment lasting a prolonged time (days to months, even years) for a given therapeutic approach.
  • Performing an assay according to the invention can be used to screen subjects prior to therapy to set a zero level for said subject.
  • the assays of the present invention provide the means to indicate therapeutic responses, failures to respond,
  • the assays of the invention may be used to stop treatment in non-responders at a very early stage. They can also be used to fine-tune dosage, minimize the number of prescribed medications, and to reduce the delay in attaining effective therapy.
  • patient care can be tailored precisely to match the needs determined by the disorder and the pharmacogenomic profile of the patient.
  • the assays of the invention can thus be used to titrate the optimal dose and to identify a positive therapeutic response.
  • Assays for quantitative assessment of the expression of eukaryotic CRISPR sequences provide a first line assessment of 'new' subjects, and provide objective measures for accurate and rapid diagnosis, in a time frame and with precision.
  • diagnostic assays are useful to identify family members or patients at high risk of developing a similar disease or condition. This permits initiation of appropriate therapy, or preventive measures, e.g. managing risk factors. These approaches are recognized to improve outcome and may prevent overt onset of the disorder.
  • Such monitoring methods eukaryotic CRISPR sequences, arrays and kits are also vital as patient monitoring tools. If pharmacological treatment is assessed to be inadequate, then therapy can be reinstated or increased; a change in therapy can be given if appropriate. As the expression of the CRISPR sequences is sensitive to the state of the disease or condition, it may provide an indication of the impact of drug therapy.
  • a method of diagnosis or monitoring the expression of CRISPR sequences may comprise quantifying the expression of the CRISPR sequences in a sample from the patient and comparing the level of expression in said sample with one or more controls.
  • the control may be a test sample of the same patient at an earlier point in time (the zero assay or any assay preceding the current one).
  • a diagnostic kit can contain probes that are specific for a group or grouping of CRISPR sequences as defined above
  • the diagnosis for the presence of a condition or disease is used to confirm a suspicion of said condition or disease.
  • the subject is already suspected of having said condition or disease at the moment that de the assay for expression of one or more of the eukaryotic CRISPR sequences is performed.
  • the invention can be considered as a method for enhancing the diagnosis of said condition or disease.
  • One of the main advantages of the present invention is that it provides an easy and reliable way to monitor progress of the condition or disease and/or effectiveness of a therapy.
  • the values for expression of one or more of the eukaryotic CRISPR sequences for a subject are determined at a certain moment (zero-value) and after an amount of time this procedure is repeated. Over the time, several repeat measurements can be performed. In the meantime therapy can e.g. be started or changed. Change(s) in the expression levels of the CRISPR sequences will then indicate the effectiveness of the therapy or the progress of the condition or disease.
  • the time elapsed between taking samples from a subject undergoing monitoring will be several days, a week, two weeks, a month, several months or longer.
  • Samples may be taken prior to and/or during and/or following therapy. Samples can be taken at intervals over the remaining life, or a part thereof, of a subject.
  • the diagnosis of a disease or condition may begin with an examination of a subject by a physician, nurse or other medical professional.
  • the term subject refers to any animal (e.g. a mammal), including but not limited to humans, non-human primates, rodents, dogs, pigs, and the like.
  • the examination may be part of a routine examination, or the examination may be due to a specific complaint including but not limited to one of the following: pain, illness, anticipation of illness, presence of a suspicious lump or mass, a disease, or a condition.
  • the subject may or may not be aware of the disease or condition.
  • the medical professional may obtain a biological sample for testing. In some cases the medical professional may refer the subject to a testing center or laboratory for submission of the biological sample.
  • the biological sample generally will be obtained by a physician, nurse, or other medical professional such as a medical technician, endocrinologist, gynecologist, cytologist,
  • sample may also be obtained by non-medical staff, such as police staff or HR staff.
  • the sample-taker may indicate the appropriate test or assay to perform on the sample, or may consult on which assays or tests are most appropriate.
  • a medical professional or other professional staff need not be involved in the initial diagnosis or sample acquisition.
  • An individual may alternatively obtain a sample through the use of an over the counter kit.
  • Said kit may contain a means for obtaining said sample, a means for storing said sample, and instructions for proper use of the kit.
  • molecular profiling services are included in the price for purchase of the kit. In other cases, the molecular profiling services are billed separately.
  • a sample suitable for use in the present invention may be any material containing tissues, cells, genes, gene fragments, gene expression products, or gene expression product fragments of an individual to be tested.
  • a sample may include but is not limited to, tissue, cells, or biological material from cells or derived from cells of an individual.
  • the sample may be a heterogeneous or homogeneous population of cells or tissues.
  • the biological sample may be obtained using any method known to the art that can provide a sample suitable for the analytical methods described herein.
  • the sample may be obtained by non-invasive methods including but not limited to: taking a hair of the subject, cutting hair or nails of the subject, scraping of the skin or cervix, lavage of the cervix, swabbing of the cheek or any other mucous part of the subject, saliva collection, urine collection, feces collection, blood or serum collection, e.g. by finger prick or venipuncture, collection of menses, tears, or semen.
  • the sample is obtained by an invasive procedure including but not limited to: biopsy, alveolar or pulmonary lavage, needle aspiration, or phlebotomy.
  • the method of biopsy may further include incisional biopsy, excisional biopsy, punch biopsy, shave biopsy, or skin biopsy.
  • the method of needle aspiration may further include fine needle aspiration, core needle biopsy, vacuum assisted biopsy, or large core biopsy.
  • nucleic acid expression product levels may include but are not limited to one or more of the following: whole or partial genome expression analysis, microarray hybridization assays, SAGE, enzyme linked immuno- absorbance assays, mass-spectrometry, immuno-histochemistry, or blotting. Additionally, other assays to confirm the diagnosis may be applied, such as additional cytological assays, assays for specific proteins or enzyme activities, assays for specific expression products including protein or RNA or specific RNA splice variants and in situ hybridization. Nucleic acid expression product levels may be normalized to an internal standard such as total mRNA or the expression level of a particular CRISPR sequence that is known only to be affected in special cases.
  • the expression of the CRISPR sequences or individual spacer sequences of the CRISPR sequences may be determined by microarray analysis using microarrays harboring probes that are able to target the CRISPR sequences as set forth in any of SEQ ID NO: 1 - 11297, more preferably the microarrays as provided in the present invention, for example, an array comprising one or more probes that are targeting at least one non-Affymetrix CRISPR sequence, or a specific group or grouping of said CRISPR sequences as defined above.
  • Microarray analysis begins with extracting and purifying nucleic acid from the biological sample, using methods known in the art. For expression analysis it may be advantageous to extract and/or purify RNA from DNA.
  • RNA- sequencing with which reliable quantification of transcripts can be measured (see e.g. Conesa, A. et al, 2016, Genome B 1O logy201617: 13, DOI: 10.1186/sl3059-016-0881-8).
  • Purified nucleic acid may further be labeled with a fluorescent, radionuclide, or chemical label such as biotin or digoxin for example by reverse transcription, PGR, ligation, chemical reaction or other techniques.
  • the labeling can be direct or indirect which may further require a coupling stage.
  • the coupling stage can occur before hybridization, for example, using aminoallyl-UTP and NHS amino-reactive dyes (like cyanine dyes) or after, for example, using biotin and labeled streptavidin.
  • the modified nucleotides e.g.
  • the aaDNA may then be purified with, for example, a column or a diafiltration device.
  • the aminoallyl group is an amine group on a long linker attached to the nucleobase, which reacts with a reactive label (e.g. a fluorescent dye).
  • the labeled samples may then be mixed with a hybridization solution which may contain SDS, SSC, dextran sulfate, a blocking agent (such as COT1 DNA, salmon sperm DNA, calf thymum DNA, PolyA or PolyT), Denhardt's solution, formamine, or a combination thereof.
  • the probe is a fragment of DNA or RNA of variable length, as defined herein,, which is used to detect in DNA or RNA samples the presence of the CRISPR nucleotide sequences (the target) that are complementary to the sequence in the probe.
  • the probe thereby hybridizes to single-stranded nucleic acid (DNA or RNA) whose base sequence allows probe-target base pairing due to complementarity between the probe and target.
  • the labeled probe is first denatured (by heating or under alkaline conditions) into single DNA strands and then hybridized to the target DNA.
  • the probe is tagged (or labeled) with a molecular marker; commonly used markers are 32 P or digoxigenin, which is nonradioactive antibody-based marker.
  • DNA sequences or RNA transcripts that have moderate to high sequence similarity to the probe are then detected by visualizing the hybridized probe via autoradiography or other imaging techniques. Detection of sequences with moderate or high similarity depends on how stringent the hybridization conditions were applied— high stringency, such as high hybridization temperature and low salt in hybridization buffers, permits only hybridization between nucleic acid sequences that are highly similar, whereas low stringency, such as lower temperature and high salt, allows hybridization when the sequences are less similar.
  • Hybridization probes used in DNA microarrays refer to DNA covalently attached to an inert surface, such as coated glass slides or gene chips, and to which a mobile cDNA target is hybridized. This mix may then be denatured by heat or chemical means and added to a port in a microarray. The holes may then be sealed and the microarray hybridized, for example, in a hybridization oven, where the microarray is mixed by rotation, or in a mixer. After an overnight hybridization, non-specific binding may be washed off (e.g. with SDS and SSC). The microarray may then be dried and scanned in a special machine where a laser excites the dye and a detector measures its emission.
  • kits can be used for the amplification of nucleic acid and probe generation of the subject methods.
  • kit that can be used in the present invention include but are not limited to Nugen WT-Ovation FFPE kit, cDNA amplification kit with Nugen Exon Module and Frag/Label module.
  • the NuGEN WT-OvationTM FFPE System V2 is a whole transcriptome amplification system that enables conducting global gene expression analysis on the vast archives of small and degraded RNA derived from FFPE samples.
  • the system is comprised of reagents and a protocol required for amplification of as little as 50 ng of total FFPE RNA.
  • the protocol can be used for qPCR, sample archiving, fragmentation, and labeling.
  • the amplified cDNA can be fragmented and labeled in less than two hours for GeneChip® 3' expression array analysis using NuGEN's FL-OvationTM cDNA Biotin Module V2.
  • the amplified cDNA can be used with the WT-Ovation Exon Module, then fragmented and labeled using the FL-OvationTM cDNA Biotin Module V2.
  • the amplified cDNA can be fragmented and labeled using NuGEN's FL-OvationTM cDNA Fluorescent Module. More information on Nugen WT- Ovation FFPE kit can be obtained on the world-wide web at
  • nugeninc.com nugeninc.com/nugen/index.cTm/products/amplification-systems/wt-ovation-ffpe/.
  • Ambion WT-expression kit can be used.
  • Ambion WT-expression kit allows amplification of total RNA directly without a separate ribosomal RNA (rRNA) depletion step.
  • rRNA ribosomal RNA
  • samples as small as 50 ng of total RNA can be analyzed on Affymetrix® GeneChip® Human, Mouse, and Rat Exon and Gene 1.0 ST Arrays.
  • Affymetrix® GeneChip® Human, Mouse, and Rat Exon and Gene 1.0 ST Arrays In addition to the lower input RNA requirement and high concordance between the
  • the Ambion® WT Expression Kit provides a significant increase in sensitivity. For example, a greater number of probe sets detected above background can be obtained at the exon level with the Ambion® WT
  • Ambion WT-expression kit may be used in combination with additional Affymetrix labeling kit.
  • AmpTec Trinucleotide Nano mRNA Amplification kit (6299-A15) can be used in the subject methods.
  • the ExpressArt® TRinucleotide mRNA amplification Nano kit is suitable for a wide range, from 1 ng to 700 ng of input total RNA. According to the amount of input total RNA and the required yields of aRNA, it can be used for 1-round (input >300 ng total RNA) or 2-rounds (minimal input amount 1 ng total RNA), with aRNA yields in the range of >1() pg. Amp Tec's proprietary TRinucleotide priming technology results in
  • Trinucleotide Nano mRNA Amplification kit can be obtained on the world-wide web at amp- tec.com/products.htm. This kit can be used in combination with cDNA conversion kit and Affymetrix labeling kit.
  • the raw data may then be normalized, for example, by subtracting the background intensity and then dividing the intensities making either the total intensity of the features on each channel equal or the intensities of a reference sequence and then the t-value for all the intensities may be calculated. More sophisticated methods include z-ratio, loess and lowess regression and RMA (robust multichip analysis) for Affymetrix chips.
  • the simplest approach to quantification is to aggregate raw counts of mapped reads using programs such as HTSeq-count (Anders, S. et al., 2015, Bioinformatics;31: 166-9) or leatureCounts [Liao, Y et al.,2014, Bioinformatics;30:923-30].
  • This gene-level (rather than transcript-level) quantification approach utilizes a gene transfer format (GTF) file containing the genome coordinates of exons and genes, and often discard multireads.
  • GTF gene transfer format
  • the measure RPKM (reads per kilobase of exon model per million reads) (Mortazavi, A. et al., 2008, Nat. Methods, 5: 1-8) is a within-sample normalization method that will remove the feature-length and library-size effects.
  • This measure and its subsequent derivatives FPKM fragments per kilobase of exon model per million mapped reads
  • FPKM fragments per kilobase of exon model per million mapped reads
  • TPM transcriptscripts per million
  • RPKM and FPKM are equivalent for SE reads and that FPKM can be converted into TPM using a simple formula (Pachter, L., arXiv.org. 2011. http://arxiv.org/abs/1104.3889).
  • the dichotomy of within-sample and between-sample comparisons has led to a lot of confusion in the literature. Correcting for gene length is not necessary when comparing changes in gene expression within the same gene across samples, but it is necessary for correctly ranking gene expression levels within the sample to account for the fact that longer genes accumulate more reads.
  • TPMs which effectively normalize for the differences in composition of the transcripts in the denominator rather than simply dividing by the number of reads in the library, are considered more comparable between samples of different origins and composition but can still suffer some biases. These must be addressed with normalization techniques such as TMM.
  • TMM normalization techniques
  • Cufflinks (Trapnell, C. et al., 2010, Nat. Bioteehnol. 28:511-5) estimates transcript expression from a mapping to the genome obtained from mappers such as TopHat using an expectation- maximization approach that estimates transcript abundances. This approach takes into account biases such as the non-uniform read distribution along the gene length. Cufflinks was designed to take advantage of PE reads, and may use GTF information to identify expressed transcripts, or can infer transcripts de novo from the mapping data alone. Algorithms that quantify expression from transcriptome mappings include RSEM (RNA-Seq by Expectation Maximization) (Li, B. and Dewey, C.N.
  • RSEM RNA-Seq by Expectation Maximization
  • kallisto/ among others. These methods allocate multi-mapping reads among transcript and output within-sample normalized values corrected for sequencing biases (Roberts, A. et al., 2011, Genome Biol. 12:R22). Additionally, the RSEM algorithm uses an expectation maximization approach that returns TPM values (Li and Dewey, supra). NURD (Ma, X. and Zhang, X., 2013, BMC Bioinformatics 11:94) provides an efficient way of estimating transcript expression from SE reads with a low memory and computing cost. Overexpression is then defined as an expression of at least twice the normal level, preferably ate least three times the normal level and most preferably at least four times the normal level.
  • the normal level is the average level of expression of the same nucleotide sequence under normal (i.e. healthy conditions) in a large number of subjects. If the value of this normal level is not available, it may be replaced by the expression level of a reference sequence. Underexpression then is defined as less than 70% of the normal expression level, preferably less than 50%, more preferably less than 30% of the normal level of expression of said sequence (or of the expression of a reference sequence).
  • the results of the expression assays may indicate a sample as negative (disease or condition free), ambiguous or suspicious (suggestive of the presence of a disease or condition), diagnostic (positive diagnosis for a disease or condition), or non-diagnostic (providing inadequate information concerning the presence or absence of the disease or condition).
  • the diagnostic results may also provide a score indicating for example, the severity or grade of the disease or condition, or the likelihood of an accurate diagnosis.
  • the diagnostic results may be indicative of a particular type or stage of a disease, or condition.
  • the diagnostic results may inform a particular treatment or therapeutic intervention for the type or stage of the specific disease or condition diagnosed.
  • the results of the assays performed may be entered into a database.
  • a disease can be assessed by assaying for the under- and/or overexpression of CRISPR sequences having specific SEQ ID NO: as is provided in the Examples below. As is demonstrated herein in some cases (detection of the over- or
  • CRISPR underexpression of only
  • one CRISPR is sufficient to form a basis for diganosis while in other cases it may be necessary or advantageous to use a profile of different CRISPR sequences.
  • some of the CRISPR sequences can be used in both approaches: as is demonstrated in Example 15 and 16 a CRISPR (or a profile/grouping of CRISPR sequences) can be used to diagnose for cancer in general, but the same CRISPR (or CRISPR profile/grouping) can be used to specifically diagnose for a particular form of cancer..
  • Example 1 CRISPRs are identified in horizontal acquired genes that reside in the human genome. From CRISP et al (Genome Biol. 2015 Mar 13; 16:50), the validated HGT acquired gene dataset was used to study whether the human genome harbors, CRISPRs, CRISPR - associated genes or CRISRP-Cas systems. We analysed 146 HGT genes and identified by making use of the CRISPRFinder software 23 genes that harbored a CRISPR of which one was accompanied with a CRISPR-associated gene cmrl (Table 1). Eighteen found their origin in protists, three in bacteria and two in plants. In 52 human genes that were of a viral origin 16, four CRISPRs were identified (Table 1). The human genome thus harbors by horizontal gene transfer acquired CRISPRs or even a CRISPR with a CRISPR-associated genes.
  • Example 2 The affymetrix U133 plus 2 probe and probe regions overlap or match with human CRISPR sequences. For this analyses the required information about the non-coding probe regions and probe positions were downloaded from
  • the U133 plus 2 non-coding probe regions and probe coordinates (25bp) (Chrl:start-end positions) match with the GRCh37/Hgl9 genome. These were uploaded as a BED file and set to GRCh Hgl9 in Galaxy (https://bioinf- galaxian.erasmusmc.nl/galaxy/).
  • the human CRISPR (Chrl:start-end positions) were also uploaded as a BED file in Galaxy. By making use of the intersect interval option allowed the retrieval of; probe positions that exactly match the human CRISPR positions (Table 2) or probe regions that overlapped the human CRISPR positions (Table 3).
  • Example 3 Probe 233266_at resembling a human CRISPR is a diagnostic marker for acute asthma attacks.
  • the publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses.
  • probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37 (also known as hgl9).
  • the human CRISPRs exactly matching or overlapping with the affymetrix U133 plus 2 microarray probes were joined as a single file resulting in 155 human CRISPR corresponding affymetrix U133 plus 2 probes (for which no clear annotation was available) showing the probe ID and chromosome start end positions of the human CRISPR (Table 4).
  • This file was also uploaded as a BED file dataset and adapted to the human assembly GRCh37.
  • GGSSMM440011229977 aanndd tthhee aaccuuttee aasstthhmmaa ppaattiieennttss aarree nnuummbbeerreedd aass GGSSMM440011229900,, GGSSMM 110011229922.. GGSSMM440011229944,, GGSSMM440011229966,, GGSSMM440011229988..
  • probe 233266_at is a marker for acute asthma attacks that require hospitalization and were triggered by a viral infection (Fig 2A).
  • CRISPR with Patent ID: 6326 is useful as a diagnostic marker to separate acute from convalescence asthma patients.
  • Example 4 probe 242924_at resembling a human CRISPR is a marker for chronic B-lymphocytie leukemia.
  • the publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses.
  • probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37.
  • the file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 3).
  • Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GSE26725 (Table 6).
  • this dataset information was obtained about the transcriptome from peripheral blood mononuclear cells obtained from chronic B-lymphocytic leukemia (CBLL) patients and healthy donors.
  • CBLL chronic B-lymphocytic leukemia
  • the healthy patients are GSM658010, GSM658011, GSM658012, GSM658013, GSM658014 and the chronic B-lymphocytic leukemia patients are GSM658015, GSM658016, GSM658017, GSM658018, GSM658019, GSM658020, GSM658021, GSM658022, GSM658023, GSM658024, GSM658025, GSM658026.
  • RNA expression values was uploaded at https://sofiware.broadinsiiii te.org/GEiNE-E/ in Morpheus which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that probe 242924_at is a marker for chronic B-lymphocytic leukemia (Fig 3A).
  • This example shows that probe 242924_at resembling a human CRISPR with Patent ID: 9342 is useful as a diagnostic marker to separate acute from convalescence asthma patients.
  • Example 5 probe 234574_at resembling human CRISPRs is a marker for a Francisella infection.
  • the publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray
  • probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset and was adapted for the human assembly GRCh37.
  • the file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted for the human assembly GRCh37 (Table 4).
  • Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS3298 (Table 7).
  • this dataset information was obtained about the transcriptome from peripheral blood mononuclear cells that were infected with the bacterial species F. tularensis subsp.
  • RNA expression values was uploaded at htt s : //soft w are .
  • probe 234574_at is a marker for a Francisella infection (Fig 4A).
  • probe 234574_at resembling a human CRISPR with Patent ID: 8709; 8713; 3664; 8711; 8712; 8714 is useful as a diagnostic marker to separate uninfected from Francisella infected patients.
  • Example 6 probe 234643_x_at resembling human CRISPRs is a marker for hepatocellular carcinoma.
  • the publication corresponding to this dataset harbors all the information w T ith respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses.
  • the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37.
  • the file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 4). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS4882 (Table 8). In this dataset information was obtained about the transcriptome from peripheral blood mononuclear cells obtained from hepatocellular carcinoma (HCC) patients were compared to healthy controls.
  • HCC samples are represented by GSM 1200294,
  • GSM1200302, GSM1200303 healthy control samples are represented by GSM1200304, GSM1200305, GSM1200306, GSM1200307, GSM1200308, GSM1200309, GSM 1200310, GSM1200311, GSM1200312 and GSM1200313.
  • This example shows that probe 234643_x_at resembling human CRISPRs with Patent IDs: 7929; 7930; 7931; 7932; 7933; 7934; 7935; 7936 is useful as a diagnostic marker to separate HCC from healthy control patients.
  • Example 7 probe 234095_at resembling a human CRISPR is a marker for high-grade prostate cancer.
  • Prostate tissue samples obtained from prostate cancer patients with a high Gleason score are represented by GSM1095883, GSM1095886 or GSM1095877, GSM1095878, GSM1095879, GSM1095880, GSM1095881, GSM1095882, GSM1095884, GSM 1095885 and was compared to healthy prostate tissue represented by GSM1095876.
  • probe 234095_at resembling human CRISPRs with Patent ID: 8566 could be useful as a diagnostic marker to separate healthy prostate tissue from high-grade prostate cancer tissue obtained from prostate cancer patients with high Gleason scores.
  • Example 8 probe 221625_at resembling human CRISPRs is a marker for chronic pediatric immune thrombocytopenia.
  • GDS5017 was used that can be obtained from
  • CRISPRs with Patent IDs: 8753 and 8757 is useful as a diagnostic marker to separate newly from chronic pediatric immune thrombocytopenia patients.
  • Example 9 probe 1566549_at resembling human CRISPRs can be used as a diagnostic marker for prostate cancer progression.
  • GDS1439 was used that can be obtained from
  • GSM 7-1875, GSM74876, GSM74877, GSM74878, GSM74879, GSM74880, tissue that is primary is represented by GSM74881, GSM74882, GSM74883, GSM74884, GSM74885, GSM74886, GSM74887 and prostate tumor tissue that is metastatic is represented by
  • GSM74888 GSM74889, GSM74890, GSM74891, GSM74892, GSM74893.
  • probe 1566549_at is a marker for metastatic prostate cancer tissue (Fig 8A).
  • This example shows that probe 1566549_at resembling a human CRISPR with Patent IDs: 9471 is useful as a diagnostic marker to separate benign and primary prostate cancer tumors from metastatic tumors.
  • Example 10 probe 234490_at resembling human CRISPRs can be used as a diagnostic marker for fertility based on sperm health.
  • GDS2697 was used that can be obtained from
  • GSM158472, GSM 158473, GSM158474, GSM158475 and teratozoospermia is represented by GSM158476, GSM158477, GSM158478, GSM158479, GSM158480, GSM 158181 , GSM158482, GSM158483.
  • This example shows that probe 234490_at resembling human CRISPRs with Patent IDs: 3664; 8711; 8712; 8713; 8714 is useful as a diagnostic marker for teratozoospermia.
  • probe 217152_at resembling human CRISPRs can be used as a diagnostic marker to distinguish between acute and latent tuberculosis.
  • GDS4966 was used that can be obtained from
  • probe 217152_at is a marker for acute tuberculosis (Fig 10A).
  • CRISPRs with Patent IDs: 8179; 8190; 8191 is useful as a diagnostic marker for active tuberculosis.
  • Example 12 probe 1557539_at resembling human CRISPRs can be used as a diagnostic marker for tibial muscular dystrophy.
  • GDS4843 was used that can be obtained from
  • Tibial muscular dystrophy patients are represented by GSM1050260, GSM105026L GSM105Q262, GSM105Q263, GSM105Q264, GSM1050265, GSM1050266 and healthy controls by GSM 1050270, GSM1050271, GSM1050272,
  • GSM1050273 GSM1050274.
  • probe 1557539_at is a marker for tibial muscular dystrophy (Fig 11A).
  • This example shows that probe 1557539_at resembling a human CRISPR with Patent ID: 6939 is useful as a diagnostic marker for tibial muscular dystrophy.
  • Example 13 probes resembling human CRISPRs can be used as a to distinguish between (un)differentiated embryonic stem cells.
  • GDS5408 was used that can be obtained from
  • Probes that would be able to distinguish in most cases are: 1554007_at, 15541()8_at, 1557339_at, 1558275_at, 1559151_at, 210679_x_at, 214979_at, 217152_at, 23046 l_s_at, 232344_at.(respectively SEQ ID NO: 5465, 1423, 68, . 7865, 7648, 6872, 8273, 8190, 8678, and 3215). In these cases SEQ ID NO: 5465 and 68 are underexpressed in undifferentiated cells, whereas the rest of the sequences are overexpressed in these cells. In the undifferentiated cells, the expression of these sequences is just the opposite.
  • Example 14 probes resembling human CRISPRs can be used as a to distinguish between influenza (un)infected bronchial epithelial cells.
  • GDS4855 was used that can be obtained from
  • GSM1179373 GSM 1 1 79371, GSM1179375 and H 1N1 infected bronchial epithelial cells by GSM1179364, GSM1179365, GSM1179366, GSM1179367, GSM1179368, GSM1179369, GSM1179370, GSM117937L GSM1179372.
  • SEQ ID NO: 5465, 8190 and 8861 are underexpressed in uninfected cells, whereas the rest of the sequences are
  • Example 15 123 unique Mitranscriptome transcripts resembling or overlapping a human CRISPR can be used as a diagnostic marker for 11 different cancers.
  • the publicly available Mitranscriptome datasets were used http I //w w ,na ture .corn/articles/ng.3192.
  • MiTranscriptome is a large-scale ab initio
  • RNA-sequencing datasets were obtained from The Cancer Genome Atlas (TCGA), the ENCODE Project, the Michigan Center for Translational Pathology, and other published sources (http ;/ ww .natoe.com/articles/ng.3192) . The entire
  • MiTranscriptome dataset was converted to a ranged summarized experiment to ease analysis using the R statistical platform (https://www.r-project.org ).
  • R statistical platform https://www.r-project.org .
  • Example 16 123 unique M itra n scr i ptome transcripts resembling or overlapping a human CRISPR that can be used as a diagnostic marker in cancer.
  • MiTranscriptome is a large-scale ab initio
  • RNA-sequencing datasets were obtained from The Cancer Genome Atlas (TCGA), the ENCODE Project, the Michigan Center for Translational Pathology, and other published sources (http ;/ ww .natoe.coni/articlee ng. 3 ⁇ 4 192) .
  • TCGA Cancer Genome Atlas
  • ENCODE Project the Michigan Center for Translational Pathology
  • other published sources http ;/ ww .natoe.coni/articlee ng. 3 ⁇ 4 192
  • MiTranscriptome dataset was converted to a ranged summarized experiment to ease analysis using the R statistical platform (https://vmw.r-proiect.org/).
  • the predicted human CRISPRs were overlapped with MiTranscriptome transcripts based on their genomic coordinates using (I tps://bioeori ductor.org/pack ge3 ⁇ 4/reiease/bioc/hti3 ⁇ 4lA jenomicRanges.html) genomic ranges, a Bioconductor software tool.
  • Mitranscriptome transcripts that resemble a human CRISPR or overlapped a human CRISPR (Table 20) were found to be differentially expressed between normal and tumor/metastatic tissue in only a single cohort (cohort-specific) (Fig. 15 and Table 19). These transcripts harbor diagnostic potential to detect one of the 11 cancers when the RNA expression value as measured by RNA sequencing is higher or lower than the AveExpr depending on the LogFc and tissue controls (Table 19).
  • Example 17 Human CRISPRs reside in transcription factor binding sites and DNase 1 hypersensitive sites. Since the human CRISPRs were found to be actively expressed we analysed whether the human CRISPRs would reside in genomic regions in which transcription factors are known to bind or are sensitive to DNase 1. For this purpose we downloaded the transcription factor binding sites and Dnasel hypersensitive clusters BED files from Encode (http: /genome.ucsc.edit EN ( .; ( . ) DE/do nloade.hti.nl) revealing their chromosome start and end positions.
  • Example 18 Human CRISPRs harbor spacer targets in phages, plasmids and viruses. Human CRISPR spacers were uploaded in the CRISPR Target finder, a tool to identify potential CRISPR RNA targets
  • the Erasmus MC identified prostate cancer related transcripts (EPCATs), as published in Jenster et al., Oncotarget (2015). Novel long non-coding RNAs appear to be expressed differently in prostate cancer patients in comparison to control patients and thus have been identified as specific diagnostic and prognostic markers for prostate cancer.
  • EPCATs prostate cancer related transcripts
  • Novel long non-coding RNAs appear to be expressed differently in prostate cancer patients in comparison to control patients and thus have been identified as specific diagnostic and prognostic markers for prostate cancer.
  • e taxon were the species from c belongs to

Abstract

The present invention relates to a method for diagnosing a disease or condition with the help of expression of eukaryotic, preferably human CRISPR sequences. Further, the present invention relates to an array with nucleotide probes that are directed against theses CRISPR sequences, preferably against the spacers of these sequences.

Description

Title: Use of human CRISPR sequences in diagnostics
The invention relates to the field of genetics, more articular human genetics, more especially the use of eukaryotic CRISPR sequences in diagnostic assays.
INTRODUCTION
CRISPR sequences are Clustered Regularly Interspaced Short Palindromic Repeat sequences that are present in bacteria and archaea. Initially these kind of sequences have been indicated as Short Regularly Spaced Repeats (SRSRs) (Mojica, F.J. et al., 2000, Mol.
Microbiol. 36:244-246), but they have been renamed in the acronym CRISPR by Jansen et al. (Jansen, R. et al., 2002, Mol. Microbiol. 43:1565-1575). Their function has been revealed later by Doudna and Charpentier, who independently from each other showed that CRISPR sequences work together with proteins from the Cas (CRISP associated) group to form a kind of immune reaction against viral infections (Pennisi, E., 2013, Science 341:833-836).
Together with Doudna and Charpentier, Jinek and others (Jinek, M. et al., 2012, Science 337:816-821) showed that Cas9, one of the Cas enzymes, in connection with an adapted version of the CRISPR (guide) sequences could be used for genetic editing. Since then the CRISPR-Cas system has been studied extensively and currently it is one of the most promising tools in genetic engineering because of its ease of use (e.g. Young, S. 2014, MIT
Technol. Review: http://www.technologyreview.com/review/524451/genome-surgery/; Mali, P. et al, 2013, Nature Meth. 10:957-963).
Although the CRISPR-Cas system has been proven to work in eukaryotes for genetic editing, it has also been found that the system is not fail-proof. A recent article (Cyranoski, D and Reardon, S., Nature News 22 April 2015) demonstrated that, although Chinese scientists had been able to genetically engineer the genomes of human embryo's, in most of the embryo's that were treated the system did not work at all, or not successfully.
Co-pending with the present application is an application (PCT/NL2016/050422) in which it is shown that in the eukaryotic genome many CRISPR sequences are present, in contrast to the current thinking that the system is exclusively found in bacteria and archaea. Further, it has been established in this application and a further application
(PCT/NL2016/050178) that the presence of these sequences in the genome may be the cause of the off-targeting effects that have been observed in the experiments with gene-editing with the CRISPR-Cas9 system in eukaryotes. Also, it was shown that the eukaryotic CRISPR sequences are expressed in cells and that expression of these sequences can occur during different physiological circumstances. Significant expression differences were observed in cell lines or subjects after exposure to (a)biotic compounds or medicines. Further, it was shown that several of the expressed CRISPR sequences could act as inhibitors of expression of the cognate sequences in the genome.
SUMMARY OF THE INVENTION
The present inventors now have surprisingly discovered that the (expression ol) eukaryotic CRISPR sequences can be used as a diagnostic tool for diagnosis of diseases, but also diagnosis of non-disease related conditions. Accordingly, the present invention comprises a diagnostic assay in which eukaryotic CRISPR sequences are used. Preferably, the CRISPR sequences used in said assay are chosen from the human CRISPR sequences of SEQ ID NO: 1 - SEQ ID NO: 10141 or any of the non-human CRISPR sequences of SEQ ID NO: 10142 - 11297. Alternatively, said diagnostic assay can be based on both the Affymetrix CRISPR sequences and the non-Affymetrix CRISPR sequences, as herein defined.
Accordingly, the invention comprises a method for diagnosing a disease or condition comprising the steps of:
a. taking a sample from a subject, preferably a human subject;
b. determining in said sample the expression profile of at least one CRISPR nucleotide sequence selected form the sequences of SEQ ID NO: 1 - 11297; c. determining on basis of said expression profile whether the disease or condition is present.
In said method the sample is preferably chosen from blood, serum, saliva, hair, urine, lymph fluid, CSF, cells and tissue. In a further preferred embodiment the step of determining the expression profile is accomplished by probing the sample with an array of probes specific for the at least one human CRISPR nucleotide sequence, preferably wherein the sample comprises mRNA extracted from cells or tissue to be investigated, preferably wherein said array of probes comprises at least one probe that is targeting a human CRISPR sequence that is not represented on the Affymetrix U133 Plus 2GeneChip®.
In another embodiment of the invention in said method multiple probes are available for different spacer sequences of the same CRISPR nucleotide sequence. Further preferred is a method , wherein the array comprises more then 50, preferably more than 100, more preferably more than 500 and more preferably more than 1000 probes.
In a further preferred embodiment said CRISPR nucleotide sequences are selected from SEQ ID NO: 1 - 10141, more preferably comprising at least one sequence defined herein as non- Affymetrix human CRISPR sequences.
Another part of the invention is an array spotted with probes targeting one or more of the nucleotide sequences of SEQ ID NO: 1 - 11297, more preferably the nucleotide sequences of SEQ ID NO: 1 - 10141, wherein said probes are short nucleotide sequences. Preferably, in said array said probes are DNA sequences with a length of 15 - 100 nucleotides, preferably of 20 - 75 nucleotide, more preferably of 22 - 50 nucleotides, more preferably of 23 - 40 nucleotides, more preferably 24 - 35 nucleotides, most preferably of 25 - 30 nucleotides, optionally provided with a label. It is further preferred that said nucleotide probes are spotted on a carrier.
In another embodiment of the invention at least one of said sequences of SEQ ID NO: 1 - 11297 does not possess any sequences that occur on an Affymetrix U- 133 Plus 2.0 GeneChip®. The invention is further directed to the use of such an array in a method for diagnosing a disease or condition.
In a specific embodiment the invention comprises a method for the diagnosis of chronic B- lymphocytic leukemia by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 9342, and diagnosing that chronic B-lymphocytic leukemia is present when SEQ ID NO: 9342 is overexpressed.
In a specific embodiment the invention comprises a method for the diagnosis of Francisella infection by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8709, and diagnosing that Francisella infection is present when SEQ ID NO: 8709 is under-expressed. In a specific embodiment the invention comprises a method for the diagnosis of hepatocellular carcinoma by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 7930, and diagnosing that hepatocellular carcinoma is present when SEQ ID NO: 7930 is
overexpressed
In a specific embodiment the invention comprises a method for the diagnosis of high-grade prostate cancer by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8566, and diagnosing that high-grade prostate cancer is present when SEQ ID NO: 8566 is under-expressed.
In a specific embodiment the invention comprises a method for the diagnosis of chronic pediatric immune thrombocytopenia by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8757, and diagnosing that chronic pediatric immune thrombocytopenia is present when SEQ ID NO: 8757 is overexpressed.
In a specific embodiment the invention comprises a method for the diagnosis of prostate cancer progression by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 9471, and diagnosing that prostate cancer progression is present when SEQ ID NO: 9471 is overexpressed.
In a specific embodiment the invention comprises a method for the diagnosis of fertility based on sperm health by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8713, and diagnosing that fertility based on sperm health is present when SEQ ID NO: 8713 is overexpressed.
In a specific embodiment the invention comprises a method to distinguish between acute and latent tuberculosis by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8190, and diagnosing that acute tuberculosis is present when SEQ ID NO: 8190 is under-expressed.
In a specific embodiment the invention comprises a method for the diagnosis of tibial muscular dystrophy by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 6939, and diagnosing that tibial muscular dystrophy is present when SEQ ID NO: 6939 is under-expressed.
In a specific embodiment the invention comprises a method to distinguish between differentiated and undifferentiated embryonic stem cells by assaying the under- or overexpression of CRISPR sequences SEQ ID NO: 5465, 1423, 68, 7865, 7648, 6872, 8273, 8190, 8678, and 3215, and diagnosing that the cells are undifferentiated if at least one of SEQ ID NO: 5465 and 68 is under-expressed and at least two of SEQ ID NO: 1423, 7865, 7648, 6872, 8273, 8190, 8678, and 3215 are overexpressed.
In a specific embodiment the invention comprises a method to distinguish between H1N1 infected and uninfected bronchial epithelial cells by assaying the under- or overexpression of CRISPR sequences 5465, 7873, 998, 1515, 9358, 8407, 8190, and 8861 and diagnosing that the cells are uninfected if at least two of SEQ ID NO: 5465, 8190 and 8861 are under- expressed and at least two of SEQ ID NO: 7873, 998, 1515, 9358 and 8407 are overexpressed. In a further embodiment the invention comprises a method for the detection of an infectious disease in a human by assaying the under- of overexpression of one or more of the CRISPR sequences provided in Table 23.
In a further embodiment the invention comprises a method for the detection of cancer in a human by assaying the under- of overexpression of one or more of the CRISPR sequences provided in Table 17. More specifically, the invention comprises a method for the detection of a specific cancer, selected from the group of Bladder urothelial carcinoma, Breast carcinoma, Gastric carcinoma, Head neck squamous cell carcinoma, Kidney carcinoma, Kidney
chromophobe, Liver hepatocellular carcinoma, Lung adenocarcinoma, Lung squamous cell carcinoma, Lung squamous cell carcinoma and Thyroid carcinoma) by assaying the under- of overexpression of one or more of the groups of CRISPR sequences provided in Table 19.
The invention further comprises the diagnostic use of one or more of the CRISPR sequences that reside in a transcription factor binding site as provided in Table 21 or that reside in a DNasel hypersensitive site as provided in Table 22.
LEGEND TO THE FIGURES Fig. 1 shows an example of a pure eukaryotic CRISPR on the human genome in chromosome 17 (chrl7:261087-261183;GRCh37 Hgl9 genome position). The RNA-seq exon coverage data reveals the transcription of a spacer (20 out of the 35 nucleotides) and repeat (30 out of 31 nucleotides) as depicted by the red markers 1 and 2 (spacer) and red marker 2 and green marker 3 (repeat). The blue block shows the transcript as detected with RNA sequencing. The spacer is found to target the human genome only by showing 100% identity against open reading frame C17orf97.
Fig. 2 shows in A) a Heatmap and in B) a scattergram for probe 233266_at resembling a none annotated region of which the probe region overlapped with a human CRISPR (Patent SEQ ID: 6326). The probe resembling a human CRISPR harbors the potential to function as a diagnostic marker to distinguish between acute asthma and convalescence patients when the RNA expression value of probe 233266_at is 28.0658 or lower (acute) or 30.2696 and higher (convalescence) (Table 4). A two-tailed unpaired T-test value with p < 0.05 indicated statistical significance (* p = 0.0002). Fig. 3 shows in A) a Heatmap and in B) a scattergram for probe 242924_at resembling a none annotated region of which the probe region overlapped with a human CRISPR (Patent SEQ ID: 9342) the RNA expression of this region detected by the probe was found to be
downregulated in the healthy control group and upregulated in the chronic B-lymphocytic leukemia patients. This probe harbors diagnostic potential when the RNA expression value is 0.0429552 or lower (Healthy control) or 0.0698454 and higher (CELL) (Table 5). A two-tailed unpaired T-test value with p < 0.05 indicated statistical significance (* p = 0.0043).
Fig. 4 shows in A) a Heatmap and in B) a scattergram for probe 234574_at resembling a none annotated region of which the probe region overlapped with human CRISPRs (Patent SEQ ID: 8709; 8713: 3664; 8711; 8712; 8714). The RNA expression of this region detected by the probe was found to be upregulated in the untreated blood monocytes compared to the Francisella species infected blood monocytes. This probe harbors diagnostic potential when the RNA expression value is 5.16552 or higher (untreated blood monocytes) compared to 4.60217 or lower (Table 6). A two-tailed unpaired T-test value with p < 0.05 indicated statistical significance (* p < 0.0001).
Fig. 5 shows in A) a Heatmap and in B) a scattergram for probe 234643_x_at resembling a none annotated region of which the probe region overlapped with human CRISPRs (Patent SEQ ID: 7929; 7930; 7931; 7932; 7933; 7934; 7935; 7936). The RNA expression of this region detected by the probe was found to be upregulated in the blood monocytes obtained from healthy controls compared to blood monocytes obtained from hepatocellular carcinoma (HCC) patients. This probe harbors diagnostic potential when the RNA expression value is 4.86397 or lower in HCC blood monocytes compared to 4.95324 or higher in blood monocytes obtained from healthy controls (Table 7). A two-tailed unpaired T-test value with p < 0.05 indicated statistical significance (* p < 0.0001).
Fig. 6 shows a Heatmap for probe 234095_at resembling a none annotated region of which the probe region overlapped with a human CRISPR (Patent ID: 8566). The RNA expression of this region detected by the probe was found to be upregulated in normal prostate tissue obtained from a prostate cancer free patient compared to prostate tissue obtained from prostate cancer patients with a high Gleason score 8 or higher. This probe harbors diagnostic potential when the RNA expression value is 478.4 or higher in prostate tissue from a prostate cancer free patient compared 163.8 or lower in prostate tissue obtained from prostate cancer patients with a high Gleason score (Table 8). Fig. 7 shows in A) a Heatmap and in B) a scattergram for probe 221625_at resembling a none annotated region of which the probe region overlapped with human CRISPRs (Patent SEQ ID: 8753 and 8757). The RNA expression of this region detected by the probe was found to be upregulated in peripheral blood T-cells obtained from children with chronic ITP compared to peripheral blood T-cells obtained from children with newly diagnosed ITP. This probe harbors diagnostic potential when the RNA expression value is 737 or higher in peripheral blood T- cells obtained from children with chronic ITP compared to 717 or lower in peripheral blood T- cells obtained from children with newly diagnosed ITP (Table 9). A two-tailed unpaired T-test value with p < 0.05 indicated statistical significance (* p = 0.0003).
Fig. 8 shows in A) a Heatmap and in B) a scattergram for probe 1566549_at resembling a none annotated region of which the probe region overlapped with a human CRISPR (Patent SEQ ID: 9471). The RNA expression of this region detected by the probe was found to be
upregulated prostate tumor tissue that was metastatic compared to prostate tumor tissue that was primary or benign. This probe harbors diagnostic potential when the RNA expression value is 338 or higher in prostate cancer tissue that is metastatic compared to 308 or lower in prostate tumor tissue that was primary or benign (Table 10). A two-tailed unpaired T-test value with p < 0.05 indicated statistical significance (* p < 0.0001).
Fig. 9 shows in A) a Heatmap and in B) a scattergram for probe 234490_at resembling a none annotated region of which the probe region overlapped with human CRISPRs (Patent SEQ ID: 3664; 8711; 8712; 8713; 8714). The RNA expression of this region detected by the probe was found to be upregulated in teratozoospermia sperm cells compared to normal sperm cells. This probe harbors diagnostic potential when the RNA expression value is 93.5249 or higher in teratozoospermia compared to 63.4615 or lower in normal sperm cells (Table 11). A two-tailed unpaired T-test value with p < 0.05 indicated statistical significance (* p < 0.0001).
Fig. 10 shows in A) a Heatmap and in B) a scattergram for probe 217152_at resembling a none annotated region of which the probe region overlapped with human CRISPRs (Patent SEQ ID: 8179; 8190; 8191). The RNA expression of this region detected by the probe was found to be upregulated in healthy controls and latent TB infected patients compared to active
tuberculosis patients. This probe harbors diagnostic potential when the RNA expression value is 8.33663 or higher in healthy controls and latent TB infected patients compared to 8.16569 or lower in active tuberculosis patients (Table 12). A two-tailed unpaired T-test value with p < 0.05 indicated statistical significance (* p < 0.0001). Fig. 11 shows in A) a Heatmap and in B) a scattergram for probe 1557539_at resembling a none annotated region of which the probe region overlapped with a human CRISPR (Patent SEQ ID: 6939). The RNA expression of this region detected by the probe was found to be upregulated in healthy controls compared to tibial muscular dystrophy patients. This probe harbors diagnostic potential when the RNA expression value is 0.546921 or higher in healthy controls compared to 0.00589085 or lower in tibial muscular dystrophy patients (Table 13). A two-tailed unpaired T-test value with p < 0.05 indicated statistical significance (* p < 0.0001). Fig. 12 shows a Heatmap for affymetrix U133 plus 2 probes resembling human CRISPRs. The RNA expression of these probes reveals that a large number allows to distinguish between undifferentiated and differentiated embryonic stem cells. These probes thus indicate that human CRISPRs might play a role in embryonic stem cell differentiation (Table 14).
Fig. 13 shows a Heatmap for affymetrix U133 plus 2 probes resembling human CRISPRs. The RNA expression of these probes reveals that a large number allows to distinguish between H1N1 influenza virus infected and uninfected bronchial epithelial cells and even between H1N1 variants. These probes thus indicate that human CRISPRs might play a role in the cellular defense against influenza viruses (Table 15).
Fig. 14 shows a Heatmap for differentially expressed MiTranscriptome transcripts resembling human CRISPRs or transcripts that overlapped with the human CRISPRs that were obtained by RNA sequencing (n=226) (Table 17). These transcripts allow to differentiate between normal and tumor tissue (Table 18). T represents the number of patients with a tumor and N the number of healthy controls. Positive log fold-change (logFC) shown in red correspond to up-regulated and a negative logFC in green in down-regulated transcripts in cancer and vice- versa.
Fig. 15 shows a Heatmap for differentially expressed MiTranscriptome transcripts resembling human CRISPRs or transcripts that overlapped with the human CRISPRs that were obtained by RNA sequencing (n=123) (Table 19 & Table 20). These transcripts allow to differentiate between normal and tumor tissue present in a specific patient cohort (Table 18). T represents the number of patients with a tumor and N the number of healthy controls. Positive log fold- change (logFC) shown in red correspond to up-regulated and a negative logFC in green in down-regulated transcripts in cancer and vice-versa.
Fig. 16. shows that the human CRISPRs (e.g. a CRISPR marked in red at position chrl2: 6201657-6201737 and patent ID 6498) overlap with regions that are known to be transcription factor binding sites, e.g., pol2 (Table 21), and/or reside in Dnasel hypersensitive sites (Table 22) (Dnasel cluster 6 in blue) indicative that this region is accessible for transcription activity. Fig. 17. Shows that a human CRISPR spacer from the human CRISPR positioned at chrl: 186600644-186600808 in the Hgl9 genome with patent ID 568 harbors a protospacer in the Human papillomavirus that is accompanied with a PAM motif TTC in the 3' strand.
DETAILED DESCRIPTION OF THE INVENTION
Unless otherwise defined, technical and scientific terms used herein shall have the meanings that are commonly understood by those of ordinary skill in the art. Furthermore, unless otherwise defined, singular terms shall include pluralities and plural terms shall include the singular. Generally, nomenclatures used in connection with molecular biology, protein, oligonucleotide or polynucleotide chemistry and hybridization technology described herein are those well-known and commonly used in the art. The present invention is not limited to the specific detection methods, detection reagents, and detection devices described herein, for these detection methods and reagents may be moderately modified or changed and achieve the same results and purposes. The scientific terms applied herein are used for concrete description rather than limiting the scope or field of the present invention. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.
As used herein, the term "microarray" refers to a collection of microscopic DNA spots aggregated and attached to a solid surface. Each DNA spot contains a small amount of a specific DNA sequence, known as a probe. These can be a short section of a nucleotide sequence that is hybridized with a cDNA or cRNA (also called anti-sense RNA) in the specimen (called target) sample under high- stringency conditions.
The term "stringency" refers to the extent to which hybridization may occur between nucleic acids with mismatched sequences. High-stringency conditions require absolute complementarity between the molecules, while low-stringency conditions permit hybridization when there are some mismatched bases. Typically, high-stringency conditions are achieved either by reducing NaCl concentration or increasing temperature up to approaching the melt temperature (Tm) of the molecules involved. An example of high- stringency conditions is hybridization at 50°C or higher (e.g. 55°C) and at 0.1 SSC (0.15M NaCl and 0.015M sodium citrate).
A nucleic acid or fragment thereof is "substantially homologous" ("or substantially similar") to another if, when optimally aligned (with appropriate nucleotide insertions or deletions) with the other nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least about 60% of the nucleotide bases, usually at least about 70%, more usually at least about 80%, preferably at least about 90%, and more preferably at least about 95, 96, 97 or 98% of the nucleotide bases.
Alternatively, substantial homology or (identity) exists when a nucleic acid or fragment thereof will hybridize to another nucleic acid (or a complementary strand thereof) under selective hybridization conditions, to a strand, or to its complement.
Selectivity of hybridization exists when hybridization that is substantially more selective than total lack of specificity occurs. Typically, selective hybridization will occur when there is at least about 55% identity over a stretch of at least about 14 nucleotides, preferably at least about 65%, more preferably at least about 75%, and most preferably at least about 90%. The length of homology comparison, as described, may be over longer stretches, and in certain embodiments will often be over a stretch of at least about nine nucleotides, usually at least about 20 nucleotides, more usually at least about 22 nucleotides, typically at least about 23 nucleotides, more typically at least about 24 nucleotides, and preferably at least about 25 or more nucleotides.
Thus, the probes to be used in the array of the invention preferably have at least 75%, more preferably at least 85%, more preferably at least 90% homology to the sequences shown in SEQ ID NO: 1 - 11297. More preferably there is at least 95%), more preferably at least 98%, homology.
Percentage (%) homology may be calculated over contiguous sequences, i.e. one sequence is aligned with the other sequence and each nucleotide in one sequence directly compared with the corresponding nucleotide in the other sequence, one residue at a time. This is called an "ungapped" alignment. Typically, such ungapped alignments are performed only over a relatively short number of residues (for example less than 50 contiguous nucleotides). Although this is a very simple and consistent method, it fails to take into consideration that, for example, in an otherwise identical pair of sequences, one insertion or deletion will cause the following residues to be put out of alignment, thus potentially resulting in a large reduction in % homology when a global alignment is performed. Consequently, most sequence comparison methods are designed to produce optimal alignments that take into consideration possible insertions and deletions without penalising unduly the overall homology score. This is achieved by inserting "gaps" in the sequence alignment to try to maximise local homology. However, these more complex methods assign "gap penalties" to each gap that occurs in the alignment so that, for the same number of identical nucleotides, a sequence alignment with as few gaps as possible - reflecting higher relatedness between the two compared sequences - will achieve a higher score than one with many gaps. "Affine gap costs" are typically used that charge a relatively high cost for the existence of a gap and a smaller penalty for each subsequent residue in the gap. This is the most commonly used gap scoring system. High gap penalties will of course produce optimised alignments with fewer gaps. Most alignment programs allow the gap penalties to be modified. However, it is preferred to use the default values when using such software for sequence comparisons. For example when using the GCG Wisconsin Best fit package (see below) the default gap penalty for nucleotide sequences is -50 and the default gap extension penalty is -3 for each nucleotide.
Calculation of maximum % homology therefore firstly requires the production of an optimal alignment, taking into consideration gap penalties. A suitable computer program for carrying out such an alignment is the GCG Wisconsin Best fit package (University of
Wisconsin, U.S.A.; Devereux et al., 1984, Nucleic Acids Research 12:387). Examples of other software that can perform sequence comparisons include, but are not limited to, the BLAST package (see Ausubel et al, 1999 ibid - Chapter 18), FASTA (Atschul et al., 1990, J. Mol. Biol., 403-410) and the GENEWORKS suite of comparison tools. Both BLAST and FASTA are available for offline and online searching (see Ausubel et al., 1999 ibid, pages 7-58 to 7-60).
However it is preferred to use the GCG Bestfit program. Although the final % homology can be measured in terms of identity, the alignment process itself is typically not based on an all-or-nothing pair comparison. Instead, a scaled similarity score matrix is generally used that assigns scores to each pair-wise comparison based on chemical similarity or evolutionary distance. An example of such a matrix commonly used is the BLOSUM62 matrix - the default matrix for the BLAST suite of programs. GCG Wisconsin programs generally use either the public default values or a custom symbol comparison table if supplied (see user manual for further details). It is preferred to use the public default values for the GCG package, or in the case of other software, the default matrix, such as BLOSUM62.
Once the software has produced an optimal alignment, it is possible to calculate % homology, preferably % sequence identity. The software typically does this as part of the sequence comparison and generates a numerical result. Nucleotide homology comparisons may be conducted, e.g. through a preferred sequence comparison program such as the GCG Wisconsin Best fit program. The default scoring matrix has a match value of 10 for each identical nucleotide and -9 for each mismatch. The default gap creation penalty is -50 and the default gap extension penalty is -3 for each nucleotide.
In the context of the present invention, a homologue or homologous sequence is taken to include a nucleotide sequence which is at least 60, 70, 80 or 90% identical, preferably at least 95 or 98%. identical at the nucleotide level over at least 20, 50, 100, 200, 300, 500 or 1000 nucleotides with the nucleotides sequences of SEQ ID NO: 1 - 11297, more preferably of SEQ ID NO: 1 - 10141.
Nucleotide sequences of the probes used in the present invention are preferably at least 15 nucleotides in length, preferably from 20 - 75 nucleotides, more preferably from 22 - 50 nucleotides, more preferably from 23 - 40 nucleotides, more preferably from 24 - 35 nucleotides, most preferably from 25 - 30 nucleotides.
Generally, the shorter the length of the polynucleotide, the greater the homology required to obtain selective hybridization. Consequently, where a probe sequence of the invention consists of less than about 30 nucleotides, it is preferred that the % identity is greater than 75%, preferably greater than 90% or 95% compared with the nucleotide sequences of SEQ ID NO: 1 - 11297, more preferably of SEQ ID NO: 1 - 10141. Conversely, where a polynucleotide of the invention consists of, for example, more than 50 or 100 nucleotides, the % identity compared with the sequences of SEQ ID NO: 1 - 11297, more preferably of SEQ ID NO: 1 - 10141may be lower, for example greater than 50%, preferably greater than 60 or 75%.
The "polynucleotide" compositions of this invention, comprising the sequences of
SEQ ID NO: 1 - 11297, more preferably of SEQ ID NO: 1 - 10141 and the probes as defined herein, include RNA, cDNA, genomic DNA, synthetic forms, and mixed polymers, both sense and antisense strands, and may be chemically or biochemically modified or may contain non- natural or derivatized nucleotide bases, as will be readily appreciated by those skilled in the art. Such chemical or biochemical modifications include, for example, labels, methylation, substitution of one or more of the naturally occurring nucleotides with an analog,
internucleotide modifications such as uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoamidates, carbamates, etc.), charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), pendent moieties (e.g., polypeptides), intercalators (e.g., acridine, psoralen, etc.), chelators, alkylators, and modified linkages (e.g., alpha anomeric nucleic acids, etc.). Also included are synthetic molecules that mimic polynucleotides in their ability to bind to a designated sequence via hydrogen bonding and other chemical interactions. Such molecules are known in the art and include, for example, those in which peptide linkages substitute for phosphate linkages in the backbone of the molecule.
The structure of a prokaryotic CRISPR array (see e.g., Horvath, P. and Barrangou, R., 2010, Science 327: 167- 170) includes a number of short repeating sequences referred to as "repeats." The repeats occur in clusters and up to 249 repeats have been identified in a single CRISPR array and are usually regidarly spaced by unique intervening sequences referred to as "spacers." Typically, CRISPR repeats vary from about 24 to 47 base pairs in length and are often palindromic. The repeats are generally arranged in clusters (up to about 20 or more per genome) of repeated units. The spacers are located between two repeats and typically each spacer has a unique sequence of about 21-72 base pairs in length. Many spacers are identical to or have high similarity with known phage sequences. It has been shown that the insertion of a spacer sequence from a specific phage into a bacterial CRISPR can confer resistance to that phage (see e.g., Barrangou, R. et al., 2007, Science 315: 1709- 1712).
In addition to repeats and spacers, a CRISPR array may also include a leader sequence and often a set of two to six associated cas genes. Typically the leader sequence is an AT-rich sequence of up to 550 base pairs directly adjoining the 5' end of the first repeat. New repeat- spacer units are almost always added to the CRISPR array between the leader and the first repeat.
As has been disclosed in co-pending application PCT/NL2016/050422 eukaryotic
CRISPR sequences follow a similar genetic make-up as the prokaryotic CRISPRs: short repeating, often palindromic sequences of 24 - 47 base pairs separated by spacers of - generally - 21-72 base pairs. A number of such eukaryotic CRISPR sequences that occur in humans is depicted in Table IA - IX of the (priority) document PCT/NL2015/050438, herein presented as SEQ ID NO: 1 - 10000, (Table 1A covers chromosome 1, table IB covers chromosome 2, etc.) or in Table IIA - IIM of said priority document, herein presented as SEQ ID NO: 10142- 11297 in which non-human eukaryotic CRISPRs are depicted. In the
PCT/NL2016/050422 application some new sequences were added, herein the CRISPR sequences of SEQ ID NO: 146 - 149, 545 - 554 and 10001-10141. These CRISPRs occasionally are found to be accompanied by a Cas gene, sometimes even more than one Cas gene.
In the present application a eukaryotic CRISPR sequence is defined as a sequence that comprises at least two partly or complete palindromic repeats of 24 - 47 base pairs and at least one spacer of about 21 - 72 base pairs, wherein the spacer is derived from a eukaryotic sequence, especially a spacer sequence that is derived from the same organism as from which the CRISPR sequence is derived. The spacer may originally be derived from a non-eukaryotic pathogen, but it will be different from the non-eukaryotic sequence because of the connection with the repeat sequences which are of eukaryotic origin. According to this definition a human CRISPR sequence would be a CRISPR sequence in which the spacer contains a human sequence or a sequence of a human pathogen (such as a retrovirus (HERV)), but of which the repeat sequences are of human origin. A specific group of eukaryotic CRISPRs are those CRISPRS that comprise spacer sequences that are only consisting of sequences that are derived from the same organisms as from which the repeat sequences are derived (see also Figure 1 of PCT NL2016/050422). These are indicated in the present application as "pure eukaryotic" CRISPR sequences. Accordingly a "pure human CRISPR sequence" is a pure eukaryotic sequence that is derived from a human being. The spacer of such a pure eukaryotic CRISPR generally is directed against a eukaryotic target sequence in such a sense that it will be capable of binding to such a sequence. It should further be mentioned that the spacer sequence does not need to be completely identical to the (eukaryotic) target. As has been proven in the work on RNAi (see below), which has been confirmed in the recent research on the CRISPR-Cas gene-editing system, inhibition of expression can also be accomplished with sequences that are less than 100% complementary to their target sequence. Because of the occurrence of mutations within the spacer sequences, which are more vulnerable to mutations than sequences coding for functional proteins, it could be that the original 100%
complementarity has become lost. Nevertheless, it appeared that the spacer sequences that the present inventors have found in the CRISPR sequences of eukaryotic organisms are highly homologous with endogenous sequences (i.e. sequences of the same organism) (see Figure 1 of PCT NL2016/050422).
More particularly, the sequences provided in SEQ ID NO:l - 11297 are comprised in the definition of eukaryotic CRISPR sequences. Further, human CRISPR sequences are defined as any of the sequences SEQ ID NO: 1 - 10141. The CRISPR sequences that are listed in the Tables IA - IX and Tables IIA - IIM of the priority document PCT/NL2015/050438, and which with some additions are now presented as SEQ ID NO: 1 - 11297, have been found by using the CRISPR Finder software
(CRISPRFinder: a web tool to identify clustered regularly interspaced short palindromic repeats. Nucleic Acids Res. 2007 May 31). The program for this should be run with the following standard default parameters: a repeat length of 23 to 55 bp, a gap size between repeats of 25 to 60 bp, one nucleotide mismatch between repeats, but these parameters may be varied in an advanced search to obtain additional CRISPRs. Further criteria a CRISPR should fit to are the following:
°The spacer size compared to the DR size: The CRISPRfinder filter is mainly added to eliminate structures having for example a 45 bp DR and a 20 bp spacer. By default, the spacer size should be from 0,6* to 2,5* the DR size.
°The spacers' similarity: This filter is set to eliminate tandem repeats. The spacers' comparison is made by aligning them (using default parameters of the ClustalW program). Spacers' similarity percentage is calculated with the function percentage_identity() of the (Bio)perl interface (AlignIO methods, ClustalW interface; Larkin, M.A. et al., 2007,
Bioinformatics 23:2947-2948). By default, this parameter is set to 60%.
°The DR conservation: The direct repeat should be well conserved. The DR scan is done using the fuzznuc program of the EMBOSS package (Rice, P. et al. 2000, Trends in Genetics 16:276-277). The allowed mismatch is equal to one-third of the DR size (default- parameters) to take into account the degenerated DR (one of the flanking DRs). Then a global mismatch score is computed as the average of mismatches (not including the degenerated DR) and this score should not exceed a threshold of 20% of the DR size(by default).
It is submitted that for the human CRISPR sequences the sequences covered in SEQ ID NO: 1 - 10141 are the total of sequences that may be discovered by screening the genome that is contained in the database. In the present finding the genomes of Homo sapiens present in the Bioconductor packages was used comprising data of about 1000 human genomes that can be retrieved from
http:/,¾iocondactor.org It is submitted that further human CRISPR sequences may be retrieved from human genomic sequences that are different from the sequences that have been assessed for the current collection of CRISPR sequences. Further, examples have been given for further sequences from eukaryotic organisms in SEQ ID NO: 10142-11297. This collection is of course by no means complete: for all species mentioned only an exemplary few CRISPR sequences have been listed and it is certain that other eukaryotic species and genera will also harbor numerous CRISPR sequences when assessed with the CRISPRfinder algorithm as described herein.
As can be seen from the sequence listing, many eukaryotic CRISPRs have only two repeats, but there are sequences which contain more than 30 repeat sequences and there is even one at human chromosome 19 with more than 150 repeat sequences. Some of the repeat sequences are recognized by the CRISPR Finder software as repeat sequences that are identical or very similar to repeat sequences that also occur in bacteria or archaea (see Table 1), but in most cases the repeat sequences, although fulfilling the criteria set for the detection of CRISPR repeat sequences, seem to be unique. As far as currently investigated there does not seem to be any specific feature of the eukaryotic CRISPR repeat sequences that would clearly distinguish them from prokaryotic or archaeal CRISPR repeat sequences, except of the course for the fact that most of the repeat sequences are unique for the eukaryotic source and no homologous sequences are thus far found in bacteria or archaea (see Figure 1 of
PCT/NL2016/050422).
Considering the source of the eukaryotic CRISPRs it seems that in some cases they could be hypothesized to have entered the eukaryotic genome from horizontal gene transfer (by whatever mechanism) from mainly protists (obtained from data from Crisp, A. et al. 2015, Genome Biol, doi: 10.1186/sl3()59-015-()607-3) although to a lesser extent also from bacteria, plants and viruses. In other cases, however, eukaryotic CRISPRs appear to have spacer sequences that are derived from viruses or other pathogens that are known to infect eukaryotic cells. In this respect it thus appears that these CRISPRs have been established through a similar mechanism as is described for bacteria and archaea. However, in the majority of the cases, the spacers are derived from sequences that are endogenous to the organism in which the CRISPR sequence is found or has been obtained from through horizontal gene transfer.
It was further established as has been disclosed in co-pending PCT L2016/050422 that these eukaryotic CRISPR sequences were transcribed, since RNA transcripts derived from the CRISPR sequences were shown to be present in eukaryotic cells.
It is acknowledged that some parts of these sequences have been disclosed as probes (without realizing that they were actually part of a CRISPR sequence) and used in all sorts of experiments and/or assays. These probes, partially or completely matching with the CRISPR sequences as provided in the present SEQ ID Nos, are contained on the Affymetrix U133 plus 2.0 GeneChipCRi. Table 1 list the CRISPR sequences where at least one of the 25 mer probes for a particular gene on the GeneChip¾ has an exact match with one of the human CRISPR sequences. In Table 2 the GeneChip® 25-mer probe sequences that only overlap with the human CRISPR sequences of the present invention have been listed. Hence, the sequences of SEQ ID NO: 1 - 10142 can be divided in two subsets, one subset for which probes can be used on the Affimetrix GeneChipS U133 Plus 2.0 (the SEQ ID Nos mentioned in Tables 2 and 3) and a larger subset of the SEQ ID Nos that have not been mentioned in Table 2 or 3. This last subset are herein designated as the "non-Affymetrix CRISPR sequences", while the first subset is indicated as the "Affymetrix CRISPR sequences".
Table 2 Overlap and exact matches between GenChipS U133 Plus 2.0 probes and human CRISPR sequences
Human CRISPRs
SEQ Probe Chr End probe Pos Probe ID (25bp) CRISPR Start CRISPR End CRISPR Probe overlap
S93 141293817 141293842 1555610_at:4 chr7 141293770 141293836 1555610. .at 19bp
141293775 141293800 1555610_at:5 chr7 141293770 141293836 25bp
4620 148991974 148991999 1556224_a :l chr7 148991951 148992067 1556224. 2Sbp
148992052 148992077 1556224_a :6 chr7 148991951 148992067 lSbp
148992003 148992028 1556224 :9 chr7 148991951 148992067 25bp
2700 142129905 142129930 1556520_at:l chr4 142129922 142130061 1556520. .at 8bp
142129899 142129924 1556520_at:3 chr4 142129922 142130061 2bp
142129901 142129926 1556520_at:7 chr4 142129922 142130061 4bp
2700 142129971 142129996 1556521_a_at:2 chr4 142129922 142130061 1556521. _a_at 25bp
142129949 142129974 15S6521_a_at:4 chr4 142129922 142130061 25bp
142129995 142130020 15S6521_a_at:5 chr4 142129922 142130061 25bp
142129923 142129948 1556521_a_at:8 chr4 142129922 142130061 25bp
142129934 142129959 1556521_a_at:10 chr4 142129922 142130061 25bp
1145 108439628 108439653 1558623_at:7 chr2 108439614 108439702 1558623. .at 25bp
108439689 108439714 1558623 :8 chr2 108439614 108439702 13bp
5710 29884038 29884063 1560230 :0 chrlO 298840S0 29884175 1560230. .at 13bp
29884060 29884085 1560230_at:5 chrlO 29884050 29884175 25bp
29884031 29884056 1560230_at:9 chrlO 29884050 29884175 6bp
2135 186542560 186542585 1561571_at:0 chr3 186542559 186542633 1561571. .at 25bp
186542611 186542636 1561571_at:2 chr3 186542559 186542633 22bp
186542576 186542601 1561571_at:S chr3 186542559 186542633 25bp
3600 29702910 2970293S 1562381_at:0 chr6 29702889 29703026 1562381. .at 25bp
9101 61089216 61089241 1562586_at:10 chr20 61089231 61089326 1562586. .at lObp
807 246679673 246679698 1563074_at:2 chrl 246679587 246679685 1563074. .at 12bp
246679650 246679675 1563074_at:5 chrl 246679587 246679685 25bp
246679588 246679613 1563074 :8 chrl 246679587 246679685 2Sbp
6914 131463436 131463461 1564984 :2 chrl2 131463458 131463545 1564984. .at 3bp
131463543 131463568 1564984 :6 chrl2 131463458 131463545 2bp
131463482 131463507 1564984_at:7 chrl2 131463458 131463545 25bp 8097 88738492 88738517 1568683_at:5 chrl6 88738515 8873861S 1568683_at 2bp
88738500 8873852S 1568683_at:8 chrl6 88738515 8873861S lObp
250 67096195 67096220 1569603_at:2 chrl 67096123 67096200 1569603_at 5bp
67096121 67096146 1569603_at:6 chrl 67096123 67096200 23bp
67096102 67096127 1569603_at:7 chrl 67096123 67096200 4bp
67096145 67096170 1569603_at:9 chrl 67096123 67096200 2Sbp
67096160 67096185 1569603_at:10 chrl 67096123 67096200 25bp
521 173457527 173457552 200845_s_at:2 chrl 173457458 173457542 200845_s_at 15bp
173457466 173457491 200845_s_at:5 chrl 173457458 173457542 25bp
173457513 173457538 200845_s_at:6 chrl 173457458 173457542 25bp
8702 6380265 6380290 202355_s :4 chrl9 6380183 6380285 202355_s 20bp
8386 78093079 78093104 202S12_at:0 chrl7 78092964 78093110 202S12_at 25bp
78093096 78093121 202812_at:4 chrl7 78092964 78093110 14bp
78093109 78093134 202812_at:8 chrl7 78092964 78093110 lbp
6000 123239512 123239537 203639_s_at:0 chrlO 123239519 123239645 203639_s_at 18bp
123239495 123239520 203639_s_at:2 chrlO 123239519 123239645 lbp
7908 15198318 15198343 204538_x_at:l chrl6 15198196 15198368 204538_x_at 2Sbp
15198274 15198299 204538_x_at:6 chrl6 15198196 15198368 25bp
15198328 15198353 204538_x_at:10 chrl6 15198196 15198368 25bp
504 169511623 169511648 204713_s_at:3 chrl 169511571 169511645 204713_s_at 22bp
169511572 169511597 204713_s_at:6 chrl 169511571 169511645 25bp
169511578 169511603 204713_s :8 chrl 169511571 169511645 25bp
8664 9492316 9492341 207417_s :2 chrl9 9491833 9492531 207417_s 25bp
9492302 9492327 207417_s :3 chrl9 9491833 9492531 25bp
9492391 9492416 207417_s_at:4 chrl9 9491833 9492531 25bp
9492456 9492481 207417_s_at:7 chrl9 9491833 9492531 25bp
9492515 9492540 207417_s_at:8 chrl9 9491833 9492531 16bp
9492412 9492437 207417_s_at:9 chrl9 9491833 9492531 2Sbp
9707 99884836 99884861 209109_s_at:3 chrX 99884792 99884892 209109_s_at 2Sbp
99884768 99884793 209109_s_at:6 chrX 99884792 99884892 lbp
6105 6452384 6452409 210013_at:l chrll 6452320 6452448 210013_at 25bp
1515 232570865 232570890 210723_x_at:2 chr2 232570820 232570905 210723_x_at 25bp
232570808 232570833 210723_x_at:3 chr2 232570820 232570905 13bp
232570796 232570821 210723_x_at:7 chr2 232570820 232570905 lbp
232570850 23257087S 210723_x_at:9 chr2 232S70820 23257090S 25bp
5017 95803505 95803530 213391_at:9 chr8 95803460 958035S4 213391_at 25bp
4907 57353921 57353946 213791_at:0 chr8 57353930 57354085 213791_at 16bp
57354057 57354082 213791_at:l chr8 57353930 57354085 25bp
57353958 57353983 213791_at:6 chr8 57353930 57354085 25bp
57353972 57353997 213791_at:8 chr8 57353930 57354085 2Sbp
6092 1977786 1977811 213897_s_at:0 chrll 1977647 1977793 213897_s_at 7bp
7908 15198218 15198243 214035_x_at:5 chrl6 15198196 15198368 214035_x_at 25bp
15198274 15198299 214035_x_at:7 chrl6 15198196 15198368 25bp
15198257 15198282 214035_x_at:9 chrl6 15198196 15198368 25bp
3363 140953458 140953483 215S41_s :6 chr5 140953216 140953536 215S41_s 25bp
140953358 140953383 215S41_s :9 chr5 140953216 140953536 25bp
1409S3351 140953376 21S541_s :10 chr5 140953216 140953536 25bp
7864 3536587 3536612 218661_at:4 chrl6 3536609 3536687 218661_at 3bp
3536681 3536706 218661_at:6 chrl6 3536609 3536687 6bp
3536649 3536674 218661_at:10 chrl6 3536609 3536687 25bp
4089 1474087 1474112 219332_at:3 chr7 1474106 1474222 219332 2Sbp
1474206 1474231 219332 :10 chr7 1474106 1474222 16bp
8812 44611888 44611913 220019_s_at:l chrl9 44611748 44612024 220019_s_at 25bp
8708 7083032 7083057 220444_at:0 chrl9 7083049 7083177 220444_at 8bp
7083114 7083139 220444_at:6 chrl9 7083049 7083177 25bp
2228 1813307 1813332 222006_at:2 chr4 1813320 1813402 222006_at 12bp
1813336 1813361 222006_at:6 chr4 1813320 1813402 25bp
1813330 181335S 222006_at:7 chr4 1813320 1813402 25bp 1813303 1813328 222006. _at:8 chr4 1813320 1813402
1813396 1813421 222006. _at:10 chr4 1813320 1813402
3145 70806719 70806744 224227. _s_at:0 chr5 70806187 70806861 224227. _s_at
70806631 70806656 224227. _s_at:2 chr5 70806187 70806861
70806642 70806667 224227. _s_at:4 chr5 70806187 70806861
70806528 70806553 224227. _s_at:7 chr5 70806187 70806861
70806561 70806586 224227. _s_at:9 chrS 70806187 70806861
70806393 70806418 224227. _s_at:10 chrS 70806187 70806861
4083 1037130 1037155 224478. _s_at:4 chr7 1037114 1037199 224478. _at
1037148 1037173 224478. _s_at:10 chr7 1037114 1037199
6713 69237537 69237562 225160. _x_at:5 chrl2 69237539 69237679 225160. _x_at
719 228161584 228161609 225899. _x_at:0 chrl 228160651 228161912 225899. _x_at
228161578 228161603 22S899. _x_at:4 chrl 228160651 228161912
7848 1036398 1036423 226913. _s_at:2 chrl6 1036422 1036498 226913. _s_at
1036450 1036475 226913. _s_at:4 chrl6 1036422 1036498
1036487 1036512 226913. _s_at:7 chrl6 1036422 1036498
7020 39623959 39623984 227040. _at:5 chrl3 39623831 39623972 227040. .at
39623970 39623995 227040. _at:10 chrl3 39623831 39623972
719 228161584 228161609 227129. _x_at:0 chrl 228160651 228161912 227129. _x_at
8768 23441546 23441571 227234. _at:5 chrl9 23441514 23441609 227234. .at
23441523 23441548 227234. _at:7 chrl9 23441514 23441609
4236 45004035 45004060 227799. _at:0 chr7 45003972 45004055 227799. .at
867S 1357773 1357798 229033. _s_at:0 chrl9 1357661 1357777 229033. -S_3t
13S7729 1357754 229033. _s_at:l chrl9 13S7661 1357777
1357701 1357726 229033. _s_at:3 chrl9 1357661 1357777
1357760 1357785 229033. _s_at:8 chrl9 1357661 1357777
8394 79224991 79225016 230448. _at:0 chrl7 79225001 79225087 230448. .at
79224982 79225007 230448. _at:3 chrl7 79225001 79225087
79225055 79225080 230448. _at:10 chrl7 79225001 79225087
8678 1357713 13S7738 230461. _s_at:0 chrl9 1357661 13S7777 230461. _s_at
1357727 1357752 230461. _s_at:8 chrl9 1357661 1357777
18 1677518 1677543 230694. _at:0 chrl 1677486 1677588 230694. .at
1677506 1677531 230694. _at:9 chrl 1677486 1677588
1624243 1624268 230694. _at:0 chrl 1624211 1624313
1624231 1624256 230694. _at:9 chrl 1624211 1624313
93S8 33216419 33216444 231888. _at:4 chr22 33216312 33216421 231888. .at
3509 2483982 2484007 232335. _at:l chr6 2483927 2484037 232335. .at
2484005 2484030 232335. _at:3 chr6 2483927 2484037
2483995 2484020 232335. _at:6 chr6 2483927 2484037
2484030 2484055 232335. _at:9 chr6 2483927 2484037
2483947 2483972 232335. _at:10 chr6 2483927 2484037
3215 86678320 86678345 232344. _at:l chr5 86678240 86678345 232344. .at
8248 40906158 40906183 232731. _x_at:0 chrl7 40906107 40906267 232731. _x_at
40906163 40906188 232731. _x_at:l chrl7 40906107 40906267
40906160 40906185 232731. _x_at:6 chrl7 40906107 40906267
40906162 40906187 232731. _x_at:8 chrl7 40906107 40906267
40906161 40906186 232731. _x_at:9 chrl7 40906107 40906267
40906156 40906181 232731. _x_at:10 chrl7 40906107 40906267
2089 171760715 171760740 232840. _at:4 chr3 171760690 171760794 232840. .at
8242 39394706 39394731 233631. _x_at:7 chrl7 39394558 39394772 233631. _x_at
39394702 39394742 233640. _x_at:7 chrl7 39394558 39394772
8017 7150954S 71S09570 234953. _x_at:0 chrl6 71509190 71S09991 234953. _x_at
71509567 71S09592 234953. _x_at:l chrl6 71509190 71S09991
71509561 71509586 234953. _x_at:2 chrl6 71509190 71509991
71509530 71509555 234953. _x_at:3 chrl6 71509190 71509991
71509629 71509655 234953. _x_at:4 chrl6 71509190 71509991
71509475 71509500 234953. _x_at:5 chrl6 71509190 71509991
71509589 71509614 234953. _x_at:6 chrl6 71S09190 71509991 71509531 715095S6 234953_x_at:7 chrl6 71S09190 71509991 25bp
71509603 71509628 234953_x_at:8 chrl6 71S09190 71509991 25bp
71509495 71509520 234953_x_at:9 chrl6 71509190 71509991 25bp
71509486 71509511 234953_x_at:10 chrl6 71509190 71509991 25bp
8890 56889123 56889148 235121_at:2 chrl9 56889039 56889160 235121_ .at 25bp
4973 82352931 82352956 235127_at:l chr8 82352875 82352961 235127. .at 2Sbp
6860 117297728 117297753 23 187_at:4 chrl2 117297706 117297818 237187. .at 25bp
117297789 117297814 23 187_at:10 chrl2 117297706 117297818 25bp
4786 19703071 19703096 237504_at:3 chr8 19703069 19703166 237504. .at 25bp
19703089 19703114 237504_at:4 chr8 19703069 19703166 25bp
19703111 19703136 237S04_at:6 chr8 19703069 19703166 25bp
9276 46011500 46011525 237S53_x_at:10 chr21 46011469 46011966 237853. _x_at 25bp
46011596 46011621 237853_x_at:10 chr21 46011469 46011966 25bp
46011941 46011966 237853_x_at:10 chr21 46011469 46011966 25bp
4599 143077493 143077518 238016_s_at:3 chr7 143077464 143077619 238016. _s_at 25bp
143077530 143077555 238016_s_at:7 chr7 143077464 143077619 25bp
1429 206982718 206982743 239268_at:3 chr2 206982711 206982794 239268. .at 2Sbp
206982690 206982715 239268_at:8 chr2 206982711 206982794 4bp
8851 5887933S 58879360 241277_x_at:0 chrl9 58879332 58879608 241277. _x_at 25bp
58879323 58879348 241277_x_at:l chrl9 58879332 58879608 16bp
58879338 58879363 241277_x_at:3 chrl9 58879332 58879608 25bp
58879413 58879438 241277_x_at:5 chrl9 58879332 58879608 25bp
58879324 58879349 241277_x_at:6 chrl9 58879332 58879608 17bp
58879415 58879440 241277_x_at:7 chrl9 58879332 58879608 25bp
58879333 58879358 241277_x_at:8 chrl9 58879332 58879608 25bp
58879330 58879355 241277_x_at:9 chrl9 58879332 58879608 23bp
8407 80338925 80338950 241468_at:3 chrl7 80338909 80338993 241468. .at 25bp
9342 28296890 28296915 242924_at:2 chr22 28296803 28296912 242924. .at 2Sbp
28296780 28296805 242924_at:3 chr22 28296803 28296912 2bp
2829686S 28296890 242924_at:4 chr22 28296803 28296912 25bp
28296794 28296819 242924_at:5 chr22 28296803 28296912 16bp
28296831 28296856 242924_at:6 chr22 28296803 28296912 25bp
7426 57860425 57860450 243246_at:0 chrl4 57860381 57860523 243246. .at 25bp
57860511 57860536 243246_at:9 chrl4 57860381 57860523 12bp
2812 174307670 17430769S 243984_at:7 chr4 174307674 174307761 243984. .at 21bp
984 40481617 40481642 244620_at:S chr2 40481625 40481704 244620. .at 17bp
6105 6452438 6452463 39763_at:7 chrll 6452320 6452448 39763_at lObp
6452432 6452457 39763_at:9 chrll 6452320 6452448 16bp
6452444 6452469 39763_at:10 chrll 6452320 6452448 25bp
6452347 6452372 39763_at:15 chrll 6452320 6452448 2Sbp
7864 3536676 3536701 45526_g_at:0 chrl6 3536609 3536687 45526_j ;_at llbp
3536665 3536690 45526_g_at:l chrl6 3536609 3536687 22bp
3536670 3536695 45526_g_at:5 chrl6 3536609 3536687 17bp
3536671 3536696 45526_g_at:7 chrl6 3536609 3536687 16bp
3536664 3536689 45526_g_at:8 chrl6 3536609 3536687 23bp
3536684 3536709 45526_g_at:13 chrl6 3536609 3536687 3bp
3536639 3536664 45S26_g_at:14 chrl6 3536609 3536687 25bp
Table 3.
SEQ ID Start probe End probe NC Probe ID CRISPR Start End CRISPR probe
68 9740286 9747632 1557339_at chrl 9741915 9741994 lS57339_at
68 9740286 9747632 1557341_x_3t chrl 9741915 9741994 1557341_x_at
250 67095468 67096502 1569603_at chrl 67096123 67096200 1569603_3t
95 17066767 17267929 216801_at chrl 17116688 17116804 216801_at
330 89150225 89226044 230400_s_at chrl 89189637 89189741 230400_s_at
331 891S0225 89226044 230400_s_at chrl 89195980 89196073 461 1.54E+08 1.54E+08 233248_at chrl 1.54E+08 1.54E+08 23324S_at
559 1.83E+08 1.83E+08 242575_at chrl 1.83E+08 1.83E+08 24257S
5867 80288507 80434864 1557807_a_at chrlO 80289681 80289817 1557807_a_at
5868 80288507 80434864 1557807_a_at chrlO 80390267 80390368
5618 3360886 3793053 1560185_at chrlO 3775980 3776065 1560185_at
561S 3360886 3793053 1560185_at chrlO 3403523 3403604
5616 3360886 3793053 1560185_at chrlO 3543094 3543198
5617 3360886 3793053 1560185_at chrlO 3699048 3699149
5656 10966689 11763895 1566503_at chrlO 11556214 11556318 1566503_at
5656 10966705 11763895 1566504_at chrlO 11556214 11556318 1566504
5819 64180584 65207333 1569041_at chrlO 64957301 64957398 1569041
5817 64180584 65207333 1569041_at chrlO 64182989 64183074
5818 64180584 65207333 1569041_at chrlO 64758405 64758499
5820 64180584 65207333 1569041_at chrlO 65094900 65094990
5631 5747858 5903379 232778_at chrlO 5774041 5774138 232778_at
5632 5747858 5903379 232778_at chrlO 5776296 5776426
5633 5747858 5903379 23277S chrlO 5781360 5781468
5634 5747858 S903379 232778_at chrlO 5870156 5870236
5635 5747858 S903379 232778_at chrlO 5884637 5884718
5711 29962387 30350458 234439_at chrlO 30252296 30252401 234439_at
5679 29962387 30350458 234439_at chrlO 30196395 30196547
5712 29962387 30350458 234439_at chrlO 30266461 30266569
6121 12442787 13279860 216431_at chrll 12967812 12967890 216431
6122 12442787 13279860 216431_at chrll 13125406 13125494
6432 1.18E+08 1.18E+08 217091_at chrll 1.18E+08 1.18E+08 217091_at
6242 58346941 58381810 226812_at chrll 58367814 58367967 226812_at
6120 11992594 11995200 232947_at chrll 11994386 11994526 232947_at
6326 84738246 84740241 233266 chrll 84739109 84739213 233266_at
6872 1.22E+08 1.23E+08 1555014_x chrl2 1.22E+08 1.22E+0S 15S5014_x_at
6871 1.22E+08 1.23E+08 1555014_x chrl2 1.22E+08 1.22E+08
6873 1.22E+08 1.23E+08 1555014_x_at chrl2 1.22E+08 1.22E+08
6939 1.33E+08 1.33E+08 1557539_at chrl2 1.33E+08 1.33E+08 1557539_at
6791 95048476 95638986 1564545_a_at chrl2 95431119 95431214 1564545
6790 95048476 95638986 1564545_a_at chrl2 95416868 95416974
6715 69801513 70214650 1565801_at chrl2 70034502 70034605 1565801_at
6716 69801513 70214650 1565801_at chrl2 70193756 70193846
6878 1.24E+08 1.24E+08 205703_at chrl2 1.24E+08 1.24E+08 205703
6872 1.22E+08 1.22E+08 210679_x_at chrl2 1.22E+08 1.22E+08 210679_x_at
6871 1.22E+08 1.22E+08 210679_x_at chrl2 1.22E+08 1.22E+08
6873 1.22E+08 1.22E+08 210679_x_at chrl2 1.22E+08 1.22E+0S
6791 95048476 9S833057 216739 chrl2 95431119 95431214 216739_at
6790 95048476 95833057 216739_at chrl2 95416868 95416974
6792 95048476 95833057 216739_at chrl2 95648950 95649039
6793 95048476 95833057 216739_at chrl2 95831780 95831866
6520 10423410 11136493 232626_at chrl2 10531650 10531735 232626
6521 10423410 11136493 232626_at chrl2 10705772 10705877
6522 10423410 11136493 232626_at chrl2 11038147 11038244
6523 10423410 11136493 232626_at chrl2 11098788 11098912
6646 49268653 49328298 236303_at chrl2 49292884 49293011 236303_at
7340 27884493 28213632 1559434_at chrl4 28088572 28088671 1559434_at
7341 27884493 28213632 1559434_at chrl4 28185735 28185838
7585 1.06E+08 1.06E+08 211633_x_at chrl4 1.06E+08 1.06E+08 211633_x_at
10014 1.06E+08 1.07E+08 211878 chrl4 1.07E+08 1.07E+08 211878_at
7585 1.06E+08 1.07E+08 211878_at chrl4 1.06E+08 1.06E+08
7518 1.06E+08 1.07E+08 211878_at chrl4 1.07E+08 1.07E+08
7583 1.06E+08 1.07E+08 216318_at chrl4 1.06E+08 1.06E+08 216318_at
7582 1.06E+08 1.07E+08 216318_at chrl4 1.06E+08 1.06E+08
7585 1.06E+08 1.07E+08 216318_at chrl4 1.06E+08 1.06E+08 7329 22447161 22985309 217065_at chrl4 22827944 22828056 21706S_at
7437 59662111 59960928 221137_at chrl4 S9824004 59824163 221137_at
7435 59662111 59960928 221137_at chrl4 59732861 59732980
7436 59662111 59960928 221137_at c rl4 59743054 59743135
7438 59662111 59960928 221137_at chrl4 59833616 59833705
7439 59662111 59960928 221137 chrl4 59916167 59916241
7437 59662111 59960928 221138_s_at chrl4 59824004 59824163 221138_s_at
7435 59662111 59960928 221138_s_at c rl4 59732861 59732980
7436 59662111 59960928 221138_s_at chrl4 59743054 59743135
7438 59662111 59960928 221138_s_at chrl4 59833616 59833705
7439 59662111 59960928 221138_s_at c rl4 59916167 59916241
7482 77297604 77335220 234454_at c rl4 77330809 77330900 234454_at
7426 57860358 57860828 243246_at chrl4 57860381 57860523 243246_at
7796 89445339 89447877 1558960_a_at chrl5 89446088 89446173 1558960_a_at
7648 34422526 35336559 1559151_at chrl5 34670007 34670131 1559151_at
7647 34422526 35336559 1559151_at chrlS 34646568 34646667
7649 34422526 35336559 15591Sl_at chrlS 34878970 34879051
76S0 34422526 35336559 1559151_at chrlS 34934736 34934839
7797 90804312 91105865 1566032_at chrlS 91054385 910544S9 1566032_at
7797 90804342 91105865 1566033_at chrl5 91054385 91054459 1566033_at
7724 64880471 65258312 217482_at chrl5 65046811 65046953 217482_at
7656 37156643 37173871 233382_at chrl5 37170130 37170212 233382_at
7865 4001312 4398935 1558275_at chrl6 4133976 4134115 155827S_at
7953 29267365 29268945 1560498_at chrl6 29268551 29268641 1560498_at
8053 87431698 87759801 1561092_at chrl6 87739575 87739930 1561092_at
8086 87431698 87759801 1561092_at chrl6 87545537 87545614
8087 87431698 87759801 1561092_at chrl6 87618761 87618849
808S 87431698 87759801 1561092_at chrl6 87753564 87753653
8050 78935711 78942438 1563460_at chrl6 78937147 78937338 1563460_at
7836 359059 438322 1564498_at chrl6 372220 372295 1564498_at
7837 359059 438322 1564498_at chrl6 375060 375159
7838 359059 438322 1564498_at chrl6 391761 391917
7839 359059 438322 1564498_at chrl6 423673 423876
8016 69694811 70327367 1565845_at chrl6 69825675 69825753 156584S_at
8018 69694811 70327367 1565845_at chrl6 70189769 70189893
8016 69694811 69950900 1565846_at chrl6 69825675 69825753
7873 5641293 5808519 1570215_at chrl6 5652722 5652820 1570215_at
7938 21526229 21905625 217490_at chrl6 21661461 21661546 217490_at
7936 21526229 21905625 217490 chrl6 21584700 21584808
7935 21526229 21905625 217490 chrl6 21552521 21552689
7937 21526229 21905625 217490_at chrl6 21648684 21648792
8050 78584635 78996239 224238_at chrl6 78937147 78937338 224238_at
8048 78584635 78996239 224238_at chrl6 78595176 78595297
8049 78584635 78996239 224238_at chrl6 78663707 78663810
8108 89357114 89556728 227661_at chrl6 89450035 89450132 227661_at
8107 89357114 89556728 227661_at chrl6 89445283 89445366
8105 893S7114 89556728 227661_at chrl6 89377847 89377944
8106 89357114 89556728 227661_at chrl6 89438071 89438171
8109 89357114 89556728 227661 chrl6 89513853 89513939
7855 1797068 1811313 230162_s_at chrl6 1799352 1799452 230162_s_at
7930 20701508 21596251 234643_x_at chrl6 21046208 21046339 234643_x_at
7929 20701508 21596251 234643_x_at chrl6 20872575 20872761
7936 20701508 21596251 234643_x_at chrl6 21584700 21584808
7931 20701508 21596251 234643_x_at chrl6 21179629 21179765
7932 20701508 21596251 234643_x_at chrl6 21180379 21180481
7933 20701508 21596251 234643_x_at chrl6 21323740 21323925
7934 20701508 21596251 234643_x_at chrl6 21524320 21524415
7935 20701508 21596251 234643_x_at chrl6 21552521 21S52689 7938 20884198 21902647 243147_x_at chrl6 21661461 21661546 243147_x_at
7930 20884198 21902647 243147_x_at chrl6 21046208 21046339
7936 20884198 21902647 243147_x_at chrl6 21584700 21584808
7931 20884198 21902647 243147_x_at chrl6 21179629 21179765
7932 20884198 21902647 243147_x_at chrl6 21180379 21180481
7933 20884198 21902647 243147_x_at chrl6 21323740 21323925
7934 20884198 21902647 243147_x_at c rl6 21524320 21524415
7935 20884198 21902647 243147_x_at c rl6 21552521 21552689
7937 20884198 21902647 243147_x_at chrl6 21648684 21648792
8379 76893103 76896234 1556836_at chrl7 76895113 76895191 1556836
8379 76893103 76896234 1556837_a_at c rl7 76895113 76895191 1556837 _at
8177 8985S35 9727777 1566803_at c rl7 9156556 9156643 1566803
8176 898S535 9727777 1566803_at chrl7 9045196 9045306
8178 8985535 9727777 1566803_at chrl7 9561213 9561347
8273 48766882 49193093 214979_at chrl7 48851027 48851109 214979
8273 48360270 49188027 216427_at chrl7 48851027 48851109 216427_at
8190 15978220 16549265 217152_at chrl7 16048049 16048223 217152_at
8191 15978220 16549265 217152_at c rl7 16174468 161745S9
8179 15978220 16549265 217152_at c rl7 16526168 16527131
8440 9574671 9933120 1563690_at chrl8 9786083 9786207 1563690_at
8441 9574671 9933120 1563690_at chrl8 9912497 9912588
8425 2199942 2519259 216771_at chrl8 2309331 2309440 216771_at
8425 2199942 2519259 216772_at ehrl8 2309331 2309440 216772_at
8566 55377244 55395934 234095_at chrl8 55382257 55382350 23409S
8829 44643460 44645650 1559770_at chrl9 44643370 44643474 1559770
8769 23487806 23824382 1562055_at chrl9 23808179 23808277 1562055
8846 53453136 53571734 1567031_at chrl9 53453142 53454363 156703 l_at
8700 4477051 5145589 207730_x chrl9 4852359 4852498 207730_x_at
8701 4477051 5145589 207730_x chrl9 5095637 5095777
8683 2514448 2646281 214227 c rl9 2631S55 26316S9 214227_at
8799 36618668 37179708 216792_at chrl9 36687618 36687728 216792_at
8757 19896720 20262762 221625_at chrl9 20206519 20206664 221625_at
8753 19896720 20262762 221625_at chrl9 20075471 20075565
8678 1357416 1358181 230461_s_at c rl9 1357661 1357777 230461_s_at
8713 8240460 8641054 234490_at chrl9 8451335 8451489 234490_at
3664 8240460 8641054 234490_at chrl9 8441283 8441390
8711 8240460 8641054 234490_at chrl9 8444097 8444291
8712 8240460 8641054 234490_at chrl9 8445717 8445832
8714 8240460 8641054 234490 chrl9 8594711 8594915
8709 S074484 8641054 234574 chrl9 8166509 8166637 234574_at
8713 8074484 8641054 234574 c rl9 8451335 8451489
3664 8074484 8641054 234574 chrl9 8441283 8441390
8711 8074484 8641054 234574 chrl9 8444097 8444291
8712 8074484 8641054 234574_at chrl9 8445717 8445832
8714 8074484 8641054 234574_at c rl9 8594711 8594915
8861 53055764 53451419 243973_at c rl9 53094839 53094931 243973_at
8862 53055764 53451419 243973_at c rl9 53407160 53407326
1423 2.04E+08 2.04E+08 1554108_at chr2 2.04E+08 2.04E+08 1554108
1424 2.04E+08 2.04E+08 1554108_at chr2 2.04E+08 2.04E+08
1545 2.4E+08 2.4E+08 1558385_at chr2 2.4E+08 2.4E+08 1558385_at
1563 2.42E+08 2.42E+08 15590S3_at chr2 2.42E+08 2.42E+0S 15S9053_at
1563 2.42E+08 2.42E+08 1559054_a_at c r2 2.42E+08 2.42E+08 lS59054_a_at
998 44502660 44548424 205800 c r2 44513354 44513464 205800_at
1421 2.04E+08 2.04E+08 243186 chr2 2.04E+08 2.04E+08 243186_at
9051 49935494 50209168 1554723_x_at chr20 50168646 50168745 1554723_x_at
9050 49935494 50209168 1554723_x_at chr20 49957571 49957687
9006 35093473 35757746 lS56701_at c r20 35185291 35185385 1556701
9008 35093473 35757746 1556701_at chr20 35431105 35431185 9007 35093473 35757746 1556701_at chr20 35323427 35323549
8980 35093473 35757746 1556701_at chr20 35541168 35S41620
9009 35093473 35757746 1556701_at chr20 35662688 35662778
8948 17594324 17662865 201205_at chr20 17609583 17609727 201205_at
9051 50037844 50363368 233706_at chr20 50168646 50168745 233706_at
9051 50037844 50425208 23370S chr20 50168646 50168745 233708_at
9031 44705219 44705821 239815_at c r20 4470S156 44705235 239815_at
9233 40128328 40581393 2381S3_at c r21 40551557 40551627 238183_at
9359 33669070 34316410 215538_at chr22 33827465 33827549 215538_at
9360 33669070 34316410 215538_at chr22 33961551 33961650
9389 41763478 41983251 215675_at c r22 41784175 41784446 215675_at
9390 41763478 41983251 215675_at c r22 41797025 41797156
9336 22516597 23248620 216301_at chr22 22936417 22936532 216301_at
9336 22764327 23241835 217193_x_at chr22 22936417 22936532 217193_x_at
9358 33209598 33216563 231888_at chr22 33216312 33216421 231888_at
9383 40526914 40994205 233697_at chr22 40801331 40801419 233697_at
9336 22786507 23241834 234707_x_at chr22 22936417 22936532 234707_x_at
1884 1.06E+08 1.06E+08 1557645_at c r3 1.06E+08 1.06E+08 lS57645_at
2031 1.56E+08 1.56E+08 1559232_a_at c r3 1.56E+08 1.56E+08 lS59232_a_at
1607 13414819 13416603 1562723_at c r3 13415593 13415693 1562723_at
1881 1.05E+08 1.05E+08 1563958_at chr3 1.05E+08 1.05E+08 1563958_at
2043 1.58E+08 1.58E+08 204782_at chr3 1.58E+08 1.58E+08 204782_at
1770 67425142 67705002 215774_s_at c r3 67456037 67456120 215774_s_at
2089 1.72E+08 1.72E+08 232840_at chr3 1.72E+08 1.72E+08 232840_at
1854 97172479 97174696 233789_at chr3 97173244 97173346 233789_at
2836 1.8E+08 1.8E+08 1562642_at chr4 1.8E+08 1.8E+08 1562642_at
2214 843064 926120 202280_at chr4 882793 882913 202280_at
2215 843064 926120 202280 chr4 890872 890965
2216 843064 926120 202280 chr4 893979 894088
2217 843064 926120 2022S0_at c r4 903248 903336
3466 1.76E+08 1.76E+08 216934_at chr5 1.76E+08 1.76E+08 216934_at
3466 1.76E+08 1.76E+08 216936_at chr5 1.76E+08 1.76E+08 216936_at
3215 86676620 86678864 232344_at chr5 86678240 86678345 232344_at
3645 41303526 41318625 221074_at c r6 41316980 41317136 221074_at
3610 31802693 31807489 222968_at chr6 31804365 31804470 22296S_at
3620 342S4850 34360300 226061_s_at chr6 34321953 34322078 226061_s_at
3619 34254850 34360300 226061_s_at chr6 34316780 34316854
3856 1.09E+08 1.09E+08 233629_at chr6 1.09E+08 1.09E+08 233629_at
3856 1.09E+08 1.09E+08 233674 chr6 1.09E+08 1.09E+08 233674_at
4091 1552185 1864233 15575S5_at chr7 1852792 1852871 15S7555_at
4092 1552185 1864233 1557S55_at c r7 1861658 1861736
4267 65273942 66354836 1559563_at chr7 65452039 65452140 1559563_at
4266 65273942 66354836 1559563_at chr7 65358544 65358703
4268 65273942 66354836 1559563_at chr7 65634491 65634593
4269 65273942 66354836 1559563_at c r7 65667233 65667305
4267 65273942 66354836 1559565_x_at c r7 65452039 65452140 155956S_x_at
4266 65273942 66354836 1559565_x_at chr7 65358544 65358703
4268 65273942 66354836 1559565_x_at chr7 65634491 65634593
4269 65273942 66354836 1559565_x_at chr7 65667233 65667305
4592 1.41E+08 1.41E+08 1562907_at chr7 1.41E+08 1.41E+08 1562907_at
4676 1.59E+08 1.59E+08 1564424_at chr7 1.59E+08 1.59E+0S 1564424_at
4677 1.59E+08 1.59E+08 1564424_at c r7 1.59E+08 1.59E+08
4679 1.59E+08 1.59E+08 1564424_at c r7 1.59E+08 1.59E+08
4678 1.59E+08 1.59E+08 1564424_at chr7 1.59E+08 1.59E+08
4412 92355014 92462708 214160_at chr7 92415915 92415995 214160_at
4556 1.28E+08 1.29E+08 233717_x_at chr7 1.29E+08 1.29E+08 233717_x_at
4557 1.28E+08 1.29E+08 233717_x_at c r7 1.29E+08 1.29E+08
4558 1.2SE+08 1.29E+08 233717_x_at chr7 1.29E+08 1.29E+08 4559 1.2SE+08 1.29E+08 233717_x_at chr7 1.29E+08 1.29E+08
4268 65598910 65917175 233853_at chr7 65634491 65634593 233853_at
4269 65598910 65917175 233853_at chr7 65667233 65667305
4091 1552185 1864233 233920_at chr7 1852792 1852871 233920_at
4092 1552185 1864233 233920_at chr7 1861658 1861736
4091 1552185 1864233 233921_s_at chr7 1852792 1852871 233921_s_at
4092 1552185 1864233 233921_s_at c r7 1861658 1861736
4267 65390693 65500634 238305_at c r7 65452039 65452140 238305_at
4812 29671888 29686020 1559278_at chr8 29679434 29679546 1559278_at
4746 7468860 7925177 1568780_at chr8 7552246 7552403 1568780_at
4748 7468860 7925177 1568780_at c r8 7891861 7891964
4747 7468860 7925177 1568780_at c r8 7569191 7569295
4749 7468860 7925177 1568780_at chr8 7908726 7908883
4938 68255956 68404101 1569405_at chr8 68295467 68295567 1569405_at
5122 1.29E+08 1.29E+08 216249_at chr8 1.29E+08 1.29E+08 216249_at
4853 42210559 42396605 231818_x_at chr8 42317234 42317313 231818_x_at
4854 42210559 42396605 23181S_x_at chr8 42339857 42339992
5465 1.14E+08 1.15E+08 1554007_at c r9 1.14E+08 1.14E+08 lS54007_at
5466 1.14E+08 1.15E+08 1554007_at c r9 1.1SE+08 1.15E+08
5467 1.14E+08 1.15E+08 1554007_at chr9 1.15E+08 1.15E+08
5224 4732996 4859264 1558489_at chr9 4856362 4856490 1558489_at
5572 1.4E+08 1.4E+08 1559166_at chr9 1.4E+08 1.4E+08 1559166
5320 36504497 36958546 1566428_at c r9 36606129 36606253 156642S
5321 36504497 36958546 1566428_at chr9 36861230 36861330
5570 1.4E+08 1.4E+08 1569981_at chr9 1.4E+08 1.4E+08 1569981_at
5569 1.4E+08 1.4E+08 1569981_at chr9 1.4E+08 1.4E+08
5571 1.4E+08 1.4E+08 1569981_at chr9 1.4E+08 1.4E+08
5540 1.38E+08 1.38E+08 203326_x_at chr9 1.38E+08 1.38E+0S 203326_x_at
5539 1.38E+08 1.38E+08 203326_x_at chr9 1.38E+08 1.38E+0S
5541 1.38E+08 1.38E+08 203326_x c r9 1.38E+08 1.38E+08
5542 1.38E+08 1.38E+08 203326_x_at chr9 1.38E+08 1.38E+08
5472 1.16E+08 1.16E+08 233390_at chr9 1.16E+08 1.16E+08 233390_at
5473 1.16E+08 1.16E+08 233390_at chr9 1.16E+08 1.16E+08
5472 1.16E+08 1.16E+08 233395_at c r9 1.16E+08 1.16E+08 233395_at
5473 1.16E+08 1.16E+08 233395_at chr9 1.16E+08 1.16E+08
5578 1.41E+08 1.41E+08 234214_at chr9 1.41E+08 1.41E+08 234214_at
5573 1.41E+08 1.41E+08 234214_at chr9 1.41E+08 1.41E+08
5574 1.41E+08 1.41E+08 234214_at chr9 1.41E+08 1.41E+08
5576 1.41E+08 1.41E+08 234214_at chr9 1.41E+08 1.41E+08
5575 1.41E+08 1.41E+08 234214 chr9 1.41E+08 1.41E+0S
5577 1.41E+08 1.41E+08 234214_at c r9 1.41E+08 1.41E+08
5579 1.41E+08 1.41E+08 234214_at chr9 1.41E+08 1.41E+08
9471 2155553 2169916 1566548_at chrX 2159579 2159659 1566548_at
9471 2155563 2169916 1566549_at chrX 2159579 2159659 1566549_at
9580 46464683 46618359 214863_at chrX 46491840 46491982 214863
9798 1.3E+08 1.3E+08 216681_at chrX 1.3E+08 1.3E+08 216681
Although the role of these CRISPRs disclosed in the present application is yet unknown, it has been established in the present invention that expression of these CRISPR sequences can be used in (medical) diagnostics.
The present invention therefore is comprising a method for diagnosing a disease or condition by assessing the expression data of one or more of the CRISPR sequences from SEQ ID NO: 1 - 10141. As is shown in the experimental section many diseases or conditions are accompanied by (or caused by?) an under- or overexpression of a (sub)set of CRISPR sequences. The data that are obtained in the present application are based on the expression data of the Affymetrix CRISPR sequences (as derived from the Affymetrix GeneChip® U133 Plus 2.0), but it is believed that also numerous CRISPR sequences from the non-Affymetrix CRISPR sequences will be equally characterized by under- or overexpression in specific diseases or conditions. For this purpose the present invention also comprises an assay using an array of probes, which array comprises at least one probe that is suited to hybridise under stringent conditions with a non-Affymetrix CRISPR sequence. Such arrays will contain at least one CRISPR sequence, but preferably more and may further contain both non-Affymetrix CRISPR sequences and Affymetrix CRISPR sequences. The size of the assay can vary, depending on the number of CRISPR sequences that is needed to provide a reliable diagnosis for a certain disease or condition and whether or not the array will be used for diagnosing more than one disease or condition. It is envisaged that an array may be constructed comprising probes for each and every CRISPR sequence from both the Affymetrix and non- Affymetrix CRISPR sequences. Further, such an array may also comprise multiple probes for one and the same CRISPR sequence, since there are indications that some of the CRISPR sequences that comprise more than one spacer sequence would be applicable in more than one way, because the various spacer sequences contained in one and the same CRISPR sequence could be used as a diagnostic for more than one disease or condition. In essence, thus, such an array would comprise probes that would be specific for each of the spacer sequences that are contained in the CRISPR sequences. Accordingly, also part of the invention is an array having at least one probe able to specifically bind to a spacer sequence of any of the non-Affymetrix CRISPR sequences. Said array could further contain probes targeting both Affymetrix
CRISPR sequences and non-Affymetrix CRISPR sequences.
The disease or condition that may be diagnosed may be any disease or condition that is known. In the experimental part it is shown that many diseases cause over- or underexpression of one or more CRISPR sequences. The word 'condition' is herein to be understood as a state of health, which can be represented by any physiologic signal (such as fever is represented by an elevated body temperature), but which state of health can also apply to a part of the body. E.g. an increased level of atherosclerosis in the blood vessels may is a condition which may lead to a disease (e.g. stroke or coronary ischemia) but this condition is confined to the blood vessels. It may be represented by an increased blood pressure or by a stiffening of the walls of the blood vessels and the like. The definition of a 'disease' is - of course - related to the definition of a condition, and a disease my be characterized as "a definite pathological process having a characteristic set of signs and symptoms". It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown (definition from Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders).
Conditions and diseases that may be diagnosed in this way are: asthma, chronic B- cell leukemia, hepatocellular carcinoma, Francisella infection, high grade prostate cancer, pediatric immune thrombocytopenia, tuberculosis, tibial muscular dystrophy,
teratozoospermia, Influenza infection, stem cell differentiation, for which examples are given in the present application (see experimental part). Many other diseases and (medical) conditions may also be diagnosed with the sequences of the present invention. In principle any condition or disease which has an effect on expression of genes would be amenable to be diagnosed with one or a subset of the probes that would be present on the presently defined arrays.
Such diseases may e.g. be Abdominal Aortic Aneurysm, Acanthamoeba Infection, ACE (Adverse Childhood Experiences), Acinetobacter Infection, Acquired Immune Deficiency Syndrome (AIDS), Adenovirus Infection, ADHD (Attention Deficit/Hyperactivity Disorder),
AFib, AF (Atrial fibrillation), AHF (Alkhurma hemorrhagic fever), ALS (Amyotrophic Lateral Sclerosis), Alzheimer's Disease, Amebiasis, Anaplasmosis, Ancylostoma duodenale Infection, Angiostrongylus Infection, Animal-Related Diseases, Anisakiasis Infection, Anthrax [Bacillus anthracis Infection], Aortic Aneurysm, Arenavirus Infection,, Ascaris Infection (Ascariasis), Aspergillus Infection (Aspergillosis), Asthma, Autism, Avian Influenza, Burkholderia cepacia Infection, Babesiosis (Babesia Infection), Bacterial Meningitis, Bacterial Vaginosis (BV), Balamuthia Infection (Balamuthia mandrillaris Infection, Balantidiasis (Balantidium
Infection), Black Lung (Coal Workers' Pneumoconioses), Blastocystis Infection (Blastocystis hominis Infection), Botulism (Clostridium botulinum Infection), Bovine Spongiform
Encephalopathy (BSE), Brainerd Diarrhea, Breast Cancer, Bronchiolitis, Bronchitis,
Brucellosis (Brucella Infection), Burkholderia cepacia Infection (B. cepacia infection), C. gattii cryptococcosis, C. neoformans cryptococcosis, Campylobacteriosis (Campylobacter Infection), Candida Infection (Candidiasis), Canine Flu, Capillariasis (Capillaria Infection), Carpal Tunnel Syndrome, Carrion's disease (Bartonella bacilliformis Infection), CCHF (Crimean- Congo hemorrhagic fever), Cerebral Palsy, Cervical Cancer, CFS (Chronic Fatigue Syndrome), Chagas Disease (Trypanosoma cruzi Infection), Chapare Hemorrhagic Fever (CHHF),
Chickenpox (Varicella Disease), CHIKV (Chikungunya Fever), Chlamydia (Chlamydia trachomatis Disease), Chlamydia trachomatis Disease, Chlamydophila (Chlamydia) pneumoniae Infection, Cholera (Vibrio cholerae Infection), Chronic Kidney Disease (CKD), Chronic Wasting Disease (CWD), Ciguatera Fish Poisoning, Classic Creutzfeldt-Jakob
Disease, Clonorchiasis (Clonorchis Infection), Clostridium difficile Infection, Clostridium perfringens infection, Coccidioidomycosis, common cold, Colorado Tick Fever (CTF), Colorectal (Colon) Cancer, Concussion, Congenital Hearing Loss, Congenital Heart Defects,
Conjunctivitis, Cooley's Anemia, Corynebacterium diphtheriae Infection, Coxiella burnetii Infection (Q Fever), Cronobacter Infection, Cryptosporidiosis (Cryptosporidium Infection), CWD (Chronic Wasting Disease), cyanobacterial algal bloom-associated illness, Cyclosporiasis (Cyclospora Infection), Cysticercosis, Cystoisosporiasis (Cystoisospora Infection),
Cytomegalovirus Infection (CMV), Deep Vein Thrombosis (DVT), Dengue Fever (DF),
Dermatophyte Infection, Diabetes, Dientamoeba fragilis Infection, Diphyllobothrium Infection (Diphyllobothriasis), Dipylidium Infection, Dirofilariasis (Dog Heartworm), Dog Flea
Tapeworm , Down Syndrome [Trisomy 21], Dracunculiasis, Dwarf Tapeworm (Hymenolepis Infection), E. coli Infection (Escherichia coli Infection), Eastern Equine Encephalitis (EEE), Ebola Virus Disease (EVD), EBV Infection (Epstein-Barr Virus Infection), Echinococcosis, EEE (Eastern Equine Encephalitis), Ehrlichiosis, Elephantiasis, Elizabethkingia Infection, Enterobius vermicularis Infection, Epidemic Typhus, Epilepsy, Fasciitis, Fasciola Infection (Fascioliasis), Fasciolopsiasis (Fasciolopsis Infection), Fetal Alcohol Spectrum Disorder, Fibromyalgia, Fifth Disease (Parvovirus B19 Infection), Folliculitis, Fragile X Syndrome (FXS), Francisella tularensis Infection, Fungal Meningitis, Fungal Pneumonia, Giardiasis (Giardia Infection), Glanders (Burkholderia mallei), Gnathostoma Infection
(Gnathostomiasis), Gonorrhea (Neisseria gonorrhoeae Infection), Gout, Granulomatous Amoebic Encephalitis (Acanthamoeba) (GAE (Acanthamoeba)), Group A Strep Infection (GAS), Group B Strep Infection (GBS), H3N2v influenza, H5N1 Influenza, HAB (Harmful Algal Bloom (HAB)-Associated Illness), Haemophilus influenzae Infection (including Hib
Infection), Hand, Foot, and Mouth Disease (HFMD), Hansen's Disease, Hantavirus Pulmonary Syndrome (HPS), Harmful Algal Bloom (HAB) -Associated Illness (HAB), Hearing Loss in Children, Heart Disease, Heat Stress, Hemochromatosis, Hemoglobinopathies, Hemophilia, Hendra Virus Disease (HeV Infection), Herpes B virus Infection, Herpes Simplex Virus Infection, Heterophyiasis (Heterophyes Infection), High Blood Pressure, Histoplasmosis (Histoplasma capsulatum Infection), HPV-Associated Cancers, Human Ehrlichiosis
(Ehrlichiosis, Human), Human Immunodeficiency Virus infection, Human Papillomavirus Infection (HPV Infection), Human Papillomavirus Vaccination (HPV Vaccination), Human Parainfluenza Virus infection (HPIV), Hymenolepis Infection, Hyperthermia, Hypothermia, II cell disease, Iatrogenic calcinosis cutis, IBIDS syndrome, Alternating Bowel Habit IBS, Constipation-predominant IBS,. Diarrhea-predominant IBS , Post-infectious IBS, Amyloidosis VI, ICF syndrome, Ichthyocrino toxic ation, Ichthyohepatotoxication, Ichthyosarcotoxism, Ichthyosiform Erythroderma, Ichthyosis, Ichthyosis bullosa of Siemens, Ichthyosis congenita biliary atresia, Ichthyosis congenita, Harlequin fetus type, Ichthyosis follicularis-atrichia- photophobia syndrome, Ichthyosis hystrix, Ichthyosis hystrix gravior, Ichthyosis hystrix, Curth Macklin type , Ichthyosis male hypogonadism, Ichthyosis mental retardation
asymptomatic spasticity, Ichthyosis mental retardation dwarfism renal impairment,
Ichthyosis microphthalmos, Ichthyosis prematurity syndrome, Ichthyosis Vulgaris, Ichthyosis- cheek-eyebrow syndrome, Dykes-Markes-Harper syndrome, IBIDS syndrome, Cholestasis, Idaho syndrome, Apraxia, Idiopathic acute eosinophilic pneumonia, Idiopathic adolescent scoliosis, Idiopathic adult neutropenia, Idiopathic alveolar hypoventilation syndrome,
Idiopathic calcinosis cutis, Calciphylaxis, Idiopathic chronic severe neutropenia, Cyclical edema syndrome, Atypical hemolytic uremic syndrome, Idiopathic diffuse interstitial fibrosis, Idiopathic dilatation of the pulmonary artery, Idiopathic dilation cardiomyopathy, Idiopathic double athetosis, Idiopathic dystonia DYT1, Idiopathic edema, Idiopathic eosinophilic chronic pneumopathy, Eosinophilic synovitis, Erythema nodosum, Diamond-Blackfan anemia, Biliary Atresia, Idiopathic facial palsy, Idiopathic gastroparesis, Giant cell myocarditis, Hydrops fetalis, Idiopathic hypereosinophilic syndrome, Idiopathic hypersomnia, Hypersomnolence,
Hypertrophic cardiomyopathy, Asbestosis, Idiopathic intestinal pseudoobstruction, Idiopathic liver cirrhosis, Gorham's syndrome, Idiopathic minimal change nephrotic syndrome,
Carnevale-Canun-Mendoza syndrome, Chronic Idiopathic Myelofibrosis, Idiopathic myopathy, Idiopathic neonatal atrial flutter, Eales Disease, Idiopathic osteoporosis, Idiopathic
Parkinson's disease, Dermatomyositis, Banti's syndrome, Idiopathic Pulmonary Fibrosis, Idiopathic pulmonary hemosiderosis, Idiopathic pulmonary hypertension, Idiopathic sclerosing mesenteritis, Idiopathic subglottic tracheal stenosis, Idiopathic Synesthesia, Idiopathic Thymus Hyperplasia, Idiopathic, hypertrophic, subaortic stenosis, Idrophrodisia, IgA nephropathy, IgA Pemphigus, IgE mediated gastrointestinal food allergy, IGF- 1 deficiency, IgG Deficiency, Hyper-IgM Syndrome, Iida-Kannari syndrome, Ileitis, Iliotibial Band Syndrome, Ilium syndrome, Capgras' syndrome, IMAGe syndrome, Imaizumi Kuroki syndrome, Hyper-IgM Syndrome, Imersluasbeck Syndrome, Imerslund's Anemia, Bessman- Baldwin syndrome, Iminoglycinuria, Immotile cilia syndrome, Drug-induced Immune
Hemolytic Anemia, Dressier (D.)syndrome, Immune thrombocytopenia, Immune
Thrombocytopenic Purpura, Acute Disseminated Encephalomyelitis, Good syndrome, Hyper- IgM Syndrome, Immunoglobulinic amyloidosis, Immunologic Deficiency Syndromes,
Immunosuppressive Measles Encephalitis, Immunotactoid glomerulonephritis, Impaired glucose tolerance, Imperforate anus, Currarino triad, Imperforate hymen, Branchio-Oculo-
Facial Syndrome, Impetigo, Impingement syndrome, Impossible syndrome, Inborn amino acid metabolism disorder, Inborn branched chain aminoaciduria, Dicarboxylicaminoaciduria, Argininosuccinic aciduria, Baber's syndrome, Inborn renal aminoaciduria, Inborn urea cycle disorder, Inclusion body myopathy, Inclusion Body Myositis, Inclusion conjunctivitis,
Achromatopsia incomplete, Incontinentia Pigmenti, Aromatase deficiency, Adult respiratory distress syndrome, Ehlers-Danlos syndrome, India tick typhus, Infant asthma, Carotenemia, Gastroesophageal Reflux Disease, Achalasia -- alacrimia syndrome, Alexander Syndrome, Hyperostosis cortical infantile, Infantile digital fibromatosis, Infantile dysphagia, Infantile epileptic- dyskine tic encephalopathy, Infantile Fibrosarcoma, Fucosidosis type 1, Infantile Glaucoma, Infantile hypophosphatasia, Infantile hypothyroidism, Gianotti-Crosti Syndrome, Cutaneous mastocytosis, Holocarboxylase synthetase deficiency, Infantile myofibromatosis, Infantile Neuroaxonal Dystrophy, Ceroid lipofuscinosis, Bile plug syndrome, Infantile parkinsonism, Anton-Vogt syndrome, Autosomal Recessive Polycystic Kidney Disease, Infantile polymyoclonus, Infantile psoriasis, Infantile pustular psoriasis, Infantile Refsum Disease, Infantile sialic acid storage disorder, Infantile sleep apnea, Epileptic encephalopathy, Infantile Spasms, Infectious arthritis, Infectious CFS, Esophagi tis, Gliomatosis cerebri, Inflammatory bowel disease, Inflammatory breast cancer, Chronic nonbacterial prostatitis, Influenza A, Influenza B, Influenza C, Basal cell carcinoma, Infundibulopelvic dysgenesis, Infundibulopelvic stenosis multicystic kidney, Inguinal hernia, Acroosteolysis,
Bisalbuminemia, Homozygotic Alpha 1 antitrypsin Defeciency, Inherited Hemolytic-Uremic Syndrome, Inherited spherocytic anemia, Iniencephaly, Insomnia, Dysentery, Insulin
Dependent Diabetes Mellitus, Insulin Resistance, Diabetic hypoglycemia, Insulinoma, Atkin- Flatiz syndrome, erythroleukemia, Intercostal neuralgia, Intermittent Explosive Disorder, Internal carotid agenesis, Hemorrhoids, Hydrocephalus, Escamilla-Lisser syndrome, Chilaiditi syndrome, Intersection syndrome, Interstitial cystitis, Fibrosing alveolitis, Ackerman
Dermatitis Syndrome, Dejerine-Sottas disease, Interstitial lung disease, Interstitial nephritis, Interstitial pneumonia, Intertrigo, Intervertebral disc disease, Amebiasis, Familial intestinal polyatresia syndrome, Bowel bypass syndrome, Intestinal capillariasis, Intestinal epithelial dysplasia, Helminthiasis, Intestinal Lymphangiectasia, Gardner syndrome, Ascariasis, Atrial myxoma, familial , Heart cancer, Benign astrocytoma, Bowen's disease, Intrahepatic cholangiocarcinoma, Goldenhar disease, Asherman's syndrome, Intussusception, Bladder Cancer, Genital psoriasis, Inversion 9 syndrome, Ankle sprain, IPEX syndrome, Aniridia, Iridocorneal dysgenesis, Iridocyclitis, Iridodialysis, Iridogoniodysgenesis typel, Chandler's syndrome, Baraitser-Winter syndrome, Biemond syndrome type 2, De Hauwere Leroy
Adriaenssens syndrome, Cogan-Reese syndrome, Iritis, Hemochromatosis, Bantu siderosis, Irons-Bhan syndrome, Irritable bowel syndrome, Irritant contact eczema, Isaacs syndrome, Ischemia, Avascular necrosis, Cardiomyopathy, Ischemic heart disease, Bywaters' syndrome, Calciphylaxis, Binswanger's Disease, Ischio-spinal dysostosis, Ischiogluteal Bursitis,
Isobutyric aciduria, Isobutyryl-coenzyme A dehydrogenase deficiency, Ectopia lentis, Follicle- stimulating hormone deficiency, Fleisher syndrome, Calvarial hyperostosis, Isopsoriasis, Isosporiasis, Isosporosiasis, Isovaleric academia, Israeli spotted fever, Isthmus coarctation, Hypomelanosis of Ito, Ivemark Syndrome, Ives-Houston syndrome, Ivic Syndrome, Ivory Epiphyses , Jackson-Barr syndrome, Jackson-Weiss Syndrome, Jacobs syndrome, Jacobsen syndrome, Jadassohn-Lewandowsky syndrome, Jaffe-Lichtenstein syndrome, Jaffer-Beighton syndrome, Amaurosis hypertrichosis, Creutzfeldt-Jakob Disease, Amaurosis hypertrichosis, Janbon syndrome, Jankovic-Rivera syndrome, Jansen type metaphyseal chondrodysplasia, Jansky-Bielschowsky disease, Janz syndrome, Japanese encephalitis, Jarcho-Levin Syndrome, Jaundice, JC virus infection, Epidermolysis bullosa inversa dystrophica, Jejunal Atresia, Jejunal diverticulosis, Jensen syndrome, Jequier-Deonna Syndrome, Jequier-Kozlowski- skeletal dysplasia, Jervell and Lange-Nielsen Syndrome, Cerebelloparenchymal disorder 3, Focal dermal hypoplasia, Jessner-Kanof syndrome, Jeune syndrome, Jeune-Tommasi syndrome, Jirasek-Zuelzer-Wilson syndrome, Job syndrome, Hyperimmunoglobulinemia E, Johanson-Blizzard Syndrome, Johnson-Hall-Krous syndrome, Alopecia, anosmia, Johnson- Munson syndrome, Johnston Aarons Schelley syndrome, Jones syndrome, Jones-Hersh-Yusk syndrome, Jorgenson syndrome Jorgenson-Lenz syndrome, Diamond-Blackfan anemia, Joubert Syndrome, Juberg-Hayward syndrome, Juberg-Marsidi syndrome, Judge -Misch- Wright syndrome, Jumper syndrome, His bundle tachycardia, Epidermolysis bullosa, Jung- Wolff-Back-Stahl syndrome, Besnier-Boeck-Schaumann disease, Jussieu syndrome, Juvenile angiofibroma, Juvenile dermatomyositis, Gigantomastia, Juvenile Glaucoma, Juvenile hyaline fibromatosis, Juvenile idiopathic arthritis, Juvenile Megaloblastic Anemia, Juvenile
Myasthenia Gravis, Juvenile myelomonocytic leukemia, Juvenile myoclonic epilepsy, Juvenile nephronophthisis, Juvenile osteoporosis, Juvenile Paget's disease, Juvenile pilocytic astrocytoma, Juvenile primary lateral sclerosis, Juvenile Retinoschisis, Juvenile Rheumatoid Arthritis, Juvenile Scleroderma, Juvenile temporal arteritis, Dercum syndrome, Kabuki syndrome, Kahrizi Syndrome, Kalan>Hafeez syndrome, Kaler-Garrity-Stern syndrome, Kallikrein hypertension, Gamborg nielsen syndrome, Kallmann Syndrome, Arthrogryposis,
Kantaputra-Gorlin syndrome, Kanzaki disease, Kaolin pneumoconiosis,
Figure imgf000033_0001
syndrome, Kaplowitz-Bodurtha syndrome, Kaposi's Sarcoma, Bluefarb-Stewart syndrome, Bafverstedt syndrome, Kaposiform hemangioendothelioma, Kapur-Toriello syndrome, Karandikar-MariaJKamble syndrome, Karsch-Neugenbauer syndrome, Kartagener syndrome, DextrocardiaJjronchiectasis-sinusitis, Hemangioma thrombocytopenia syndrome, Kashani- Strom-Utley syndrome, KashinJ3ek disease, Kasznica-Carlson-Coppedge syndrome.
Katayama fever, Katsantoni-PapadakouJ^agoyanni syndrome, Kaufman oculocerebrofacial syndrome, Kawasaki disease, KBG Syndrome, Kearns-Sayre Syndrome, Kelley-Seegmiller syndrome, Keloid, Kennerknecht syndrome, Kenny-Caffey Syndrome, Kenya fever, Kenya tick typhus, Keralytic Winter Erythema, Keratitis, Keratoacanthoma, Keratoconus, Keratoderma, Keratolysis exfoliativa, Keratomalacia, Keratosis, Kerion celsi, Kernicterus, Kersting-Hellwig syndrome, Keshan disease, Ketoacidosis, Beta ketothiolase deficiency, Keutel syndrome, Kidney arteriovenous fistula, Kidney Cancer, Kidney failure, Kienbock disease, Kifafa seizure disorder, Kikuchi disease, Killian syndrome, Kimura disease, King-Denborough syndrome, Kleeblattschaedel syndrome, Kleine
Figure imgf000033_0002
syndrome,
Kleptolagnia, Klinefelter syndrome, Klippel Feil Syndrome, Klippel-Trenaunay Syndrome, Klotz syndrome, Dejerine-Klumpke syndrome, Kluver-Bucy Syndrome, Kniest dysplasia, Knismolagnia, Knobloch syndrome, Kocher-Debre-Semelaigne syndrome, Kohler, disease, Kohler syndrome, Freiberg disease, Degos Disease, Kohlschutter-Tonz syndrome, Roller syndrome, Konigsmark-KnoxJ iussels syndrome, Koone-Rizzo-Elias syndrome, Koro syndrome, Korovnikov syndrome, Koroxenidis Syndrome, Korsakoff's psychosis, Korula- Wilson-Salomonson syndrome, Kostmann syndrome, Kosztolanyi syndrome, Kote-Katsantoni Syndrome, Kotzot -Richter syndrome, Koussef Nichols syndrome, Kowarski syndrome, Kozlowski Celermajer Tink syndrome, Kozlowski-Brown-Hardwick syndrome, Kozlowski- Celermajer syndrome, Kozlowski-Rafinski-Klicharska syndrome, Kozlowski- Warren- Fisher syndrome, Krabbe disease, Krabbe leukodystrophy, Krabbe Disease, Kraemer syndrome, Kramer- PoUnow disease, Breisky disease, Krause syndrome, Krause-Kivlin syndrome, Kreibig opticomalacia, Krieble Bixler syndrome, Krukenberg carcinoma, Gerlier disease, Kuf Disease, Kugel-Stoloff syndrome, Barre-Lieou syndrome, Kumar levick syndrome, Kunze riehm syndrome, Kurczynski-Casperson syndrome, Kuru, Kurz syndrome, Kuskokwim disease, Kuster syndrome, Kuster-Majewski-Hammerstein syndrome, Kwashiorkor, Chinese
Restaurant Syndrome, Kyasanur-Forrest disease, Kyphosis, Kyrle disease, Eosinophilia- myalgia syndrome, LI Syndrome, Laband Syndrome, Labile Hypertension, Labrador lung, Labrynthitis, Lachiewicz-Sibley syndrome, Lacrimoauriculodentodigital syndrome, Lactate dehydrogenase deficiency, Lactic Acidosis, Galactocele, Lactose Intolerance, Lactotroph adenoma, Cadasil, LADD Syndrome, Ladda Zonana Ramer syndrome, LADHSC deficiency, Davis-Lafer syndrome, Ascher syndrome, Lafora body disease, Lagnonector, Laing distal myopathy, Hay fever, Lambdoid synostosis familial, Lambert syndrome, Lambert-Eaton Myasthenic Syndrome, Lambliasis, Lamellar Cataract, Landau-Kleffner Syndrome , GM1 gangliosidosis, Landouzy-Dejerine muscular dystrophy, Landy-Donnai syndrome, Danger mesomelic dysplasia, Langer-Nishino-Yamaguchi syndrome, Langerhans Cell Histiocytosis, Langerhans cell sarcoma, Lantronudia, Lanzietri syndrome, Laplane-Fontaine-Lagardere syndrome, Diffuse large B-cell lymphoma, Large cell carcinoma, Large granular lymphocyte leukemia, Large plaque parapsoriasis, Laron Dwarfism, Larsen syndrome, Laryngeal carcinoma, Laryngeal papillomatosis, Gay-Feinmesser-Cohen syndrome, Laryngitis,
Laryngomalacia, Larynx atresia, Larynx Cancer, Lassa fever, Lasseur-Graham-Little syndrome, Bessman-Baldwin syndrome, Common Variable Immunodeficiency, Latent tuberculosis, Lateral body wall complex, Goldenhar disease, Latham-Munro syndrome, Lathosterolosis, Lathyrism, Biber-Haab-Dimmer dystrophy, Lattice corneal dystrophy, Laugier-Hunziker syndrome, Launois syndrome, Launois-Bensaude adenolipomatosis, Froelich's syndrome, Laurence -Moon Syndrome, Laurence-Prosser-Rocker syndrome,
Lawrence-Seip syndrome, Lawrence-Seuo syndrome, Laxative abuse syndrome, Lazy leukocyte syndrome, Amaurosis congenita of Leber, Hepatoma, Aagenaes syndrome, Le
Marec-Bracq-Picaud syndrome, Coffin syndrome 1, Leber hereditary optic neuropathy, Leber miliary aneurysm, Leber optic atrophy, Ledderhose disease, Lederer's anemia, Legg-Calve- Perthes disease, Legionella infection, Legionnaires' disease, Camurati-Engelmann Disease, Delleman-Oorthuys syndrome, Leigh syndrome, Leiner Disease, Leiomyoma, Leiomyomatosis, Leiomyosarcoma, Leishmaniasis , Lele syndrome, Lemierre's syndrome, Lenegre disease, Lennox- Gastaut Syndrome, Lentigo maligna, Lenz Majewski hyperostotic dwarfism,
LEOPARD Syndrome, Lepidopterism, Leprechaunism, Leprosy, Leptomeningitis,
Leptosadism, Leptospirosis, Leri Pleonosteosis, Leri-Weil syndrome, Leriche syndrome, Lesch- Nyhan syndrome, Leschke syndrome, Bell mania, Letterer-Siwe disease, Leucinosis,
Leukemia, Leukocyte Adhesion deficiency (LAD), Leukocytoclastic angiitis, Halo nevi,
Leukodystrophy, Leukoencephalopathy, Breisky disease, Leukomalacia, Leukonychia totalis, Leukoplakia, Heller-Dohle disease, Leuven dysfibrinogenemia, Levator syndrome, Levie- Stefanovic-Nikolic syndrome, Levine-Critchley syndrome, Levocardia, Levy-Yeboa Syndrome, Lewandowsky-Lutz dysplasia, Lewis (F.) syndrome, Leydig cells hypoplasia, Lhermitte-Cornil- Quesnel syndrome, Lhermitte-Duclos disease, Lhermitte-McAlpine syndrome, Li-Fraumeni syndrome, Lichen amyloidosis, Lichen nitidus, Lichen planus, Lichen sclerosis, Lichstenstein syndrome, Dana syndrome, Brachydactyly, Focal dermal hypoplasia, Apraxia, Allen-Masters syndrome, Fanconi syndrome, Burning feet syndrome, Limb-girdle Muscular Dystrophy,
Limb -mammary syndrome, Limbic encephalitis, Limited cutaneous systemic sclerosis, CREST syndrome, Lindsay-Burn syndrome, Lindstrom syndrome, Linear IgA dermatosis, Linear porokeratosis, Hairy tongue, Linguatula serrata infection, Brinton disease, Lip cancer, Cheilitis, Lipedema, Lipid storage myopathy, Lipoamide dehydrogenase deficiency,
Lipoatrophic diabetes, Lipodermatosclerosis, Lipodystrophy, Dunnigan syndrome, Lipoedema, Ceroid storage disease, Lipogranulomatosis, Lipoid proteinosis of Urbach and Wiethe, Lipoma, Lipomyelomeningocele, Lipoprotein glomerulopathy, Lipoproteine lipase deficiency,
Lipoproteinemia, Liposarcoma, Lissauer paralysis, Lissencephaly, Listeriosis, Littoral cell angioma, Liver abscess, Liver cancer, Liver cirrhosis, Liver fibrosis, Budd-Chiari syndrome, Lobstein disease, Lobular carcinoma, Dysautonomia, Localized epiphyseal dysplasia,
Localized Scleroderma, Loeffler's endocarditis, Loewenthal syndrome, Loeys-Dietz syndrome, Loffredo-Cennamo-Cecio syndrome, Logic syndrome, Loiasis, Long QT syndrome, Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, Craniosynostosis, Loose anagen syndrome, Lopes-Marques de Faria syndrome, LORD, Lordosis, Los Angeles
dysfibrinogenemia, Louse-borne diseases, Hypokalemia, Hyperacusis, Lowe oculocerebrorenal syndrome, Dejerine-Klumpke syndrome, Lower esophageal ulcer, Lowry syndrome, Lowry- Maclean syndrome, Lowry-Wood syndrome, Lubarsch-Pick syndrome, Lubinsky syndrome, Lubs syndrome, Lucey Driscoll syndrome, Lujan-Fryns syndrome, Lumbago, Lumbar Spondylosis, Lundberg syndrome, Lung cancer, Lupus, Lurie-Kletsky syndrome, Lutz- Lewandowsky epidermodysplasia verruciformis, Lutz-Miescher Disease, Lutz-Richner-Landolt syndrome, Lygerastia, Lyme disease, Lymph node neoplasm, Lymphadenitis, Bafverstedt syndrome, Lymphangiectasis, Lymphangioleiomyomatosis, Lymphangiomas, Lymphangitis, Lymphatic Filariasis, Lymphatic malformation (LM), Lymphatic neoplasm, Lymphedema, Lymphoblastic lymphoma, Lymphocytic Choriomeningitis, Lymphocytic colitis,
Lymphogranuloma venereum, Lymphoid interstitial pneumonia, Lymphoma, Lymphomatoid Granulomatosis, Lymphomatoid papulosis, Lymphomatous thyroiditis, Lymphopenia, Lynch Syndrome, Lysinuric protein intolerance, Lysteria monocytoigeneses meningitis, M/SCHAD deficiency, Mac Duffie's syndrome, MacDermot-Winter syndrome, Machado-Joseph Disease, Machinery accidents, Atrophoderma vermiculata, Macleod-Fraser syndrome, Macrocephaly, Macrocytic anemia, Macrocytic Hyperchromic Anemia, Macrocytosis, Macrodactyly,
Macroepiphyseal dysplasia, Macroglossia, Macrogyria, Macrogyria, Macrophagic
myofasciitis, Macrophilia, Macrosomia, Macrostomia, ,Macrothrombocytopenia, Macula halo syndrome, Macular amyloidosis, Macular degeneration, Macular dystrophy, Macules, hereditary, Madelung deformity, Madokoro-Ohdo-Sonoda syndrome, MADSAM, Maffucci Syndrome, Maghazaji syndrome, Magnesium deficiency, Magnetic gait, Magrassi-Leonardi syndrome, Majeed syndrome, Majocchi disease, Major affective disorder, Major depressive disorder, Major depressive disorder related fibromyalgia, Major histocompatibility complex class I deficiency, Major histocompatibility complex class II deficiency, Major Ulcerative Stomatitis, Mai de debarquement, Malakoplakia, Malaria, Male Breast Cancer, Male infertility, Malignant astrocytoma, Malignant brain tumors ... type of Brain cancer, Malignant Buotonneuse fever, Malignant fibrous histiocytoma, Malignant germ cell tumor, Malingering, Malonic aciduria, Malouf syndrome, Malt Worker's disease, Mammary polyadenomatosis, Mania, Mann syndrome, Manouvrier syndrome, Mansonelliasis, Mantle cell lymphoma, Manz syndrome, Map-dot-fingerprint dystrophy, Maple syrup urine disease, Marasmus, Marburg disease, Marchiafava-Bignami disease, Marchiafava-Micheli disease, Marcus-Gunn
phenomenon, Marden-Walker Syndrome, Marden-Walker-like syndrome, Mareck's disease, Marek's disease, Marfan syndrome, Marfan-Like syndrome, Marginal glioneuronal
heterotopia, Marie type ataxia, Marie Unna congenital hypotrichosis, Marie-Bamberg syndrome, Marie-Sainton syndrome, Marie-See Syndrome, Marie-Strumpell disease,
Marinesco-Sjogren syndrome, Maroteaux-Fonfria syndrome, Maroteaux-Stanescu-Cousin syndrome, Maroteaux-Verloes-Stanescu syndrome, Marsden syndrome, Marsden-Nyhan- Sakati syndrome, Marseilles fever, Marshall syndrome, Marshall-Smith Syndrome, Martsolf syndrome, MASA Syndrome, MASS syndrome, Massa-Casaer-Ceulemans syndrome, Mast cell sarcoma, Mastalgia, Mastitis, Mastix, Mastocytosis, Mastofact, Mastoiditis, Matsoukas syndrome, Matsoukas-Liarikos-Giannika syndrome, Maumenee syndrome, Mauriac syndrome, May-Hegglin thrombocytopenia, May- White syndrome, Mayaro fever, Mayer-Rokitansky- Kuster-Hauser, syndrome, Mazabraud syndrome, Mazoperosis, Mc Leod neuroacanthocytosis syndrome, MC4R deficiency, McAlister dysplasia, McArdle disease, McBurney's sign,
McDonough syndrome, McDowall syndrome, McGillivray syndrome, McGrath Syndrome, McKusick-Kaufman syndrome, McLain-Dekaban syndrome, McLetchie-Aikens syndrome, McMurray's sign, Meadows syndrome, Measles, Meckel Syndrome, Medial Medullary
Syndrome, Mediastinal shift, Mediastinitis, Mediterranean myoclonic epilepsy,
Mediterranean Spotted Fever, Medium and long chan 3-hydroxyacyl-coenzyme A
dehydrogenase deficiency, Medium and short chain 3-hydroxyacyl-CoA dehydrogenase deficiency, Medium-Chain Acyl-CoA Dehydrogenase Deficiency, Medullary carcionoma, Medullary cystic kidney disease, Medulloblastoma, Megacolon, Megaduodenum ,
Megalencephaly, Megaloblastic Anemia, Megalocytic interstitial nephritis, Megarbane syndrome, Megarbane-Jalkh Syndrome, Megarbane-Loiselet syndrome, Mehes syndrome, Meibomitis, Meier-Blumberg-Imahorn syndrome, Meier-Rotschild syndrome, Meige syndrome, Meigel Disease, Meinecke syndrome, Melanoma, Melanosis diffusa congenita, MELAS, Meleda Disease, Melhem-Fahl syndrome, Melioidosis, Melkersson-Rosenthal Syndrome, Melnick-Fraser syndrome, Melnick-Needles syndrome, Melolagnia, Melorheostosis,
Membranoproliferative glomerulonephritis, Mende syndrome, Mendelson syndrome, Meninges cancer, Meningioma, Meningitis, Meningocele, Meningococcal disease, Meningoencephalocele, Meningomyelocele, Menkes Disease, Menorrhagia, Meralgia paresthetica, Meretoja syndrome, Merkel cell cancer, Mesangial proliferative glomerulonephritis, Mesangial sclerosis, diffuse, Mesangiocapillary glomerulonephritis type , Mesenteric Adenitis, Mesenteric artery syndrome, Mesomelia, Mesothelioma, Metabolic Acidosis, Metabolic Syndrome,
Metachondromatosis, Metachromatic Leukodystrophy, Metagonimiasis, Metaphyseal acroscyphodysplasia, Metapneumoviral infection, Metatarsus adductus, Metatrophic dysplasia, Metatropic dwarfism, Methaemoglobinaemia, Methimazole -- Teratogenic Agent, Methylcobalamin deficiency, Methylene tetrahydrofolate reductase deficiency,
Methylmalonate Semialdehyde Dehydrogenase Deficiency, Methylmalonic acidemia,
Metrorrhagia, Metz dysfibrinogenemia, Mevalonic aciduria, Meyenburg-Altherr-Uehlinger syndrome, Michelin Tire Baby Syndrome, Michels-Caskey syndrome, Mickleson syndrome, Mickulicz disease, Microcephaly-oculo-digito-esophageal-duodenal syndrome, Microcoria, congenital, Microcornea , Microcytic Anemia, Microcytosis, Microdontia -- hypodontia -- short stature, Micrencephaly, Microlissencephaly, Microsomia -- hemifacial -- radial defects, Microspherophakia with hernia, Microsporidiosis, Microtia type I , Microvascular angina, Microvillus Inclusion Disease, Middle ear infection, Midline lethal granuloma, Miescher Elastoma, Miescher's granuloma, Miescher's syndrome, Miescher's trichofolliculoma, Mietens syndrome, Migraine, Mikaelian syndrome, Mikulicz syndrome, Mikulicz's Disease, Milia, Milk-Alkali syndrome, Miller Fisher Syndrome, Miller Syndrome, Miller-Dieker syndrome, Millian erythema, Milner-Khallouf-Gibson syndrome, Minamata disease, Mineral deficiency, Minicore disease, Minicore myopathy with external ophthalmoplegia, Mirror hand syndrome, Mitral atresia, Mitral regurgitation, Mitral stenosis, Mitral valve disease, Mitral-valve prolapse, Mittelschmerz, Mixed apnea, Mixed asthma, Mixed Cerebral Palsy, Mixed connective tissue disease, Mixed granulocytic asthma, Mixed sclerosing bone dystrophy, Mixed type non small cell carcinoma, Mixed-state bipolar disorder, Mixoscopy, Miyoshi myopathy, MLCRD Syndrome, MN1, MODY syndrome, Moebius Syndrome, Mohr syndrome, Mohr- Tranebjaerg syndrome, Moller-Barlow disease, Moloney syndrome, MOMO syndrome, Monakow syndrome, Mondini Dysplasia, Mondor's disease, Monilethrix, Monkeypox,
Monoamine oxidase A deficiency, Monogenic obesity, Monomelic Amyotrophy, Mononen- Karnes-Senac syndrome, Mononeuritis multiplex, Mononucleosis, Monster cell malignant melanoma, Montefiore syndrome, Moore Smith Weaver syndrome, Morava-Mehes syndrome, Morel-Wildi syndrome, Morgellons Disease, Moriaphilia, MORM syndrome, Morning sickness, Morphea, Morphoeic basal cell carcinoma, Morquio syndrome, Morse-Rawnsley-Sargent syndrome, Mortimer's disease, Morton's Neuroma, Motion sickness, Motor neuropathy, Mottled cyanosis , Mouldy shower curtain hypersensitivity pneumonitis, Mounier-Kuhn syndrome, Mount Reback syndrome, Mountain fever, Mousa-Al Din-Al Nassar syndrome, Mouth cancer, Mouth ulcers, Mowat- Wilson syndrome, Moyamoya Disease, Moynahan syndrome, MPS 3 C, MPS 3 D, MPS-IV (Morquio Disease), MRKH syndrome, MRXS- Christianson, MRXS9, MSBD syndrome, MSI-H colorectal cancer, MSI-L colorectal cancer, MSS colorectal cancer, Mucha-Habermann Disease, Mucinous carcinoma, Muckle-Wells syndrome, Mucoepidermoid Carcinoma, Mucolipidoses, Mucopolysaccharidosis ,
Mucormycosis, Mucosal leishmaniasis (espundia), Mucositis, Muenke Syndrome, Mulibrey Nanism syndrome, Muller-Barth-Menger syndrome, Mullerian aplasia, Multicentric reticulohistiocytosis, Multiple Myeloma, Multiple Sclerosis, Multiple Sulfatase Deficiency, Multiple synostoses syndrome 1, Mumps, Mungan syndrome, Munk disease, MURCS
Association, Murine typhus, Murray Valley encephalitis, Muscle cramps, Muscle Hypertonia, Muscle Hypotonia, Muscle spasm, Muscle-eye-brain syndrome, Muscular Dystrophy ,
Myasthenia Gravis, Mycetoma, Mycobacterial infections, Mycoplasma pneumoniae, Mydriasis, Myelinopathies, Myelitis, Myelocerebellar disorder, Myelocytic leukemia-like syndrome, familial, chronic , Myelodysplastic/myeloproliferative disease, Myelofibrosis, Myelofibrosis- osteosclerosis, Myelogenous leukemia, Myeloid Sarcoma, Myeloid splenomegaly,
Myelokathexis syndrome, Myeloma, Myelopathy, Myeloperoxidase deficiency, Myelpathic anemia, Myhre Syndrome, Myiasis, Myocarditis, Myoclonic dystonia, Myoclonus ,
Myoglobinuria, Myokymia, Myoma (fibroid), Myopathy, Myopia , Myosarcoma , Myositis, Myotonic Dystrophy, Myxedema, Myxoid liposarcoma, Myxoid melanoma, Meniere's disease, Menetrier's disease, N syndrome , N-acetyl glutamate synthetase deficiency, N- acetyl- alpha- glucosaminidase sulfamidase deficiency, Nablus mask-like facial syndrome, Nacrochlesis , NADH cytochrome B5 reductase deficiency , Naegleria, Nager Syndrome, Naguib syndrome, Nakajo syndrome, NAME syndrome, Nance-Horan Syndrome, Nancy dysfibrinogenemia, Nanophthalmia, Nanukayami, Narcolepsy, Nathalie syndrome, Native American myopathy, Navajo neurohepatopathy, Navajo poikiloderma, Naxos disease, Neck Arthritis, Neck Cancer , Neck-tongue syndrome, Necrobacillosis, Negative rheumatoid factor polyarthritis, Nelson Syndrome, Nemaline myopathy, Neovascular glaucoma, Nephritis, Nephroblastoma,
Nephrocalcinosis, Nephrolithiasis type 1, Nephronophthisis , Nephropathy, Nephrosclerosis, Nephrosis , Nerve cancer , Nesidioblastosis of pancreas , Netherton syndrome ichthyosis , Neu-Laxova Syndrome , Neuhauser-Daly-Magnelli syndrome, Neuhauser-Eichner-Opitz syndrome, Neuralgia, Neuraminidase deficiency, Neuritis, Neuroacanthocytosis,
Neuroblastoma, Neurocutaneous melanosis, Neurocysticercosis, Neurodermatitis,
Neuroepithelioma, Neurofibromatosis, Neurofibrosarcoma, Neuroma , Neuromyelitis Optica, Neuromyotonia , Neuropathy , Neurosis, Neurosyphilis , Neutropenia, Nevo syndrome, Nevoid melanoma, Newcastle Disease, Nezelof Syndrome, Nguyen syndrome, Nicolaides- Baraitser syndrome, Nicolau syndrome, Nielsen-Jacobs syndrome, Niemann-Pick disease, Nierhoff-Hubner syndrome, Nievergelt syndrome, Nijmegen Breakage Syndrome, Nipah virus encephalitis, NISCH syndrome, NISH Syndrome , Nivelon-Nivelon-Mabille syndrome, Noble- Bass-Sherman syndrome, Nocardiosis, Nocturia, Nodular basal cell carcinoma, Nodular goiter , Nodular Prurigo, NOMID syndrome, Non cardiogenic pulmonary oedema, Non- alcoholic steatohepatitis (NASH), Non-allergic asthma, Non-atopic asthma, Non-Hodgkin's Lymphoma, Non-ketotic hyperglycinemia, Nonkeratan-sulfate-excreting Morquio syndrome, Nonne-Milroy disease, Noonan Syndrome ,Noonan-like syndrome, Normochromic anemia, Normocytic anemia ,Norrie Disease, Norum disease, Norwalk gastroenteritis, Nosolagnia , Notalgia paresthetica , Nothnagel acroparesthesia, Nova syndrome, Nummular dermatitis, Nyssen-Van Bogaert syndrome, Nystagmus, O'Donnell-Pappas syndrome, O'Higgins disease, Obal syndrome, Obesity, Obliterative portal venopathy, Obsessive-compulsive disorder, Odontoma, Oesophagostomiasis, OFD syndrome , OHSS, Ohtahara Syndrome, Okamuto Satomura syndrome, Oklahoma dysfibrinogenemia, Olecranon bursitis, Oligodendroglioma, Oligospermia, Oliguria, Oliver syndrome , Oliver-McFarlane syndrome, Olivopontocerebellar Atrophy, Oilier Disease, Olmsted syndrome, Omenn syndrome, Omodysplasia, Omsk hemorrhagic fever , Onchyomycosis, Ondine syndrome, Onychogryphosis, Onychophagia, Ophthalmitis, Opisthorchiasis, Opisthotonos, Opitz G/BBB Syndrome, Oppenheim's dystonia, Opsismodysplasia, Optic atrophy, Optic neuritis, Optic pathway glioma, Oral cancer, Oral facial digital syndrome, Oral leukoplakia, Orbit tumor, Orbital lymphangioma, Orchitis, Ornithine transcarb amylase (OTC) Deficiency, Ornithinemia, Oropharyngeal cancer , Ortolani's sign, Osgood-Schlatter Disease, Oslam syndrome, Osier's disease, Osler-Rendu- Weber syndrome 2, Osier- Vaquez disease, Oslo dysfibrinogenemia, Osteitis, Osteoarthritis, Osteochondroma, Osteochondrosis, Osteogenesis imperfecta, Osteoid Osteoma, Osteoma, Osteomalacia , Osteomyelitis, Osteopetrosis, Osteopoikilosis, Osteoporosis,
Osteoradionecrosis, Osteosarcoma, Osuntokun syndrome, Otitis, Oto-facio-osseous-gonadal syndrome, Otocephaly syndrome, Otodental dysplasia, Otoony chop er one al syndrome,
Otosclerosis, Ouvrier-Billson syndrome, Ovarian Cancer , Ovarian carcinosarcoma,
Ovarioleukodystrophy, Owren Parahemophilia, Oxalosis, Ozolagnia, Pachydermoperiostosis , Pachygyria , Pachyonychia congenital syndrome, Paget's Disease, Palate cancer,
Palindromic rheumatism, Pallidopyramidal syndrome, Pallister Killian Mosaic Syndrome , Pallister-Hall Syndrome, Pallister-Killian Syndrome, Pallister-Ulnar mammary syndrome, Palmer-Pagon syndrome, Panacinar Emphysema, Pancoast's syndrome, Pancolitis,
Pancreatic cancer, Pancreatitis, Pancreatoblastoma, Pancytopenia, Panhypopituitarism, Panniculitis, Panophthalmitis, Panostotic fibrous dysplasia, Panuveitis, Papillary renal cell carcinoma, Papillitis, Papilledema, Papilloma, Paprika splitter's lung, Paprika splitter's lung -- Mucor Stolonifer, Papular mucinosis, Papular urticaria, Paracoccidioidomycosis, Paracusia, Paraganglioma, Paragonimiasis, Parainfluenza, Paralysis, Paraomphalocele, Paraphilias, Paraphimosis , Parapsoriasis , Parasomnia, Paresis, Paresthesia, Parkinson's Disease, Paronychia, Parotid gland cancer, Parotitis, Paroxysmal atrial tachycardia,
Paroxysmal kinesigenic choreoathetosis, Paroxysmal ventricular fibrillation, Parry Romberg Syndrome, Pars Planitis, Parsonage Turner syndrome , Partington X-linked mental retardation syndrome, Pashayan syndrome, Passos-Bueno syndrome, Patau syndrome , Patel- Bixler syndrome, Patterson-Stevenson syndrome, Pauciarticular chronic arthritis,
Paucigranulocytic asthma, PCBD, Pearson's anemia, Peeling skin syndrome, PEHO-like syndrome, Pelger-Huet anomaly, Pelizaeus-Merzbacher Disease, Pellagra, Pelvic Cancer, Pemphigus, Pendred syndrome, Penis Cancer, Pentalogy of Cantrell, Pentosuria, PEPCK Deficiency, Peptic Ulcer, Perennial rhinitis, Pericardial Mesothelioma, Pericarditis,
Perichondritis, Perimyositis, Periodontitis, Perioral dermatitis, Periorbital Cellulitis, Periosteal chondrosarcoma, Periostitis , Peripartum cardiomyopathy, Peripheral neuritis, Peripheral neuroectodermal tumor, Peripheral uveitis, Perisylvian syndrome, Peritoneum cancer, Peritonitis, Periventricular laminar heterotopia, Pernicious anemia, Perniosis, Peromelia, Peroxisomal bifunctional enzyme deficiency, Peters anomaly, Petit mal epilepsy, Petit-Fryns syndrome , Petty-Laxova-Wiedemann syndrome, Peutz-Jeghers Syndrome, Peyronie's disease, Pfeiffer syndrome, Pfeiffer-Mayer syndrome, Pfeiffer-Palm-Teller syndrome, Pfeiffer-Tietze-Welte syndrome, Pfeiffer- Weber- Christian syndrome, Pfiesteria piscicida infection, Phacomatosis pigmentokeratotica, Phaeohyphomycosis, Pharyngitis, Pharynx cancer, Phenylketonuria, Pheochromocytoma, Philadelphia-negative chronic myeloid leukemia, Philemanmania, Phillips- Griffiths syndrome, Phimosis, Phlebitis,
Phocomelia syndrome , Phosphoenolpyruvate carboxykinase (PEPCK) deficiency,
Phosphoglucomutase deficiency, Phosphoglycerate Kinase Deficiency,
Phosphoribosylpyrophosphate synthetase deficiency, Phosphoserine aminotransferase deficiency, Photosensitivity , Phrynoderma, Phyllodes tumor, PIBIDS syndrome, Picardi- Lassueur-Little syndrome, Pick's Disease, Pickwickian syndrome, PID-like dyspareunia, Pierre Robin's sequence, Pierson Syndome, Pigeon Breeder's disease, Pigment-dispersion syndrome, Pigmentary retinopathy, Pigmented basal cell carcinoma, Pili annulati, Pili multigemini, Pili torti, Pillay syndrome, Pilomatrixoma , Pilonidal disease, Pilotto syndrome, Acne, Pindborg Tumor, Pineal Teratoma, Piriformis Syndrome, Pitt-Hopkins syndrome , Pitt-Rogers-Danks syndrome, Pituitary Cancer, Pityriasis, Piussan-Lenaert- Mathieu syndrome, Plagiocephaly, Plantar Fasciitis, Plaque psoriasis, Plasma cell leukemia, Plasmacytoma anaplastic, Pleural cancer, Pleurisy, Pleuropulmonary blastoma , Plexosarcoma, Plica Syndrome, Plum syndrome, Plummer-Vinson syndrome, Pneumococcal meningitis, Pneumococcal pneumonia, Pneumocystosis, Pneumocytosis, Pneumonia,
Pneumonitis, Pneumothorax, Podder-Tolmie syndrome, POEMS syndrome, Poikilocytic anemia, Poikiloderma of Kindler, Poikiloderma of Rothmund-Thomson, Pointer syndrome, Poland Syndrome, Polio, Pollitt syndrome, Polyarteritis, Polyarthritis, Polycystic kidney disease, Polycystic liver disease, Polycythemia, Polydactyly, Polyembryoma ,Polyendocrine deficiency syndrome, Polymer Fume Fever, Polymicrogyria , Polymyalgia rheumatica, Polymyocytis, Polyneuritis, Polyomavirus Infections, Polyp, Polytopic Dystelephalangy, Pompe disease, Poncet-Spiegler's cylindroma, Pontiac fever, Porencephaly, Porphyria, Port- wine stain, Portal thrombosis, Portsmouth syndrome, Portuguese type amyloidosis,
Positional plagiocephaly, Post-ADD chronic fatigue syndrome, Post-polio syndrome,
Postperfusion syndrome, Potassium deficiency , Potocki-Lupski syndrome, Potter syndrome, Powell-Buist-Stenzel syndrome, Powell-Chandra-Saal syndrome, Powell-Venencie-Gordon syndrome, Prader-Willi syndrome, Pratesi syndrome, Pre-invasive breast cancer,
Pregnancy-related conditions, Prehypertension , Premature aging , Premenstrual syndrome, Presbycusis, Presbylarynx, Presbyopia, Pretibial Myxedema , Priapism, Primary
agammaglobulinemia, Primerose syndrome, Primrose Syndrome, Prinzmetal's variant angina, Prion disease, Proctalgia , Proctitis, Progeria, Prolactinoma, Prolapse,
Prolymphocyte leukemia , Prostate Cancer, Prostatitis , Protanopia , Protein C deficiency, Protein S deficiency, Proteinuria, Proteus Syndrome, Protoporphyria, Protozoan infections , Proud-Le vine- Carpenter syndrome, Prurigo, Pseudo-torch syndrome, Pseudoachondroplasia, Pseudoaldosteronism, Pseudogout , Pseudohypoaldosteronism , Pseudomonas infections, Pseudopolycythaemia, Psittacosis , Psoriasis, Psychoneurosis, Psychosis, Ptosis , Pulmonary alveolar microlithiasis , Pulmonary edema, Pulmonary fibrosis, Pulmonary hemangiomatosis, Pulmonary hypertension, Pulmonary valve disease , Pulp Worker's disease , Purpura,
Pycnodysostosis , Pyelonephritis , Pyle disease, Pylephlebitis , Pyloric stenosis, Pyomyositis , Pyridoxine deficiency , Pyrolagnia , Pyrosis , Pyruvate carboxylase deficiency , Pyruvate decarboxylase deficiency , Pyruvate dehydrogenase deficiency , Pyruvate dehydrogenase phosphatase deficiency , Pyruvate Kinase Deficiency, Q fever, Quadriplegia, Quattrin mcpherson syndrome, Quebec platelet disorder, Queensland tick typhus, Quinsy, Rabies, Rabson-Mendenhall syndrome, Rademacher disease, Radial Hemimelia, Radial Ray
Deficiency, Radial Tunnel Syndrome, Radiation sickness, Radiculopathy, Radio renal syndrome, Radioulnar synostosis, Raine syndrome ,Rajab-Spranger syndrome, Ramban- Hasharon syndrome, Rambaud-Galian syndrome, Ramon Syndrome, Ramos-Arroyo Syndrome, Ramos-ArroyoClark syndrome, Ramsay Hunt Syndrome, Randall disease, Rapadilino syndrome, Rape trauma syndrome, Rapp-Hodgkin syndrome, Rasmussen encephalitis, Rathburn disease, Ray-Peterson-Scott syndrome, Raynaud's phenomenon, Rayner-Lampert- Rennert syndrome, Reactive angioendotheliomatosis, Reactive arthritis, Reardon-Hall-Slaney syndrome, Reardon-Wilson-Cavanagh syndrome, Rebound hypertension, Recrudescent typhus, Rectal cancer Rectosigmoid neoplasm, Rectractile mesenteritis, Red green colour blindness, Red neck syndrome, Reese-Ellsworth syndrome, Refsum Disease, Regional lymphadenopathy, Reiter's syndrome, Renal cancer, Renal colic, Renal glucosuria, Renal mucormycosis, Renal nutcracker syndrome, Renal osteodystrophy, Renal rickets, Renal Tubular Acidosis, Renier- Gabreels-Jasper syndrome, Renoanogenital syndrome, Renon-Delille syndrome, Renoprival hypertension, Renovascular Hypertension, Renovascular stenosis, Renpenning syndrome, Reovirus infection, Respiratory Syncytial Virus Infections, Respiratory syncytial virus-related Cold, REST syndrome, Restless Legs Syndrome, Reticuloendotheliosis, Retinal degeneration, Retinitis Pigmentosa, Retinoblastoma,
Retinohepatoendocrinologic syndrome, Retinopathy, Rett's syndrome, Revesz Debuse syndrome, Reye's Syndrome, Reynolds syndrome, Rh Disease, Rhabditida Infections,
Rhabdoid tumor, Rhabdomyolysis, Rhabdomyosarcoma, Rheumatism, Rheumatoid arthritis, Rhinitis, Rhino-orbito-cerebral phycomycosis, Rhinophyma, Rhinosporidiosis,Rhinovirus infection, Rhnull syndrome, Rhombencephalosynapsis, Rhonchi, RHYNS syndrome, Ribbing syndrome, Rice millers' syndrome, Richards-Rundle syndrome, Richieri Costa Guion Almeida Cohen syndrome, Richter syndrome, Rickettsial disease, Riddle syndrome, Riedel syndrome, Rieger Syndrome, Rietti-Greppi-Micheli syndrome, Rift Valley Fever, Right hemisphere syndrome, Right pneumonectomy syndrome, Riley Shwachman syndrome, Rimbaud- Passouant-Vallat syndrome, Rippling muscle disease, Ritter syndrome, River Blindness,
Roberts Pseudothalidomide Syndrome, Robinow Sorauf syndrome, Robinow-Unger syndrome, Robinson syndrome, Roch-Leri mesosomatous lipomatosis, Rocio encephalitis, Rocky Mountain spotted fever,
Rodrigues blindness, Roifman syndrome, Rokitansky Van Bogaert syndrome,
Rokitansky- Kuster-Hauser syndrome, Rolland-Desbuquois syndrome, Rollet syndrome, Romano-Ward syndrome, Romberg's sign, Rombo syndrome, Rommen-Mueller-Sybert syndrome, Ronchese syndrome, Rosacea, Rosenberg- Chutorian Syndrome, Rosenberg-Lohr syndrome, Roseola infantum, Rot-Bernhardt syndrome, Rothmund-Thomson Syndrome, Rotor syndrome, Round-head spermatozoa syndrome, Roussy-Levy hereditary areflexic dystasia, Roux-en-Y syndrome, Rowley syndrome, Rowley-Rosenberg syndrome, Roy-Maroteaux-Kremp syndrome, Rubella virus antenatal infection, Rubinstein-Taybi like syndrome, Rud Syndrome, Rudd-Klimek syndrome, Rudiger syndrome, Ruvalcaba Churesigaew Myhre syndrome, Ruvalcaba syndrome, Ruzicka-Goerz-Anton syndrome, Saal-Bulas syndrome, Sabin-Feldman syndrome, Sabinas brittle hair syndrome, Sabouraud syndrome, Saccharopinuria Sackey- Sakati-Aur syndrome, Sacroilitis, Saethre-Chotzen Syndrome, Saguenay-Lac Saint Jean -- COX deficiency, Saint Louis dysfibrinogenemia, Saito-Kuba-Tsuruta syndrome, Sakamoto disease,
Sakati syndrome, Salcedo syndrome, Salivary gland cancer, Sallis-Beighton syndrome,
Salmonella infection, Salpingitis, Salti-Salem syndrome, Salvioli syndrome, Samson-Gardner syndrome, Samson- Viljoen syndrome, Sanderson-Fraser syndrome, Sandfly fever, Sandhaus Ben-Ami syndrome, S an dhoff Disease, Sandifer syndrome, Sandrow syndrome, Sanfilippo syndrome, Santavuori Disease Santos Syndrome, Santos-Mateus-Leal syndrome, SAPHO syndrome, Sarcoglycanopathy, Sarcoidosis, Sarcoma, Sarcosinemia, Sarcosporidiosis, Sarrouy disease, SARS, Sassoon hospital syndrome, Satchmo syndrome, Satoyoshi syndrome, Saul- Wilkes-Stevenson syndrome, Say syndrome, Say-Barber-Miller syndrome, Say-Carpenter syndrome, Say-Field-Coldwell syndrome, Say-Meyer syndrome, SBCAD deficiency, Scabies, Scalp -- ear -- nipple syndrome, Scaphotrapeziotrapezoid arthrodesis, Scapulocostal syndrome, Scapuloperoneal amyotrophy, Scapuloperoneal myopathy, Scapuloperoneal Syndrome, SCARF syndrome, Scarlet fever, Scarring alopecia, Schaap-Taylor-Baraitser syndrome, SCHAD deficiency, Schaefer-Stein-Oshman syndrome Schafer syndrome, Schanz disease, Schatzki ring, Scheie syndrome, Scheuermann's disease, Schilder's Disease, Schimmelpenning- Feurstein-Mims Syndrome, Schindler disease, Schinzel Giedion Syndrome, Schistosomiasis, Schizophrenia, Schlegelberger-Grote syndrome, Schmitt-Gillenwater-Kelly syndrome,
Schneckenbecken dysplasia, Schnitzler syndrome, Schofer beetz bohl syndrome, Scholte syndrome, Schopf-Schulz-Passarge syndrome, Schrander-Stumpel, Theunissen, Hulsmans syndrome, Schridde syndrome, Schroder syndrome, Schroer-Hammer-Mauldin syndrome, Schwannoma, Schwannomatosis, Schwartz newark syndrome, Schwartz, Cohen- Addad, Lambert syndrome, Schwartz-Jampel Syndrome, Schwartz- Lelek syndrome, Schweitzer kemink malcolm syndrome, Sciatica, SCID, Scissor gait, Scleredema adultorum, Scleritis, Scleroderma, Sclerosing Cholangitis, Sclerosing Lymphocytic Lobulitis, Sclerosis,
Sclerosteosis, Sclerotylosis, Scoliosis, Scotoma, Scott Craniodigital Syndrome, Scott syndrome, Scrub typhus, Scurvy, Sea sickness, Seat-belt syndrome, Sebaceous gland carcinoma,
Sebastian syndrome, Seborrheic keratosis, Seborrhoea, Secernentea Infections, Seckel syndrome Secretory breast carcinoma, Seemanova-Lesny syndrome, Segawa Syndrome, Seghers syndrome, Selig-Benacerraf-Greene syndrome, Selye syndrome, Seminal vesiculitis, Seminoma, Semmerkrot-Haraldsson-Weenaes syndrome, Sener syndrome, Sengers-Hamel- Otten syndrome, Senile amyloidosis, Senile osteoporosis, Senior-Loken Syndrome, Sennetsu Fever, Sensory ataxia, Senter syndrome, Seow-Najjar syndrome, Sepsis, Septicemia, Septo- Optic Dysplasia, Sequeiros-Sack syndrome, Serine deficiency, Seroma, Seronegative Arthritis, Serotonin Syndrome, Serpiginous choroiditis, Serratia infection, Sertoli-leydig cell tumors, Serum sickness, Setleis Syndrome, Seven point syndrome, Sezary syndrome, Shaken Baby Syndrome, Shaver's disease, Sheehan Syndrome, Sheffield syndrome, Shell nail syndrome, Shigella infection, Shigellosis, Shingles, Shock, Short Bowel Syndrome, Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD), Short QT syndrome, Shprintzen-Goldberg syndrome, Shwachman syndrome, Shy-Drager Syndrome, SIADH, Sialadenitis, Sialidosis, Sialorrhea, Sialuria syndrome, SIBIDS syndrome, Siccardi syndrome, Sick building syndrome, Sick sinus syndrome, Sickle Cell Anemia, Sideroblastic anemia, Siderosis, Siegler-Brewer-Carey syndrome, Siemens syndrome, Sigmoid diverticulitis, Signet ring cell melanoma, Silent sinus syndrome, Silicosiderosis, Silicosis, Sillence syndrome, Silver-Russell dwarfism, Silverman- Handmaker syndrome, Simell-Takki syndrome, Simian B virus infection, Simpson
Dysmorphia Syndrome, Simp son- Golabi-Behmel syndrome, Sindbis fever, Singleton-Merten
Syndrome, Sinonasal undifferentiated carcinoma, Sinus arrhythmia, Sinus bradycardia, Sinus cancer, Sinus tachycardia, Sinusitis, Sitosterolemia Sixth nerve palsy, Sjogren's Syndrome, Skin Cancer, Slap-cheek syndrome, Slavotinek-Pike-Mills-Hurst syndrome, Sleep apnea, Sleepwalking, Slipped epiphysis, Slocumb syndrome, Small bowel bacterial overgrowth syndrome, Small Cell Lung Cancer, Small cell melanoma, Small Intestine Cancer, Smallpox, Smith disease, Smith-Fineman-Myers syndrome 1, Smith-Lemli-Opitz Syndrome, Smith- Magenis Syndrome, Smith-Martin-Dodd syndrome, Smokers Syndrome, Sneddon Syndrome, Sneddon- Wilkinson disease, Snyder-Robinson syndrome, Solar urticarial, Solitary
Extramedullary Plasmacytoma, Somatostatinoma, Sommer-Hines syndrome, Sonoda syndrome, Sopite syndrome, Soto's Syndrome, Southworth symptom complex, Spanlang- Tappeiner syndrome, Spasmodic dysphonia, Spasmodic Torticollis, Sphenoid Sinusitis, Spherocytic anemia, Spherocytosis, Sphingolipidosis, Spina bifida, Spinal stenosis,
Spinocerebellar Ataxia, Spira syndrome, Spirometra theileri infection, Spirurida Infections, Spitzoid melanoma, Spleen Cancer, Spondylarthritis, Spondylitis, Spondylosis, Spongiform encephalopathy, Sporotrichosis, Sprain, Spranger syndrome, Sprue, Spur-cell anemia,
Squamous Cell Skin Cancer, Squint, SSADH deficiency (succinic semialdehyde dehydrogenase deficiency), St. Anthony's fire, St. Louis encephalitis, Stalker- Chitayat syndrome, Stampe- Sorensen syndrome, Stanescu syndrome, Stargardt Disease, Stauffer syndrome, Steatorrhea, Steinfeld syndrome, Stenosis, Stevens-Johnson Syndrome, Stevenson- Carey syndrome, Stewart-Treves syndrome, Sthenolagnia, Stickler Syndrome, Stiff skin syndrome, Stokes Adams syndrome, Stoll Levy Francort Syndrome, Stoll-Alembik-Finck syndrome, Stoll- Geraudel-Chauvin syndrome, Stomach cancer, Stomatitis, Storm syndrome, Stratton- Parker syndrome, Strauss syndrome, Streptococcal Infections, Stridor, Stroke, Strongyloidiasis, Strudwick syndrome, Stryker-Halbeisen syndrome, Stuart-Bras disease, Stuccokeratosis, Sturge-Weber Syndrome, Stuve-Wiedemann syndrome, Suberosis, Subpulmonary stenosis, Succinyl-CoA acetoacetate transferase deficiency, Sugarman syndrome, Sulfite oxidase deficiency, Summitt syndrome, Sump Syndrome, Sundown syndrome, Supine hypotensive syndrome, Suppurative parotitis, Supraglottic laryngeal cancer, Supranuclear ocular palsy, Sutton Disease Swayback, Sweet Syndrome, Swyer syndrome, Sydenham chorea, Sylvester (P.E.) syndrome, Symmastia, Sympathetic ophthalmitis, Synovial cancer, Synovial sarcoma, Synovitis, Syphilis, Syringomyelia, Systemic lupus erythematosus, T-cell acute lymphoblastic leukemia , T-cell lymphoma, T- Lymphocytopenia , Tabatznik syndrome, Tachycardia,
Taeniasis, Taijin-KyofuSho syndrome, Takahara syndrome , Takayasu arteritis , Tako- Tsubo syndrome , Tangier disease , TAR syndrome, Tardive Dyskinesia , Tarsal Synostosis .Tarsal tunnel syndrome , TAU syndrome , Taussig Bing syndrome , Tay-Sachs disease , Teebi-Kaurah syndrome , Teebi-Shaltout syndrome , Tel-Hashomer camptodactyly syndrome , Telangiectasia , Telfer-Sugar-Jaeger syndrome , Temtamy syndrome , Tendinitis ,
Tenosynovitis, Teratoma, Testotoxicosis , Tetanus ,Tetrahydrobiopterin Deficiency, Thakker- Donnai syndrome, Thalamic Syndrome (Dejerine Roussy) , Thalassemia , Thick skull syndrome, Thieffry and Sorrell Dejerine syndrome , Thiele syndrome, Thies Reis syndrome, Thiopurine S methyltranferase deficiency , Thomas syndrome, Thomas- Jewett-Raines syndrome, Thompson-Baraitser syndrome, Thong-Douglas-Ferrante syndrome, Thoracic celosomia, Thoracic outlet syndrome, Throat cancer, Thrombasthenia, Thrombocytopathy, Thrombocytosis, Thrombosis, Thrush, Thurman-Hillier syndrome, Thurston syndrome, Thymic epithelial tumor, Thymoma, Thymus Cancer, Thyroid cancer, Thyroiditis,
Thyrotoxicosis factitia , Tic disorders, Tietz Albinism-Deafness Syndrome, Tiglic acidemia, Timme syndrome, Timothy syndrome, Tinea, Tinnitus, Tollner-Horst-Manzke syndrome, Tolosa-Hunt Syndrome, Tome-Brune-Fardeau syndrome, Tongue Cancer, Toni-Fanconi syndrome, Tonsilitis, TORCH Syndrome, Toriello syndrome, Toriello-Higgins-Miller syndrome, Torticollis, Torulopsis, Touraine-Solente-Gole syndrome, Tourette Syndrome, Townes-Brocks Syndrome, Toxemia, Toxocariasis, Toxoplasmosis, Tracheal cancer, Tracheal stenosis syndrome, Tracheitis, Trachoma, Transthyretin amyloidosis, TRAPS (TNF- receptor-associated periodic syndrome), Treacher-Collins Syndrome, Treft-Sanborn-Carey syndrome, Tremor, Treponema infection, Trichinosis, Trichodental syndrome,
Trichofolliculoma, Trichomoniasis, Trichorhinophalangeal syndrome , Trichorrhexis nodosa syndrome, Trichoscyphodysplasia, Trichosporin infection, Trimethylaminuria , Triopia, Triose phosphate-isomerase deficiency, Triple-X syndrome, Tripsolagnia, Trochanteric bursitis, Troell- Junet syndrome, Troilism, Trophoblastic Cancer, Tropical sprue , Troyes dysfibrinogenemia, Trueb-Burg-Bottani syndrome, Trypanosomiasis, Tsukuhara syndrome, Tuberculosis, Tubular carcinoma, Tungiasis, Turcot syndrome, Turner Syndrome, Turpin syndrome, Tylosis, Type 1 diabetes, Type 2 diabetes, Type A Influenza, Type B Influenza, Type C Influenza, UDP-Galactose-4-epimerase deficiency, Uhl anomaly, Uhthoff syndrome, Ulcerative colitis, Ulcerative proctosigmoiditis, Ulerythema ophryogenesis, Unverricht- Lundborg disease, Upington disease, Upton Young syndrome, Uremia, Ureter cancer,
Urethral syndrome, Urethritis, Urofacial syndrome, Urticaria, Usher Syndrome, Uveitis, Vacuolar myopathy, Vagina cancer, Vaginal candidiasis, Vaginosis (bacterial vaginosis), Vail syndrome, Valinemia, Van Allen Myhre syndrome, Van Bogaert disease, Van Bogaert- Hozay syndrome, Van Bogaert-Scherer-Epstein Disease, Van Buchem disease, Van De Berghe Dequeker syndrome, Van den Bosch syndrome, Van der Woude syndrome, Van Goethem syndrome, Van Maldergem Wetzburger Verloes syndrome, Van Regemorter
Pier quin Vamos syndrome, Van Wyk-Grumbach syndrome, Vaquez disease, Varadi Papp syndrome, Variant Creutzfeldt-Jakob disease, Variegate porphyria, Varix, Vasculitis, Venous Thrombosis, Ventricular arrhythmia, Ventricular septal defect, Ventricular tachycardia, Verloes Bourguignon syndrome, Verloes Gillerot Fryns syndrome, Verloes Van Maldergem Marneffe syndrome, Verloes-David Syndrome, Verloes-Deprez syndrome, Verloove Vanhorick Brubakk syndrome, Vertigo, Vestibular neuritis, Vibrio infection,
Victory disease, Vilanova-Canadeli syndrome, Vildervanck syndrome 4, Viljoen Kallis Voges syndrome, Viljoen Smart syndrome, Viljoen Winship syndrome, Vincent's disease, Viral Hepatitis, Viral meningitis, Viral pericarditis, Viral prostatitis, Viremia, Vitamin deficiency, Vitiligo, Von Gierke Disease, Von Hippel-Lindau Disease, Von voss Cherstvoy syndrome, Von Willebrand disease, Vulva cancer, Vulvitis, Vulvovaginitis, W syndrome, Waaler Aarskog syndrome, Waardenburg syndrome, Wagener syndrome, Wagner syndrome, Wagner-Stickler Syndrome, WAGR Syndrome, Walbaum Titran Durieux Crepin syndrome, Waldenstrom macroglobulinemia, Waldmann disease, Walker Dyson syndrome, Walker- Warburg Syndrome, Wallenberg's Syndrome, War sailor syndrome, Warburg Sjo Fledelius syndrome, Warburton Anyane Yeboa syndrome, Warfarin syndrome, Warm Autoimmune Hemolytic Anemia, Warman Mulliken Hayward syndrome, Wart, Warthin's tumor, Wasting Syndrome, Water- Electrolyte Imbalance, Waterhouse-Friderichsen syndrome, Watson syndrome, WDHA syndrome, Weary Syndrome, Weatherall syndrome, Weaver Johnson syndrome, Weaver Williams syndrome, Weber- Christian disease, Webster Deming syndrome, Wegener's granulomatosis, Wegmann Jones Smith syndrome, Weil syndrome, Weill- Marchesani Syndrome, Weinstein Kliman Scully syndrome, Weismann-Netter-Stuhl
Syndrome, Weleber Hecht Bigley syndrome, Wellesley Carmen French syndrome, Wells syndrome, Werner syndrome, Wernicke-Korsakoff syndrome, West African Trypanosomiasis, West nile encephalitis, West Nile fever, Westphal disease, Whelan syndrome, WHIM syndrome, Whiplash, Whipple's Disease, Whistling face syndrome, Whitaker syndrome, White platelet syndrome, Wieacker syndrome, Wie acker- Wolff Syndrome, Wiedemann Oldigs Oppermann syndrome, Wiedemann Opitz syndrome, Wiedemann-Beckwith syndrome, Wiedemann-Tolksdorf syndrome, Wiesbaden dysfibrinogenemia, Wildervanck syndrome, Wilkes Stevenson syndrome, Williams Syndrome, Williams-Campbell syndrome, Wilms tumor, Wilson's Disease, Winchester Syndrome, Wine Grower's lung, Winkelman Bethfe Pfeiffer syndrome, Winkelmann Syndrome, Winship Viljoen Leary syndrome, Winter Harding Hyde syndrome, Winter Shortland Temple syndrome, Wisconsin syndrome, Wiskott-Aldrich Syndrome, Witkop syndrome, Wittwer sydnrome, Wohlmann-Caglkar syndrome, Wohlwill- Andrade syndrome, Wolcott-Rallison syndrome, Wolf-Hirschhorn Syndrome, Wolf-Parkinson- White syndrome, Wolffian tumor, Wolfram Syndrome, Wolman disease, Wood trimmer's disease, Woods Black Norbury syndrome, Woods Leversha Rogers syndrome, Woodworker's lung, Woringer syndrome, Worster Drought syndrome, Worth syndrome, Wright Dyck syndrome, Wrinkly skin syndrome, Wyatt disease, Wyburn Mason's syndrome, Xerocytosis, Xeroderma, Xerostomia, Yager-Young syndrome, Yellow fever, Yersiniosis, Yim Ebbin syndrome, Yolk sack tumour, Young Hughes syndrome, Young McKeever Squier syndrome, Young Simpson syndrome, Young syndrome, Yunis Varon syndrome, Yunis-Varon Syndrome, Yusho disease, Zadik Barak Levin syndrome, Zanier-Roubicek syndrome, Zanoli-Vecchi syndrome, Zazam Sheriff Phillips syndrome, Zechi-Ceide Syndrome, Zellweger Syndrome, Zerres Rietschel Majewski syndrome, Ziehen- Oppenheim syndrome, Zieve syndrome,
Zimmerman-Lab and syndrome, Zip rkowski- Adam syndrome, Ziprkowski-Margolis syndrome, Zlotogora syndrome, Zollinger- Ellison syndrome, Zori Stalker Williams syndrome, Zunich neuroectodermal syndrome, Zunich-Kaye syndrome, Zurich dysfibrinogenemia, Zuskas Disease and Zygomycosis.
In alternative embodiments of aspects of the invention the disease is an auto- immune disease selected from the group consisting of Achlorhydra Autoimmune Active Chronic Hepatitis; Acute Disseminated Encephalomyelitis; Acute hemorrhagic
leukoencephalitis; Addison's Disease; Agammaglobulinemia; Alopecia areata; Amyotrophic Lateral Sclerosis; Ankylosing Spondylitis; Anti-GBM/TBM Nephritis; Antiphospholipid syndrome; Antisynthetase syndrome; polyarticular Arthritis; Atopic allergy; Atopic
Dermatitis; Autoimmune Aplastic Anemia; Autoimmune cardiomyopathy; Autoimmune enteropathy; Autoimmune hemolytic anemia; Autoimmune hepatitis; Autoimmune inner ear disease; Autoimmune lymphoprolilerative syndrome; Autoimmune peripheral neuropathy; Autoimmune pancreatitis; Autoimmune polyendocrine syndrome; Autoimmune progesterone dermatitis; Autoimmune thrombocytopenic purpura; Autoimmune uveitis; Balo disease/Balo concentric sclerosis; Bechets Syndrome; Berger's disease; Bickerstaffs encephalitis; Blau syndrome; Bullous Pemphigoid; Castleman's disease; Celiac disease; Chagas disease; Chronic Fatigue Immune Dysfunction Syndrome; Chronic inflammatory demyelinating
polyneuropathy; Chronic recurrent multifocal osteomyelitis; Chronic lyme disease; Chronic obstructive pulmonary disease; Churg-Strauss syndrome; Cicatricial Pemphigoid; Coeliac Disease; Cogan syndrome; Cold agglutinin disease; Complement component 2 deficiency; Cranial arteritis; CREST syndrome; Crohns Disease; Cushing's Syndrome; Cutaneous leukocytoclastic angiitis; Dego's disease; Dercum's disease; Dermatitis herpetiformis;
Dermatomyositis; Diabetes mellitus type 1; Diffuse cutaneous systemic sclerosis; Dressler's syndrome; Discoid lupus erythematosus; Eczema; Endometriosis; Enthesitis-related arthritis; Eosinophilic fasciitis; Eosinophilic gastroenteritis; Epidermolysis bullosa acquisita; Erythema nodosum; Essential mixed cryoglobulinemia; Evan's syndrome; Fibrodysplasia ossificans progressiva; Fibromyalgia/Fibromyositis; Fibrosing aveolitis; Gastritis; Gastrointestinal pemphigoid; Giant cell arteritis; Glomerulonephritis; Goodpasture's syndrome; Graves' disease; Guillain-Barre syndrome; Hashimoto's encephalitis; Hashimoto's thyroiditis;
Haemolytic anaemia; Henoch-Schonlein purpura; Herpes gestationis; Hidradenitis
suppurativa; Hughes syndrome; Hypogammaglobulinemia; Idiopathic Inflammatory
Demyelinating Diseases; Idiopathic pulmonary fibrosis; Idiopathic thrombocytopenic purpura; IgA nephropathy; Inclusion body myositis; Inflammatory demyelinating polyneuopathy;
Interstitial cystitis; Irritable Bowel Syndrome (IBS); Juvenile idiopathic arthritis; Juvenile rheumatoid arthritis; Kawasaki's Disease; Lambert-Eaton myasthenic syndrome;
Leukocytoclastic vasculitis; Lichen planus; Lichen sclerosus; Linear IgA disease; Lou Gehrig's Disease; Lupoid hepatitis; Lupus erythematosus; Majeed syndrome; Meniere's disease;
Microscopic polyangiitis; Miller-Fisher syndrome; Mixed Connective Tissue Disease; Morphea; Mucha-Habermann disease; Muckle-Wells syndrome; Multiple Myeloma; Multiple Sclerosis; Myasthenia gravis; Myositis; Narcolepsy; Neuromyelitis optica; Neuromyotonia; Occular cicatricial pemphigoid; Opsoclonus myoclonus syndrome; Ord thyroiditis; Palindromic rheumatism; PANDAS; Paraneoplastic cerebellar degeneration; Paroxysmal nocturnal hemoglobinuria; Parry Romberg syndrome; Parsonnage-Turner syndrome; Pars planitis;
Pemphigus; Pemphigus vulgaris; Pernicious anaemia; Perivenous encephalomyelitis; POEMS syndrome; Polyarteritis nodosa; Polymyalgia rheumatica; Polymyositis; Primary biliary cirrhosis; Primary sclerosing cholangitis; Progressive inflammatory neuropathy; Psoriasis; Psoriatic Arthritis; Pyoderma gangrenosum; Pure red cell aplasia; Rasmussen's encephalitis; Raynaud phenomenon; Relapsing polychondritis; Reiter's syndrome; Restless leg syndrome; Retroperitoneal fibrosis; Rheumatoid arthritis; Rheumatoid fever; Sarcoidosis; Schizophrenia; Schmidt syndrome; Schnitzler syndrome; Scleritis; Scleroderma; Sjogren's syndrome;
Spondyloarthropathy; Sticky blood syndrome; Still's Disease; Stiff person syndrome; Subacute bacterial endocarditis (SBE); Susac's syndrome; Sweet syndrome; Sydenham Chorea;
Sympathetic ophthalmia; Takayasu's arteritis; Temporal arteritis; Tolosa-Hunt syndrome; Transverse Myelitis; Ulcerative Colitis; Undifferentiated connective tissue disease;
Undifferentiated spondyloarthropathy; Vasculitis; Vitiligo; Wegener's granulomatosis;
Wilson's syndrome; and Wiskott-Aldrich syndrome.
In further alternative embodiments said disease is a skin disease selected from the group consisting of Acneiform eruptions; Autoinflammatory syndromes; Chronic blistering; Conditions of the mucous membranes; Conditions of the skin appendages; Conditions of the subcutaneous fat; Congenital anomalies; Connective tissue diseases (such as Abnormalities of dermal fibrous and elastic tissue); Dermal and subcutaneous growths; Dermatitis (including Atopic Dermatitis, Contact Dermatitis, Eczema, Pustular Dermatitis, and Seborrheic
Dermatitis); Disturbances of pigmentation; Drug eruptions; Endocrine -related skin disease; Eosinophilic; Epidermal nevi, neoplasms, cysts; Erythemas; Genodermatoses; Infection- related skin disease; Lichenoid eruptions; Lymphoid-related skin disease; Melanocytic nevi and neoplasms (including Melanoma); Monocyte- and macrophage-related skin disease;
Mucinoses; Neurocutaneous; Noninfectious immunodeficiency-related skin disease; Nutrition- related skin disease; Papulosquamous hyperkeratotic (including Palmoplantar
keratodermas); Pregnancy-related skin disease; Pruritic; Psoriasis; Reactive neutrophilic; Recalcitrant palmoplantar eruptions; Resulting from errors in metabolism; Resulting from physical factors (including Ionizing radiation-induced); Urticaria and angioedema; Vascular- related skin disease.
In further alternative embodiments the disease is an endocrine disease selected from the group consisting of Adrenal disorders; Glucose homeostasis disorders; Thyroid disorders; Calcium homeostasis disorders and Metabolic bone disease; Pituitary gland disorders ; and Sex hormone disorders.
In further alternative embodiments the disease is an eye disease selected from the group consisting of Disorders of eyelid, lacrimal system and orbit; Disorders of conjunctiva; Disorders of sclera, cornea, iris and ciliary body; Disorders of lens; Disorders of choroid and retina (including Chorioretinal inflammation, Other disorders of choroid, Chorioretinal disorders in diseases classified elsewhere, Retinal detachments and breaks, Retinal vascular occlusions, Gther retinal disorders, Glaucoma; Disorders of vitreous body and globe; Disorders of optic nerve and visual pathways; Disorders of ocular muscles, binocular movement, accommodation and refraction; Visual disturbances and blindness; and Other disorders of eye and adnexa.
In further alternative embodiments the disease is a neurological disorder selected from the group consisting of Abarognosis; Acquired Epileptiform Aphasia; Acute disseminated encephalomyelitis; Adrenoleukodystrophy; Agenesis of the corpus callosum; Agnosia; Aicardi syndrome; Alexander disease; Alien hand syndrome; Allochiria; Alpers' disease; Alternating hemiplegia; Alzheimer's disease; Amyotrophic lateral sclerosis (see Motor Neurone Disease); Anencephaly; Angelman syndrome; Angiomatosis; Anoxia; Aphasia; Apraxia; Arachnoid cysts; Arachnoiditis; Arnold-Chiari malformation; Arteriovenous malformation; Ataxia
Telangiectasia; Attention deficit hyperactivity disorder; Auditory processing disorder;
Autonomic Dysfunction; Back Pain; Batten disease; Behcet's disease; Bell's palsy; Benign Essential Blepharospasm; Benign Intracranial Hypertension; Bilateral frontoparietal polymicrogyria; Binswanger's disease; Blepharospasm; Bloch-Sulzberger syndrome; Brachial plexus injury; Brain abscess; Brain damage; Brain injury; Brain tumor; Brown-Sequard syndrome; Canavan disease; Carpal tunnel syndrome; Causalgia; Central pain syndrome; Central pontine myelinolysis; Centronuclear myopathy; Cephalic disorder; Cerebral aneurysm; Cerebral arteriosclerosis; Cerebral atrophy; Cerebral gigantism; Cerebral palsy; Cerebral vasculitis; Cervical spinal stenosis; Charcot-Marie-Tooth disease; Chiari
malformation; Chorea; Chronic fatigue syndrome; Chronic inflammatory demyelinating polyneuropathy (CIDP); Chronic pain; Coffin Lowry syndrome; Coma; Complex regional pain syndrome; Compression neuropathy; Congenital facial diplegia; Corticobasal degeneration; Cranial arteritis; Craniosynostosis; Creutzfeldt-Jakob disease; Cumulative trauma disorders; Cushing's syndrome; Cytomegalic inclusion body disease (CIBD); Cytomegalovirus Infection; Dandy-Walker syndrome; Dawson disease; De Morsier's syndrome; Dejerine-Klumpke palsy; Dejerine-Sottas disease; Delayed sleep phase syndrome; Dementia; Dermatomyositis;
Developmental dyspraxia; Diabetic neuropathy; Diffuse sclerosis; Dravet syndrome;
Dysautonomia; Dyscalculia; Dysgraphia; Dyslexia; Dystonia; Empty sella syndrome;
Encephalitis; Encephalocele; Encephalotrigeminal angiomatosis; Encopresis; Epilepsy; Erb's palsy; Erythromelalgia; Essential tremor; Fabry's disease; Fahr's syndrome; Fainting;
Familial spastic paralysis; Febrile seizures; Fisher syndrome; Friedreich's ataxia;
Fibromyalgia; Gaucher's disease; Gerstmann's syndrome; Giant cell arteritis; Giant cell inclusion disease; Globoid Cell Leukodystrophy; Gray matter heterotopia; Guillain-Barre syndrome; HTLV- 1 associated myelopathy; Hallervorden-Spatz disease; Head injury;
Headache; Hemifacial Spasm; Hereditary Spastic Paraplegia; Heredopathia atactica polyneuritiformis; Herpes zoster oticus; Herpes zoster; Hirayama syndrome;
Holoprosencephaly; Huntington's disease; Hydranencephaly; Hydrocephalus;
Hypercortisolism; Hypoxia; Immune -Mediated encephalomyelitis; Inclusion body myositis; Incontinentia pigmenti; Infantile phytanic acid storage disease; Infantile Refsum disease; Infantile spasms; Inflammatory myopathy; Intracranial cyst; Intracranial hypertension; Joubert syndrome; Karak syndrome; Kearns-Sayre syndrome; Kennedy disease; Kinsbourne syndrome; Klippel Feil syndrome; Krabbe disease; Kugelberg-Welander disease; Kuru; Lafora disease; Lambert-Eaton myasthenic syndrome; Landau- Kleffner syndrome; Lateral medullary (Wallenberg) syndrome; Learning disabilities; Leigh's disease; Lennox-Gastaut syndrome; Lesch-Nyhan syndrome; Leukodystrophy; Lewy body dementia; Lissencephaly; Locked-In syndrome; Lou Gehrig's disease (See Motor Neurone Disease); Lumbar disc disease; Lumbar spinal stenosis; Lyme disease - Neurological Sequelae; Machado-Joseph disease
(Spinocerebellar ataxia type 3); Macrencephaly; Macropsia; Megalencephaly; Melkersson- Rosenthal syndrome; Menieres disease; Meningitis; Menkes disease; Metachromatic leukodystrophy; Microcephaly; Micropsia; Migraine; Miller Fisher syndrome; Mini-stroke (transient ischemic attack); Mitochondrial myopathy; Mobius syndrome; Monomelic amyotrophy; Motor Neurone Disease; Motor skills disorder; Moyamoya disease;
Mucopolysaccharidoses; Multi-infarct dementia; Multifocal motor neuropathy; Multiple sclerosis; Multiple system atrophy; Muscular dystrophy; Myalgic encephalomyelitis;
Myasthenia gravis; Myelinoclastic diffuse sclerosis; Myoclonic Encephalopathy of infants; Myoclonus; Myopathy; Myotubular myopathy; Myotonia congenita; Narcolepsy;
Neurofibromatosis; Neuroleptic malignant syndrome; Neurological manifestations of AIDS; Neurological sequelae of lupus; Neuromyotonia; Neuronal ceroid lipofuscinosis; Neuronal migration disorders; Niemann-Pick disease; Non 24-hour sleep-wake syndrome; Nonverbal learning disorder; O'Sullivan-McLeod syndrome; Occipital Neuralgia; Occult Spinal
Dysraphism Sequence; Ohtahara syndrome; Olivopontocerebellar atrophy; Opsoclonus myoclonus syndrome; Optic neuritis; Orthostatic Hypotension; Overuse syndrome; Palinopsia; Paresthesia; Parkinson's disease; Paramyotonia Congenita; Paraneoplastic diseases;
Paroxysmal attacks; Parry-Romberg syndrome; Pelizaeus-Merzbacher disease; Periodic Paralyses; Peripheral neuropathy; Persistent Vegetative State; Pervasive developmental disorders; Photic sneeze reflex; Phytanic acid storage disease; Pick's disease; Pinched nerve; Pituitary tumors; PMG; Polio; Polymicrogyria; Polymyositis; Porencephaly; Post-Polio syndrome; Postherpetic Neuralgia (PHN); Postinfectious Encephalomyelitis; Postural
Hypotension; Prader-Willi syndrome; Primary Lateral Sclerosis; Prion diseases; Progressive hemifacial atrophy; Progressive multifocal leukoencephalopathy; Progressive Supranuclear Palsy; Pseudotumor cerebri; Rabies; Ramsay-Hunt syndrome (Type I and Type II);
Rasmussen's encephalitis; Reflex neurovascular dystrophy; Refsum disease; Repetitive motion disorders; Repetitive stress injury; Restless legs syndrome; Retrovirus-associated myelopathy; Rett syndrome; Reye's syndrome; Rhythmic Movement Disorder; Romberg syndrome; Saint Vitus dance; Sandhoff disease; Schizophrenia; Schilder's disease; Schizencephaly; Sensory integration dysfunction; Septo-optic dysplasia; Shaken baby syndrome; Shingles; Shy-Drager syndrome; Sjogren's syndrome; Sleep apnea; Sleeping sickness; Snatiation; Sotos syndrome; Spasticity; Spina bifida; Spinal cord injury; Spinal cord tumors; Spinal muscular atrophy; Spinocerebellar ataxia; Steele-Richardson-Olszewski syndrome; Stiff-person syndrome;
Stroke; Sturge-Weber syndrome; Subacute sclerosing panencephalitis; Subcortical
arteriosclerotic encephalopathy; Superficial siderosis; Sydenham's chorea; Syncope;
Synesthesia; Syringomyelia; Tarsal tunnel syndrome; Tardive dyskinesia; Tarlov cyst; Tay- Sachs disease; Temporal arteritis; Tetanus; Tethered spinal cord syndrome; Thomsen disease;
Thoracic outlet syndrome; Tic Douloureux; Todd's paralysis; Tourette syndrome; Toxic encephalopathy; Transient ischemic attack; Transmissible spongiform encephalopathies;
Transverse myelitis; Traumatic brain injury; Tremor; Trigeminal neuralgia; Tropical spastic paraparesis; Trypanosomiasis; Tuberous sclerosis; Von Hippel-Lindau disease; Viliuisk Encephalomyelitis ; Wallenberg's syndrome; Werdnig-Hoffman disease; West syndrome;
Whiplash; Williams syndrome; Wilson's disease; and Zellweger syndrome.
In further alternative embodiments the disease is a cardiovascular disease selected from the group consisting of Angina; Atherosclerosis ; Cerebrovascular Accident (Stroke) ;
Cerebrovascular disease; Congestive Heart Failure; Coronary Artery Disease; Myocardial infarction (Heart Attack); and Peripheral vascular disease.
In our previous application PCT/NL2016/050422 it was demonstrated that expression of most of the eukaryotic CRISPRs, especially those that have spacers which are directed to endogenous nucleotide sequences, may lead to changes in the gene regulation of the cell in which it is expressed. This is likely to be caused by the same mechanism that is also used with the CRISPR technology in prokaryotes: through RNAi. As has been mentioned above, the CRISPR sequences are expressed in the eukaryotic cell, but they appear to be expressed in small, siRNA-like sequences. The fact that RNAi also may be applied in the eukaryotic cell has been established long ago (the scientific work was found fit for the Nobel prize), and RNAi has since then been one of the mechanisms to influence gene expression
(predominantly used in genetic engineering of plant cells and for studying gene expression and gene knock-out). Whether or not the now discovered relation between disease conditions and under- or overexpression of the CRISPR sequences is a causative factor of the disease or just the result of biochemical processes that occur during the disease or condition is unclear. In any case, it appears that under- or overexpression of CRISPR sequences in relation to control is indicative of a disease or condition. It may be that because of the disease the expression of genes and gene regulation is affected, such as production of tumor suppressor genes or production of inflammatory factors. Also production of signal compounds (hormones, neurotransmitters) and receptors for messenger molecules may be affected in certain conditions or diseases.
It is submitted that general phenomena that are not specific for one type of disease or condition may be related to the under- or overexpression of several CRISPR sequences. These then can show up for any disease where such a pleiotropic phenomenon appears. For instance, if several CRISPR sequences are under- or overexpressed under a condition of fever, this under- or overexpression will also occur in all kind of infectious diseases that are accompanied by fever. As is shown in the experimental part, several panels of the Affymetrix CRISPR sequences are specific for certain diseases or conditions.
To make diagnosis more reliable, it is preferred to add more than one
probe/CRSISPR sequence into the assay. Especially, if the CRISPR sequence relates to a pleiotropic effect, it will not be able to specifically diagnose for one disease or condition, and an assay with a multiplicity of CRISPR sequences is advisable. .
In the experimental part it is indicated which groups (sets of CRISPR sequences) are deemed to be applicable for the diagnosis of the mentioned conditions and diseases. As can be seen in many cases a set of more than one CRISPR sequence is indicated. However, such a set may optionally be complemented with any number of the non-Affymetrix CRISPR sequences. Accordingly, a set of CRISPR sequences suitable for diagnosing a specific condition or disease may comprise 2 (probes specific for 2) CRISPR sequences, but may also comprise 3 probes/sequences, where the third marker is chosen from any of the sequences indicated further in the set and/or one or more of the non-Affymetrix CRISPR sequences that is under- or overexpressed in said specific condition or disease. Alternatively, it may comprise 4 sequences, 5 sequences, 6 sequences and more. It is emphasized that the more (specific) sequences are assayed, the more reliable the diagnosis will be.
Further, a set of sequences which are applicable for the current invention may consist of a combination of the Affymetrix CRISPR sequences mentioned in the Examples and non-Affymetrix CRISPR sequences that are also specific for the same condition or disease.
Several further important aspects have also been discovered. One finding is that many of the human (and very probably also other eukaryotic) CRISPR sequences can be found in the binding sites for transcription factors (see Example 17, Fig. 16 and Table 21). Although the reason why many of the CRISPR sequences can be found in these binding sites is currently unknown, this already indicates a potential for diagnostic use of said CRISPR sequences. First of all, the transcription factors themselves are known to be involved in a multitude of cellular processes and a change in the proper binding of transcription factors to their binding sites in general would be a signal for an abnormal condition or disease. One of the aspects in which such a change in binding is influential for the disease condition is through the appearance of mutations in these binding sites, resulting in a less efficient binding and the presence of diseases (e.g. reported by Snyder et al., PNAS 2013, 9607-9612 and Fraser et al., Cell 2016, 730-741). It has further been published that transcription factor binding motifs, such as the transcription factor motifs CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 and the transcription factor motifs PAX5, EGRl, XBP1, SREBP1, OLF1, MZFl, NFY, NFKAPPAB, MYCMAX, NFE2, and RP58 were each up-regulated (sometimes more than twofold) in Down syndrome samples compared to normal samples (Kong et al., Braz. J. Med. Biol. Res. 2014, 834-841).
In a similar way it has been established that several CRISPR sequences are comprised or comprise target sites for DNAse 1 (as listed in Table 22 and Fig. 16). As is indicated in Example 17, it is believed that these sites play a role in human disease
pathologies and as such would be useful in diagnosis of these diseases.
Another finding is exemplified in Table 23 and Example 18 and Figure 17. There it is shown that many (about 175) of the human CRISPR sequences encode for RNA spacer molecules (listed in Table 23 and each uniquely included as SEQ ID NO: 11310 - 11487) that are directed to protospacer targets that are present in viral and bacterial genomes. Except for the fact that the protospacer target sequences may be available in more than one micro- organism(some are present in several, even more than 20 different species of microorganisms), it was also found that these protospacer sequences were accompanied by PAM sequences, which would indicate that indeed these protospacers would be targets for a Cas9-like nuclease activity for which the (eukaryotic) spacer can act as a guide RNA. Further, it can be argued that upon infection with one of the listed micro-organisms the expression of the human CRISPR sequences that harbour the spacer that is directed against the protospacer that is present in the infecting micro-organism will be increased, which then means that the upregulation of the expression of said CRISPR sequences is indicative for an infection. In this regard not only the presence of an infection can be diagnosed on basis of an expression profile of the CRISPR sequences, but even the identity of the micro-organisms can in many cases be established on genus or even species level. Again a further additional evidence for the diagnostic power of the CRISPR sequences of the present invention is provided in Example 19. The EPCAT sequences as provided in Table 24 have been found to be differently expressed in patients suffering from prostate cancer and thus would be useful as a diagnostic tool for detecting the presence of cancer tissue or the predisposition for prostate cancer. Accordingly, the group of CRISPR sequences mentioned in Table 24 can be characterized as a separate group of CRISPR sequences.
For purposes of the present description, the CRISPR sequences can be grouped in many different groups. As already has been indicated above, the sequences SEQ ID NO: 1 - 10141 can be considered to be human CRISPR sequences. A further group as indicated above are the human non-Affymetrix CRISPR sequences. Now a further category can be indicated: human non-Affymetrix non-EPCAT sequences, which group consists of all human CRISPR sequences except for the sequences provided in Tables 2, 3 and 24.
These human non-Affymetrix non-EPCAT sequences can further be divided into several groupings. The groupings can for instance be indicated per (human) chromosome.
In that case the groups may be characterized as follows:
Chromosome 1: SEQ ID NO:
373,374,375,and,376,377,378,379,380,381,382, 12,383,384,385,386,387,388,389,390,3 91,69,392,393,394,395,396,397,398,399,400,70,401,402, 13,403,404,405,406,407,408,409, ^ ,411,71,412,413,414,415,416,72,73,417,418,419,420,421,422,423,424,425,426,427,428,429,430, 431,432,433,434,435,436,437,74,75,76,77,78,79,80,82,83,84,85,85,86, 15, 16,87, 148, 149,445,446, 447,442,448,450,440,452,453,441,455,456,439,457,458,459,460,461,462,463,464,88,465,89,466, 467,468,469,90,470,91,92,471,472,473,93,474,94,475,476,477,478,479,480,481, 1308,482,483,48 4,485,486,487,488, 17, 1,489,490,491,492,493,494,495,496,497, 18,2,498,499,500,501,502,503,50 4,505,506,507,508,95,509,510,511,512,513,514,515,516,517,518,519,520,521,522,523,524,96,52 5,526,4,527,528,529,530,531,532,533,534, 19,535,536,537,539,540,97,98,541,542,543,99,544,55 5,556,557,558,559,560,561,562,563,564,565,566,567,568,569,570,571,572,573,574,575,576,577, 578, 579, 580, 581, 582, 583, 584, 538, 100, 585, 586, 587, 588, 589, 590, 591, 592,593, 594, 595, 596, 597, 5 98,599,20,600,601,602,603,604,605,606,607,608,609,610,611,612,613,614,615,616, 101,617,618, 619,620,621, 102,21,622,623,624,625,628,629,630,631,632,633,634,635,636,637,22,638,639,640, 641,642,643, 103,23,644, 104,and, 106, 105,and, 107,645,646,545,649,650,651,652,653,654,655,65 6,657,658,659,660,661,662,663, 108,664,665,666,667,668,669,670,671,672,673,674,675,676,677, 24,683,684,685,686,687,688,689,690,691,692,693,694, 109,695,696,697,698,25,699,700,701,546, 702,703,704,705,110,706,707,708,709,710,111,711,712,112,713,714,715,716,113,717,718,719,6 78,679, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 74 0, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 114, 757, 758, 759, 760, 761, 762,763,547,764,765,766,769,770,115,771,772,773,774,775,116,776,777,778,779,780,781,782,7 83,784,785,786,787,788,789,790,791,792,117,118,793,794,795,796,797,798,799,800,801,802,80 3,804,805,806,807,808,809,810,811,812,813,814,815,816,119,817,818,819,820,821,120,822,823, 824,825,826,548,549,550, 121, 122, 123, 124, 125, 126, 128, 146, 127, 129,26, 130, 131, 132,27,28, 133,2 9,30,134,31,135,136,137,138,139,32,3,33,140,141,142,34,143,144,145,150,151,152,153,35,154,1 55,36, 156,37, 157,38, 158,5,39, 159,40, 160, 161,41, 162, 163,42,43, 164, 165, 166, 167, 168,44, 169, 170 , 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,45, 185, 186, 187, 188, 189,46,47, 190, 191, 192,48, 193, 194, 195, 196, 197, 198, 199,200,201,202,203,204,206,49,50,207,51,208,52,209,205 ,210,211,212,213,214,215,216,217,53,218,219,220,221,222,223,224,225,226,227,228,229,230,23 lI232,54,233,234,55,235,236,56,237,57,238I239,240,5,and,8,241,242,243,244,58,245,246,59,60, 61,247,248,62,249,250,251,252,253,254,255,256,6,9,257,258,259,260,261,262,263,264,63,265,7, 10,266,267,268,269,270,271,272,273,274,275,276,64,277,278,279,280,281,282,283,284,285,286, 287,288,289,290,291,292,293,294,295,296,297,298,299,300,65,301,302,303,304,306,305,307,30 8,309,310,311,66,67,312,313,314,315,316,317,318,319,320,321,322,323,324,325,326,327,147,32 8,329,330,331,332,333,334,335,336,337,338,339,340,341,342,343,344,345,346,347,348,349,350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361,68, 362, 363, 364, 365, 11, 366, 367, 368, 369, 370, 371, 372
Chromosome 2: SEQ ID NO:
1132, 1133, 1134,887, 1135, 1136, 1137,888,841, 1138, 1139, 1140, 1141, 1142,889, 1143,8 90,1144,1131,1145,1146,1147,1148,1149,1150,1151,1152,1153,1154,1155,1156,1157,1158,1159 ,1160,1161,1162,842,1163,1164,1165,1166,1167,1168,1169,1170,1171,1172,1173,1174,1175,11 76,1177,1178,1179,891,1180,1181,1182,1183,1184,1185,1186,1187,1188,1189,1192,892,1193,1 194, 1195, 1196, 1197, 1190, 1198, 1199,893, 1200, 1201,894, 1202, 1203,843,895, 1204, 1205, 1206,89 6,1207,1208,897,1209,1210,1211,1212,1213,1214,1215,844,1216,1217,1218,845,1219,1220,122 1, 1222, 1223, 1191, 1224, 1225, 1226, 1227, 1228,898, 1229, 1230, 1231, 1232, 1233, 1234, 1235, 1236,8 99, 1237, 1238, 1239, 1241,900, 1243,901, 1244, 1245, 1246,902,903, 1247, 1248,846,904, 1249, 1250, 1 251, 1252, 1253, 1254, 1255, 1256, 1257, 1258, 1259, 1260,847, 1261, 1262, 1263,905, 1264, 1265, 1266, 1267, 1268, 1269, 1270,906, 1271, 1272, 1273,848,849, 1274, 1275, 1276, 1277, 1278, 1279, 1280, 1281, 907, 1282, 1283, 1284, 1285,908, 1286, 1287, 1288, 1289, 1291, 1292,909, 1293, 1294, 1295, 1296, 1297, 1298, 1299, 1300, 1301, 1302, 1303, 1304, 1305, 1306, 1307, 1308, 1309, 1310, 1311, 1312, 1313, 1314, 13 15, 1316, 1317, 1318,910, 1319, 1320, 1321, 1322, 1323,850, 1324, 1325, 1326, 1327, 1328, 1329, 1330, 1 331, 1332, 1333, 1334, 1335, 1336, 1337, 1338,911, 1339, 1340,912, 1341, 1342, 1343, 1344,913, 1345, 1 349, 1350, 1351,914,851, 1352, 1353, 1354,915, 1355, 1356, 1357,852, 1358, 1359, 1360, 1361, 1362, 13 63, 1364, 1365, 1366,853, 1367, 1368, 1369, 1370, 1371, 1372, 1373, 1374, 1375, 1376, 1377, 1346,916, 1 378, 1379, 1380, 1381, 1382, 1347, 1383, 1384, 1385, 1386, 1387, 1388, 1389, 1390, 1391, 1392, 1393, 139 4,917, 1395,854, 1396, 1397, 1398, 1399,855, 1400, 1401,856, 1402, 1403, 1404, 1405, 1406, 1407, 1408, 857, 1409, 1410, 1411, 1412, 1413, 1414,858, 1415, 1416, 1417, 1418, 1419, 1420, 1421, 1422, 1423, ^ , 1425, 1426, 1427, 1428, 1429, 1430, 1431, 1432, 1433, 1434,918, 1435, 1436, 1437, 1438, 1439, 1440, 14 41, 1442, 1443, 1444, 1445, 1446, 1447, 1448, 1449, 1450, 1451, 1452, 1453,919, 1454, 1455, 1456, 1457, 1458, 1459, 1460,920, 1461, 1462, 1463, 1464, 1465,859, 1466, 1467, 1468, 1469, 1470, 1471, 1472, 1473 , 1474, 1475, 1476, 1480, 1478,921, 1482, 1483,922, 1484, 1485,832,860, 1486, 1487, 1488, 1489, 1490, 1 491, 1492, 1493, 1494, 1495, 1496, 1497, 1498, 1499,923, 1500, 1501, 1502, 1503, 1504, 1505, 1506, 1507 , 1508,861, 1509, 1510, 1511, 1512, 1513, 1514, 1515, 1516, 1517, 1518,862, 1519, 1520, 1521, 1522, 152 3, 1524, 1525, 1526, 1527, 1528, 1529, 1530, 1531, 1532, 1533, 1534, 1535, 1536, 1537, 1538, 1479, 1539, 1540, 1541,924, 1542, 1543, 1544, 1545, 1546, 1547, 1548, 1549, 1550, 1551, 1552, 1553, 1554, 1555, 155 6,925, 1557, 1558, 1559, 1560, 1561, 1562, 1563, 1564, 1565, 1566, 1567, 1568, 10066, 10065, 1569, 1006 7, 10068,863,926,927,928,929,930,931,932,933,934,935,936,864,937,938,939,940,941,942,943,9 44,945,946,865,866,947,867,948,949,950,951,952,868,953,954,833,955,956,957,958,959,960,96 1,962,963,964,965,966,967,968,969,970,971,834,972,973,974,835,975,976,977,978,979,980,8 981,982,983,984,986,987,988,989,990,870,991,992,993,994,995,996,997,998,999, 1000, 1001, 100 2, 1003, 1004, 1005, 1006, 1007, 1008,871, 1009, 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, 1 019, 1020, 1021,872,873, 1022, 1023, 1024, 1025, 1026, 1027, 1028, 1029, 1030, 1031, 1032, 1033, 1034, 1035, 1036, 1038, 1039, 1040, 1041, 1042, 1043, 1044, 1045, 1046, 1047, 1048,874, 1049, 1050, 1051, 105 2, 1053,875, 1054, 1055,836, 1056, 1037, 1057, 1058,837, 1059,876, 1060, 1061, 1062, 1063, 1064, 1065, 1066, 1067, 1068, 1069, 1070,838, 1071,877, 1072, 1073, 1074, 1075, 1076, 1077, 1078, 1079, 1080, 1081 , 1082, 1083,831,878, 1084, 1085, 1086,879, 1088, 1089, 1090, 1091,880, 1092, 1093,839, 1094, 1095, 10 96, 1097, 1098, 1099, 1100, 1101, 1102, 1103, 1104, 1105, 1106, 1107,881, 1108, 1109, 1110, 1111, 1112,
1113, 1114, 1115,882,883,884, 1117, 1118, 1119,840, 1120, 1121, 1122, 1123, 1124, 1125, 1126,885, 11 27, 1128,886, 1129
Chromosome 3: SEQ ID NO:
1862, 1863, 1864, 1865, 1866, 1867, 1868, 1869, 1870, 1871, 1872, 1873, 1874, 1875, 1876, 18 77, 1878, 1879, 1880, 1860, 1881, 1594, 1882, 1596, 1883, 1884, 1885, 1886, 1887, 1888, 1889, 1890, 1892 , 1893, 1894, 1891, 1895, 1896, 1597, 1897, 1898, 1899, 1900, 1901, 1902, 1903, 1598, 1904, 1905, 1906, 1 907,1908,1909,1910,1911,1599,1600,1912,1913,1601,1914,1915,1916,1917,1918,1919,1920,192 1, 1922, 1923, 1924, 1602, 1925, 1603, 1926, 1604, 1927, 1928, 1929, 1930, 1931, 1932, 1933, 1934, 1935, 1936, 1937, 1938, 1939, 1940, 1941, 1605, 1942, 1945, 1606, 1946, 1947, 1948, 1949, 1950, 1951, 1952, 19 53, 1954, 1955, 1943, 1956, 1957, 1958, 1959, 1960, 1607, 1961, 1962, 1944, 1963, 1964, 1965, 1966, 1967 , 1968, 1969, 1970, 1971, 1972, 1973, 1974, 1975, 1976, 1978, 1608, 1979, 1980, 1981, 1982, 1983, 1984, 1 985, 1986, 1987, 1988, 1609, 1989, 1990, 1991, 1992, 1993, 1994, 1995, 1610, 1996, 1997, 1998, 1999,200 0,2001,1611,2002,2003,2004,2005,2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016, 2017,2018,2019,1612,2020,2021,2022,1613,2023,2024,2025,2026,2027,2028,2029,1614,2030,20 31,2032,2033,2034,2035,1615,2036,1616,1617,1574,2037,2038,2039,2040,2041,1618,2042,2043 ,2044,2045,2046,2047,2048,2049,2050,2051,2052,2053,2054,1619,2055,2056,2057,2058,2059,2 060,2061,2062,2063,2064,2065,2066,2067,2068,2069,2070,2071,2072,2073,2074,2075,2076,207 7,1620,2078,1621,2079,2080,2081,2085,2086,2087,2088,2089,1595,2090,1622,2091,2092,2093, 2094,2095,2096,2097,2098,2099,2100,1623,2101,1624,2102,2103,2104,2105,2106,2107,2108,21 09,2110,2111,2112,2113,2114,1625,1626,2115,2116,2117,2118,2119,2120,1575,2121,2123,2124 ,2125,1627,2126,2127,2128,2129,2130,2131,2132,2133,2134,2135,2136,2137,2138,2139,2140,2 141,2142,2143,2144,2145,2146,1628,2147,2150,2148,2151,2^
9,2158,2159,2160,2161,2162,1630,2163,2164,2165,2166,2167,2168,2169,2170,2171,2172,2173,
2174,2175,2176,2177,2178,2179,2180,2181,2182,2183,2184,2185,2186,2187,2188,2189,2190,21
91,2192,2193,2194,2195,2196,2197,2198,2199,2200,2201,2202,2203,2204,2205,2206,2621,1631 , 1632, 1635, 1636, 1637, 1638, 1639, 1640, 1633, 1641, 1642, 1643, 1644, 1645, 1646, 1647, 1648, 1649, 1 576, 1650, 1651, 1652, 1653, 1654, 1655, 1656, 1657, 1658, 1661, 1662, 1663, 1664, 1659, 1665, 1666, 166 7, 1668, 1669, 1670, 1671, 1672, 1577, 1673, 1674, 1675, 1676, 1677, 1678, 1679, 1680, 1681, 1682, 1683, 1684, 1685, 1686, 1687, 1688, 1578, 1689, 1690, 1691, 1692, 1693, 1694, 1695, 1696, 1697, 1698, 1699, 17 00, 1702, 1703, 1704, 1579, 1570, 1705, 1706, 1707, 1708, 1709, 1710, 1711, 1712, 1713, 1714, 1715, 1716 ,1717,1718,1701,1719,1571,1720,1721,1722,1723,1724,1725,1726,1727,1729,1730,1731,1732,1 733, 1734, 1735, 1736, 1737, 1738, 1739, 1740, 1741, 1742, 1743, 1580, 1744, 1745, 1746, 1581, 1747, 174 8, 1749, 1582, 1752, 1753, 1754, 1755, 1583, 1756, 1757, 1758, 1584, 1759, 1760, 1761, 1762, 1763, 1764, 1585, 1765, 1572, 1766, 1767, 1768, 1769, 1770, 1750, 1771, 1772, 1773, 1774, 1775, 1776, 1777, 1586, 17 78,1780,1781,1782,1783,1784,1785,1786,1787,1788,1789,1790,1791,1792,1793,1794,1795,1796 , 1797, 1798, 1799, 1800, 1587, 1801, 1802, 1803, 1804, 1805, 1806, 1807, 1808, 1809, 1810, 1811, 1812, 1 813, 1815, 1816, 1817, 1818, 1819, 1820, 1821, 1822, 1823, 1824, 1825, 1588, 1589, 1826, 1827, 1828, 159 0, 1829, 1830, 1831, 1832, 1833, 1834, 1591, 1835, 1836, 1837, 1838, 1839, 1592, 1840, 1840, 1593, 1841, 10074, 10075, 10076, 1849, 1843, 1844, 1845, 1846, 1847, 1848, 10077, 1850, 1851, 1842, 1852, 1853, 18 54, 1573, 1855, 1856, 1857, 1858, 1859
Chromosome 4: SEQ ID NO:
2559,2560,2561,2562,2563,2564,2565,2566,2567,2568,2569,2570,2571,2572,2573,25 74,2575,2576,2219,2577,2578,2579,2580,2581,2582,2583,2584,2585,2586,2587,2279,2280,2588 ,2589,2590,2591,2592,2593,2596,2600,2601,2602,2603,2594,2281,2604,2595,2605,2606,2607,2 282,2608,2609,2610,2611,2612,2613,2220,2283,2614,2615,2284,2616,2617,2618,2619,2285,262 0,2286,2621,2287,2622,2623,2624,2625,2626,2627,2628,2629,2630,2632,2633,2221,2288,2634, 2208,2635,2636,2637,2638,2639,2640,2641,2222,2642,2643,2644,2645,2646,2647,2648,2649,26 50,2651,2652,2653,2289,2654,2655,2656,2657,2658,265
,2669,2670,2671,2672,2673,2674,2675,2676,2677,2678,2290,2223,2679,2680,2682,2683,2684,2 685,2686,2687,2688,2661,2689,2690,2691,2291,2692,2693,2694,2695,2292,2696,2697,2698,269 9,2700,2701,2702,2703,2704,2705,2706,2707,2708,2709,2710,2711,2712,2713,2714, 10079,2715 ,2716,2717,2718,2719,2293,2720,2721,2721,2294,2295,2722,2723,2724,2725,2726,2727,2296,2 225,2297,2728,2729,3973,2730,2731,2732,2733,2734,2735,2736,2737,2738,2739,2740,2741,274 2,2743,2744,2745,2746,2747,2748,2298,2749,2750,2751,2752,2753,2754,2755,2756,2757,2758, 2759,2760,2761,2762,2763,2764,2765,2766,2767,2768,2769,2770,2299,2771,2772,2773,2739,27 74,2775,2776,2300,2301,2777,2778,2779,2780,2781,2782,2783,2784,2785,2786,2226,2227,2787 ,2788,2789,2790,2791,2797,2798,2799,2800,2801,2802,2803,2804,2805,2806,2807,2808,2809,2 810,2811,2812,2813,2814,2815,2816,2817,2818,2819,2302,2820,2821,2822,2823,2303,2278,282 4,2825,2826,2827,2828,2829,2304,2830,2305,2831,2832,2833,2834,2835,2836,2837,2838,2839, 2840,2841,2844,2228,2845,2846,2847,2848,2849,2850,2851,2852,2853,2854,2855,2856,2857,28 58,2859,2860,2861,2862,2863,2864,2865,2866,2867,2306,2868,2869,2870,2871,2872,2873,2307 ,2874,2842,2875,2876,2877,2878,2879,2880,2881,2843,2308,2882,2883,2884,2885,2886,2309,2 887,2888,2889,2890,2891,2892,2893,2894,2895,2896,2897,2898,2899,2900,2310,2311,2312,231 5,2316,2317,2318,2319,2320,2321,2322,2323,2324,2325,2313,2326,2327,2328,2329,2330,2331, 2209,2332,2333,2334,2335,2336,2337,2338,2339,2210,2229,2340,2341,2342,2343,2344,2345,23 46,2347,2348,2349,2350,2351,2352,2353,2354,2355,2356,2357,2358,2359,2360,2361,2362,2 ,2231,2363,2232,2364,2365,2366,2233,2367,2234,2368,2369,2370,2371,2372,2235,2373,2236,2 374,2375,2376,2377,2378,2237,2379,2380,2381,2382,2383,2238,2239,2240,2384,2385,2386,238 7,2388,2241,2389,2390,2391,2242,2392,2393,2394,2395,2396,2397,2398,2399,2400, 10078,2401 ,2402,2403,2404,2405,2406,2243,2407,2408,2409,2410,2411,2412,2244,2413,2414,2415,2416,2 417,2418,2419,2245,2420,2421,2422,2423,2246,2247,2248,2249,2250,2251,2252,2253,2254,225 5,2211,2460,2428,2428,2462,2429,2464,2212,2256,2465,2466,2467,2468,2469,2470,2471,2472, 2473,2474,2257,2475,2476,2477,2478,2258,2479,2480,2481,2482,2483,2259,2260,2484,2485,24 86,2487,2488,2489,2490,2261,2491,2262,2492,2493,2494,2495,2496,2497,2498,2499,2500,2501 ,2502,2503,2504,2213,2505,2263,2506,2507,2508,2509,2510,2511,2264,2512,2513,2514,2515,2 516,2517,2518,2265,2266,2519,2520,2521,2522,2523,2524,2267,2525,2526,2214,2527,2528,252 9,2530,2531,2215,2532,2533,2216,2268,2269,2217,2534,2535,2270,2537,2538,2539,3289,2536, 2540,2541,2542,2543,2544,2545,2546,2547,2271,2548,2272,2549,2550,2273,2274,2275,2218,25 51,2276,2277,2552,2553,2554,2555,2556,2557,2558
Chromosome 5: SEQ ID NO:
3251,3252,2972,2973,3253,3254,3255,3256,3257,3258,3259,3260,3261,3262,3263,3264,3265,32 66,3267,3268,3269,3270,3271,3272,3273,3274,3275,3276,3277,3278,2924,3279,3280,3281,3282 ,3283,2925,3284,3285,3286,3287,3288,3289,3290,3291,3292,3293,3294,3295,3296,2976,3297,3 298,3299,3300,3301,3302,3303,3304,2977,3305,3306,3307,3308,3309,2926,3310,3311,3312,331 3,2978,3314,2979,3315,3316,3317,3318,3319,3320,2980,3321,3322,3323,3324,3325,3326,3327, 3328,3329,3330,2927,3331,2928,3332,2981,2982,3333,3334,3335,3336,2983,3337,3338,3339,33 40,3341,3342,3343,3344,3345,2984,3346,3347,3348,3349,2985,3350,3351,2929,3352,3353,3354 ,3355,3356,3357,3358,3359,3360,3361,2930,3362,2986,2987,3365,3366,3363,3367,3368,3369,3 370,3371,3372,3373,2988,3374,2989,2990,3375,3376,2991,3377,3378,3379,2931,3380,3381,338 2,3383,3384,3385,3386,3387,3388,3389,3390,2992,3391,3392,3393,2932,3394,3395,3396,3397, 3398,3399,3400,3401,3402,3403,3404,3405,3406,2933,2993,2934,3407,3408,3409,3410,3411,34 12,3492,3413,3415,3416,3417,3418,3419,3420,3421,3422,3423,3424,3425,3426,2935,3427,3428 ,3429,3414,3430,3431,2936,2937,2994,3432,2995,2996,3433,3434,3435,3436,3437,3438,3439,3 440,3441,2997,3442,2938,3443,3444,3445,2998,3447,3448,3449,2999,3000,3450,3451,3452,345 3, 3454, 3455,2939, 3456,3457, 3458, 3459, 3460, 3461,2902, 3462, 3463, 3464, 3465, 3466, 3467, 3468, 3469,3470,3471,3472,3473,3474,3475,3476,3477,3478,3479,3480,3481,3482,3483,3484,3485,34 86,3487,3488,3001,2905,3002,3003,3004,2940,3005,3006,3007,2941,3008,3009,3010,3011,3012 ,2906,3013,3014,2907,3015,2942,3016,3017,3018,3019,3020,2943,3021,3022,3023,3024,2908,2 944,3025,3026,3027,3028,3029,3030,2945,3031,3032,2909,3033,3034,3035,3036,3037,2946,303 8,3039,2947,3040,3041,3042,3043,3044,3045,3046,3050,2948,3051,3052,3053,3054,3055,2949, 3056,3057,3058,3059,3060,3061,3062,3063,2950,3064,3065,3066,3067,3068,3069,3070,3071,30 72,3073,3074,3075,3076,3077,3078,3079,3080,3081,3082,3083,3084,3085,3086,3087,2904,3088 ,3089,3090,3091,3092,3093,3094,2910,3095,3096,3097,2951,3098,3099,3100,3101,3102,3103,3 104,3105,3106,2911,3107, 10080,3108,3109,2903,3110,3169, 10081, 10082, 10083,2912, 10084, 10 085,2952,2953,2954,2955,2956,3113,2913,3114,3115,3116,3117,3118,3119,3120,3121,3122,291 4,3123,3124,3125,3126,3127,3128,3129,2957,3130,3112,3131,3132,3133,2958,3134,3135,3136, 3137,3138,3139,3140,3141,3142,2959,2915,3146,3147,3148,3149,3150,3151,2960,3152,3153,31 54,3155,2961,2916,2917,3156,3157,3158,2962,3159,3160,3161,3162,3143,3163,3164,3165,2963 ,3166,3167,3168,3144,3169,2918,3170,3145,3171,3172,3173,3174,2919,3175,3176,3177,3178,3 179,3180,3181,3182,3183,3184,3185,2920,3186,3187,3188,3189,3190,3191,3192,3193,2964,292 1,2965,3194,3195,3196,3197,3198,3199,3200,3201,3202,2966,3203,3204,3205,2967,2922,3206, 3207,3208,3209,2968,3210,3211,3212,3213,3214,3215,2923,3216,3217,3218,3219,3220,3221,32 22,3223,3224,3225,3226,3227,3228,3229,3230,3231,3232,3233,3234,3235,3236,3237,2969,3238 ,2970,3239,3240,3241,3242,3243,3244,2971,3245,3246,3247,3248,3249,3250 Chromosome 6: SEQ ID NO:
3819,3820,3541,3823,3824,3825,3826,3827,3828,3829,3542,3830,3831,3832,3833,3834,3835,38 36, 3837, 3838, 3839, 3840, 3841, 3842, 3843,3821, 3844, 3845, 3846, 3847, 3848, 3849, 3543, 3493, 3850 , 3851, 3852, 3853, 3854, 3855, 3856, 3857, 3544, 3545, 3546, 3858, 3859, 3860,3861, 3862, 3863, 3864,4 688, 3865, 3866, 3867, 3868, 3869, 3870, 3547, 3871,3548, 3872, 3873, 3874, 3875, 3876, 3877, 3878, 387 9, 3822, 3880, 3881, 3882, 3883, 3884, 3885, 3886, 3887, 3888, 3889, 3890, 3891,3549, 3892, 3893, 3894, 3895,3896,3897,3898,3899,3900,3901,3902,3903,3904,3905,3906,3907,3908,3909,3911,3912,39 13,3914,3915,3916,3917,3918,3919,3920,3921,3922,3923,3924,3925,3926,3927,3928,3929,3930 ,3931,3932,3933,3934,3935,3936,3937,3938,3939,3940,3941,3942,3943,3550,3944,3945,3946,3 947, 3948, 3949, 3950, 3951, 3952, 3953, 3954, 3955,3956, 3957, 3958, 3959, 3960, 3961, 3962, 3963, 396 4,3965,3966,3910,3967,3968,3969,3970,3971,3972,3973,3974,3975,3976,3977,3978,3979,3980, 3981,3982,3983,3551,3984,3985,3986,3987,3988,3989,3990,3991,3992,3993,3994,3995,3503,39 96,3997,3504,3998,3999,4000,4001,4002,4003,4004,4005,4006,3552,4007,3553,4008,4009,4010 ,4011,3554,4012,4013,4014,4015,4016,4017,4018,4019,4020,3555,4021,4022,4023,3556,4024.4 025,4026,4027,4028,4029,4030,4031,4032,3505,4033,4034,4035,4036,4037,4038,4039,3557,404 0,3558,4041,4042,4043,4045,4047,4048,4049,4050,4051,3559,4052,4053,4054,4055,4056,4057, 4058,4059,4060,4061,4062,4063,4064,4065,4066,4067,4068,4069,4070, 10087, 10088, 10089, 100 90,4071,3560,3506,3494,3561,3562,3563,3564,3507,3565,3566,3567,3569,3570,3571,3572,3573 ,3508.3574,3575,3576.3577,3578,3509.3579,3580,3581,3510,3582,3583,3584,3586,3587,3588,3 512,3589,3590,3591,3592,3593,3513,3594,3595,3596,3597,3514,3598,3599,3515,3600,3601,351 6,3603,3604,3605,3606,3607,3608,3609,3610,3517,3611,3612,3489,3613,3614,3615,3616,3617, 3618,3619,3620,3621,3622,3623,3624,3625,3518,3626,3627,3628,3629,3630,3519,3631,3632,35 20, 3633, 3634, 3635, 3636, 3637, 3521, 3638.3639, 3522, 3644, 3645, 3646, 3647.3648, 3649, 3650.3651 ,3652,3653,3654,3655,3656,3657,3658,3659,3660,3661,3662,3663,3664,3665,3666,3667,3668,3 669,3670,3671,3672,3673,3674,3675,3676,3677,3678,3679,3680,3523,3681,3682,3683,3684,368 5, 3524, 3496, 3686, 3687,3688, 3497, 3641, 3640, 3689, 3690, 3691, 3692, 3693, 3699, 3700, 3701, 3585, 3695,3696,3697,3498,3490,3499, 10086,7058,3525,3703,3704,3705,3706,3707,3708,3709,3710,3 711,3712,3713,3714,3715,3716.3526,3717,3718.3719,3720,3721,3722,3723,3500.3724,3725,372 6,3727,3527,3728,3528,3729,3730,3491,3731,3732,3529,3733,3734,3530,3735,3736,3737,3738, 3530,3739,3740,3741,3742,3743,3531,3501,3744,3532,3745,3746,3747,3748,3749,3750,3751,37 51,3752,3753,3754,3755,3756,3757,3758,3759,3760,3761,3762,3763,3764,3766,3766,3767,3768 ,3769,3533,3770,3771,3772,3773,3774,3775,3776,3777,3778,3779,3780,3781,3782,3783,3784,3 785,3786,3787,3788,3789,3790,3791,3792,3793,3794,3534,3795,3535,3492,3796,3502,3797,353 6,3798,3799,3537,3800,3801,3802,3803,3804,3806,3538,3807,3539,3808,3809,3810,3540,3811, 3812,3813,3814,3815,3816,3817,3818
Chromosome 7: SEQ ID NO:
4451,4452,4453,4454,4455,4456,4457,4458,4459,4460,4448,4461,4462,4463,4464,44 65,4466,4467,4468,4082,4469,4470,4083,4471,4472,4473,4474,4475,4476,4477,4478,4479,4480 ,4481,4136,4482,4483,4484,4485,4486,4487,4488,4489,4490,4491,4492,4493,4494,4498,4499,4 084,4500,4501,4502,4133,4503,4504,4085,4495,4505,4506,4507,4508,4509,4510,4086,4511,451 2, 10092,4513,4514,4515,4516,4517,4137,4518,4087,4138,4519,4520,4521,4522,4523,4524,4525 ,4526,4527,4496,4528,4529,4139,4530,4531,4532,4533,4534,4535,4536,4537,4538,4140,4539,4 540,4689,4541,4542,4543,4544,4545,4546,4141,4547,4142,4548,4143,4549,4550,4551,4552,414 4,4553,4554,4555,4556,4557,4558,4559,4145,4560,4561,4146, 10093,4147,4562,4563,4564,4148 ,4565,4566,4567,4568,4569,4570,4571,4572,4573,4574,4575,4576,4149,4577,4578,4579,4580,4 581,4582,4583,4584,4585,4586,4150,4587,4588,4589,4590,4011,4592,4593,4594,4595,4596,459 8,4599,4600,4601,4088,4602,4603,4604,4605,4606,4607,4608,4609,4610,4611,4612,4089,4613, 4614,4615,4090,4616,4617,4618,4619,4151,4620,4621,4622,4623,4624,4626,4152,4627,4628,46 29,4153,4625,4630,4631,4632,4633,4154,4634,4635,4636,4637,4638,4639,4640,4641,4642,4643 ,4644,4645,4646,4647,4648,4649,4650,4651,4155,4652,4653,4654,4655,4656,4657,4658,4659,4 660,4661,4662,4663,4664,4665,4666,4667,4668,4669,4670,4671,4156,4672,4673,4674,4675,467 6,4677,4678,4679,4680,4681,4682,4157,4158,4159,4134,4160,4161,4162,4091,4163,4092,4093, 4164,4165,4094,4095,4096,4097,4098,4099,4166,4167,4168,4169,4135,4100,4170,4171,4172,41 01,4173,4174,4175,4176,4177,4178,4179,4180,4102,4181,4182,4183,4103,4184,4104,4185,4186 ,4105,4106,4075,4187,4076,4190,4191,4192,4193,4194,4195,4196,4197,4198,4188,4199,4200,4 201,4202,4203,4204,4107,4205,4206,4207,4208,4209,4210,4211,4212,4213,4214,4215,4216,410 8,4217,4218,4219,4220,4221,4222,4109,4189,4110,4223,4224,4225,4077,4111,4112,4226,4227, 4228,4229,4230,4231,4113,4232,4233,4234,4235,4236,4114,4237,4115,4238,4239,4240,4241,42 42,4243,4116,4244,4117,4245,4246,4247,4248,4249,4250,4251,4252,4118,4285,4286,4287,4288 ,4289,4290,4119,4120,4291,4292,4293,4294,4295,4296,4297,4298,4299,4300,4301,4302,4303,4 304,4305,4306,4307,4121,4308, 10094, 10095, 10097, 10098, 10099, 10100, 10101, 10102, 10096,430 9, 10103, 10104,4122,4256,4257,4258,4259,4260,4253,4254,4123,4255,4261,4078,4262,4263,426 4,4265, 10105,4079,4266,4267,4268,4269,4270,4271,4272,4273,4274,4275,4276,4277,4278,4279 ,4280,4281,4124,4074,4282,4309,4310,4311,4125,4312,4313,4126,4314,4127,4315,4316,4317, 1 0106,4318,4319,4320,4321, 10091,4322,4323,4324,4325,4326,4327,4328,4329,4330,4331,4332,4 333,4334,4335,4336,4337,4338,4339,4340,4341,4342,4243,4344,4348,4349,4350,4351,4352,435 3,4354,4355,4356,4357,4358,4359,4360,4361,4362,4363,4364,4365,4366,4367,4368,4369,4370, 4371,4372,4373,4374,4375,4128,4376,4080,4129,4377,4378,4379,4130,4380,4381,4131,4401,44 02,4403,4404,4405,4406,4407,4408,4409,4410,4411,4081,4412,4413,4414,4415,4416,4417,4418 ,4419,4420,4421,4132,4422,4423,4424,4425,4426,4427,4428,4382,4429,4430,4383,4384,4385,4 431,4432,4386,4433,4387,4388,4389,4390,4391,4392,4434,4435,4436,4393,4394,4395,4437,439 6,4438,4439,4440,4441,4397,4398,4399,4442,4443,4444,4445,4400,4446,4447
Chromosome 8: SEQ ID NO:
4755,5027,5028,4756,5029,5030,4701,5031,5034,5035,5036,5037,4757,5038,5039,5040,5041,50 42, 5043, 5044, 5045, 5046, 5047, 5048, 5049, 5050, 5051 ,4702, 5052, 5053, 5054, 5055,4703, 5056, 5032 ,5057,4758,5058,5059,5060,5061,5033,5062,5063,5064,5065,4704,5066,5067,5068,5069,5070,5 071,5072,5073,5074,4705,5075,5076,5077,5078,5079,5080,5081,4706,4759,5082,5083,5084,508 5,5086,5087.5088,5089,4760.5090,5091,5092.4761,4684,5093.5094,5095,4688.5099,5100,5101. 5102,4685,5103,5104,5105,4762,4763,5106,5107,5108,5109,5110,5111,4764,5112,4765,4766,46 86,5113,5114,5115,4767,5116,5117,5118,5119,5120,5121,5122,5123,5124,5125,5126,5126,5127 ,5128,5132,5133,5134,5135,5136,5137,5138,5139,5140,5141,5142,5143,4768,5144,5145,5146,4 707,5147,4769,5148,5149,5150,4770,5151,5152,5153,5154,5155,5156,5157,5129,5158,5130,515 9,5160,5161,5162,5163,5164,5165,5166,4708,5167,5168,5169,5170.5171.5172,5173.5174,5 5176,5177, 10109,5178,5179,5180,5181,5182,5183,5184,5185,5186,5187,5188,5189,5190,5191,5 192,5193,5194,5195,5196,5197,5198,5199,5200,5201,5202,5203,5204,4771,5205,5206,5207,520 8,5209,5210,4709,4711,4689,4772,4712,4773,4774,4713,4775,4776,4777,4714,4778,4715,4779, 4780,4716.4781,4782.4783.4784,4785.4786,4787,4788.4717,4789,4790.4791,4792, 10107.4793,4 718,4794, 10108,4795,4796,4797,4798,4799,4800,4801,4722,4802,4803,4804,4805,4806,4807,48 08,4809,4810,4723,4811,4811,4724,4812,4813,4814,4815,4816,4817,4725,4818,4819,4726,4820 ,4821,4822,4823,4824,4825,4826,4690,4727,4827,4691,4828,4829,4830,4831,4832,4833,4834,4 835,4836,4837,4838,4839,4840,4841,4842,4843,4844,4845,4846,4847,4728,4849,4850,4851,485 2,4853.4854,4855,4856.4857,4858,4859.4860,4729,4692.4730,4683,4731.4861,4862,4732,4733, 4863,4864,4865,4866,4867,4868,4869,4870,4871,4872,4873,4874,4875,4876,4877,4734,4878,48 81,4882,4735,4883,4884,4885,4886,4887,4878,4888,4889,4890,4891,4892,4893,4894,4895,4896 ,4897,4898,4736,4899,4900,4901,4902,4903,4904,4905,4906,4907,4908,4693,4909,4910,4694,4 911,4912,4913,4914,4915,4916,5158,4917,4918,4919,4920,4695,4921,4696,4922,4737,4738,492 3,4697,4924,4925,4926,4927,4739,4740,4928,4929,4930,4931,4932,4933,4934,4935,4936,4937, 4938,4939,4940,4941,4741,4942,4943,4944,4945,4946,4742,4743,4947,4948,4949,4950,4744,49 51,4745,4952,4953,4954,4746,4747,4955,4956,4957,4958,4959,4960,4961,4962,4963,4964,4748 ,4965,4749,4966,4967,4968,4969,4970,4971,4750,4698,4687,4972,4973,4974,4975,4976,4977,4 978.4979,4980,4980.4981,4982,4751.4983,4984,4985,4986,4987,4988,4989,4699,4700,4990,499 1,4992,4993,4994,4995,4752,4996,4997,4998,4999,4753,5001,5002,5003,5004,5005,5006,5007, 5008,5009,4754,5010,5011,5012,5013,5014,5015,5016,5017,5018,5019,5020,5021,5022,5023,50 24,5025,5026
Chromosome 9: SEQ ID NO:
5429,5237,5430,5431,5432,5433,5434,5238,5436,5239,5240,5437,5438,5439,5440,52 41, 5441, 5442, 5443, 5435, 5444, 5445, 5446, 5447, 5448, 5449, 5450, 5451, 5452, 5242, 5453, 5454, 5243 , 5214, 5455, 5456, 5457, 5458, 5459, 5244, 5460, 5461, 5245, 5462, 5463, 5464,5465, 5466, 5467, 5468, 5 469,5470,5471,5472,5473,5474,5475,5476,5477,5478,5246,5479,5480,5481,5247,5482,5483,548 4, 5485, 5486, 5248, 5249,5487, 5488, 5250, 5251, 5489, 5490, 5491, 5492, 5493, 5252, 5494, 5495, 5496, 5497, 5498, 5499, 5500, 5253, 5501, 5502, 5503, 5504, 5505, 5506, 5507, 5508, 5509, 5510, 5212, 5511,55 12,5513,5514,5254,5515,5516,5517,5518,5519,5522,5523,5524,5525,5526,5527,5528,5529,5530 , 5531, 5532, 5533, 5534, 5535, 5536, 5537, 5538, 5539, 5540, 5541, 5542, 5543,5544, 5545, 5546, 5547, 5 548, 5549, 5520, 5550, 5521, 5551, 5552, 5553, 5554,5555, 10115, 5556, 5557, 5558, 5559, 5560, 5561, 55 62,5563,5564,5565,5566,5567,5568,5569,5570,5571,5572,5573,5574,5575,5576,5577,5578,5579 , 5580, 5581, 5582, 5215, 5255, 5256, 5218, 5257, 5258, 5219, 5259, 5260, 5220,5261, 5262, 5263, 5264, 5 265,5266,5267,5268,5269,5270,5271,5272,5273,5274,5275,5276,5277,5278,5221,5222,5223,527 9, 5280, 5281,5282, 5283,5284, 5285, 5286, 5287, 5288, 5289, 5290, 5291,5292, 5293, 5294, 5295,5296, 5297, 5298, 5299, 5300, 5301, 5302, 5303, 5304, 5305, 5306, 5307, 5308, 5309, 5310, 5311,5312, 5313, 53 14, 5315, 5316, 5317, 5318, 5319, 5320, 5321, 5322, 5323,5324, 5325, 5326, 5327, 5328, 5327, 10110, 532 8,5328,5336, 10111,5341,5340,5334, 10112, 10113,5335,5224,5225,5226,5227,5332, 10114,5228,5 333,5334,5335,8459,5229,5336,5230,5337,5231,5338,5338,5343,5344,5345,5346,5347,5348,534 9, 5350, 5351, 5352, 5232,5353, 5354, 5355, 5329, 5356, 5357,5358, 5359, 5360, 5361, 5362, 5363, 5364, 5233,5365,5366,5367,5368,5234,5369,5370,5374,5375,5216,5376,5377,5378,5379,5380,5381,52 13,5382,5383,5384,5235,5385,5217,5386,5387,5388,5389,5390,5391,5392,5393,5394,5395,5396 ,5397,5398,5399,5400,5401,5402,5403,5404,5405,5406,5407,5408,5409,5410,5411,5412,5413,5 372,5414,5415,5416,5417,5418,5419,5420,5236,5421,5422,5423,5424,5425,5426,5427,5428
Chromosome 10: SEQ ID NO:
5930, 5931, 5932, 5934, 5935, 5936, 5652, 5653, 5654, 5937, 5938, 5596, 5939, 5655, 5940, 59
41,5942,5943,5944,5597,5945,5946,5947,5948,5949,5950,5951,5952,5953,5954,5955,5956,5957 , 5958, 5959, 5960, 5961, 5962, 5963, 5964, 5965, 5966, 5967, 5968, 5969, 5970,5971, 5656, 5972, 5973, 5 974,5975,5976,5977,5978,5979,5598,5980,5981,5982,5983,5984,5985,5986,5987,5988,5989,599 0,5933,5599,5991,5995,5996,5997,5998,5999,6000,5992,6001,5657,6002,5600,6003,6004,6005, 6006,6007,6008,6009,6010,6011,6012,6013,6014,6015,5601,6016,6017,6018,6019,6020,6021,60 22,6023,6024,6025,6026,6027,6028,6029,6030,6031,6032,6033,6034,6035,6036,6037,6038,552, 6041,6042,6043,6044,6045,6046,6047,5993,6048,6049,6050,6051,6052,6053,6054,6055,6056,60 57,6058,6059,6060,6061,6062,6063,6064,6065,5658,5659,5660,5602,5661,5603,5662,5663,5664 ,5665,5666,5667,5667,5668,5669,5604,5605,5670,5671,5672,5673,5674,5675,5676,5677,5678,5 606,5680,5607,5681,5682,5683,5684,5685,5686,5687,5688,5608,5689,5690,5691,5692,5693,569 4,5695,5696,5697,5698,5699,5700,5609,5701,5702,5703,5610,5611,5704,5705,5706,5707,5708, 5709,5612,5710,5679,5711,5712,5715,5716,5717,5718,5719,5713,5720,5613,5714,5721,5722,57 23,5724,5725,5614,5726,5727,5615,5728,5729,5730,5731,5732,5733,5734,5616,5735,5736,5737 ,5738,5739,5617,5740,5741,5742,5743,5744,5745,5618,5746,5747,5748,5749,5750,5751,5752,5 753,5586,5754,5619,5620,5621,5587,5759,5760,5761,5588,5762,5763,5764,5765,5766,5767,562 2,5757,5758,5768,5769,5770,5771,5772,5773,5777,5778,5775,5623,5779,5624,5780,5781,5782, 5585,5783,551,5625,5626,5785,5786,5787,5788,5789,5790,5627,5791,5628,5792,5793,5589,579 4,5629,5590,5630,5795,5796,5797,5798,5799,5631,5632,5633,5800,5591,5801,5634,5802,5635, 5636,5803,5592,5782,5804,5805,5806,5807,5808,5809,5810,5811,5812,5637,5813,5593,5584,58 14,5815,5638,5816,5817,5594,5818,5819,5820,5821,5822,5823,5824,5825,5826,5827,5828,5829 , 5830, 5639, 5831, 5832, 5595, 5833, 5834, 5835, 5836, 5837, 5838, 5839, 5840,5841, 5842, 5640, 5843, 5 845,5847,5641,5848,5849,5850,5851,5852,5853,5854,5855,5856,5857,5858,5859,5860,5642,586 1, 5862, 5863, 5864, 5865,5866, 5643, 5867, 5868, 5969, 5870, 5871, 5872, 5873, 5644, 5874, 5875, 5876, 5877, 5878, 5879, 5880, 5881, 5882, 5883, 5884, 5885, 5886, 5887, 5888, 5889, 5890, 5891, 5892, 5893, 58 94, 5895, 5896, 5897, 5898, 5899, 5900, 5645, 5901, 5902, 5903, 5904, 7108, 5905, 5906, 5907, 5908, 5646 ,5909,5910,5911,5912,5913,5647,5914,5915,5916,5917,5918,5919,5920,5648,5921,5922,5923,5 924, 5925, 5649, 5650, 5926, 5651, 5927, 5928, 5929
Chromosome 11: SEQ ID NO:
6371,6112,6372,6373,6374,6375,6376,6113,6114,6377,6378,6115,6379,6380,6381,63 82,6383,6384,6385,6386,6116,6387,6388,6389,6390,6391,6392,6393,6394,6395,6396,6397,6398 ,6399,6400,6401,6402,6067,6403,6404,6405,6117,553,6406,6407,6408,6409,6410,6411,6412,64 13,6118,6414,6415,6416,6417,6418,6419,6084,6420,6421,6422,6085,6423,6424,6425,6426,6427 ,6428,6429,6430,6431,6432,6433,6434,6435,6119,6436,6437, 10003,6120,6439,6440,6441,6442, 6443,6444,6445,6446,6447,6448,6449,6450,6451,6452,6438,6453,6454,6455,6456,6457,6458,61 21,6459,6086,6460,6461,6462,6463,6122,6464,6465,6466,6467,6468,6469,6470,6471,6472,6087 ,6473,6474,6475, 10004,6123,6088,6124,6125,6126,6068,6127,6089,6090,6128,6129,6069,6091, 6130,6131,6132,6092,554,6133,6135,6136,6137,6138,6139,6140,6141,6142,6143,6144,6093,614 5,6146,6147,6148,6149,6094,6150,6151,6152,6153,6095,6154,6155,6156,6157,6158,6159,6096, 6097,6160,6161,6162,6163,6164,6165,6070,6166,6167,6168,6169,6170,6171,6172,6173,6174,61 75,6176,6177,6178,6179,6180,6181,6182,6183,6184,6185,6186,6187,6188,6189,6190,6191,6192 ,6193,6194,6195,6196,6197,6198,6199,6200,6201,6202,6203,6204,6205,6206,6071,6207,6208,6 209,6098,6210,6211,6212,6213,6214,6215,6072,6216,6217,6218,6219,6220,6221,6222,6073,622 3,6224,6225, 10001,6099, 10002,6226,6227,6228,6229,6230,6231,6232,6233,6234,6235,6100,623 6,6101,6102,6237,6238,6239,6240,6103,6241,6242,6243,6244,6245,6247,6248,6104,6249,6250, 6251,6252,6253,6254,6255,6256,6257,6105,6258,6259,6260,6074,6261,6262,6263,6264,6265/ 66,6267,6268,6269,6270,6271,6272,6246,6273,6274,6275,6276,6277,6278,6279,6280,6281,6282 ,6283,6284,6285,6286,6287,6288,6289,6290,6292,6293,6075,6294,6295,6296,6297,6298,6299,6 300,6301,6302,6303,6304,6305,6306,6307,6308,6309,6310,6076,6311,6106,6312,6313,6314,610 7,6108,6315,6316,6317,6077,6318,6319,6320,6321,6322,6323,6324,6325,6078,6326,6327,6328, 6329,6330,6331,6332,6333,6334,6335,6336,6337,6079,6338,6339,6340,6080,6341,6342,6343,63 44,6345,6346,6347,6081,6348,6349,6350,6351,6352,6066,6353,6354,6355,6356,6357,6082,6358 ,6109,6359,6360,6361,6083,6362,6363,6364,6110,6365,6366,6367,6368,6111,6369,6370
Chromosome 12: SEQ ID NO:
0011,6806,6807,6808,6514,6809,6515,6810,6811,6812,6516,6813,6517,6814,6518,65 19,6815,6816,6817,6818,6819,6520,6820,6821,6822,6823,6824,6825,6521,6826,6827,6828,6829 ,6830,6831,6832,6833,6834,6835,6836,6837,6522,6523,6838,6839,6524,6840,6841,6842,6843,6 844,6845,6846,6847,6848,6849,6850,6851,6852,6853,6854,6525,6855,6856,6857,6858,6859,686 0,6861,6862,6863,6864,6865,6866,6867,6868,6869,6870,6871,6872,6873,6874,6875,6876,6877, 6878,6879,6880,6881,6882,6883,6884,6885,6886,6526,6887,6888,6889,6890,6891,6892,6893,68 94,6895,6896,6527,6897,6898,6899,6900,6901,6482,6902,6903,6904,6905,6906,6907,6908,6909 ,6910,6911,6912,6913,6914,6915,6916,6917,6918,6919,6920,6921,6922,6923,6528,6924,6925,6 926,6927,6928,6929,6930,6931,6932,6933,6934,6935,6936,6937,6938,6939,6940,6941,6942,694 3,6944,6945,6946,6947,6948,6949,6950,6951,6952,6953,6954,6955, 10012,6529,6530,6531,6532 ,6533,6534,6483,6535,6536,6537,6538,6539,6540,6541,6542,6543,6544,6545,6546,6547,6548,6 477,6484,6549,6550,6551,6552,6553,6555,6556,6557,6558,6559,6560,6561,6562,6563,6564,656 5,6566,6567,6568,6569,6570,6571,6572,6478,6573,6574,6575,6485,6576,6486,6577,6578,6579, 6580,6581,6582,6583,6584,6487,6585,6586,6587,6588,6589,6590,6591,6592,6593,6594,6595,65 96,6597,6554,6598,6599,6600,6601,6602,6603,6604,6605,6488,6606,6607,6608,6609,6610,6611 ,6612,6613,6614,6615,6616,6617,6618,6619,6620,6621,6489,6622,6490, 10005, 10006, 10007, 100 08, 10009, 10010,6626,6627,6628,6491,6629,6630,6631,6632,6633,6634,6635,6636,6637,6638,66 39,6492,6640,6493,6641,6642,6643,6644,6494,6625,6645,6646,6647,6648,6649,6650,6651,6652 ,6653,6654,6655,6656,6657,6658,6495,6659,6660,6661,6496,6662,6663,6664,6665,649
667,6668,6669,6670,6671,6672,6673,6674,6675,6676,6677,6678,6679,6680,6681,6682,6683,668 4,6685,6686,6687,6688,6689,6691,6692,6693,6694,6695,6498,6696,6697,6698,6699,6479,6700, 6701,6499,6702,6703,6704,6705,6500,6501,6706,6707,6708,6709,6480,6710,6711,6712,6713,67 14,6715,6716,6717,6718,6719,6720,6721,6722,6723,6724,6725,6502,6726,6727,6728,6729,6730 ,6731,6732,6503,6733,6734,6735,6736,6737,6738,6690,6739,6740,6741,6742,6504,6743,6744,6 745,6746,6747,6505,6748,6749,6750,6751,6752,6753,6754,6755,6756,6757,6506,6758,6759,676 0,6761,6507,6508,6762,6763,6764,6765,6766,6767,6509,6768,6769,6770,6771,6772,6510,6773, 6511,6774,6775,6776,6777,6778,6779,6780,6781,6782,6512,6783,6784,6785,6786,6787,6788,67 89,6790,6791,6792,6793,6794,6795,6796,6797,6798,6481,6513,6799,6800,6801,6802,6803,6804 ,6805
Chromosome 13: SEQ ID NO:
7227,7228,7229,7232,7233,7234,7235,7236,7237,7238,7239,7240,7241,7242,7243,72 44, 7245, 7246, 7247, 7248, 7249, 7250, 7251, 7252, 7253, 7254, 7255, 7256, 7257, 7258, 7259, 7260, 7261 , 7262, 7263, 7264, 7265, 7266, 7230, 7267, 7268, 7269, 7270, 7271, 7272, 7273, 7274, 7275, 7276, 7277, 7 278, 7279, 7280, 7281, 7282, 7283, 7284, 7285, 7286, 7287, 7231, 7288, 7289, 7290, 7291, 7292, 7293, 729 4, 7295, 7296, 7297, 7298, 7299, 7300, 7301, 7302, 7303, 7304, 7305, 7306, 7307, 7308, 7309, 7310,7311, 7312,6958,6959,6960,6963,6964,6965,6966,6967,6968,6969,6970,6971,6972,6973,6974,6975,69 76,6977,6978,6979,6980,6981,6982,6983,6984,6985,6986,6987,6988,6989,6990,6991,6992,6993 ,6994,6995,6996,6997,6998,6999, 7000, 7001, 7002, 7003, 7004, 7005, 7006,7007, 7008, 7009, 7010, 7 011,7012,7013,7014,7015,7016,7017,7018,7019,7020,7021,7022,7023,7024,7025,7027,7028,702 9, 7030, 7031, 7032, 7033, 7034, 7035, 7036, 7037, 7026, 7038, 7039, 7040, 7041, 7042, 7043, 7044, 7045, 7046, 7047, 7048, 7049, 7050, 7051, 7052, 7053, 7054, 7055, 7056, 7057, 7058, 7059, 7060, 7061, 7062, 70 63, 7064, 7065, 7066, 7067, 7068, 7069, 7070, 7071, 7072, 7073, 7074, 7075, 7076, 7077, 7078, 7079, 7080 , 7081, 7082, 7083, 7084, 7085, 7086, 7087, 7088, 7089, 7090, 7091, 7092, 7093, 7094, 7095, 7096, 7097, 7 098,7099,7100,7101,7102,7103,7104,7105,7106,7107,7108,7109,7110,7111,7112,7113,7114,711 5,7116,7117,7118,7119,7120,7121,7122,7123,7124,7125,7126,7127,7128,7129,7130,7131,7132, 7133,7134,7135,7136,7137,7138,7139,7140,7141,7142,7143,7144,7145,7146,7147,7148,7149,71 50,7151,7152,7153,7154,7155,7156,7157,7158,7159,7162,7163,7164,7165,7166,7167,7168,7169 ,7160,7170,7171,7172,7173,7174,7175,7176,7177,7178,7179,7180,7181,7161,7182,7183,7184,7 185,7186,7187,7188,7189,7190,7191,7192,7193,7194,7195,7196,7197,7198,7199 ,7200,7201,720 2,7203,7204,7205,7206,7207,7208,7209,7210,7211,7212,7213,7214,7215,7216,7217,7218,7219, 7220, 7221, 7222, 7223, 7224, 7225, 7226
Chromosome 14: SEQ ID NO:
7556,7557,7560,7561,7562,7563,7564,7565,7566,7558,7567,7568,7569,7570,7571,75 72, 7573, 7574, 7575, 7576, 7577, 7578, 7579, 7580, 7581, 7582, 7583, 7585, 7518, 10014, 10015, 7587, 73 13, 7314, 7315, 7316, 7317, 7318, 7319, 7320, 7321, 7322, 7324, 7325, 7326, 7327, 7328, 7329, 7330, 7331 , 7332, 7333, 7334, 7335, 7336, 7337, 7338, 7339, 7340, 7341, 7342, 7343, 7344, 7345, 7346, 7347, 7348, 7 349, 7350, 7351, 7352, 7353, 7354, 7355, 7356, 7357, 7358, 7359, 10013, 7360, 7361, 7362, 7363, 7364, 73 65, 7366, 7367, 7368, 7369, 7370, 7371, 7372, 7373, 7374, 7375, 7376, 7377, 7378, 7379, 7380, 7381, 7382 , 7383, 7384, 7385, 7386, 7387, 7388, 7389, 7390, 7391, 7392, 7393, 7394, 7395, 7396, 7397, 7398, 7399, 7 400,7401,7402,7403,7404,7405,7406,7407,7408,7409,7410,7411,7412,7413,7414,7415,7416,741 7, 7418, 7419, 7420, 7421, 7422, 7423, 7424, 7425, 7426, 7427, 7428, 7429, 7430, 7431, 7432, 7433, 7434, 7435, 7436, 7437, 7438, 7439, 7440, 7441, 7442, 7444, 7445, 7446, 7447, 7448, 7449, 7450, 7451, 7452, 74 53, 7454, 7455, 7456, 7457, 7458, 7459, 7460, 7461, 7462, 7463, 7464, 7465, 7466, 7467, 7468, 7469, 7470 , 7473, 7474, 7475, 7476, 7471, 7477, 7478, 7479, 7472, 7480, 7481, 7482, 7483, 7484, 7485, 7486, 7487, 7 488, 7489, 7493, 7494, 7495, 7496, 7497, 7498, 7499, 7500, 7501, 7502, 7503, 7504, 7505, 7506, 7490, 750 7,7508,7509,7510,7511,7512,7513,7514,7515,7516,7517,7518,7519,7520,7521,7491,7522,7523, 7524, 7525, 7526, 7527, 7528, 7529, 7530, 7531, 7532, 7533, 7534, 7535, 7536, 7537, 7538, 7539, 7540, 75 41,7542,7543,7544,7545,7546,7547,7548,7549,7550,7551,7552,7553,7554,7555
Chromosome 15: SEQ ID NO: 7773, 7819, 7820, 7821, 7822, 7823, 7824, 7825, 7827, 7828, 7829, 7830, 7831, 7832, 7833, 10 021,7590,7593,7594,7591,7595,7596,7589,7597,7598, 10016, 10017, 10018, 10019, 10020,7595,76 09, 7610, 7611, 7612, 7613, 7614, 7592, 7615, 7616, 7617, 7618, 7619, 7620, 7621, 7622, 7623, 7624, 7602 , 7603, 7604, 7605, 7629, 7630, 7631, 7632, 7633, 7634, 7635, 7636, 7637, 7638, 7639, 7640, 7641, 7642, 7 643, 7644, 7645, 7646, 7647, 7648, 7649, 7650, 7651, 7652, 7653, 7654, 7655, 7656, 7657, 7658, 7659, 766 0,7661,7662,7663,7664,7665,7666,7667,7668,7669,7670,7671,7672,7673,7674,7675,7676,7677, 7678, 7679, 7680, 7681, 7682, 7683, 7684, 7685, 7686, 7687, 7688, 7689, 7690, 7691, 7692, 7693, 7694, 76 95, 7696, 7697, 7698, 7699, 7700, 7701, 7702, 7703, 7704, 7705, 7706, 7707, 7708, 7709, 7710, 7711, 7712 ,7714,7715,7716,7717,7718,7719,7720,7721,7722,7723,7724,7726,7727,7728,7729,7730,7713,7 731,7732,7733,7734,7735,7736,7737,7738,7739,7740,7741,7742,7743,7744,7745,7746,7747,774 8, 7749, 7750, 7751, 7752, 7753, 7754, 7755, 7756, 7757, 7758, 7759, 7760, 7761, 7762, 7763, 7764, 7765, 7766, 7767, 7768, 7769, 7770, 7771, 7772, 7774, 7775, 7776, 7777, 7778, 7779, 7780, 7780, 7781, 7782, 77 83,7784,7785,7786,7787,7788,7789,7790,7791,7792,7793,7794,7795,7796,7797,7798,7799,7800 ,7801,7802,7803,7804,7805,7806,7807,7808,7809,7810,7811,7812,7813,7814,7815,7816,7817,7 818
Chromosome 16: SEQ ID NO:
7889, 7890, 7848, 7891, 7849, 7892, 7893, 7894, 7895, 7896, 7850, 7897, 7851, 7898, 7899, 79 00, 7852, 7901, 7902, 7903, 7853, 7904, 7905, 7906, 7907, 7908, 7909, 7910, 7911, 7854, 7912, 7913, 7835 ,7914,7915,7916,7917,7918,7919,7855,7920,7921,7922,7923,7924,7888,7925,7928,7856,7929,7 930, 7857, 7931, 7932, 7933, 7934, 7935, 7936, 7937, 7938, 7939, 7858, 7940, 7859, 7941, 7927, 7942, 794 3, 7944, 7860, 7945, 7946, 7947, 7861, 7948, 7949, 7950, 7951, 7952, 7953, 7954, 7955, 7862, 10024, 1002 5, 10026,8126, 10027, 10028, 10029, 10030, 10031, 10032, 10023,7964, 10033, 10034, 10035, 10036, 10 037,8127, 7863, 10038, 10039, 7864, 7836, 7837, 7838, 7865, 7839, 7866, 7867, 7965, 7868, 7966, 7869, 7 967,7968,7969,7970,7971,7972,7973,7870,7974,7871,7975,7976,7977,7978,7872,7979,7980,798 1, 7873, 7982, 7983, 7984, 7985, 7986, 7987, 7988, 7989, 7990, 7991, 7992, 7874, 7993, 7840, 7875, 7995, 7994,7876,7996,7997,7998,7999,8000,8001,8002,8003,8004,8005,8006,8007,8008,8009,8010,80 11,8012,7877,8013,8014,8015,8016,8018,8019,8020,7841,7878,8021,8017,8022,8023,8024,8025 ,8026,8027,8028,8029,7879,8030,7834,8031,8032,8033,8034,8035,8036,8037,8038,8039,8040,^ 041,8042,8043,7880,8044,8045,8046,8047,8048,8049,8050,8051,8052,7842,8055,8056,7881,805 7,8058,8059,8060,8061,7882,8062,7843,8063,8064,8065,8066,8067,7844,8068,8069,7883,8070, 7884,8071,8072,8073,8074,8075,8076,8077,8078,8079,8080,8081,8082,8083,8084,8085,8086,80 87,8053,8088,8089,8090,8091,8092,7845,8093,8094,8095,8096,8097,8098,8054,8099,8100,8101 ,8102,8103,8104,8105,8106,8107,8108,8109,8110,8111,8112,8113,8114,8115,8116,8117,8118,8 119,8120,8121,8122,8123,8124, 10040,5582, 10022,7885,7886,7846,7847,7887
Chromosome 17: SEQ ID NO:
8180,8181,8145,8146,8147,8182,8148,8183,8184,8129,8185,8149,8186,8187,8150,81 88,8189,8190,8191,8151,8179,8192,8193,8194,8195,8196,8197,8198,8199,8200,8152,8201,8202 ,8203,8153,8130,8204,8205,8206, 10041, 10042, 10043, 10044,8154, 10045, 10046, 10047, 10048, 10 049, 10050, 10051, 10052,8208,8155,8131,8156,8157,8132, 10053, 10054,8133, 10055, 10056,8158, 8216, 10057, 10058, 10059,9517,8217,8218,8219,8220,8221,8222,8223,8224,8225,8226,8125,822 7,8228,8159,8160, 10060,8229,8230,8231,8232,8233,8234,8161,8235,8162,8239,8240, 10061,823 6,8241,8242,8242,8243,8244,8245,8246,8247,8248,8249,8250, 10062,8251,8252,8253,8163,8134 ,8164,8254,8255,8256,8257,8258,8259,8260,8261,8262,8263,8264,8265,8266,8267,8165,8268,8 269,8270,8271,8135,8272,8273,8274,8275,8276,8277,8278,8279,8280,8281,8282,8136,8283,828 4,8285,8286,8287,8288,8289,8290,8291,8292,8293,8294,8295,8128,8296,8137,8297,8298,8299, 8300,8301,8302,8303,8304,8305,8306,8307,8308,8309,8166,8310,8138,8311,8312,8313,8167,81 68,8314,8315,8316,8317,8318,8319,8320,8321,8322,8323,8169,8324,8325,8326,8327,8328,8329 ,8330,8331,8332,8333,8334,8335,8336,8337,8338,8339,8340,8341,8342,8344,8345,8346,8347,8 170,8348,8349,8350,8351,8352,8353,8354,8355,8171,8356,8139,8357,8358,8359,8360,8361,836 2,8363,8364,8365,8366,8367,8368,8369,8370,8371,8372,8373,8172,8375,8375,8376,8377,8378, 8379,8380,8173,8381,8382,8384,8385,8386,8387,8388,8389,8390,8391,8392,8393,8394,8395,81 40,8396, 10063,8397,8398,8399,8400,8401,8402,8403,8404,8405,8406,8407,8408,8409,8410,841 1,8412,8413,8414,8415,8141,8174,8175,8142,8176,8177,8178,8143,8144
Chromosome 18: SEQ ID NO:
8418,8442,8419,8420,8443,8444,8445,8446,8447,8448,8449,8421,8450,8451,8452,84 53,8454,8455,8422,8456,8457,8459,8460,8462,8423,8424,8463,8464,8465,8466,8467,8468,8469 ,8470,8471,8472,8473,8474,8475,8476,8425,8477,8478,8461,8479,8480,8481,8482,8483,8484,8 416,8485,8486,8487,8488,8489,8490,8491,8492,8426,8493,8494,8495,8427,8496,8497,8498,849 9,8500,8501,8428,8502,8503,8504,8505,8506,8507,8508,8509,8510,8511,8512,8513,8514,8515, 8516,8518,8519,8520,8521,8522,8429,8523,8430,8524,8525,8526,8527,8528,8529,8530,8531,85 32,8533,8534,8535,8536,8537,8538,8539,8517,8540,8541,8542,8543,8544,8545,8546,8547,8548 ,8549,8550,8431,8551,8432,8552,8553,8554,8555,8556,8557,8558,8559,8560,8561,8562,8563,8 564,8565,8566,8567,8568,8569,8570,8571,8572,8573,8574,8575,8433,8576,8577,8434,8578,857 9,8580,8581,8582,8583,8584,8585,8435,8586,8587,8588,8589,8590,8591,8592,8593,8594,8595, 8596,8597,8598,8599,8600,8601,8602,8603,8604,8605,8606,8607,8608,8436,8609,8610,8611,86 12,8613,8614,8615,8616,8617,8618,8619,8620,8621,8622,8623,8624,8625,8437,8626,8627,8628 ,8629,8630,8631,8632,8633,8634,8635,8636,8637,8638,8639,8640,8641,8642,8643,8644,8645,8 646,8647,8648,8649,8650,8651,8652,8653,8654,8655,8656,8657,8658
Chromosome 19: SEQ ID NO:
8676,8659,8677,8678,8679,8680,8660,8681,8682,8753,8757,8758,8759,8760,8761,87 62,7976,8763,8764,8765,8766,8755,8767,8768,8769,8770,8665,8771,8772,8773,8683,8684,8685 ,8775,8776,8686,8779,8687,8780,8781,8688,8783,8784,8689,8666,8690,8691,8785,8786,8787,8 788,8789,8790,8791,8792,8793,8794,8795,8796,8692,8693,8797,8798,8694,8799,8695,8800,880 1,8802,8803,8804,8805,8667,8806,8807,8696,8808,8809,8810,8811,8816,8817,8818,8819,8820, 8821,8822,8697,8823,8698,8824,8825,8699,8826,8827,8828,8813,8812,8829,8830,8831,8832,88 33,8834,8835,8836,8837,8668,8838,8839,8700,8840,8841,8842,8843,8853,8854,8855,8701,8856 ,8857,8858,8859,8860,8845,8861,8862,8863,8846, 10064,8864,8847,8865,8866,8867,8868,8848, 8869,8871,8872,8873,8874,8875,8876,8877,8878,8879,8880,8881,8882,8883,8884,8885,8886,88 87,8888,8889,8890,8891,8892,8893,8894,8895,8849,8850,8896,8897,8898,8899,8851,8852,8669 ,8670,8661,8662,8702,8703,8671,8704,8663,8705,8706,8707,8672,8708,8673,8709,8710,8711,8 712,8713,8714,8674,8715,8675,8716,8717,8664
Chromosome 20: SEQ ID NO:
8925,8926,8927,8928,8929,8930,8931,8932,8933,8934,8935,8936,8937,8938,8939,89 00,8940,8941,8942,8943,8944,8904,8945,8946,8947,8948,8905,8949,8950,8951,8906,8952,8953 ,8954,8956,8907,8957,8958,8959,8960,8961,8962,8963,8964,8965,8955,8966,8967,8968,8969,8 970,8971,8983,8984,8989,8990,8991,8992,8993,8994,8995,8996,8997,8998,8999,9000,9001,890 8,9002,9003,9004,9005,8909,9006,9007,9008,8980,9009,9010,9011,9012,9013,9014,9015,9016, 8910,9017,9018,9019,9020,8911,9021,9022,9023,9024,9025,9026,9027,9028,9029,9030,9031,90 32,9033,8901,9034,9035,9036,9037,9038,8912,9039,9040,9041,9042,9043,9044,9045,9046,9047 ,9048,9049,9050,9051,8913,8914,8915,9052,9053,9054,9055,9056,9057,9058,9059,9060,9064,9 065,9066,9067,9068,9069,9070,9071,9072,9073,9074,9075,9076,9061,9077,9078,9079,9080,908 1,9082,9083,9084,9085,9086,9087,9088,9089,9090,9091,8916,9092,9093,9094,9095,9096,9097, 9098,9062,9099,9100,9101,9102,9103,9104,9105,9106,9107,9108,9109,9110,9111,9112,9113 14,9115,9116,9117,9118,9119,9120,9121,9122,9063,9123,9124,9125,9126,9127,9128,9129,9130 ,9131,9132,9133,8917,8918,8919,8920,8902,8921,8903,8922,8923,8924
Chromosome 21: SEQ ID NO:
9145,9146,9147,9148,9149,9150,9151,9152,9153,9154,9155,9156,9157,9158,9159,91 60,9161,9162,9163,9164,9165,9166,9167,9168,9169,9170,9171,9173,9174,9175,9176,9177,9178 ,9179,9180,9181,9182,9183,9184,9185,9186,9187,9188,9189,9190,9191,9192,9193,9194,9195,9 196,9197,9198,9199,9200,9201,9202,9203,9204,9205,9206,9207,9208,9209,9210,9211,9212,921 3,9214,9215,9216,9217,9172,9218,9219,9220,9221,9222,9223,9224,9225,9226,9227,9228,9229, 9230,9231,9232,9233,9234,9235,9236,9239,9237,9240,9241,9242,9243,9244,9245,9246,9247,92 48,9249,9250,9251,9252,9253,9254,9255,9256,9257,9258,9259,9260,9261,9262,9263,9264,9265 ,9266,9267,9268,9269,9270,9271,9272,9273,9238,9274,9275,9276,9277,9278,9279,9280,9281,9 282,9283,9284,9285,9286,9287,9288,9289,9290,9291,9292,9293,9294,9295,9296,9297,9298,929 9,9300,9301,9302,9303,9304,9305, 10069,9137
Chromosome 22: SEQ ID NO:
7318, 10070,9318,9319,9320,9321,9322,9323,9324,9327,9328,9325,9326,9329,9330,9 331,9332,9333,9334,9335,9336,9337,9338,9339,9340,9341,9342,9343,9344,9345,9346,9347,934 8,9349,9350,9351,9352,9353,9354,9355,9356,9357,9358,9359,9360,9361,9362,9363,9364,9365, 9366,9367,9368,9369,9370,9371,9372,9373,9374,9375,9376,9377,9378,9379,9380,9381,9383,93 84,9385,9386,9387,9388,9389,9390,9391,9392,9393,9394,9395,9396,9397,9398,9399,9382,9400 ,9401,9402,9403,9404,9405,9406,9407,9408,9409,9410,9411,9412,9413,9414,9415,9416,9417,9 418,9419,9420,9421,9422,9423,9424,9425,9426,9427,9428,9429,9430, 10071,9431,9432,9433,94 34,9435, 10072,9437,9438,9439,9440,9441,9442,9443,9444,9445,9446,9447,9448,9449,9450, 100 73
Chromosome X SEQ ID NO:
9708,9709,9710,9451,9452,9711,9712,9713,9714,9715,9716,9717,9718,9719,9720,97 21,9722,9705,9723,9724,9725,9726,9727,9495,9496,9728,9729,9730,9731,9732,9733,9734,9735 , 10139,9737,9738,9739,9740,9741,9742,9743,9744,9706,9745,9746,9747,9748,9749,9750,9751, 9752,9753,9754,9755,9756,9757,9758,9759,9760,9761,9762,9763,9764,9765,9766,9767,9768,97 70,9497,9771,9772,9773,9774,9775,9776,9777,9498,9499,9778,9779,9780,9781,9782,9783,9784 ,9500,9785,9786,9787,9788,9789,9790,9501,9791,9792,9793,9794,9795,9796,9797,9502,9798,9 799, 10140,9800,9801,9802,9803,9804,9805,9503,9806, 10141,9504,9807,9505,9808,9809,9462,9 810,9811,9812,9813,9814,9815,9816,9817,9822,9823,9824,9825,9826,9827,9828,9829,9830,983 1,9832,9833,9834,9836,9837,9838,9839,9840,9841,9842,9843,9844,9845,9847,9833,9848,9849, 9850,9463,9851,9852,9853,9854,9506,9855,9856,9857,9858,9859,9860,9861,9862,9863,9864,94 64,9865,9866,9868,9507,9465,9508,9509,9510,9511,9493,9512,9466,9494,9513,9467,9468,9515 ,9469,9516,9517,9518,9519,9471,9520,9472,9521,9522,9523,9454,9473,9524,9525,9514,9526,9 527,9528,9529,9530,9531,9532,9533,9534,9535,9536,9537,9538,9539,9540,9541,9453,9542,954 3,9544,9545,9546,9547,9548,9474,9549,9550,9551,9475,9552,9553,9554,9555,9556,9557,9558, 9562,9563,9476,9564,9565,9566,9567,9568,9569,9455,9570,9456,9571,9572,9573,9574
76,9577,9559,9578,9477,9579,9580,9478,9581,9582,9479,9480,9583, 10116,9586,9587,9560,956 1,9481,9588,9589,9590,9591,9592,9593,9482,9594,9596,9597,9598,9599, 10117,9601,9602,9603 ,9604,9605,9606,9483,9607,9608,9609,9610,9611, 10118,10119,9484, 10120, 10121, 10122, 10123, 10124, 10125, 10126,9485, 10127, 10128, 10129, 10130,9486, 10131,9487,9565, 10132, 10133, 10134, 10135, 10136,9488, 10137, 10138,9618,9619,9489,9620,9621,9622,9623,9624,9625,9626,9627,96 28,9629,9630,9631,9632,9633,9634,9635,9636,9490,9637,9638,9639,9640,9641,9642,9643,9644 ,9491,9645,9646,9045,9647,9648,9649,9650,9651,9652,9653,9654,9655,9656,9657,9658,9659,9 660,9661,9662,9663,9664,9665,9666,9667,9668,9669,9670,9671,9457,9672,9673,9674,9675,949 2,9676,9677,9678,9679,9680,9681,9682,9684,9685,9686,9683,9687,9688,9689,9690,9691,9692, 9693,9458,9694,9695,9696,9697,9698,9699,9459,9460,9700,9701,9702,9703,9704,9461,9707
Chromosome Y SEQ ID NO:
9881,9923,9882,9924,9925,9926,9927,9928,9929,9930,9931,9883,9932,9933,9884,99 34,9935,9936,9937,9938,9939,9940,9941,9942,9943,9944,9945,9946,9947,9885,9948,9949,9873 ,9950,9951,9952,9953,9886,9887,9888,9954,9955,9890,9956,9957,9920,9958,9891,9959,9960,9 961,9962,9892,9963,9964,9965,9966,9967,9968,9969,9970,9971,9972,9973,9974,9975,9976,997 7,9978,9979,9980,9981,9982,9983,9984,9985,9986,9987,9988,9989,9990,9991,9992,9993,9893, 9994,9995,9894,9895,9896,9874,9875,9897,9871,9898,9899,9900,9901,9996,9902,9903,9904,99 05,9906,9907,9872,9908,9909,9910,9876,9911,9912,9913,9914,9915,9916,9917,9877,9918,9878 ,9879,9880,9919,9869,9870,9921,9922
Of course in the given ranges the CRISPR sequences of Table 2, 3 and 24 need to be excluded.
A further grouping of human, non-Affymetrix, non-EPSCAT sequences can be provided by the sequences as provided in Table 21 (CRISPR sequences related to transcription factor binding sites), Table 22 (CRISPR sequences related to DNAse 1 binding sites) and Table 23 (CRISPR sequences harbouring spacer sequences that target to protospacer sequences of viruses or bacteria). Of course sequences that are provided in Table 2, 3 and/or 24 can be distracted from these groupings, thereby providing novel sets of CRISPR sequences.
Also groupings can be made with respect to the function of the CRISPR sequences. For Examples 15 and 16 a group of CRISPR sequences that is differently expressed in cancer tissues can be distinguished (the CRISPR sequences listed in Table 17), where this group can be further distinguished in CRISPR sequences that are differently expressed with respect to one particular type of cancer (as indicated in Fig. 15 and Table 19).
Further, although these CRISPR sequences form part of the group of Affymetrix sequences, the sequences that are specified in each of the Examples 3 - 14 which may be used as diagnostic tools according to the specific condition or disease exemplified in these examples can each be seen as a grouping of CRISPR sequences according to the invention. Although in the case of Affymetrix CRISPR sequences each individual CRISPR sequence may already be known, the fact that such a sequence can be advantageously used as a diagnostic tool and especially a group of CRISPR sequences as specified in each and every example of Examples 3 - 14 for such a diagnostic purpose may be considered as novel and inventive over the prior art.
It is to be understood that wherever in the present description the use of a CRISPR sequence for diagnostic purposes is described, this can also be interpreted as the use of a group or grouping of CRISPR sequences as defined above for diagnostic purposes. In that sense also assays with a group or grouping of CRISPR sequences as defined above and arrays comprising a group of CRISPR sequences as defined above are considered to be part of the invention.
The assays that are useful in the present invention are preferably quantitative assays, in which the quantity of expression in the sample can be determined. This can - in principle - be achieved with all kinds of detection methods as exemplified below. While interpreting the results of such an assay, various other health determinants such as sex, age, smoking status, urbanicity, food and alcohol intake may be taken into account.
It is also contemplated that the specific expression of a CRISPR sequence can related to other factors such as sex, where in males a higher expression may be found than in females, or to a factor such as age, where in elderly persons a higher level of expression may be found than in younger persons. The measured values should of course be interpreted in the light of these correlations, which would be known to the skilled person, or which would be easily discernible on basis of control sample assays. .
A kit for diagnosing or monitoring a disease or condition is provided. Suitably a kit according to the invention may contain an array according to the invention and one or more reagents and one or more consumables; optionally together with instructions for use of the kit in accordance with any of the methods defined herein. The diagnosis of a disease or condition permits integration of diagnostic procedures and therapeutic regimes. Currently effectiveness of medical treatment may be difficult to test (e.g. in cases of little physiologic effects, such as mood diseases), and it has thus far not been possible in many cases to perform rapid assessment of therapy response. Traditionally, many disease therapies require treatment lasting a prolonged time (days to months, even years) for a given therapeutic approach. Performing an assay according to the invention can be used to screen subjects prior to therapy to set a zero level for said subject. The assays of the present invention provide the means to indicate therapeutic responses, failures to respond,
unfavourable side-effect profiles, and degree of medication compliance. The assays of the invention may be used to stop treatment in non-responders at a very early stage. They can also be used to fine-tune dosage, minimize the number of prescribed medications, and to reduce the delay in attaining effective therapy. Thus by monitoring expression of one or more CRISPR sequences according to the invention, patient care can be tailored precisely to match the needs determined by the disorder and the pharmacogenomic profile of the patient. The assays of the invention can thus be used to titrate the optimal dose and to identify a positive therapeutic response.
Assays for quantitative assessment of the expression of eukaryotic CRISPR sequences, such as provided by the present invention, provide a first line assessment of 'new' subjects, and provide objective measures for accurate and rapid diagnosis, in a time frame and with precision.
Furthermore, diagnostic assays, such as provided by the present invention, are useful to identify family members or patients at high risk of developing a similar disease or condition. This permits initiation of appropriate therapy, or preventive measures, e.g. managing risk factors. These approaches are recognized to improve outcome and may prevent overt onset of the disorder.
Such monitoring methods, eukaryotic CRISPR sequences, arrays and kits are also vital as patient monitoring tools. If pharmacological treatment is assessed to be inadequate, then therapy can be reinstated or increased; a change in therapy can be given if appropriate. As the expression of the CRISPR sequences is sensitive to the state of the disease or condition, it may provide an indication of the impact of drug therapy.
Diagnostic kits for the diagnosis and monitoring of a condition or disease are described herein. A method of diagnosis or monitoring the expression of CRISPR sequences may comprise quantifying the expression of the CRISPR sequences in a sample from the patient and comparing the level of expression in said sample with one or more controls. For monitoring, the control may be a test sample of the same patient at an earlier point in time (the zero assay or any assay preceding the current one). A diagnostic kit can contain probes that are specific for a group or grouping of CRISPR sequences as defined above
Preferably, the diagnosis for the presence of a condition or disease is used to confirm a suspicion of said condition or disease. This means that preferably the subject is already suspected of having said condition or disease at the moment that de the assay for expression of one or more of the eukaryotic CRISPR sequences is performed. In this respect, the invention can be considered as a method for enhancing the diagnosis of said condition or disease.
One of the main advantages of the present invention is that it provides an easy and reliable way to monitor progress of the condition or disease and/or effectiveness of a therapy. To this end, the values for expression of one or more of the eukaryotic CRISPR sequences for a subject are determined at a certain moment (zero-value) and after an amount of time this procedure is repeated. Over the time, several repeat measurements can be performed. In the meantime therapy can e.g. be started or changed. Change(s) in the expression levels of the CRISPR sequences will then indicate the effectiveness of the therapy or the progress of the condition or disease.
Suitably, the time elapsed between taking samples from a subject undergoing monitoring will be several days, a week, two weeks, a month, several months or longer.
Samples may be taken prior to and/or during and/or following therapy. Samples can be taken at intervals over the remaining life, or a part thereof, of a subject.
Thus, in this way, in a non-invasive and easy manner, the progress of the condition or disease can be monitored.
The diagnosis of a disease or condition may begin with an examination of a subject by a physician, nurse or other medical professional. As used herein, the term subject refers to any animal (e.g. a mammal), including but not limited to humans, non-human primates, rodents, dogs, pigs, and the like. The examination may be part of a routine examination, or the examination may be due to a specific complaint including but not limited to one of the following: pain, illness, anticipation of illness, presence of a suspicious lump or mass, a disease, or a condition. The subject may or may not be aware of the disease or condition. The medical professional may obtain a biological sample for testing. In some cases the medical professional may refer the subject to a testing center or laboratory for submission of the biological sample.
The biological sample generally will be obtained by a physician, nurse, or other medical professional such as a medical technician, endocrinologist, gynecologist, cytologist,
phlebotomist, radiologist, (forensic) pathologist or a pulmonologist, but the sample may also be obtained by non-medical staff, such as police staff or HR staff. The sample-taker may indicate the appropriate test or assay to perform on the sample, or may consult on which assays or tests are most appropriate.
In some embodiments of the present invention, a medical professional or other professional staff need not be involved in the initial diagnosis or sample acquisition. An individual may alternatively obtain a sample through the use of an over the counter kit. Said kit may contain a means for obtaining said sample, a means for storing said sample, and instructions for proper use of the kit. In some cases, molecular profiling services are included in the price for purchase of the kit. In other cases, the molecular profiling services are billed separately. A sample suitable for use in the present invention may be any material containing tissues, cells, genes, gene fragments, gene expression products, or gene expression product fragments of an individual to be tested. A sample may include but is not limited to, tissue, cells, or biological material from cells or derived from cells of an individual. The sample may be a heterogeneous or homogeneous population of cells or tissues. In any case, the biological sample may be obtained using any method known to the art that can provide a sample suitable for the analytical methods described herein.
The sample may be obtained by non-invasive methods including but not limited to: taking a hair of the subject, cutting hair or nails of the subject, scraping of the skin or cervix, lavage of the cervix, swabbing of the cheek or any other mucous part of the subject, saliva collection, urine collection, feces collection, blood or serum collection, e.g. by finger prick or venipuncture, collection of menses, tears, or semen. In other cases, the sample is obtained by an invasive procedure including but not limited to: biopsy, alveolar or pulmonary lavage, needle aspiration, or phlebotomy. The method of biopsy may further include incisional biopsy, excisional biopsy, punch biopsy, shave biopsy, or skin biopsy. The method of needle aspiration may further include fine needle aspiration, core needle biopsy, vacuum assisted biopsy, or large core biopsy..
The general methods for determining nucleic acid expression product levels are known to the art and may include but are not limited to one or more of the following: whole or partial genome expression analysis, microarray hybridization assays, SAGE, enzyme linked immuno- absorbance assays, mass-spectrometry, immuno-histochemistry, or blotting. Additionally, other assays to confirm the diagnosis may be applied, such as additional cytological assays, assays for specific proteins or enzyme activities, assays for specific expression products including protein or RNA or specific RNA splice variants and in situ hybridization. Nucleic acid expression product levels may be normalized to an internal standard such as total mRNA or the expression level of a particular CRISPR sequence that is known only to be affected in special cases.
In preferred embodiments of the present invention, the expression of the CRISPR sequences or individual spacer sequences of the CRISPR sequences may be determined by microarray analysis using microarrays harboring probes that are able to target the CRISPR sequences as set forth in any of SEQ ID NO: 1 - 11297, more preferably the microarrays as provided in the present invention, for example, an array comprising one or more probes that are targeting at least one non-Affymetrix CRISPR sequence, or a specific group or grouping of said CRISPR sequences as defined above. Microarray analysis begins with extracting and purifying nucleic acid from the biological sample, using methods known in the art. For expression analysis it may be advantageous to extract and/or purify RNA from DNA. It may further be advantageous to extract and/or purify mRNA from other forms of RNA such as tRNA and rRNA. Especially useful is RNA- sequencing with which reliable quantification of transcripts can be measured (see e.g. Conesa, A. et al, 2016, Genome B1Ology201617: 13, DOI: 10.1186/sl3059-016-0881-8).
Purified nucleic acid may further be labeled with a fluorescent, radionuclide, or chemical label such as biotin or digoxin for example by reverse transcription, PGR, ligation, chemical reaction or other techniques. The labeling can be direct or indirect which may further require a coupling stage. The coupling stage can occur before hybridization, for example, using aminoallyl-UTP and NHS amino-reactive dyes (like cyanine dyes) or after, for example, using biotin and labeled streptavidin. The modified nucleotides (e.g. at a 1 aaUTP: 4 TTP ratio) are added enzymatically at a lower rate compared to normal nucleotides, typically resulting in 1 every 60 bases (measured with a spectrophotometer). The aaDNA may then be purified with, for example, a column or a diafiltration device. The aminoallyl group is an amine group on a long linker attached to the nucleobase, which reacts with a reactive label (e.g. a fluorescent dye).
The labeled samples may then be mixed with a hybridization solution which may contain SDS, SSC, dextran sulfate, a blocking agent (such as COT1 DNA, salmon sperm DNA, calf thymum DNA, PolyA or PolyT), Denhardt's solution, formamine, or a combination thereof. The probe is a fragment of DNA or RNA of variable length, as defined herein,, which is used to detect in DNA or RNA samples the presence of the CRISPR nucleotide sequences (the target) that are complementary to the sequence in the probe. The probe thereby hybridizes to single-stranded nucleic acid (DNA or RNA) whose base sequence allows probe-target base pairing due to complementarity between the probe and target. The labeled probe is first denatured (by heating or under alkaline conditions) into single DNA strands and then hybridized to the target DNA.
To detect hybridization of the probe to its target sequence, the probe is tagged (or labeled) with a molecular marker; commonly used markers are 32P or digoxigenin, which is nonradioactive antibody-based marker. DNA sequences or RNA transcripts that have moderate to high sequence similarity to the probe are then detected by visualizing the hybridized probe via autoradiography or other imaging techniques. Detection of sequences with moderate or high similarity depends on how stringent the hybridization conditions were applied— high stringency, such as high hybridization temperature and low salt in hybridization buffers, permits only hybridization between nucleic acid sequences that are highly similar, whereas low stringency, such as lower temperature and high salt, allows hybridization when the sequences are less similar. Hybridization probes used in DNA microarrays refer to DNA covalently attached to an inert surface, such as coated glass slides or gene chips, and to which a mobile cDNA target is hybridized. This mix may then be denatured by heat or chemical means and added to a port in a microarray. The holes may then be sealed and the microarray hybridized, for example, in a hybridization oven, where the microarray is mixed by rotation, or in a mixer. After an overnight hybridization, non-specific binding may be washed off (e.g. with SDS and SSC). The microarray may then be dried and scanned in a special machine where a laser excites the dye and a detector measures its emission. The image may be overlaid with a template grid and the intensities of the features (several pixels make a feature) may be quantified Various kits can be used for the amplification of nucleic acid and probe generation of the subject methods. Examples of kit that can be used in the present invention include but are not limited to Nugen WT-Ovation FFPE kit, cDNA amplification kit with Nugen Exon Module and Frag/Label module. The NuGEN WT-Ovation™ FFPE System V2 is a whole transcriptome amplification system that enables conducting global gene expression analysis on the vast archives of small and degraded RNA derived from FFPE samples. The system is comprised of reagents and a protocol required for amplification of as little as 50 ng of total FFPE RNA. The protocol can be used for qPCR, sample archiving, fragmentation, and labeling. The amplified cDNA can be fragmented and labeled in less than two hours for GeneChip® 3' expression array analysis using NuGEN's FL-Ovation™ cDNA Biotin Module V2. For analysis using Affymetrix GeneChip® Exon and Gene ST arrays, the amplified cDNA can be used with the WT-Ovation Exon Module, then fragmented and labeled using the FL-Ovation™ cDNA Biotin Module V2. For analysis on Agilent arrays, the amplified cDNA can be fragmented and labeled using NuGEN's FL-Ovation™ cDNA Fluorescent Module. More information on Nugen WT- Ovation FFPE kit can be obtained on the world-wide web at
nugeninc.com/nugen/index.cTm/products/amplification-systems/wt-ovation-ffpe/.
In some embodiments, Ambion WT-expression kit can be used. Ambion WT-expression kit allows amplification of total RNA directly without a separate ribosomal RNA (rRNA) depletion step. With the Ambion® WT Expression Kit, samples as small as 50 ng of total RNA can be analyzed on Affymetrix® GeneChip® Human, Mouse, and Rat Exon and Gene 1.0 ST Arrays. In addition to the lower input RNA requirement and high concordance between the
Affymetrix® method and TaqMan® real-time PCR data, the Ambion® WT Expression Kit provides a significant increase in sensitivity. For example, a greater number of probe sets detected above background can be obtained at the exon level with the Ambion® WT
Expression Kit as a result of an increased signal-to-noise ratio. Ambion WT-expression kit may be used in combination with additional Affymetrix labeling kit. In some embodiments, AmpTec Trinucleotide Nano mRNA Amplification kit (6299-A15) can be used in the subject methods. The ExpressArt® TRinucleotide mRNA amplification Nano kit is suitable for a wide range, from 1 ng to 700 ng of input total RNA. According to the amount of input total RNA and the required yields of aRNA, it can be used for 1-round (input >300 ng total RNA) or 2-rounds (minimal input amount 1 ng total RNA), with aRNA yields in the range of >1() pg. Amp Tec's proprietary TRinucleotide priming technology results in
preferential amplification of mRNAs (independent of the universal eukaryotic 3'-poly(A)- sequence), combined with selection against rRNAs. More information on AmpTec
Trinucleotide Nano mRNA Amplification kit can be obtained on the world-wide web at amp- tec.com/products.htm. This kit can be used in combination with cDNA conversion kit and Affymetrix labeling kit.
The raw data may then be normalized, for example, by subtracting the background intensity and then dividing the intensities making either the total intensity of the features on each channel equal or the intensities of a reference sequence and then the t-value for all the intensities may be calculated. More sophisticated methods include z-ratio, loess and lowess regression and RMA (robust multichip analysis) for Affymetrix chips.
The simplest approach to quantification is to aggregate raw counts of mapped reads using programs such as HTSeq-count (Anders, S. et al., 2015, Bioinformatics;31: 166-9) or leatureCounts [Liao, Y et al.,2014, Bioinformatics;30:923-30]. This gene-level (rather than transcript-level) quantification approach utilizes a gene transfer format (GTF) file containing the genome coordinates of exons and genes, and often discard multireads. Raw read counts alone are not sufficient to compare expression levels among samples, as these values are affected by factors such as transcript length, total number of reads, and sequencing biases. The measure RPKM (reads per kilobase of exon model per million reads) (Mortazavi, A. et al., 2008, Nat. Methods, 5: 1-8) is a within-sample normalization method that will remove the feature-length and library-size effects. This measure and its subsequent derivatives FPKM (fragments per kilobase of exon model per million mapped reads), a within-sample normalized transcript expression measure analogous to RPKs, and TPM (transcripts per million) are the most frequently reported RNA-seq gene expression values. It should be noted that RPKM and FPKM are equivalent for SE reads and that FPKM can be converted into TPM using a simple formula (Pachter, L., arXiv.org. 2011. http://arxiv.org/abs/1104.3889). The dichotomy of within-sample and between-sample comparisons has led to a lot of confusion in the literature. Correcting for gene length is not necessary when comparing changes in gene expression within the same gene across samples, but it is necessary for correctly ranking gene expression levels within the sample to account for the fact that longer genes accumulate more reads.
Furthermore, programs such as Cufflinks that estimate gene length from the data can find significant differences in gene length between samples that cannot be ignored. TPMs, which effectively normalize for the differences in composition of the transcripts in the denominator rather than simply dividing by the number of reads in the library, are considered more comparable between samples of different origins and composition but can still suffer some biases. These must be addressed with normalization techniques such as TMM. Several sophisticated algorithms have been developed to estimate transcript-level expression by tackling the problem of related transcripts' sharing most of their reads.
Cufflinks (Trapnell, C. et al., 2010, Nat. Bioteehnol. 28:511-5) estimates transcript expression from a mapping to the genome obtained from mappers such as TopHat using an expectation- maximization approach that estimates transcript abundances. This approach takes into account biases such as the non-uniform read distribution along the gene length. Cufflinks was designed to take advantage of PE reads, and may use GTF information to identify expressed transcripts, or can infer transcripts de novo from the mapping data alone. Algorithms that quantify expression from transcriptome mappings include RSEM (RNA-Seq by Expectation Maximization) (Li, B. and Dewey, C.N. 2011, BMC Informatics, 12:323), eXpress (Roberts, A. and Pachter, L., 2013, Nat. Methods 10:71-3), Sailfish (Anders, S. et al., supra) and kallisto (littps: iiorpacfaler,wo
kallisto/) among others. These methods allocate multi-mapping reads among transcript and output within-sample normalized values corrected for sequencing biases (Roberts, A. et al., 2011, Genome Biol. 12:R22). Additionally, the RSEM algorithm uses an expectation maximization approach that returns TPM values (Li and Dewey, supra). NURD (Ma, X. and Zhang, X., 2013, BMC Bioinformatics 11:94) provides an efficient way of estimating transcript expression from SE reads with a low memory and computing cost. Overexpression is then defined as an expression of at least twice the normal level, preferably ate least three times the normal level and most preferably at least four times the normal level. The normal level is the average level of expression of the same nucleotide sequence under normal (i.e. healthy conditions) in a large number of subjects. If the value of this normal level is not available, it may be replaced by the expression level of a reference sequence. Underexpression then is defined as less than 70% of the normal expression level, preferably less than 50%, more preferably less than 30% of the normal level of expression of said sequence (or of the expression of a reference sequence).
The results of the expression assays may indicate a sample as negative (disease or condition free), ambiguous or suspicious (suggestive of the presence of a disease or condition), diagnostic (positive diagnosis for a disease or condition), or non-diagnostic (providing inadequate information concerning the presence or absence of the disease or condition). The diagnostic results may also provide a score indicating for example, the severity or grade of the disease or condition, or the likelihood of an accurate diagnosis. In some cases, the diagnostic results may be indicative of a particular type or stage of a disease, or condition. The diagnostic results may inform a particular treatment or therapeutic intervention for the type or stage of the specific disease or condition diagnosed. In some embodiments, the results of the assays performed may be entered into a database.
As follows from the Examples, a disease can be assessed by assaying for the under- and/or overexpression of CRISPR sequences having specific SEQ ID NO: as is provided in the Examples below. As is demonstrated herein in some cases (detection of the over- or
underexpression of only) one CRISPR is sufficient to form a basis for diganosis while in other cases it may be necessary or advantageous to use a profile of different CRISPR sequences. Also, some of the CRISPR sequences can be used in both approaches: as is demonstrated in Example 15 and 16 a CRISPR (or a profile/grouping of CRISPR sequences) can be used to diagnose for cancer in general, but the same CRISPR (or CRISPR profile/grouping) can be used to specifically diagnose for a particular form of cancer..
EXAMPLES
Example 1 CRISPRs are identified in horizontal acquired genes that reside in the human genome. From CRISP et al (Genome Biol. 2015 Mar 13; 16:50), the validated HGT acquired gene dataset was used to study whether the human genome harbors, CRISPRs, CRISPR - associated genes or CRISRP-Cas systems. We analysed 146 HGT genes and identified by making use of the CRISPRFinder software 23 genes that harbored a CRISPR of which one was accompanied with a CRISPR-associated gene cmrl (Table 1). Eighteen found their origin in protists, three in bacteria and two in plants. In 52 human genes that were of a viral origin 16, four CRISPRs were identified (Table 1). The human genome thus harbors by horizontal gene transfer acquired CRISPRs or even a CRISPR with a CRISPR-associated genes.
Example 2 The affymetrix U133 plus 2 probe and probe regions overlap or match with human CRISPR sequences. For this analyses the required information about the non-coding probe regions and probe positions were downloaded from
http://www.aff ymetrix.com/estore/catalog/131455/AFFY/Human+
Genome+U133+Plus+2.()+Array#l_3. The U133 plus 2 non-coding probe regions and probe coordinates (25bp) (Chrl:start-end positions) match with the GRCh37/Hgl9 genome. These were uploaded as a BED file and set to GRCh Hgl9 in Galaxy (https://bioinf- galaxian.erasmusmc.nl/galaxy/). The human CRISPR (Chrl:start-end positions) were also uploaded as a BED file in Galaxy. By making use of the intersect interval option allowed the retrieval of; probe positions that exactly match the human CRISPR positions (Table 2) or probe regions that overlapped the human CRISPR positions (Table 3).
Example 3 Probe 233266_at resembling a human CRISPR is a diagnostic marker for acute asthma attacks. For this analyses dataset GDS3615 was used that can be obtained from https://www.ncbi.nlm.nih.gov/ sites/GDSbrowser?acc=GDS3615. The publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37 (also known as hgl9). The human CRISPRs exactly matching or overlapping with the affymetrix U133 plus 2 microarray probes were joined as a single file resulting in 155 human CRISPR corresponding affymetrix U133 plus 2 probes (for which no clear annotation was available) showing the probe ID and chromosome start end positions of the human CRISPR (Table 4). This file was also uploaded as a BED file dataset and adapted to the human assembly GRCh37. Using the galaxy join two ddaattaasseett ooppttiioonn rreessuulltteedd iinn 115555 pprroobbeess tthhaatt rreesseemmbbllee hhuummaann CCRRIISSPPRRss ffoorr wwhhiicchh tthhee RRNNAA eexxpprreessssiioonn ccoouulldd bbee rreettrriieevveedd ffrroomm ddaattaasseett GGDDSS33661155.. IInn tthhiiss ddaattaasseett iinnffoorrmmaattiioonn wwaass oobbttaaiinneedd ffrroomm ppeerriipphheerraall bblloooodd m moonnoonnuucclleeaarr cceellllss ffrroomm cchhiillddrreenn wwiitthh aann aaccuuttee aasstthhmmaa aattttaacckk dduurriinngg eexxaacceerrbbaattiioonn aanndd aatt ssuubbsseeqquueenntt ccoonnvvaalleesscceennccee ((TTaabbllee 55)).. TThhee ccoonnvvaalleesscceennccee ppaattiieennttss aaxxee nnuummbbeerreedd aass GGSSMM 11001128899.. GGSSMM440011229911,, GGSSMM440011229933,, GGSSMM - Κ10Π 1229955.. GGSSMM440011229977 aanndd tthhee aaccuuttee aasstthhmmaa ppaattiieennttss aarree nnuummbbeerreedd aass GGSSMM440011229900,, GGSSMM 110011229922.. GGSSMM440011229944,, GGSSMM440011229966,, GGSSMM440011229988..
TThhee eexxcceell ffiillee wwiitthh pprroobbeess rreesseemmbblliinngg hhuummaann CCRRIISSPPRRss aanndd RRNNAA eexxpprreessssiioonn vvaalluueess wwaass uuppllooaaddeedd
Figure imgf000086_0001
uussiinngg MMoorrpphheeiiiiss wwhhiicchh rreessuulltteedd iinn the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that probe 233266_at is a marker for acute asthma attacks that require hospitalization and were triggered by a viral infection (Fig 2A). The RNA expression values detected by probe 233266_at obtained from peripheral blood mononuclear cells from children with an acute asthma attack during exacerbation (n=5) and at subsequent convalescence (n=5) were added in Graphpad prism to generate a scattergram (Fig 2B). This example shows that probe 233266_at resembling a human
CRISPR with Patent ID: 6326 is useful as a diagnostic marker to separate acute from convalescence asthma patients.
Example 4 probe 242924_at resembling a human CRISPR is a marker for chronic B-lymphocytie leukemia. For this analyses dataset GSE26725 was used that can be obtained from https://www.ncbi.nlm.nih.gov/sites/ GDSbrowser?acc=GSE26725. The publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37. The file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 3). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GSE26725 (Table 6). In this dataset information was obtained about the transcriptome from peripheral blood mononuclear cells obtained from chronic B-lymphocytic leukemia (CBLL) patients and healthy donors. The healthy patients are GSM658010, GSM658011, GSM658012, GSM658013, GSM658014 and the chronic B-lymphocytic leukemia patients are GSM658015, GSM658016, GSM658017, GSM658018, GSM658019, GSM658020, GSM658021, GSM658022, GSM658023, GSM658024, GSM658025, GSM658026.
The excel file with U133 plus 2 microarray probes resembling human CRISPRs and
RNA expression values was uploaded at https://sofiware.broadinsiiii te.org/GEiNE-E/ in Morpheus which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that probe 242924_at is a marker for chronic B-lymphocytic leukemia (Fig 3A). The RNA expression values detected by probe 242924_at (SEQ ID NO: 9342, see Table 4) obtained from peripheral blood mononuclear cells from healthy controls (n=5) and chronic B-lymphocytic leukemia (n=12) were added in Graphpad prism to generate a scattergram (Fig 3B). This example shows that probe 242924_at resembling a human CRISPR with Patent ID: 9342 is useful as a diagnostic marker to separate acute from convalescence asthma patients.
Example 5 probe 234574_at resembling human CRISPRs is a marker for a Francisella infection. For this analyses dataset GDS3298 was used and can be obtained from https://www.ncbi.nlm.nih.gov/sites/GDSbrowser? aec=GI)S3298. The publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray
preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset and was adapted for the human assembly GRCh37. The file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted for the human assembly GRCh37 (Table 4). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS3298 (Table 7). In this dataset information was obtained about the transcriptome from peripheral blood mononuclear cells that were infected with the bacterial species F. tularensis subsp. Novicida or F. tularensis subsp. Tularensis or left uninfected. Untreated blood monocytes axe depicted as GSM305430, GSM305432, GSM305434, GSM305436, GSM305438, GSM305440. Blood monocytes infected with F. tularensis subsp. Novicida or F. tularensis subsp. Tularensis are depicted as GSM305429, GSM305431, GSM305433, GSM305435 or GSM305437, GSM305439, GSM305441, GSM305442, respectively.
The excel file with U133 phis 2 microarray probes resembling human CRISPRs and
RNA expression values was uploaded at htt s : //soft w are .
broaclinstifate.org/GENE-E/ in Morpheus, which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that probe 234574_at is a marker for a Francisella infection (Fig 4A). The RNA expression values detected by probe 234574_at (SEQ ID NO: 8709, see Table 4) obtained from uninfected peripheral blood mononuclear cells (n=6) and Francisella infected (n=8) were added in Graphpad prism to generate a scattergram (Fig 4B). This example shows that probe 234574_at resembling a human CRISPR with Patent ID: 8709; 8713; 3664; 8711; 8712; 8714 is useful as a diagnostic marker to separate uninfected from Francisella infected patients.
Example 6 probe 234643_x_at resembling human CRISPRs is a marker for hepatocellular carcinoma. For this analyses dataset GDS4882 was used that can be obtained from https://www.ncbi.nlm.nih.gov/sites/GDSbrowser? acc=GDS4882. The publication corresponding to this dataset harbors all the information wTith respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37. The file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 4). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS4882 (Table 8). In this dataset information was obtained about the transcriptome from peripheral blood mononuclear cells obtained from hepatocellular carcinoma (HCC) patients were compared to healthy controls.. HCC samples are represented by GSM 1200294,
GSM 1200295, GSM1200296, GSM1200297, GSM1200298, GSM1200299, GSM1200300, GSM 1200301. GSM1200302, GSM1200303 healthy control samples are represented by GSM1200304, GSM1200305, GSM1200306, GSM1200307, GSM1200308, GSM1200309, GSM 1200310, GSM1200311, GSM1200312 and GSM1200313. The excel file with U133 plus 2 micro-array probes resembling human CRISPRs and RNA expression values was uploaded at t-1pe://¾oftware.broadinetitiite,org/GENE-E in Morpheus which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that probe 234643_x_at is a marker for HCC (Fig 5A). The RNA expression values detected by probe 234643_x_at obtained from peripheral blood mononuclear cells from healthy controls (n=10) and HCC (n=10) were added in Graphpad prism to generate a scattergram (Fig 5B). This example shows that probe 234643_x_at resembling human CRISPRs with Patent IDs: 7929; 7930; 7931; 7932; 7933; 7934; 7935; 7936 is useful as a diagnostic marker to separate HCC from healthy control patients.
Example 7 probe 234095_at resembling a human CRISPR is a marker for high-grade prostate cancer. For this analyses dataset GDS5072 was used that can be obtained from https://www.ncbi.nlm.nih.gov/sites /GDSbrowser?acc=GDS5072. The
publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37. The file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 4). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS5072 (Table 9). In this dataset information was obtained from high-grade prostate cancer tissue obtained from prostate cancer patients with high Gleason scores the RNA expression was compared to normal prostate tissue. Prostate tissue samples obtained from prostate cancer patients with a high Gleason score are represented by GSM1095883, GSM1095886 or GSM1095877, GSM1095878, GSM1095879, GSM1095880, GSM1095881, GSM1095882, GSM1095884, GSM 1095885 and was compared to healthy prostate tissue represented by GSM1095876.
The excel file with U133 plus 2 microarray probes resembling human CRISPRs and RNA expression values was uploaded at ht.tpe://.software.broadinetitiite,org/GENE-E in Morpheus, which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that probe 234095_at is a potential marker for high-grade prostate cancer tissue (Fig 6). This is based on the finding that the RNA expression requires a value of 478.4 or higher in normal prostate tissue (n=l) in comparison to high-grade prostate cancer tissue with RNA expression values of 163.8 and lower. This example shows that probe 234095_at resembling human CRISPRs with Patent ID: 8566 could be useful as a diagnostic marker to separate healthy prostate tissue from high-grade prostate cancer tissue obtained from prostate cancer patients with high Gleason scores.
Example 8 probe 221625_at resembling human CRISPRs is a marker for chronic pediatric immune thrombocytopenia. For this analyses dataset GDS5017 was used that can be obtained from
https://www.ncbi.nlm.nih.gov/sites/GDSbrowser?acc=GDS5017. The publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U 133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37. The file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 4). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS5017 (Table 10). In this dataset information was obtained about the transcriptome from Newly diagnosed and chronic pediatric immune thrombocytopenia using peripheral blood T-cells. Newly diagnosed immune thrombocytopenia children are represented by GSM1141222, GSM1141223, GSM1141224, GSM l 1 11225. GSM1141226, GSM1141227, SM1141228 and were compared to children with chronic immune thrombocytopenia represented by GSM1141229, GSM 1 1 1 1230. GSMl 141231, GSM l 1 1 1232. GSM l 1 1 1233 and GSM l 1 1 1231.
The excel file with U133 plus 2 microarray probes resembling human CRISPRs and RNA expression values was uploaded at h tip s ://sof ί w are .broadins ii lute . org/GENE - El in Morpheus which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that probe 221625_at is a marker for chronic pediatric immune thrombocytopenia (Fig 7A). The RNA expression values detected by probe 234643_x_at obtained from peripheral blood T cells from newly diagnosed pediatric immune thrombocytopenia patients (n=7) and chronic pediatric immune thrombocytopenia patients (n=6) were added in Graphpad prism to generate a scatter gram (Fig 7B). This example shows that probe 221625_at resembling human
CRISPRs with Patent IDs: 8753 and 8757 is useful as a diagnostic marker to separate newly from chronic pediatric immune thrombocytopenia patients.
Example 9 probe 1566549_at resembling human CRISPRs can be used as a diagnostic marker for prostate cancer progression. For this analyses dataset GDS1439 was used that can be obtained from
https://www.ncbi.nlm.nih.gov/sites/GDSb rowser?acc=GDS 1439. The publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37. The file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 4). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS1439 (Table 11). In this dataset information was obtained about the transcriptome from patients with prostate cancer tissue being benign, primary or metastatic. Tumor tissue that is benign is represented by
GSM 7-1875, GSM74876, GSM74877, GSM74878, GSM74879, GSM74880, tissue that is primary is represented by GSM74881, GSM74882, GSM74883, GSM74884, GSM74885, GSM74886, GSM74887 and prostate tumor tissue that is metastatic is represented by
GSM74888, GSM74889, GSM74890, GSM74891, GSM74892, GSM74893.
The excel file with U133 plus 2 microarray probes resembling human CRISPRs and RNA expression values was uploaded at https://software.broadinstitute org/GENE-E/ in Morpheus which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that probe 1566549_at is a marker for metastatic prostate cancer tissue (Fig 8A). The RNA expression values detected by probe 1566549_at obtained from benign and primary prostate cancer (n=13) and metastatic prostate cancer (n=6) were added in Graphpad prism to generate a scattergram (Fig 8B). This example shows that probe 1566549_at resembling a human CRISPR with Patent IDs: 9471 is useful as a diagnostic marker to separate benign and primary prostate cancer tumors from metastatic tumors.
Example 10 probe 234490_at resembling human CRISPRs can be used as a diagnostic marker for fertility based on sperm health. For this analyses dataset GDS2697 was used that can be obtained from
https://www.ncbi.nlm. nih.gov/sites/GDSb rowser?acc=GDS2697. The publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37. The file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 4). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS2697 (Table 12). In this dataset information was obtained about the transcriptome from patients with het teratozoospermia and healthy sperm. Normal sperm cells are represented by GSM158463, GSM158464, GSM 15 105, GSM158466, GSM158467, GSM158468, GSM158469, GSM158470, GSM 158-171. GSM158472, GSM 158473, GSM158474, GSM158475 and teratozoospermia is represented by GSM158476, GSM158477, GSM158478, GSM158479, GSM158480, GSM 158181 , GSM158482, GSM158483. The excel file with U133 plus 2 microarray probes resembling human CRISPRs and RNA expression values was uploaded at h ί tp s : softw a re , br o a di nstit u te.org/GENE- E/ in Morpheus which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that probe 234490_at is a marker for teratozoospermia (Fig 9A). The RNA expression values detected by probe 234490_at obtained from normal sperm (n=13) and teratozoospermia (n=8) were added in Graphpad prism to generate a scattergram (Fig 9B). This example shows that probe 234490_at resembling human CRISPRs with Patent IDs: 3664; 8711; 8712; 8713; 8714 is useful as a diagnostic marker for teratozoospermia. Example 11 probe 217152_at resembling human CRISPRs can be used as a diagnostic marker to distinguish between acute and latent tuberculosis. For this analyses dataset GDS4966 was used that can be obtained from
https://www.ncbi. nlm.nih.gov/sites/GDSbrowser?acc=GDS4966. The publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37. The file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 4). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS4966 (Table 13). In this dataset information was obtained about the transcriptome from patients with active pulmonary tuberculosis (PTB), latent TB infection (LTBI) and healthy controls. Active pulmonary tuberculosis patients are represented by GSM1327526, GSM1327533, GSM1327531,
GSM1327540, GSM1327529, GSM1327527, GSM1327530, GSM1327535, GSM1327528 latent tuberculosis patients by GSM1327539, GSM1327551, GSM1327547, GSM1327545,
GSM1327543, GSM1327548 and healthy controls by GSM1327541, GSM1327542,
GSM1327550, GSM1327546, GSM1327549, GSM1327544.
The excel file with U133 plus 2 microarray probes resembling human CRISPRs and RNA expression values was uploaded at https://software.broadinstifrute.org GENE-'E in
Morpheus which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that probe 217152_at is a marker for acute tuberculosis (Fig 10A). The RNA expression values detected by probe 217152_at obtained from active tuberculosis patients (n=19) and latent tuberculosis and healthy controls (n=12) were added in Graphpad prism to generate a scattergram (Fig 10B). This example shows that probe 217152_at resembling human
CRISPRs with Patent IDs: 8179; 8190; 8191 is useful as a diagnostic marker for active tuberculosis.
Example 12 probe 1557539_at resembling human CRISPRs can be used as a diagnostic marker for tibial muscular dystrophy. For this analyses dataset GDS4843 was used that can be obtained from
https://www.ncbi.nlm.nih.gov/sites/GDSb rowser?acc=GDS4843. The publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37. The file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 4). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS4843 (Table 14). In this dataset information was obtained about the transcriptome from patients with tibial muscular dystrophy (TMD) and healthy controls. Tibial muscular dystrophy patients are represented by GSM1050260, GSM105026L GSM105Q262, GSM105Q263, GSM105Q264, GSM1050265, GSM1050266 and healthy controls by GSM 1050270, GSM1050271, GSM1050272,
GSM1050273, GSM1050274. The excel file with U133 plus 2 microarray probes resembling human CRISPRs and RNA expression values was uploaded at
https ://software . broa dmsti u te .or g/G KX - B/ in Morpheus which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that probe 1557539_at is a marker for tibial muscular dystrophy (Fig 11A). The RNA expression values detected by probe 1557539_at obtained from tibial muscular dystrophy patients (n=7) and healthy controls (n=5) were added in Graphpad prism to generate a scattergram (Fig 11B). This example shows that probe 1557539_at resembling a human CRISPR with Patent ID: 6939 is useful as a diagnostic marker for tibial muscular dystrophy.
Example 13 probes resembling human CRISPRs can be used as a to distinguish between (un)differentiated embryonic stem cells. For this analyses dataset GDS5408 was used that can be obtained from
https://www.ncbi. nlm.nih.gov/sites/GDSbrowser?acc= GDS5408. The publication
corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCh37. The file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 4). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS5408 (Table 15). In this dataset information was obtained about the transcriptome from undifferentiated and differentiated embryonic stem cells. Differentiated embryonic stem cell are represented by GSM1309419, GSM1309420, GSM1309423, GSM1309424 and
undifferentiated by GSM1309417, GSM1309418, GSM1309421, GSM1309422. The excel file with U133 plus 2 microarray probes resembling human CRISPRs and RNA expression values was uploaded at h t t s : //soft w re . br o a dinsti a te .or /G E E - E/ in Morpheus which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that different probes resembling human CRISPRs can be used to distinguish between (un)differentiated embryonic stem cells (Fig 12). Probes that would be able to distinguish in most cases are: 1554007_at, 15541()8_at, 1557339_at, 1558275_at, 1559151_at, 210679_x_at, 214979_at, 217152_at, 23046 l_s_at, 232344_at.(respectively SEQ ID NO: 5465, 1423, 68, . 7865, 7648, 6872, 8273, 8190, 8678, and 3215). In these cases SEQ ID NO: 5465 and 68 are underexpressed in undifferentiated cells, whereas the rest of the sequences are overexpressed in these cells. In the undifferentiated cells, the expression of these sequences is just the opposite.
Example 14 probes resembling human CRISPRs can be used as a to distinguish between influenza (un)infected bronchial epithelial cells. For this analyses dataset GDS4855 was used that can be obtained from
https://www.ncbi.nlm. nih .gov/sites/GDSb rowser?acc=GDS4855. The publication corresponding to this dataset harbors all the information with respect to the methods, such as study design, sample collection, RNA analyses, Affymetrix U133 plus 2 microarray preparation, data analyses, further validation of the obtained data and statistical analyses. For our analyses the probe identification numbers, expression values and sample IDs were retrieved from this dataset copied in a notepad file and uploaded in Galaxy as a BED file dataset adapted to the human assembly GRCb.37. The file with the 155 human CRISPR resembling probes was also uploaded as a BED file dataset and adapted to the human assembly GRCh37 (Table 4). Using the join two dataset option resulted in 155 probes that resemble human CRISPRs for which the RNA expression could be retrieved from dataset GDS4855 (Table 16). In this dataset information was obtained about the transcriptome from uninfected and H1N1 infected bronchial epithelial cells. Uninfected bronchial epithelial cells are represented by
GSM1179373, GSM 1 1 79371, GSM1179375 and H 1N1 infected bronchial epithelial cells by GSM1179364, GSM1179365, GSM1179366, GSM1179367, GSM1179368, GSM1179369, GSM1179370, GSM117937L GSM1179372. The excel file with U133 plus 2 microarray probes resembling human CRISPRs and RNA expression values was uploaded at
https://software.broadii stitute.org/GENE-E/ in Morpheus which resulted in the generation of a heatmap showing in red an increase in expression and in blue a decrease in RNA expression compared to the mean of each expression value obtained for each probe resembling a human CRISPR. This lead to the identification that different probes resembling human CRISPRs can be used to distinguish between uninfected and H 1N1 infected bronchial epithelial cells (Fig 13). Probes that would be able to distinguish in most cases are: 15540()7_at, 1570215_at,
205800_at, 210723_at, 231888_at, 241468_at, 243973_at.(respectively SEQ ID NO: 5465, 7873,. 998, 1515, 9358, 8407, 8190, and 8861). In these cases SEQ ID NO: 5465, 8190 and 8861 are underexpressed in uninfected cells, whereas the rest of the sequences are
overexpressed in these cells. In the infected cells, the expression of these sequences is just the opposite.
Example 15 123 unique Mitranscriptome transcripts resembling or overlapping a human CRISPR can be used as a diagnostic marker for 11 different cancers. For this analyses the publicly available Mitranscriptome datasets were used http I //w w ,na ture .corn/articles/ng.3192. MiTranscriptome is a large-scale ab initio
transcriptome meta- assembly from 6471 RNA-Seq libraries using Tophat
Figure imgf000096_0001
and Cufflinks (http://cole-trapnell- ί ah . i U ;s ;l : . io/c fflin ks/) . RNA-sequencing datasets were obtained from The Cancer Genome Atlas (TCGA), the ENCODE Project, the Michigan Center for Translational Pathology, and other published sources (http ;/ ww .natoe.com/articles/ng.3192) . The entire
MiTranscriptome dataset was converted to a ranged summarized experiment to ease analysis using the R statistical platform (https://www.r-project.org ). To discover potential diagnostic human CRISPR targets in cancer the predicted human CRISPRs were overlapped with MiTranscriptome transcripts based on their genomic coordinates using
Figure imgf000097_0001
genomic ranges, a
Bioconductor software tool. Differential analysis of the MiTranscriptome transcripts (beta) which overlapped with the human CRISPRs was performed using limma on log2-transformed FPKM (plus pseudocount of 1) using a disease cohort- specific normal versus cancer/metastatic design and Benjamini-Hochberg correction. Additional heuristic filtering was performed with the following criteria: absolute) logFC >= 0.5 and an adjusted p-value (BH) <= 0.05.
Differential analysis was performed only on MiTranscriptome disease -cohorts with >=10 normal & >= tumor/metastatic samples, filtering 59 disease -cohorts of the 70 available cohorts available. After filtering the available MiTranscriptome cohorts (n=70), removing cohorts with less than 10 normal and 10 cancer samples, we were left with 11 disease-cohorts (Bladder urothelial carcinoma, Breast carcinoma, Gastric carcinoma, Head neck squamous cell carcinoma, Kidney carcinoma, Kidney chromophobe, Liver hepatocellular carcinoma, Lung adenocaxcinoma, Lung squamous cell carcinoma, Lung squamous cell carcinoma and Thyroid carcinoma) (Fig. 14 and Table 18). Of the human CRISPR-overlapping MiTranscriptome transcripts, 226 transcripts were found to be differentially expressed (logFC >= 0.5, adjusted p-value <= 0.05) between normal and tumor/metastatic tissue in one or multiple cohorts
(Table 17). These transcripts harbor diagnostic potential to detect one or multiple numbers of the 11 cancers when the RNA expression value as measured by RNA sequencing is higher or lower than the AveExpr depending on the LogFc and tissue controls (Table 17).
Example 16 123 unique M itra n scr i ptome transcripts resembling or overlapping a human CRISPR that can be used as a diagnostic marker in cancer.
For this analyses the publicly available Mitranscriptome datasets were used
htt ://w w ,n ture .corn/articles/ng.3192. MiTranscriptome is a large-scale ab initio
transcriptome meta-assembly from 6471 RNA-Seq libraries using Tophat
Figure imgf000097_0002
and Cufflinks (http://cole-trapnell-
I ah . i U ;s ;l : . io/c fflin ks/) . RNA-sequencing datasets were obtained from The Cancer Genome Atlas (TCGA), the ENCODE Project, the Michigan Center for Translational Pathology, and other published sources (http ;/ ww .natoe.coni/articlee ng. ¾ 192) . The entire
MiTranscriptome dataset was converted to a ranged summarized experiment to ease analysis using the R statistical platform (https://vmw.r-proiect.org/). To discover potential diagnostic human CRISPR targets in cancer the predicted human CRISPRs were overlapped with MiTranscriptome transcripts based on their genomic coordinates using (I tps://bioeori ductor.org/pack ge¾/reiease/bioc/hti¾lA jenomicRanges.html) genomic ranges, a Bioconductor software tool. Differential analysis of the MiTranscriptome transcripts (beta) which overlapped with the human CRISPRs was performed using limma on log2-transformed FPKM (plus pseudocount of 1) using a disease cohort- specific normal versus cancer/metastatic design and Benjamini-Hochberg correction. Additional heuristic filtering was performed with the following criteria: absolute) logFC >= 0.5 and an adjusted p-value (BH) <= 0.05 (Table 19). Differential analysis was performed only on MiTranscriptome disease -cohorts with >=10 normal & >= tumor/metastatic samples, filtering 59 disease -cohorts of the 70 available cohorts available. After filtering the available MiTranscriptome cohorts (n=70), removing cohorts with less than 10 normal and 10 cancer samples, we were left with 11 disease-cohorts (Bladder urothelial carcinoma, Breast carcinoma, Gastric carcinoma, Head neck squamous cell carcinoma, Kidney carcinoma, Kidney chromophobe, Liver hepatocellular carcinoma, Lung adenocarcinoma, Lung squamous cell carcinoma, Lung squamous cell carcinoma and Thyroid carcinoma) (Fig. 15 and Table 18). 123 Mitranscriptome transcripts that resemble a human CRISPR or overlapped a human CRISPR (Table 20) were found to be differentially expressed between normal and tumor/metastatic tissue in only a single cohort (cohort-specific) (Fig. 15 and Table 19). These transcripts harbor diagnostic potential to detect one of the 11 cancers when the RNA expression value as measured by RNA sequencing is higher or lower than the AveExpr depending on the LogFc and tissue controls (Table 19).
Example 17 Human CRISPRs reside in transcription factor binding sites and DNase 1 hypersensitive sites. Since the human CRISPRs were found to be actively expressed we analysed whether the human CRISPRs would reside in genomic regions in which transcription factors are known to bind or are sensitive to DNase 1. For this purpose we downloaded the transcription factor binding sites and Dnasel hypersensitive clusters BED files from Encode (http: /genome.ucsc.edit EN(.;(.)DE/do nloade.hti.nl) revealing their chromosome start and end positions. These datasets were uploaded and set to GRCh/Hgl9 in Galaxy (h tp8:/ )iomf-gajaxian.eraei¾aenK\^/gajaxy ). The human CRISPR chromosome start and end positions were also uploaded as a BED file in Galaxy. By making use of the join two dataset option allowed the retrieval of human CRISPR positions that resides in transcription factor binding sites (Fig. 16 and Table 21) and/or DNasel hypersensitive sites (Fig. 16 and Table 22). Of note are the findings that indicate that the transcription factors themselves are potential biomarkers in disease identification as reported by Kaur et al, BMC Systems Biology 2011, 5: 144 and Blobel et al., Genes & Cancer 2011, 1178-1188. Mutations in the transcription factor binding sites are reported to result in less efficient binding of a transcription factor or binding of a different transcription factors and such mutations have been linked to specific diseases as reported by Snyder et al., PNAS 2013, 9607-9612 and Fraser et al., Cell 2016, 730-741. In addition Dnase I hypersensitive sites are suggested to play a role in human disease pathologies as reported by Stamatoyannopoulos et al., Science 2012, 1190- 1195.
Example 18 Human CRISPRs harbor spacer targets in phages, plasmids and viruses. Human CRISPR spacers were uploaded in the CRISPR Target finder, a tool to identify potential CRISPR RNA targets
(ht p :/ bioanalysis .otago. ac .n¾ CR IS FRTar get/cri ¾pr analysis .html) . This led to the
identification that human CRISPR spacers harbor potential targets (protospacers)
accompanied with a PAM motif in phages, plasmids and viruses (Fig. 17 and Table 23). It is hypothesized that these CRISPR sequences are overexpressed upon infection with the relevant micro-organism and thus would serve as diagnostic tool for infection, where also the infection can be determined on a micro-organism genus or species level.
Example 19 Human CRISPRs overlap with EPCATs, non-coding RNAs, that harbor diagnostic and prognostic potential in prostate cancer. The Erasmus MC identified prostate cancer related transcripts (EPCATs), as published in Jenster et al., Oncotarget (2015). Novel long non-coding RNAs appear to be expressed differently in prostate cancer patients in comparison to control patients and thus have been identified as specific diagnostic and prognostic markers for prostate cancer. These sequences and human CRISPR chromosome start and end positions were uploaded as a BED file in Galaxy
(http.s://usegalaxy.org/). Making use of the join two dataset option allowed the retrieval of human CRISPR positions that overlapped with the Erasmus MC identified EPCATS (Table 24). It is submitted that all of these CRISPR sequences thus could be used as markers for the presence of or susceptibility for prostate cancer. In addition, EPCAT2F176, EPCAT15F849, EPCAT1F273, EPCAT3R522, EPCAT5F602 were identified as the most specific diagnostic or prognostic markers for prostate cancer. Please note that the software that was available at h t s ://sof ί w are , broadin stit te . or g/G ENE- E/ has been moved to https:/7eoit are .broadinstitute.org/morpheiis/ and
http.s://eoftware.broaclm^^ Table 1 Identification of CRISPRs and Cas genes in the human genome acquired by HGT (CRISP et al; Genome Biol.
2015 Mar 13;16:50)
Gene ID 3 CRISPR Origin of the crispr c Gene name / description d Taxon e Phyiogenetic validation
ENSG000001 1 G726 Yes Trypa osoma ccngo!er-se FRAME inmiiy monsbei 12 protist Validated
ENSG00000148444 Yes D ict y oste i i u m iasc i cu ί at u m COMM domain containing 3 protist Validated
ENSG0 0002256 M Yes Leishmania bfaziensis zinc finger protein 469 protist Not-validated shisa homoiog 9 (Xenopus
ENSGQ0000237515 Yes Trypanosoma congolense laevis) protist Not-validated ci'ockpoii-i w !' forkhoad i' !
ring finger domains, E3 ubiquitin
ENSG0 00007260 Yes Capsaspora owczarzaki ptoiein liQ.lSO protist Not-validated enoyl-CoA, hydratase/3- hydroxyacyl CoA
ENSG00000113790 Yes Capsaspora owczarzaki dehydrogenase protist Not-validated zinc hncier. RAN- bicdmg riomam
ENSGWCKJ0121988 Yes Monoslga brevicolfe cornrsinicg 3 prolis: Validated
ENSGQ0000136059 Yes Capsaspora owczarzaki viiiin-like protist Not-validated
ENSG00000 H2 20 Yes Trypanosoma brucei gambiense r.rgiiisno decaf boj-yinse protist ot-.T:lida:e i
WD repeat containing planar cell
ENSG00000143951 Yes Trypanosoma congo!ense polarity effector protist Not-validated
CNSGO0OO0145555 Yes Capsaspora owczarzaki myosin X protist Validated
ENISG000001561 10 Yes Ricinus communis adenosine kinase plant Not-validated
mi.'t nini! suf!cwsdo icdiiciasp
ENSG000001 /5S06 Yes Cyanot sc sp. bactona Validated
E SG00000179832 Yes plus CMR1 Capsaspora owczarzaki HEATR7A protist Not-validated family with sequence similarity
ENSGO0O0O 185958 Yes Trichomonas vagin l 186. inc!!iibei A protist Not-validated
ENSG00000232774 Yes Trypanosoma congolense RP1 1 -47122.3 protist Not-validated
ENSG0 000136153 Yes Polysphondy!ium pallidum Li domain 7 protist Validated
ENSGQ0000140718 Yes Micrornonas pusilla fat mass and obesity associated plant Validated
ENS 000001 -48219 Yes Plasmodium yoeiii yoeiii astrofaciin 2 protist Not-vahdnimj i
globoside alpha- ϊ ,3- - acetylgalactosaminyltransferase
ENSGQ0000148288 Yes Parachiamydia acanthamoebae 1 bacteria Validated
ENS 00000205 09 Yes Bordetella pe rii 5\3'-nucleotidase. mitochondrial bacteria Validated
ENSG00000216937 Yes Plasmodium yoeiii yoeiii coiied-coil domain containing 7 protist Vaiidated
FYN oncogene it;!a;od to SRC.
CNSOOOOOOij 1081 Yes Rous sarcoma virus F R. YES Virus O
ST3 beta-galactoside alpha-2,3-
ENSG00000110080 Yes Deerpox virus siaiyitransferase 4
C-type lectin <
ENSG0 00018iVW3 Yes Dee pcx Vfr member A
v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog
ENSG00000197122 Yes Rous sarcoma virus (avian)
3 gene code for the gene that was found to be obtained by HGT and can be further analysed at
http://www.ensembl.org/Homo_.sapiens/lnfo/lndex
D shows that the CRISPRFinder software identified in this gene a CRISPR element whether or not in combination with a CRISPR-associated gene
c species were the CRISPR containing gene is acquired from by HGT
d gene description indication its potential function
e taxon were the species from c belongs to
! phylogenetic validation whether the genes were acquired by HGT
Table 4 Affymetrix U133 Plus 2 microarray non-coding probes that resemble human CRlSPRs
Probe chr pos Start probe pos End probe Pos Probe ID CRISPR Chr pos Start CRISPR End CRISPR Patent 1 chrl 9740286 :>7.r.'63J 1557339_at chrl 9741915 9741994 chrl 9740286 9747632 1557341_x_at chrl 9741915 9741994 68 chrl 17066767 17267929 216801„at chrl 17116688 17116804 95 chrl 89150225 89226044 230400_s_at chrl 89189637 89189741 330 chrl 89150225 89226044 chrl 89195980 89196073 331 chrl 1677173 1677680 230694_at chrl 1677486 1677588 18 chrl 154190317 154191927 233248...at chrl 154191089 154191172 461 chrl 183441660 183495902 242575_at chrl 183488154 183488259 559 chrl 67096195 67096220 1569603_at chrl 67096123 67096200 250 chrlO 80288507 80434864 15578Q7_a_at chrlO 80289681 80289817 5867 chrlO 80288507 80434864 chrlO 80390267 80390368 WOK chrlO 3360886 3793053 15601S5_at chrlO 3775980 3776065 5618 chrlO S .i 0S% 37y=Kv> ; chrlO WO J52 4 3403604 5615 chrlO 3360886 3793053 chrlO 3543094 3543198 5616 chrlO ¾oO.\<ii: 3793053 chrlO 3699048 3699149 5617 chrlO 29883503 29885308 1560230_at chrlO 29884050 29884175 5710 chrlO 10966689 11763895 1566503_at chrlO 11556214 11556318 5656 chrlO 10966705 11763895 1566504_at chrlO 11556214 11556318 5656 chrlO 64180584 r:2 7 ! ? 1569041„at chrlO 64957301 64957398 5815 chrlO 64180584 65207333 chrlO 64182989 64183074 5817 chrlO 64180584 chrlQ e..i75MO:-. i..! 7:".S- !'> 5818 chrlO 64180584 65207333 chrlO 65094900 65094990 5820 chrlO 5747858 , 7 s ChrlO 5774041 5774138 5631 chrlO 5747858 5903379 chrlO 5776296 5776426 5632 chrlO '.-.7" ;S- H 5903379 chrlO 5781360 5781468 chrlO 5747858 5903379 chrlO 5870156 5870236 5634 chrlO 5747858 5903379 chrlO '>Si 7 WS 171 H 5635 chrlO 29962387 30350458 234439„at chrlO 30252296 30252401 5711 chrlO 29962387 30350458 chrlO 30196395 30196547 5679 chrlO 29962387 30350458 chrlO 30266461 30266569 5712 chrll 12442787 13279860 216431.. at chrll 12967812 12967890 6121 chrll 12442787 13279860 chrll 13125406 13125494 6122 chrll 117690789 117695434 217G91_at chrll 117692380 117692515 6432 chrll 58346941 58381810 226812_at chrll 58367814 58367967 6242 chrll 11992594 11595200 232947_at chrll 11994386 11994526 6120 chrll 84738246 84740241 233266_at chrll 84739109 84739213 6326 chrl2 122103201 122514540 1555014_x_3t chrl 2 122174568 122174740 6872 chrl2 122103201 122514540 chrl2 122174321 122174450 6871 chr 12 122103201 122514540 Chrl2 122 122333375 «5 » chrl2 133090373 133092116 1557539_at chrl2 133091123 133091212 6939 chrl2 95048476 95638986 1564545_a_at chrl2 95431119 95431214 6791 chrl2 95048476 95638986 chrl2 95416868 95416974 6790 chrl2 131463.356 131463885 1564984_3t c.hrl2 131463458 131463545 6914 chrl2 69801513 70214650 1565801_at chrl2 70034502 70034605 6715
Chrl2 69801513 70214650 chrl2 70193756 70193846 6716 chrl2 124196959 124243070 205703_at chrl2 124216111 124216190 6878 chrl2 122087645 122459181 210679._x_at chrl2 122174568 122174740 6872 chrl2 122087645 122459181 chrl2 122174321 122174450 6871 chrl2 122087645 122459181 c rl2 1 2H3268 1 2 i3 W> 6873 chrl2 95048476 95833057 216739_at chrl2 95431119 95431214 6791 chrl2 95048476 95833057 chrl2 95416868 95416974 6790 chrl2 95048476 95833057 chrl2 95648950 95649039 6792 chrl2 95048476 1583 *05 ? Chrl2 95831780 95831866 chrl2 10423410 11136493 232626_at chrl2 10531650 10531735 6520 chrl2 10423410 11136493 chrl2 10705772 10705877 6521 chrl2 10423410 11136493 chrl2 11038147 11038244 6522 chrl2 10423410 11136493 chrl2 11098788 11098912 (:'»21 chrl2 49268653 49328298 236303„at chrl2 49292884 49293011 6646 chrl4 27884493 2R? ! if; J 2 1559434_3t c.hrl4 2ifiKB¾7.' 28088671 7340 chrl4 27884493 28213632 chrl4 28185735 28185838 7341 chrl4 106330425 106453116 211633..x...at chrl4 106342983 106343084 7585 chrl4 106322286 106967485 211878_at chrl4 106765150 106765547 10014 chrl4 106322286 106967485 chrl4 106342983 106343084 chrl4 106322286 106967485 chrl4 106531849 106531973 7518 chrl4 106173474 106518511 216318_at c rl4 106244826 106244914 75K 5 chrl4 106173474 106518511 chrl4 106227348 106227431 7582 chrl4 106173474 106518511 chrl4 106342983 106343084 7■->*-> chrl4 22447161 22985309 217065_at chrl4 22827944 22828056 7329 chrl4 59662111 59960928 221137.. at Chrl4 59824004 59824163 -: chrl4 59662111 59960928 chrl4 59732861 59732980 7435 chrl4 59662111 ■ :' 92S chrl4 59743054 59743135 :·-'. , chrl4 59662111 59960928 chrl4 59833616 59833705 7438 chrl4 59662111 59960928 chrl4 59916167 59916241 7439 chrl4 59662111 59960928 22113S._s._at chrl4 59824004 59824163 7437 chrl4 77297604 7 M',?2 234454_at c.hrl4 7 ? ΐ ί ¾· 77.330900 ?4Η.' chrl4 57860358 57860828 243246_at chrl4 57860381 57860523 7426 chrl5 89445339 89447877 1558960...a. at chrlS 89446088 89446173 7796 chrl5 34422526 35336559 1559151_at chrl5 34670007 34670131 7648 chrl5 3 5 .Γ.26 .55.Π .59 chrl5 34646568 34646667 7647 chrl5 34422526 35336559 chrl5 34878970 34879051 7649 chrlS 34422520 V: 53G5 i chrlS 340.147 Hi ?4<) ί-18ϊ" 7650 chrlS 90804312 91105865 1566032_at chrl5 91054385 91054459 7797 chrl5 90804342 91105865 1566033_at chrlS 91054385 91054459 7797 chrl5 64880471 65258312 217482 at chrl5 65046811 65046953 7724 chrl5 37173871 _\;.55;; .-i chrl5 37170130 37170212 7656 chrl6 4001312 4398935 1558275_at chrl6 4133976 4134115 7865 chrl6 29268945 1560498„at chrl6 29268551 29258641 '■: 5 chrl6 87431698 87759801 1561092_at chrie 87739575 87739930 8053 chrl6 87431698 87759801 chrl6 87545537 87545614 8086 chrl6 87431698 87759801 chrl6 87618761 87618849 8087 chrie 87431698 87759801 Chrie 753¾o.l 87753653 8088 chrl6 78935711 78942438 1563460_at chrl6 78937147 78937338 8050 chrie 359059 -!.iS.i.7 ? 1564498_at chrl6 λ 71Μύ 7836 chrl6 359059 438322 chrl6 375060 375159 7837 chrl6 359059 4 K 522 chrl6 391761 391917 A H chrl6 359059 438322 chrl6 423673 423876 7839 chrie 69694811 70327367 1565845_3t chrie 69825675 69825753 8016 chrl6 69694811 70327367 chrl6 70189769 70189893 8018 chrie 69694811 69950900 chrie 69825753 8016 chrl6 5641293 5808519 1570215_at chrl6 5652722 5652820 7873 chrl6 21526229 21905625 217490._at chrl6 21661461 21661546 7938 chrie 21526229 21905625 chrie 21584700 21584808 7936 chrl6 21526229 21905625 chrie 21552521 21552689 7935 chrl6 21526229 21905625 chrie 21648684 21648792 7937 chrl6 ?S:,S .16 ¾:". 78996239 .'.7.·! .? 58 .it chrl6 7W7 ] 57 78937338 8050 chrl6 78584635 78996239 chrl6 78595176 78595297 8048 chrie 78584635 WJfc 5') Chrie 78663707 78663810 8049 chrl6 89357114 89556728 227661_at chrl6 89450035 89450132 8108 chrie 89357114 89556728 chrl6 89445283 89445366 8107 chrl6 89357114 89556728 chrl6 89377847 89377944 8105 chrl6 89357114 chrl6 89438071 89438171 8106 chrl6 89357114 89556728 chrl6 89513853 89513939 8109 chrie 1797068 1811313 230162_s_at chrie 1799352. 1799452 7855 chrie 20701508 21596251 234643_x_at chrl6 21046208 21046339 7930 chrie 20701508 21596251 chrie .'0K / .7:"i?¾ 20872761 7929 chrl6 20701508 21596251 chrl6 21584700 21584808 7936 chrl6 20701508 21596251 chrie 21179629 21179765 7931 chrie 20701508 21596251 chrie 21180379 21180481 7932 chrie 20701508 21596251 chrie 21323740 2 Π23')2': ' ¾ 5 chrl6 20701508 21596251 chrie 21524320 21524415 7934 chrie 20701508 21596251 chrl6 21552521 .7 J V".2..,H9 7>i chrl6 20884198 21902647 243147„x_at chrl6 21661461 21661546 7938 chrie .7(5X84 l«8 21902647 Chrie 21046208 21046339 ?η··0 chrl6 20884198 21902647 chrl6 21584700 21584808 7936 chrie 20884198 21902647 chrie 21179629 21179765 7931 chrl6 20884198 21902647 chrl6 21180379 21180481 7932 chrl6 20884198 21902647 chrl6 1 ¾ 3740 21323925 7933 chrl6 20884198 21902647 chrl6 21524320 21524415 7934 chrl6 20884198 21902647 chrl6 2155252.1 21552689 7935 chrl6 20884198 21902647 chrl6 21648684 21648792 7937 chrl7 76893103 7ί ·!>7Η 1556836...at chrl7 76895113 76895191 8379 chrl7 76893103 76896234 1556837_a_at chrl7 76895113 76895191 8379 chrl7 8985535 ■rnrjri 1566803_at chrl7 9156556 9156643 8177 chrl7 8985535 9727777 chrl7 9045196 9045306 8176 chrl7 8985535 9727777 chrl7 9561213 9561347 8178 chrl7 48766882 49193093 214979_at chrl7 48851027 48851109 8273 chrl7 48360270 49188027 216427_at chrl7 48851027 48851109 r. / i chrl7 15978220 16549265 217152_at chrl7 16048049 16048223 8190 chrl7 15978220 16549265 Chrl7 16174468 16174559 8191 chrl7 15978220 16549265 chrl7 16526168 16527131 8179 chrl7 80338925 80338950 241468_at chrl7 80338909 S-!OV chrl8 9574671 9933120 1563690_at chrl8 9786083 9786207 8440 chrl8 9574671 9933120 chrlS 9912497 9912588 8441 chrl8 2199942 2519259 216771_at chrl8 2309331 2309440 8425 chrlS 2519259 216772_at chrlS 2.iOS.¾3! 2309440 842.5 chrl8 55377244 55395934 234095_at chrl8 55382257 55382350 8566 chrl9 44643460 44645650 1559770...at chrl9 44643370 44643474 8829 chrl9 23487806 23824382 1562055_at chrl9 23808179 23808277 8769 chrl9 53453136 53571734 1567031_at chrl9 53 5.U 2 53454363 8846 chrl9 4477051 5145589 207730._x_at chrig 4852359 4852498 8700 chrlS 4477051 5145589 c rl9 5095637 5095777 8701 chrl9 2514448 2646281 214227_at chrl9 2631555 2631659 8683 chrl9 36618668 37179708 216792_at chrl9 36687618 ϊόί,Κ77_>8 8799 chrl9 19896720 20262762 221625_at chrl9 20206519 20206664 8757 chrl9 19896720 20262762 Chrl9 20075471 20075565 8753 chrl9 1357416 1358181 230461_s_at chrl9 1357661 1357777 8678 chrl9 8240460 8641054 chrlS 8451335 8451489 8713 chrl9 8240460 8641054 chrl9 8441283 8441390 3664 chrl9 8240460 8641054 chrl9 8444097 8444291 8711 chrl9 8240460 8641054 chrl9 8445717 8445832 8712 chrl9 8240460 8641054 chrl9 8594711 8594915 8714 chrl9 8074484 8641054 234574_at chrl9 8166509 8166637 8709 chrl9 8074484 8641054 chrl9 8451335 8451489 8713 chrl9 8074484 8641054 chrl9 8441283 8441390 3664 chrl9 8074484 8641054 chrl9 8444097 8444291 8711 chrl9 8074484 8641054 chrig 8445717 8445832 8712 chrlS 8074484 8641054 c rl9 8594711 8594915 8714 chrl9 53055764 53451419 243973_at chrl9 53094839 53094931 8861 chrl9 53055764 53451419 chrl9 53407160 53407326 ,2 chr2 203879602 203922164 1554108 at chr2 203911738 203911829 1423 chr2 3S :>-. 203922164 chr2 203915535 2 5 1 ·;ι·3ί- 1424 chr2 240223182 240228954 1558385_at chr2 240225882 240225968 1545 chr2 242118127 242119813 1559053„at c r2 242118169 242118244 1563 chr2 242118127 242119813 1559054_a_at chr2 242118169 242118244 1563 chr2 l.i:-.0.?6iVI A V: 1S .U 205800_at chr2 i-i:; i 3 i i 44513464 chr2 55852072 55858573 233635„at chr2 55857156 55857247 1026 chr2 203500210 203589692 243186.. at Chr2 035 * 13 203534830 1421 chr2 232570865 232570890 210723_x_at chr2 232570820 232570905 1515 chr20 49935494 50209168 1554723_x_at chr20 50168646 50168745 9051 chr20 49935494 50209168 chr20 49957571 49957687 9050 chr20 iS'.J'VWl 35757746 15567Ql_at chr20 35185291 r> l Kr>3HS 9006 chr20 35093473 35757746 chr20 35431105 35431185 9008 chr20 3 ".0'i. i7 . 35757746 chr20 3 ". ¾2. i2 / , i.' 3 ".5'i 9007 chr20 35093473 35757746 chr20 35541168 35541620 8980 chr20 35093473 35757746 chr20 3%t,.' " 78 9009 chr20 35429452 35431186 1560476_at chr20 35431105 35431185 9008 chr20 17594324 17662865 201205._at chr20 17609583 17609727 8948 chr20 50037844 50363368 233706_at chr20 50168646 50168745 9051 chf20 50037844 50425208 233708„at c r20 50168646 50168745 9051 chr20 44705219 44705821 239815_at chr20 44705156 44705235 9031 chr20 61089216 61089241 1562586_at chr20 61089231 61089326 9101 chr21 40128328 40581393 238183„at chr21 40551557 40551627 9233 chr22 33669070 34316410 215538.. at Chr22 3 ? ki' 33827549 9359 chr22 33669070 34316410 chr22 33961551 33961650 9360 chr22 41763478 41983251 215675_at chr22 41784175 41784446 9389 chr22 41763478 41983251 chr22 41797025 41797156 9390 c r22 22516597 23248620 216301„at chr22 22936417 iwm i 9336 chr22 22764327 23241835 217193._x_at chr22 22936417 22936532 9336 chr22 33209598 231888_at chr22 33216312 332.16421 !i3:".S chr22 40526914 40994205 233697_at chr22 40801331 40801419 9383
Chr22 22786507 234707..x ..at chr22 22936417 .■?:>ΉΓ ·Ϊ.> 9336 chr22 28296463 28297355 242924_at chr22 28296803 28296912 9342 chr3 106146913 106148922 1557645_at chr3 106147511 106147661 1884 chr3 155563133 155564208 1559232_a_at chr3 155563617 155563716 2031 chf'3 13414815 13416603 1562?23„at c r3 13415593 13415693 1607 chr3 105097299 105107052 1563958_at chr3 105102206 105102308 1881 chr3 15S288976 204782_at chr3 158316774 158316919 203 5 chr3 67425142 67705002 215774_s_at chr3 67456037 67456120 1770 chr3 171758835 171760763 232840.. at Chr3 171760690 171760794 2089 chr3 97172479 97174696 233789_at chr3 97173244 97173346 1854 chr4 142128796 142130411 1556520_at chr4 142129922 142130061 2700 chr4 142128796 142130411 1556521_a_at chr4 142129922 142130061 2700 chr4 179895985 179898053 1562642 at chr4 179897657 179897750 2836 chr4 843064 926120 202280„at chr4 882793 882913 2214 chr4 843064 926120 c.hr4 890872 890965 2215 chr4 843064 926120 chr4 893979 894088 2216 chr4 843064 926120 chr4 903248 JO ¾ -j.¾ , 2217 chr5 175819344 175825274 216934_at chr5 175824293 175824425 3466 chr5 175819344 175825274 216936._at chr5 17-.S242 3 175824425 3466 chr5 86676620 86678864 232344_at chr5 86678240 86678345 3215 chf'6 41303526 41318625 2210?4„at c r6 41316980 41317136 i j. S chr6 31802693 31807489 222968_at chr6 31804365 31804470 3610 chr6 34254850 34360300 chr6 .i.H. » i 34 3 :. S 362·') chr6 34254850 34360300 chr6 34316780 34316854 3619 chro 108947347 108948671 233629. at chr6 10894S653 108948760 chr6 108947347 108948667 233674_at chr6 108948653 108948760 3856 chr7 1552185 1864233 1557555_at chr7 1852792 1852871 4091 chr7 1552185 1864233 chr7 1861658 1861736 4092 chr7 66354836 1559563_ at chr7 65452039 65452140 4267 chr7 65273942 66354836 chr7 65358544 65358703 4266 chr7 66354836 c.hr7 65634491 65634593 ■UhS chr7 65273942 66354836 chr7 65667233 65667305 4269 chr7 66354836 1559565 . x. at chr7 65452140 4267 chr7 140860426 141203524 1562907_at chr7 140900044 140900216 4592 chr7 158501449 158571509 1564424_at chr7 158525274 4676 chr7 158501449 158571509 chr7 158538994 158539106 4677 chr7 158501449 158571509 c r7 158562319 158562419 4679 chr7 158501449 158571509 chr7 158550234 158550344 4678 chr7 92355014 214160_at chr7 92415915 92415995 4412 chr7 128311570 129406533 233717_x_jit chr7 128504820 128504898 4556 chr7 128311570 129406533 Chr7 128859001 128859101 4557 chr7 128311570 129406533 chr7 128907038 128907135 4558 chr7 128311570 129406533 chr7 129219046 129219136 4559 chr7 65598910 65917175 233853_at chr7 65634491 65634593 4268 chr7 65598910 65917175 chr7 65667233 65667305 4269 chr7 1552185 1864233 233920„at chr7 1852792 1852871 4091 chr7 1864233 233921_s_at c.hr7 1852792 1852871 4091 chr7 65390693 65500634 238305_at chr7 65452039 65452140 4267 chrS 29671888 29686020 155927S...at chrS 29679434 29679546 4812 chr8 7468860 7925177 1568780_at chrS 7552246 7552403 4746 chr8 7468860 79251 / 7 chrS 7891861 7891964 4748 chr8 7468860 7925177 chr8 7569191 7569295 4747 chr8 7468860 7925177 c r8 7908726 7908883 4749 chr8 68255956 68404101 1569405_at chr8 68295467 68295567 4938 chr8 128806803 128952702 216249_at chr8 128843268 128843360 51 22 chr8 42210559 42396605 231818 x at chr8 42317234 42317313 4853 chr8 42210559 42396605 chrS 42339857 42339992 4854 chr9 114311101 114766258 1554007_at chr9 114456269 114456364 5465 chr9 114311101 114766258 c r9 114511136 114511246 5466 chr9 114311101 114766258 chr9 114655624 114655711 5467 chr9 4732996 4859264 1558489_at chr9 1S%36.> 4856490 Λ>4 chr9 140477240 140479471 1559166_at chr9 140478444 140478563 5572 chr9 ¾6 0449> 36958546 1566428. at Chr9 36606253 5320 chr9 36504497 36958546 chr9 36861230 36861330 5321 chr9 140259247 140390859 1569981_at chr9 140358201 140358306 5570 chr9 140259247 140390859 chr9 140305319 140305466 5569 chr9 140259247 140390859 chr9 140377663 140377754 5571 chr9 137533804 137734739 203326_x_at chr9 137607871 137607955 5540 chr9 137533804 137734739 c.hr9 137582488 137582575 5539 chr9 137533804 137734739 chr9 137669386 137669518 5541 chr9 137533804 137734739 ch r9 137709495 137709575 chr9 115812397 116244326 233390_at chr9 115902868 115902992 5472 chr9 115812397 .l ! 6M .f> chr9 116099115 116099217 5473 chr9 115812397 116244326 233395_at chr9 115902868 115902992 5472 chr9 140505276 141019359 234214_at c r9 140958689 140958786 5578 chr9 140505276 141019359 chr9 140678911 140679019 5573 chr9 140505276 141019359 chr9 140694439 140694549 5574 chr9 140505276 141019359 chr9 140864389 140864494 5576 chr9 140505276 141019359 Chr9 140696790 140696885 5575 chr9 140505276 141019359 chr9 140897556 140897669 5577 chr9 140505276 141019359 chr9 140987155 140987277 5579 chrX 2155553 2169916 1566548_at chrX 2159579 2159659 9471 chrX 2155563 2169916 1566549_at chrX 2159579 2159659 9471 chrX 46464683 46618359 214863._at chrX 46491840 46491982 9580 chrX 129757874 130037208 216681_at chrX 129965144 j 2>)9i. "..?2 9798
Table 5 GDS3615 RNA expression values of U133 plus 2 probes resembling human crisprs
Patient numbers
Probe ID GSM401289 GSM401291 GSM401293 GSM401295 GS 401297 GSM401290 GSM401292 GSM401294 GSM401296 GSM401298
1554007 at ■H .1021 73. Ϊ357 U 1:> 7 1 « J •i9. :.is C.S 01 14 (.263
1554108_at 22.7903 25.7686 26.5449 30.2121 29.2647 20.7681 31.0883 24.3228 32.9765 24.8669 i ' -i ;.- j x if 7. S096 ; 7«i»75 7.05437 7.72296 ¾ i) .¾;> 8 ν.;κ/κ·3 ; s -i" S. 584 ! ; .? is 7.86801
1555014_x_at 28.3207 28.6164 26.6521 29.8841 27.7492 29.7805 25.0606 24.4032 23.0854 28.251
1556520_at 11.8612 10.1588 8.71372 It;.12 :S 9.28039 9.03762 10.2623 <> i V/h 8.99473 10.6076
1556521_a_at 7.90661 7.99772 7.42665 7.89037 8.02253 9.57011 7.80774 9.53987 7.69188 8.22846
15567Ql_at 30.5017 34.8751 Ώ.02-: i )■-,=.■■. 2*./0J 9 2><.-H / - W(>9 u i'.,:;
1556836_at 20.7441 17.0549 17.5142 15.5055 13.8274 16.2225 15.4996 18.3297 13.2004 14.6926
1556837..a...at 19.4853 12.8744 1 i.r:0i?. 15.065 1 ;· 736 J 2 l iiV.' 13.4841 12.9952
1557339^at 10.1086 10.793 12.597 10.8852 10.294 11.4945 10.6249 10.6323 10.5264 10.138
155734 l_X_3t 14.6313 15.4547 15.5719 ι .ν ¾;υ;· 12.9436 j f» i¾:>s; 14.2611 14.1945 12.8541 L 1.02 52
1557539_at 89.8469 55.136 83.399 60.6336 51.947 93.7979 55.247 46.7153 42.1076 50.4535
1557555„at il i* 12 24.6794 29.5369 21.9522 2f,.*725 . 0.5 7 ] 2;!.-;->S" r; 19.9533 27
1557645_at 10.5363 10.7162 11.0853 9.4634 9.54568 11.4258 11.0513 9.52882 9.58411 11.1069
1557807_3_at 11.5948 16.4265 13.2635 .t i. ½9S 10.601 15.0016 13.3869 12.05 if. 11.07 10.4527
1558275_at 29.7844 31.341 35.5711 35.5989 32.5676 27.4367 41.4354 37.9098 27.4486 38.7197
1558385 at 16,5863 15.6125 19.5683 15.2581 I .20 V 19,5673 I G.i.'UI 15,8413 15.5372 17.1459
1558489 . at 19.0405 20.938 14.0206 18.819 18.6535 14.5923 18.0795 14.3143 14.6388 15.7853
1558960_a_3t > 3 047 26.4K.?S 24.9047 ?.'■). I .'V. 74.0 V18 27 :,7 5 25.2308 24.8738 2.2.°S83 26.8 iij
1559053_at 11.5466 9.53091 9.49467 9.37825 11.2783 10.5706 10.4848 10.5328 9.1605 9.82439
1559Q54_a_at 26.855 20 227 1 2\>.W! 21.9309 b- J27 26.3109 25 185=1 ,5 i i 19.8471 20 322
1559151_at 7.31458 7.47851 7.06881 6.54876 7.88544 8.38499 8.15399 7.1502 8.75984 7.88166
1559166_at .17.429 H.S202 19.9858 i'^ .i02 J Γ .Γ.Κίί·. 18.4811 19.1747 17.3881 16.554S 22 07K ¾
1559232_a_at 121.266 92.7985 96.6302 105.286 87.2138 84.8354 83.6986 72.6173 62.2955 98.891
1559278_ at H >, V. 10. 12 1 9.14763 10.22; / 10 7(,2ί. ■i 3MS 11.2806 10.0877 9.11122 9.41521
1559434_at 8.26053 8.00026 8.04973 7.83424 8.41962 8.45644 7.35791 7.79333 7.56306 7.28381
1559563_3t 15.8951 20.7173 20.204 20.6634 n.'w;2 14.2096 20.4697 19.4544 17.7452 18.1647
1559565 x at 17.0015 18.359 20.1538 20.3618 16.9285 19.5914 20.7851 20.8473 20.6365 22.1882
1559770 S.80785 87 J l.?5 K./yioi 9.58367 8 13.V18 Ιϋϋ 81063 i J/l » i v.»/
1560185, .at 8.81206 8.72676 9.67402 8.78846 7.61431 8.70921 8.15073 8.89197 8.30978 7.62899
.at U.2 ?>,(., 11.9874 11.6681 12.1585 I2.I.W2 16.2708! 11.9172 I >.2i',2\> 12.lt!', 12.4493
1560476. .at 23.8329 20.016 19.3391 18.1301 19.2809 30.1485 18.9945 19.7808 17.8112 22.1112
1560498_at 13.0426 13.5115 13.1799 r> ¾7SJ¾ H.blH 16.8357: 11.1786 15./ 3 ¾ 13.7386 11.937
1561092. .at 30.3926 28.1751 36.9715 32.8975 22.6296 25.1816 23.5396 23.5233 18.0154 27.6794
1562055. .·->' 17 >oh 19.2586 16.9336 17. 17,8838 7 I 6 i.l ::¾¾i¾§i: j'.' 9225 27 K, i
1562586r .at 38.5716 37.6457 30.2784 29.8225 26.0549 39.8686 32.9739 26.129 24.1558 28.7966
1562642_3t .87-S0 11.1211 12.459 11.2019 11.3915 12.2116: 9.85416 J 11.4092 9.99801
1562723. .at 36.2198 30.2391 31.7588 20.8463 21.2834 29.3224 25.9452 27.086 25.4112 22.4186
1562907. .at 14.8977 15.4555 15.8967 1 ¾ =)8b.< 14.078 13.6176: 16.4393 15.5451 u.;;!?fc 16.0363
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1564424 ..at 149.354 ί.η ί Ϊ7 105.077 Si.-.l Oil': Λ. l2i-'< 100.787: 57,9537 IG.-iWi 5'i i.165
1564498. .at 41.114 34.6642 30.4097 35.2485 33.6857 37.944 33.7911 36.3745 34.2052 44.85
1564545. A. i¾ 18.0781 16.9568 21.2854 1 . .?4S 18.4181 272751 16.4033 K- v-yj?. 16.5494 19.1163
1564984. .at 27.0044 28.7295 23.7289 20.0231 22.2494 31.3288 25.254 22.6858 26.5519 23.5692
1565801 .at 9.85503 11.1131 9.74903 126002 1 i >MS 10.1899: 10.5326 10.7833 10.112 10.9955
1565845. .at 30.9055 20.1784 16.5478 16.8291 17.4094 28.2077 21.0881 23.8001 18.9862 22.7438
1566032_at 10.252 13.1176 15.5175 i J I J.270S J'.'?¾1J: 12. 0¾ 12.1977 12.1229 J ¾)5
Figure imgf000110_0002
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1566504_at 16.7762 18.7632 ,?0'-V-;17 20.0136 2i.-i2'.:l 19.5571: 21 S7.-.1 J 7.06'-)2 19.9639 21.3.M2
1566548. .at 24.0281 26.4967 22.0404 23.0967 23.2102 24.7457 23.6118 23.4913 20.9209 22.7947
1566549. .at 24.0464 25.5944 S4I >■:, 2f-.;:U3 HiOJb',! 2;;. n; i024<U 26.9495 35.1095
1566803. .at 22.2339 21.0965 21.375 21.0852 21.1189 21.2454 20.5386 21.0588 19.5705 20.4005
1567031 at 11.1056 10.5475 10.8294 15.5125 11.9319 I 161.9: 12.8204 H.7I7K \2 lb<?l"> 12.1249
1568780. .at 63.5285 34.3328 48.5884 38.8849 29.2612 55.0862 36.4353 43.655 42.6228 34.1025
1569041 ..at 5/M; 21.160ή 25.1056 25 <>8 ! 25.9rf7i IS.27 20.0741 03
1569405_at 11.5356 11.502 11.6188 13.3627 13.636 11.767 13.3142 11.8463 11.8334 12.3315
1569603_3t '-ι ^Ώ 9.192*2 10.0815 9.94803 -i.73¾2i 977021 9.2)042 9.41653 8.59484 <;.7-il K
1569981_at 7.4264 7.07277 6.69604 6.93383 6.79005 7.17213 6.68189 6.38524 6.08011 6.59092
1570215. at 16,3914 14.7135 15.896 1 Ϊ ;10 i.-l 14.744 15,6124 15.0441 14,3378 14.0158 14.6058
201205_at 26.8249 28.4432 30.1492 27.1169 27.494 29.9631 24.2505 29.8709 28.272 29.3813
202280 . ii 17.75-1 14,0953 16.8802 13.5805 12.6707 16.2134 i.5.12Ki .2 IK 7 i.2.(;433 12.12
203326_x_3t 68.9932 59.1691 57.4077 54.3622 53.9855 68.9065 55.9547 57.6001 51.8003 60.0542
20.5 ,i; 16.7502 ](; 7K7 17.3119 16.9783 16.153 18.5895 17.9256 18.5494 15.2537 16.1921
205703_at 11.5742 11.1377 11.9582 12.6352 11.4962 12.2203 11.908 13.1365 12.2864 10.3174
11.905 12.5095 Ί 2 <>!>2.-> i i.2396 15..102 ! 15.4487 12.14¾S 12.0476 14.0608 14.2866
207730 x at 642.565 356.282 326.758 363.864 368.491 669.073 339.1 295.017 262.546 378.401
.? 10» ;')>...-!) ■!:> · 121 185.382 214.487 217.991 :>2i!.357 342,148 207.331 I Si .102 JM «; 257.85
210723_x_at 36.4895 27.9589 29.4278 31.0441 31.7554 34.4993 31.6993 28.444 26.6117 30.8872
211653 -,1 161.374 84.6088 «; 'η>!?. 82 a 41 * 167.75 22 S.5S7 14'3 ..>. 132.716 18.; 8; 11? 00.'.
211878_at 20.7043 17.4937 18.5461 16.9933 19.9765 23.3013 19.0743 21.412 20.7143 18.4788
214160_at 13.1848 'iSb 13.8126 i? 2ii< ,; 11.5357 11.3117 10.9052 12.8852 " S3:!'i5 11.7567
214227_at 19.9473 18.3928 17.4945 17.2135 14.368 18.5279 16.9247 15.8631 16.6412 15.8102 1 .1! 1 . ί32Κ 15.6936 16.7543 16.7822 13.7161 1-1.22 ¾S 13.7435 li.Wi. i t '-, !.'.7)75
214979_at 15.7874 19.3058 19.5833 20.0906 17.4766 21.4595 20.4781 21.8094 16.3928 19.7695
27,7966 14.7814 15.3401 19.247.¾ 1 ;.-)ϋί- 29.6824 17.4681 17,9773 15.766 14.8445
215675_at 34.5089 30.6499 27.5864 29.0617 27.039 33.6279 29.3603 32.0958 25.2842 28.5177
21.V//-J ·.· .¾! 10.5012 10.436 14.0362 1ι>.ί· 2ί¾ 10.6024 13.8503 U 01i>2 16.6 IK ! i 98 :,
216249_at 21.5286 15.0723 17.9829 21.7569 20.3556 19.2698 19.891 19.2728 19.3809 20.5902 ΐ··";οι .!· 33.(:Ι8'! 50 572. 39.735 J .-l%4 ί·. 702 5">, 18t,2 36.0617 5·. I «■
216318_at 34.3213 27.0983 24.4023 25.0724 22.1523 28.9414 24.686 26.5306 20.0688 22.3871
21012? ..i Vi.2><!> 23. !?(>6 /o*/.-> 2 -, 5 VI J 27. W.-. 23.<"<J 2" 1:10¾ j v l 20.0341
216431_at 11.2212 13.6839 14.2352 14.4821 12.6322 14.8207 13.2447 13.5163 13.6662 16.8379 1(,i l .>; 7.23488 27H < 3¾K l 9.73183 9.6660? 8.83698 9.37147 10.7833 9.19017 Ι021 Ϊ7
216739_at 33.8061 38.1019 35.3363 35.7948 34.8811 38.3271 33.0221 44.0308 31.2202 36.4544
;tc>;vi ..r 15.2416 1 ¾ J $ ~i J 12 3558 12 .2 J1 12.0895 j -i ν. 12.5442 13.066 12.1262 11.9119
216772_at 11.5523 10.3103 12.6132 13.8803 11.5814 11.6699 12.4602 11.9685 11.6448 11.6468
,], -> _3t 1.¾ S?t>'j 18.9307 17.1446 17.5:,32 17. IK; J 160627 146216 141225 166863 145889
216801. 19.7631 24.2125 21.5399 27.7391 27.371 21.9911 25.2994 24.1255 21.1985 26.6154
2Ι.-Ή-Ί 18.0634 17.4729 16.6158 17.2522 16.524 14.644 I ί 19.2505 13.6377 17.688
216936. _at 28.5983 30.5384 26.6832 23.3771 26.8046 32.0578 33.7009 29.4552 27.3346 32.3644
217010. ..l J .-..H/ 10.3184 9.23009 11.0611 12.5159 9.78601 9.97678 11.3444 0 .-X.2 JO 2372
217091. _at 6.39273 6.70375 7.82247 6.27135 7.18245 6.78688 6.85385 9.33081 6.42507 7.00822
21711-2. 65.9407 ■101222 40.306 34.5041 ΐ·1.(,<!.! 40.2129 ■II Sill- -iS.-i:> i 33 ^ M 32.6419
217193, _x_at 40.7272 24.4785 31.8532 27.6677 28.4342 40.1835 28.4818 28.2933 27.492 23.7249
2174S? .at 3S.5 7 29.4094 21.9204 ¾;i .J:> 3 .i?..ibr¾ .vj'-.2j; 5 ¾ so:, i 46.1951 45.815 38.5666
217490, .at 31.0365 33.069 27.0283 25.1526 25.7867 27.0837 24.928 30.1085 25.0757 26.9022
221074. ,at 27.1871 26.9897 IRK] 21 19.4076 2>AVA 24 i",.5 i i 21.0179 22.-;κ', 18.3153 227602
221137. .at 14.1816 14.1292 16.5391 14.5521 13.6546 17.3016 14.4461 14.5965 13.5108 15.9388
221138 _s_at 14.6223 17.8695 16.9317 . . 572 15.7189 12.3 i*n 12.5226 ] i .".77 14.7689 14.1491
221625. .at 15.1379 15.1976 14.4735 15.4531 16.1696 12.8606 14.4119 17.2927 13.7474 20.0138 22«f-.i. .·« f.:.-Hi.i 56.5239 -if- 23M . ); 58.3553 73,0715 51.6844 ■ΙΓ; ¾01 45.6037 71.4256
224238, .at 9.4351 10.76 9.60312 10.4672 10.8109 9.08715 13.5798 13.0863 11.2034 11.2578
2?t>0(;l _s_at 11 '>■-.!>* 15.0487 15.3614 17.1799 n..w>] 14.6195 ].?».¾> JC; 15.4714 17.1623
226812, _at 19.2199 20.0225 23.9958 20.866 20.1563 17.0617 18.7767 17.1208 17.8577 18.3068
2>:n><:.\ 33.07¾ 2377-iS 2^.57/1 32.0464 2.5.)'17/ 2H ;3 36¾S 2>./ι·ν; 20.3479 22.2377
230162. _s_at 19.0063 19.2234 17.8679 20.167 18.4089 20.7383 17.1945 18.5639 18.5103 18.6547
_s_at 10.9733 15.3419 Ί ¾ * 5 2(> 1222 IH.H^J 11.6768 13.24 14.2375 17.53 Ώ J.2K5
230461. _s_at 123.535 53.5869 39.0069 32.4572 44.4393 107.355 61.4515 71.3936 43.6001 36.5248
2«rV-H. 1.V7(,.\ 71 (.043 24.0603 23.6197 19.6586 23.'.· 19.8163 23,441 18.4861 18.282
231818. _x_at 129.885 70.3797 73.9876 78.4987 82.1838 116.333 63.9362 63.323 60.6542 70.1171
7-ii'.:¾ .at 7K084 30.2418 35.i:23 34.9015 26.6 s25 5-j .i'-)'.: 5 V) 552'.: 30.7487 2S.0W(:
232344. .at 71.2001 37.1094 26.5023 21.5779 47.2726 83.9142 114.818 68.8068 63.6117 50.0939 -;2f i-, .at 28 (;-*if. 17.8769 17.1947 I...J50-) l->. >72 22.3117 16.1999 18.1134 19.12 12 ;02
232778. .at 125.972 80.9908 118.825 122.034 92.9161 89.3641 69.8344 76.5582 53.3614 81.8502
232 Γ- at 8.51024 .:n l ^ 10.0392 ■■' 1 10.7182 '■> *r,7Z. i 10.5879 10.5154 9.80834 9.08772
232947. .at 8.89068 10.9244 9.48232 10.3165 9.86886 9.5138 9.94579 9.64741 8.56823 9.76065
233248. .·« 51,2451 44.1389 4i-0J01 52.8315 11. t')3 V 43,2846 11.0222 36,4385 V .'li 52.7964
233266. _at 30.2696 34.3943 33.6204 32.1675 33.3459 25.3465 28.0658 23.4137 23.7982 26.1571 at U.7.129 10.6217 10.6675 10. i 9 I023W 10.6491 11.171 10.6082 10.9271 10.2581
23 3% _at 16.9018 16.4704 15.7182 15.717 14.8504 15.0374 15.5834 17.1248 12.9372 15.0655
Λ¾; ' , .·« 2 .122 12.1355 14.178 li.-'OS . 12.Γ;'ιί·2 17,4427 18.0621 14,5527 12.0894 13.1413
233629, .at 12.7663 14.3555 14.9908 14.044 13.1826 15.0572 15.7572 17.2429 14.7393 14.0433
' ¾ ill ' > 19.6676 11.4878 12.3794 14.1'J-1S 1 ¾ '"i^ 16.9699 i.j 5i:v, 1.M 83 12.8763
233674. .at 23.9077 49.3986 53.1909 63.2293 33.2696 35.0437 60.0319 68.5565 67.0925 46.0184
235t/)7 S (: i?A S.t>212', 8.3412 *. V r>',2 H4I-VJ7 2( 1<> 7.40113 S S4V/7 S. H, 1 7.63471
233706. .at 85.4439 24.1523 23.749 17.1186 22.882 58.1221 24.8891 24.6735 23.8262 19.2778
233708. ..l 15.3105 17.9789 15.6532 1 i.?f>\\ 14.6161 13.4956 16.3691 13.3498 15.7818 JS Ϊ70Ϊ
233717. _x_at 23.0021 22.7923 27.1444 23.5803 21.894 22.9608 22.2257 26.3569 20.6751 22.7363 4ΐ «<· S -S:> I'! 7Μ..2Λ7 8.68381 7·Κ>7 7 7.-54217 8.07912 7.60763 7.-57'-t\ y i? 7.90513
233853. _at 10.925 12.3567 10.6869 11.5954 10.9028 10.6135 10.7039 10.3018 10.7731 11.501
235920 .at 29.311 ! '-v:27 25.5147 26.2i4t 35.6196 27.01 2-i.O-iK'.: 222816 24.5758
233921. A.at 41.068 31.0829 47.7246 29.002 42.4288 44.6761 45.535 59,3703 33.7904 39.4069
234095. ,at 2<; ΊΆΆ 15.1618 17.6295 17 on 77 1 >:VAH 20x27 18.7871 18.6927 16.9501 16.2838
234214. _at 40.9 44.2666 43.0547 41.9572 42.096 47.9096 44.5383 43.5007 40.8765 36.1237 HU» at 27..M12 72 23.9319 25.bK2-! 2¾ 5¾f>i 25.9844 22.90(0 24. <* 25.-! 17!
234454. _at 18.4149 20.5697 18.7894 20.9805 18.0665 19.3885 19.6742 18.4568 16.3907 18.6229
234490. .·« JS'. 'U 14.8159 16.409 ι*. ν>--: 14.6168 19,0115 14.1049 Jf. -H 8 13.6181 15.2436
234574. .at 58.7405 47.6057 45.084 98.6579 32.2601 48.3483 39.7224 35.339 37.151 37.9564
23*Mi. 74.7973 (Λ.ΒΓS 60.958 52.9368 ■■jy.77: > 50.4514 ii»,Ji>67 50.0426 .'.?>.. V) S i 71 !9 :,
234707. _x._at 48.5938 40.041 48.4607 38.4115 44.2836 46.7977 50.676 55.9883 46.6721 40.4893
2i.--i . 42.K557 5->»=r. i 56.2175 4i.(;t!7(; Kt.752=1 41.1411 41.2171 46.8803 =10 =14 > 1 51.3454
238183. .at 59.6863 70.2661 71.8529 74.2905 71.1305 74.8864 71.7577 77.1744 72.8998 71.1309
2 ¾S ¾05 ..l 11.5697 11.3945 11.9667 11.2639 11.9908 10.87.33 U.K 22 12.1191 10.0872
239815. _at 366.119 275.038 361.403 334.89 255.937 234.12 273.103 220.701 167.651 252.742
241468. 2:>.0.17i ·."-■ Of.'U ?. Λ/7?. 25.57.13 :>795i(. 6.8fr 26.1121 .M. G 7270:->; 2 (. 770
242575. _at 15.625 13.349 16.1239 19.0338 13.885 11.2791 13.2239 14.2309 15.0728 19.7699
;-i,?92.-J _at 9.12335 17.3793 1505S3 ?.¾.?:»¾ 1 9.59208 13.9118 13.5753 17.4007 14.1046
243147. x_at 153.578 93.8261 98.7342 107.374 97.3786 129.281 98.7611 93.112 75.0918 104.399
2 3186_3t II 27.1311 22.4569 29.1779 23.731 21.6173 243246_at 15.3006 30.1215 32.1726 44.9071 26.8931 19.2281 25.2163 28.7668 19.9436 35.0675 215'Γ,Ί 37.6001 2i 11... 22.8777 >?> >:n\ 2=)Λ,ι.2 2X 1002 30. 72-J _·(, 51 -JiVlM-i
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230461 jO.214635 : -0.202418 0 j-0.116396 j0.0497591 .0.127335 _ iO.0386794 : -0.0497828 .617838 jo.348715 j0.511452 0.257592 j 0.32654 j0.358647 .0315506 jo.370989 j-0.124488
230694 0146654 ■0 11753 jjjliilj|j|jj il¾lljj|j leiijjjjjjjjjj jjj||||¾||j| iii mii 0162169 00525775 liieii 000383759 .0515156 0.2656S1 0160014 CJ.4S761
23181S : -0.145524 -0.0231562 0.0469775 jo jO.576109 0.218957 j0.43825 jO.22954 .231288 jO.81563 j0.0744767 0.414256 -0.29178 .451097 .271363 jO.586913 j0.41326
23-888..* 00986753 jiliilll 0.236421 0 llUliil 0177607 C .51718 .186115 !!iitll lllliiijl j 00481892 •018457 .0878186 0.0878180 •0026063
232344 j .00340176 mm -0.0479522 jO.169971 jO.512312 -0.904418 j 0.0499392 -00887413 -0.671737 j-0.297147 j-0.264642 0.34693 j 0.0868902 j 1.33269 0.832163 j 1.2341 jO.839868iiiiiiiii l|ji ljjjjjjj 0.256857 0 094239= tt 1365.58 0.7023» 0.0514383 jlj Ujjjjjjjj 113453 300346 0.2C«3.59 -0.142475 1.3934 0.692038 095182.5 3.08154
232778 j-0.240778 ;o 0.182886 j -0.248333 jO.330378 0.00275278 j -0.660209 j:0802023 -0.00449896 j-0.133427 j-0.597358 0.106697 j-1.16788 i-0.658404 -0.418931 j-0.811295 j-0.688356
232840 j4¾ililjjjjj 0 04 «97 .19833 j| l¾ ijjjj 0 S529i¾ C.G434146 •0. 23175 •0265063 ■0.43236 0479975 23.5926 0.119422 <.28i!639 •0260514 j ili jjjjjjjjj j | ||jjjjj
232947_at j .344722 jo 0.0214756 j-0.0310357 jO.272576 -0.0:346863 j-0.0156596 j-0.238348 -0.223912 -0.0197899 j0.47436 .0270412 j 0.054671 j-0.0735962 -0.0310357 :-0.0855339 :-0.Q803356
233248 -0.0599237 |ijj|llljjjjjjj 0051-856 0.259724 0.111269 0.304678 jiiiiiljjjjjjjjjj .6i:&944 112916 0.382016 -0.28M17 jjiiliejjjjjjjjj •0233112 733136 321786
233266 jo -0.208299 0.481614 jO.157888 0.00400686 -0.357411 jo.0756733. :0.507996 .0.628859... -0.381219 j-0.19404 .0094738 j:q.0769529 j:0.370368 0.394411 j 0.116796 j-0.0929222
ZiS.S_2.at j|l !! ljjjjjj 0.355542 030547B 0.150229 0.236367 ■0.17056 0.0597436 0.1S2236 jjjjjjjllliiiijjjjjjjj .278194 0 0.222723 0.0274312 ■0.174032 -00874403
233390 jO.137789 "jo -0.026525 : 0.0935478 :- 13892 0.158982 jO.113997 j0.0966952 0.203323 jO.168038 :- 198768 0.0145025 j-0.245577 j-0.0436981 0.225208 : -0.190083 j-0.10903
233395_st llil§iljj ■000350523 ft CV 118-1 §11111111111 0.0151939 ■0.110105 jililiijjjjj 0.21855 llliiiljjj 0.101501 .177374 0.018893 0 «181i jliii iij -000350523 lilliijll
233629 jO.230453 jo 0.0148468 j -0.166456 j-0.384676 -00435753 j0.181425 j0.0523229 -0.206739 j-0.0826995 j-0.284295 0.194792 jO.0649068 j-0.163695 -0.136889 j-0.0826995 jo
233fi35..at 129=35 -0226684 -«0306953 ||j fi |jjjjjjjjj •0.49356 0757357 373854 1.52103 2.12354 1.59411 |jj|ij| |jjjjjjj 0515749 jj $ jjjjjjjjjjj 236959 I.SilSt l
233674 j0.0716043 jo 0.151204 j-0.987679 :-0.769392 0.638061 j0.70576 j 1.21994 1.29537 .800127 jO 114236 -0.831881 j0.771728 j0.400048 2.34955 .1598S4 jO.225624
233637..:* 0072=1.15 -0180695 -0.105769 0.370751 •0.0351455 0.0507519 -00560904 sfiiiii -0.0466406 0.351948 HHHil 0.219593 jj (|||jjjjjjjjj jjjjjl jjjjjjjjj l l ijjjjjjjj
233706 jo j-0.141025 0.110124 • -0.0273938 :0.00384092 0.842833 j 0.443938 j-0.155458 1.14965 i0.461366 jo.119249 0.0811462 j-0.0947406 :-0.0215049 -0.0380697 •0.0811462 .012486 j|i||| ||j|j 0.12061-.· -0.164S2S 0 .0!9618 GC936022 80473974 0 6224/ jjjil| ||jjjjjjjj 0.391795 0.572414 •0.219335 125547 0.451764 C.140075 •C.12K6X
233717 j-0.0272183 0.281991 0.03582.18 j -0.201467 jo 0.267903 j0.2917O5 0.0983832 .210606 jo.S03233 :-0.0159085 0.404272 jO.164442 j0.164442 .57078S i .0326037 .0O6O048.l
23.5789 j j |iiljjjjjjjj ■0.0440044 0 0.0676692 ||j | i jjjjjjjjjj -0.154202 0.0310853 -0.13.8369 ΙΙΙΙ ΙΙ 0.151643 0.0736458 -0.1.iSS42 -;).0i)04-W3Sl -0.123656 .iS5fc614 0.25¾45 C.3 B12
233853 : -0.0585868 jO.103261 -0.0244861 jo :0.0280266 0.304613 : 0.516689 j0.0107965 .187644 jo.0951917 j0.362431 0.391755 jO.540262 j0.33417 .0186224 0107965 j:0.0839758
233S20 !§¾§§!! ■0.06763!» -0.236B91 0 0.0249481 ■0.137286 ■ 0.231736 -0.291326 017684» 0.17iS.» j|li ¾jjj -0.128295 -i -0.146i=19 .0748711 0.167618 0.257322
233921 i-0.971591 :o 0.164805 -0.492649 0.320904 -0.422778 j 1.32595 j- 1.22267 .688773 -1.24658 j-0.249228 -1.10502 : -0.00341415 .495568 -1.13889 j-0.30431 j-0.0211744 eiiiiii •0.234533 ■000208616 0.690588 0 iiiiiii ilililllj 0478389 jjjj jjS$¾ jjjj j |jjj 0561075 lljlllilll •0.270925 '-0.067S693 C.J32945 -703 0.2135S8 j j llljjj
234214 jO.116413 jo .0391221 j-0.0925717 j0.O822215 0.0914445 j-0.0117831 jO.18952 .434076 jO.230277 j0.179297 •0.0391221 j-0.239846 j-0.227973 -00391221 j-0.322S61 j-0.0391221
0.0531754 jj|jjjjjjjjjjjjjjj jjj|j | 6jjjj 142563 -00155792 00659895 0.2S304 0.301054 jjj ¾| ||jjjjj 0.058367 064250= -0153271 -0.205045 •0.401661 l l jjjjjjj 0.174046 -02-7=97
2344S4 .0.1675 -00938787 -0.0742555 jo jO.0277567 0.222243 j -0.0611389 :0.0389538 0.0603256 j0.0164976 j0.222204 0.0545125 j .244615 222243 0.0164976 j-0.175269 : -0.106861 j i$ ijjjjjjjjjjjj •0.072162= 014705 -0117251 0.214795 0.140Π9 •0.300522 jjj ¾¾ jjjjj 0.0671401 0208636 -013.3415 0.5632.15 •0.0239558 0.0=14261 0107485
234574_at jo.0212393 jo 0.0614152 j -0.0599713 j-0.439342 1.47464 j 1.38473 jo.383024 0.837186 j0.405169 jO.0877862 -0.0934167 jo.0711899 j-0.74721 -0.255514 :-0.588035 j -0.432962
234643 ιιΐϋϋϋΐι 0 •0447896 .1G259 j ||ii|jjjjjjjjjjjj -32989 -0.102223 0.2253 046265 j!!ll|| |jjjjjjjjjj 339673 2.06193 1.18K85 1.0668K 0.593 2446 269621
234707 j .0662947 jo -0.0866256 jO.171365 jO.392197 -0.20489 j-0.044384 j-0.113257 -0.127011 :-0.238042 j-0.046638 -0.294S17 j 0.0101562 j-0.0662947 -0.0278578 j-0.189463 j-0.26766 illiiilll 0.350343 0 0.011847 -0.021ifti5 0.0684009 0.137561 C.388524 0.04-842 Λ251135 0236189 ||| ijjjjjjjjjjj 0.188524 C.1SS524 0.730404 0.0275321 j|jll ijjjjjjjjjjj .476761
238183 j-0.149339 j-0.00639486 0.281712 j0.0391321 jo 1.50499 j-0.195792 j 0.0197988 1.04441 jO.194015 j0.368251 .23666 j-0.094305 jo.63986 -0.0668364 j0.57519 j-0.396945
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Table 9 GDS5072 RNA expression values of U133 plus 2 probes resembling human crisprs
Patient numbers
Probe ID GSM 1095883 GSM1095886 GS 1095877 GSM1095878 GSM1095879 GS 1095880 GSM 1095881 GSM 1095882 GSM1095884 GSM1095885 GSM1
1554007_at 547.b 2 ^. 978.1 518.5 -to--, ; 3291.7 1032 197.1 895.7 1710
1554108_at 106.2 123.1 180.2 341.5 284.1 151.8 56.3 16 65.9 195.8 192.4
1554723.x. at 4.7 18.2 17 2.1 34.9 1.6 1.5 27.6 1.1 .3 i■:.
1555014_x_at 146.7 68.5 123.3 298.3 302.8 231 264.6 42.4 111.2 45.3 194.5
1556520_at i.20.2 46.4 bii.S 19 31.8 74.3 144 5S.K 93 7 75.5 45
1556521_a_at 62.7 42.8 28.2 2.7 5.5 53.4 3 18.5 5.3 2 2.8
1556701_at 19.9 99.6 19.4 17.7 12.7 2i <; 2 >A 67.1 17 23 21
1556836_at 5.1 4.4 16.6 2.7 6.5 5.9 22 3 8.1 4.2 42.5
1556837_a_at J 2 2 C..2 i 3 i 10.6 19.2 10.3 3..1 4.6
1557339_at 3.8 21.8 2.5 8.3 16.8 2.2 26.7 10.3 8.3 9.1 1.5
1557341..x..3t 73,7 19.3 14.4 36.4 70 a Λ.8 14.9 3.4 .1 ΐ >
1557539_at 131.8 92.1 162.9 134.3 270.8 252.2 227.3 8.6 21.1 65.2 176.8
1557555_3t 5.3 76.9 sC t. 60.2 ?()■;.') 578 7 t'- > 27-i 9 5 53 8 li> ■
1557645_at 17.3 70.8 32.2 35.1 41.8 78.2 40.9 3 45.3 61.9 12.5
1557807_a_at 3 S 24 7 ? ;.7 If-..7 4.1 30.6 5.0» 16.2 5.5 1<>
1558275_at 156.7 198.3 881.4 375.9 622.5 835 406.3 403.1 393.7 198.5 265.7
1 ¾ 5 :! .' t<;.2 62.9 109.2 69.1 8. S 0 2 118.2 K3.4 106.5 215.9
1558489_at 3.9 3.4 9.4 6 33.9 5.6 14.1 47.5 10 1.5 12
J .V^'JGO.. 15.4 8 22.2 31.8 1■; 5 143.6 12,7 16.7 2-1./ 13.5 tO.f.
1559053_at 115 5 58.4 101.7 127.7 90.2 140 95.7 58.3 29.2 51.4
1559054_a_3t K-1.7 265.1 297. 401.6 fi i» 7 WW .5 451.4 7 10 ?. 313.1 166.8 667.1
1559151_at 119.2 76.2 82.1 6.4 6.3 60.9 2.5 57.1 23.5 81.1 42.4
1559166_at 17.6 6.5 K.9 1 >. / 18.7 94.6 14.3 1 ii 15.1 15 >.
1559232_a_at 200.5 88.1 345.6 121.4 551.6 323.9 171.5 156.3 63.1 48 235.3
1559278_at 15.9 3.7 50.8 2 7 ?. .! 25.it 12 10.4 9 7 }.?. 8.3
1559434_at 3.4 14 2.1 1.5 36 4.4 5.9 2.7 2.1 4.3 1.8
1559563..3t 14,1 12.9 8 9 8.4 11 78 9 S:\ -S 13.7 20.2 6.1
1559565_x_at 11.6 6.3 9.8 123.1 10.5 6.7 18.7 39.5 46.1 7.9 35.3
1559770_3t Γ· 8 16.3 5.1 18.9 b > 17 -i 3 25 ·1 51.1 29.3 6.4
1560185 nt 2.6 3.3 8 2.7 3.2 26.3 50.4 29 1.5 2.8 3.6
1560.^0.. it 1ti j 105.3 ί, ί.7 55.2 90.4 76,6 i4.6 18.7 41.5 108. 3
1560476_at 75.1 70.9 300 192.9 233.6 221.8 262.3 72.2 81.6 50.8 190.4
1560498_at 7.1 10.6 5.5 S.K K.3 9.6 4.1 3 '■> 7.4 7.3
1561092. at 54.2 77.1 81.4 6.3 17.8 12.4 29.8 8 18 12.1 32.1
1562055„at 135.1 76.7 121.2 61.8 107 S 106.5 2 J. 11.9 SS 4 :o.{. 5-5.7
1562586_at 6.3 19.6 37 15.4 29.9 22.7 25 17.5 13.2 19.7 13
1562642_.at /Λ5 » 2.C. 29. J 31.5 16.9 62 23.7 6.1 H 40.4
1562723_at 4.6 110.8 80 116.2 74.4 37.5 82.6 57.8 65.7 116 109.7 ι ¾ω«0 ...-!ΐ 77,1 81.9 38 ¾ ;") 1 3.6 ■1 1 :>..? 7 n 26.1 10.7 >..?.
1563460_at 44.6 7.5 64.8 4.8 77.6 59.1 145.4 35.7 3.9 34.2 72.3
1563690_3t >. -. 2.1 10 5 4 8 ¾ 5 4.5 10.7 0.8 6.1 1.1 12.2
1563958_at 6.2 6.1 16.6 65.1 37.6 93.2 11.4 95.7 4 44.5 49.7
1564424_at 3 if) 2 46.1 177.4 101.4 5?fe. J ■i i? i J20.6 2 57 -1 54.6 c(. :> M M,
1564498_at 136 247.7 241.9 462.6 336.6 300.3 242.3 121 204.3 157.9 218
1564545_3_at 77.8 10 36.b 17.9 W.b 44 14.2 10.9 19.7 36.9 i *
1564984_at 12 52 19.1 9 5.1 66.5 77 14 8.8 31.2 9.8
1565801. at 51 31.5 90.7 llllilllll 6.3 46 2.4 43.1 3,9
1565845_at 130.6 57.1 157.2 18 30 176.7 100.3 43.8 101.2 24.7 18.5
1 'ioiiO J.? 111.9 27 ·) 17.8 16.7 1 J7 6 0 . 28 9 40.6 58 '·· 61.2 61.4 566033..at 8.7 17.6 51.5 5.7 65.3 7.8 7.8 60.9 25.6 7.6 3.2
1566428„3t 1.7 10.1 1.5 12 3 1.5 4.7 31.3 2.8 1.1
1566503_at 18.1 26.2 13.8 18.6 26.1 119.3 17.3 10.6 6.4 18.8 12.6
15665Q4_at 51.1 68.7 80.2 135.5 128.3 2b * 56.4 2 * 79 42.it
1566548_at 6.5 14.1 62.8 31.1 8.2 23.2 8.5 21.9 30.1 16.8 19.2
1566549..at 90.7 72.6 133 «3 6 l l i ii 164.6 I ii(, 7 ; 1 3 118.1 48.6 211.6
1566803_at 8.5 9.4 25.6 15.7 15.3 59.6 11.5 7.6 11.7 4.3 14.9
1567031_at 68.S 3S.7 2Z 5 66.1 1 4 7 59.3 ' o 3 13.1 38.9 ■35 2 4 .6
1568780 at 71.4 45.3 80.6 133.1 312.3 508 242.3 266.3 14.2 71.3 364.6
1569041_at 320 2 626.5 K_> ; 131 55 1 25.1 7ii.y ■i'M. ¾
1569405_at 22.1 17.1 17.9 43.6 13.5 40.7 2.3 52.7 23.7 14 18.4
1569603„3t 63.6 61.S 31.1 34.7 35.3 55 5 56.7 ;(: 7 45 4 57.7 52.7
1569981_at 3.2 1.4 11.8 15.4 1.8 2.2 53.9 17.8 10.6 12 2.8
1570215_at 20.2 2S 5 7.1 11.1 i i. i 10.5 ■;M 2.1 1 .3 2.0.3 .1 3.7
201205_at 191.1 105.1 182.3 206 322 280.1 245.1 247.8 136.8 152.7 189.1
2022KO .il •.'2 5 •1.2 44.1 5.9 10.5 li!!!!!!l! 6.4 3 «. ■ ΐ 1 24,4
203326_x_at 61.7 54.8 21.2 41.9 27.5 23.9 82.4 35.7 63.4 14.8 18.9
;o i ;s?....r 15.4 J.4 8. 5 10.1 K0.7 52.1 ;:■) M. t
205703_at 93.4 6.6 12.1 8.8 6.8 7.3 11.1 30.4 48.1 4.6 5.7
2058Q0„at 2 5 10.9 3.<S 4.2 5. 5 7.2 3.8 6.7 3.5 3 4
207730_x_3t 2498.2 821.4 3827.1 3824.6 5293.1 5825.2 4171.6 2206.3 1155.9 979 4748.9
2 ) Of.7·» 1375.9 424 1991.9 Ί 834.3 2<>85 5 2416.1 1 ¾(.',·.■-> 1511.2 VY) 505.8 1364.5
210723_x_at 112.5 147.6 160.9 105.3 162.9 173.7 156.6 139.3 134.9 95.4 140.7
211633..X..at fi 6.7 16.8 7.6 V/ '-. 7.5 10.9 10.9 ΐ¾.ί· '■1.2 26.7
211878_at 9.8 33.2 13.4 2.6 20.5 10.4 6.4 6.8 25.9 3.1 14.1
2 1 4 ΚΛ .ii 45.3 36.9 2-1. b 5.4 10.5 C.K. I 11.6 10.8 5 14.8 1!)
214227_at 7.5 7.1 56 24.4 54.3 21.5 9.7 24.7 22.3 7.2 41.2
2 1.5 hi , .!· 5 41.9 34.1 I S K Γ! 5 54 2 1.8 7 -■; 7.6 4.4 ί'1
214979_at 32.9 44 58 38.1 51.4 47.8 49.6 16.3 13.3 26.2 62.4
2 155-58 .Λ 61.1 19.S 5.8 ¾ 7 17.7 78.7 liiiiiiiiiiiiiiiiii 58 1 3.2 .7
215675_at 13 4.4 21.6 11.5 41.1 25.5 14.3 4.1 18.7 14.1 5.5
215774. s... at 13.8 ■ , 4,9 3 -S 2 f- 2.;· 3 5.4
216249_at 67.1 92.7 102 41.7 67.8 52.2 100.7 53.7 25.3 10.8 26.9
; tc>3 i .it 107.2 178.1 149.6 116.5 Ι ϋ.Κ 130.1 12 J.H 116.6 205.S 174.5 5 .2
216318_at 88.9 20.1 80.3 21.4 66.8 75.3 54.1 29.5 36.7 43.5 32.1 1f;.J 7 :ii 15.4 S f; 10.6 4.9 10■> 7.7 7.5 5.5 2.7 K.3 11.8
216431_at 8 23.1 4.9 4.4 15.1 10.6 13.7 4.1 8.2 18.4 15.1 K;f>8 t .1! 45.7 1.9 16.1 ;ox 22.5 8 5 2 2 liiiiiiiiiiiiiiii 16.7 6.1
216739_at 118.6 125.8 309.7 207.6 105.8 178.6 330.8 98.4 90.2 107.1 40.2
:' u;;vi ....i 88.1 5-5 7 40.1 13 Si,.2 ■58.3 101.6 52.8 /.'■) 65.3 63.3
216772. _at 3.3 2.9 5.9 5.1 51.7 5 40.7 1.9 50.1 70.5 6.2 10792 at 42.9 137.8 8.8 !» j.4 9.1. ) 10.4 h ->7.9 30.2 42.4
216801. _at 117 109.6 89.5 94.3 14.8 106.9 176.8 104.1 140.5 121.6 99.6
4.4 59.9 46.8 17 4.6 ΊΛ 74.3 56 t rt.S
216936, 146.8 33.1 67.1 12 17.9 153.8 43.7 34.2 65.1 66.9 9.1 η /ύΐΛ _3t i.2.3 li.S 8.2 37 8 46. 1 9. 5 l li>.8 4.1 i-i 24.2 5.1
217091. .at 28.8 16.8 31.6 15.1 44 31.8 42.1 13.4 1.3 10.7 2.3
2 1715 644.5 26.1 W.H 1403.1 1341 1843.9 760.4 183.9 j ii i 570. j
217193. _x_at 119.1 121.8 184.7 86.9 72.6 112.2 71.3 106.6 33.7 75.8 64.3
..l m .> 181 5* ί (> <2.f. 900 1075.9 W i." 324.7 '^ .!> 149.5 J}%
217490, 93.7 51.8 189 106.1 176.6 179 124.3 51.5 80.2 82.2 193.5
22107 t .■li 2 t 9 7.4 18.2 9.2 I'-U 70 6 19.4 7 ;' 5.3 15.5 7. -5
221137. _at 85.8 13.1 7 6.9 52.5 82.9 83.7 62.4 5 27.2 10.5
22 1 L W . .s_at 109.1 64 5 70.4 19 i.O 77 f» J 6--U 22.1 5.2 s.¾ 97.5
221625. .at 41.2 9.5 60 143.4 86.9 192.1 8.2 66.9 20.9 30.1 85.3
222968, ,at Si t 4 509 214.1 515.7 1 Vi.l 228 o 27 >A fe2* 9 •5b 296.1 6
224238. _at 5.5 10.7 12.5 2.3 5.4 6.4 8.8 1.9 14.7 5.4 25
2200( 1 _s_at 8 iiiiiiiiiiiii 13.5 7.1 4.5 11.8 4.4 5» 4.4 3 2 5..!
226812. _at 11 5.5 18.1 61.7 16.3 56.3 77.1 9.1 83 8.4 55.5
727ί·61. 5.5 11111 9.0 (,.7 5.1 8.8 6.8 9.rf ■-..?. 6,7
230162. s_at 5 14.6 69.2 10.2 82.9 6.8 46 10.4 4.6 5.6 13
23040 _s_at 10.'.7 15.7 42.9 92 8 l.?f: 7 56.3 95.9 32.0 77 110.2
230461. .s at 1599.6 735.6 334 921.4 1724.4 1949.3 3403.4 762.8 754.7 339.6 1588.1
2 3f)t/).'i 1 =1 6.5 81 K.4 6.1 =13 9 40.3 9.4 24.4 ΛΊ.8 3.4
231818. _x_at 25.5 127.8 50 160.7 37.6 193.9 245.5 45.3 149.4 40.8 159.9
2318S8. ..l K>..( 199.5 «o <) 11.6 97 SO. I 94.1 32.8 llllillillll 02.K 31.2
232344. _at 220 86.7 252.8 199.2 220.7 193.9 402.3 273.5 89 93.1 352.7 « '!\ 103.6 9.1 35.9 144 l« -n >, 2 V. 9 179.7 2.9 53.1 12 1 . ΐ
232778. _at 139.9 103.7 358 376.1 426.8 504.4 109.8 257 105.7 70.4 592.8
; -!,?'.: 10 .at 6 40.1 22 45.6 20.1 jt. i; 1.5 2. -2 2.6 31
232947. _at 5.2 18.2 19.5 30.9 4.5 2.9 3.5 1.7 1.8 2.1 79.3
^JWIS .ιί 98 ;l 38 76.4 i.?5 152.2 301 3 ¾ 6 :, 28.1 61.4
233266_at 107.8 120.2 82.9 80.7 38.7 97.9 69.2 76 23.5 12.4 92.3
2Ji"JS2 .!· Γ,-'ι =1 7.3 17 8 -> 1.3 2 H I >.l •i :··: 2) b J 3.2 ■13.7
233390_at 8.6 12.2 8.9 23.6 3 6.9 14.5 5.1 7.6 3.7 6.1
. i ¾ 5 ..l 5.5 5.7 5.9 5.-J 6 ■■..2 7.8 4.4 7.4 3.7
233629_at 21.5 19.7 44.4 14.4 42.3 9.7 8.6 28.2 6 59.5 6.2 W:..l: 116.6 4.1 0.;' 61.5 t«8 147.8 5.9 48.6 15.9 65.5 45.6
233674 at 258 48.5 344.1 395.2 613.9 1409.6 332.9 325 222.2 134.3 727.9
233697_at 1.3 19.9 H.~. 11.8 4.1 1.6 30.5 4.5 27.4
233706_at 9.2 12.5 55.7 23.8 11.9 11.1 85.5 52.4 10.7 10.6 23.4 337 ;; ,j! 72 6.5 4,5 49.5 1.5 4 41 8.2 7-1 2.7 J.'-l
233717_x_at 30.4 16.9 44.1 71.3 165.3 30.2 32.8 29.5 17.6 18 15 3W .1! 10 18.6 0.:t 7 123.7 >>.; MM it 1 27 i¾
233853_at 66 16.1 67.5 3.2 35 61.5 23.4 33.7 49.3 51.8 52.1
233920..3Ϊ 9.1 129.4 37.1 61.2 107.4 ■)S.S 67 iJ2 32.2 16.3
233921_s_at 29.3 38.4 633.1 85.8 528.6 980.2 488.5 231.5 93.4 64.2 526.1
2340° 5 .ii 3.1 41.8 85.6 1 if: G j.08 163.8 69.3 ■■3.4 51.9 ■17 .4
234214_at 34.6 199.8 150.4 93.9 102.8 217.8 21.7 104 72.2 54.7 103.6 J-5-H'1 .!! 22 f, 78.1 42.6 w. K 98.8 12».5 "C.S 39.5 26.7 17.2 85.6
234454_at 4.1 30 66.3 112 27.1 22.7 62.5 5.5 1.6 52.9 49.8
.Λ 55.8 /28 70.8 ■-,2.2 121.7 84.3 161.7 32.1 3 <..¾ 64.2. 70.7
Figure imgf000132_0001
234707_x_at 21.3 10 29.8 17.7 50.2 25.5 15.1 5.8 12.3 70.3 50.7
7363·.)¾ .it 107.2 112.1 (Si' i 38.7 i-71 I S 164.6 50 77.5 109.4 57
238183_at 18.5 8.7 42.6 8.1 57.5 67.5 19 150 74.4 11.1 98.2
2'ii'.i(V} ,ji 37.2 1.9 10.5 3.5 25.2 52 1.6 31.7 1.9 2.8 9.1
239815_at 933.4 191.4 994 1637.1 1934 1126.1 884 450.1 421.8 395.4 845.2
241468_at . P.H 4. it 145.1 ! 20 t><2 ! y, *.■-> 189.3 874 107.1 it Ϊ 45.6.2
242575_at 33.9 7.6 13.9 35.1 80.8 53.4 72.1 9.2 7.6 41.9 5.5
5i 4.6 36.5 90.4 Ή.2 61.6 >n 1.7 53 f.').f.
243147_x_at 797.9 301.4 926.1 816.7 1196.3 1625.6 700.4 332.3 72 294.5 825.2 13.7 130 159.6 19.7 47.2 52. ) 84 73 7 112.9 14.3 ii 2
243246_at 199 50.9 73.6 96.6 186 130 74.4 81.2 52.5 46 86.7
150.2 312.7 250.1 2 i0 ί .>(>-?.■> ■ i 164,5 194.4 166.3 337.8
Table 10 GDS5017 RNA expression values of U133 plus 2 probes resembling human
crisprs
Patient numbers
Probe ID GSM1141222 GS 1141223 GSM1141224 GSM1141225 GSM1141226 GSM1141227 GSM1141228 GSM1141229 GSM1141230 GS 1141231 GSM1141232 GS 1141233 6SM114123
1554007 at 418 1019 404 TV, A l l 2.101 2168 1 1649 lrff,0 896
1554108_at 196 123 156 401 358 355 156 588 595 702 485 530 238 i ' -i ;.- j x if ! 3S 109 0 9 29 52 !!!!!!!!!!!!
1555014_x_at 108 8 141 34 52 17 106 77 47 35 76 77 111
1556520_at iiiiiiiiiiiiiiiiiii 52 47
1556521_a_at 2 3 25 3 25 1 2 7 1 1 null 31 21
15567Ql_at 111111111111 8 29 16 40 .12
1556836_at 2 3 36 27 4 1 28 41 7 3 5 17 2
1556837..a...at liiiiiiiiiiii 8 11 4 13
1557339_at 6 62 10 22 33 33 60 19 5 7 16 10 37
155734 l_X_3t 30 ss 83 41 SO 27 12 1') 49
1557539_at 1294 701 1251 285 378 878 384 406 609 386 712 667 864
1557555„at 1361 w, ? 1660 465 .. ;-! 1423 KR" 499 1403 I J W <iv; lj-32 1102
1557645_at 20 6 3 4 4 5 72 8 2 7 1 2 13
1557807_3_at 13 lillililililililii 29 2.1 23
1558275_at 75 241 157 120 124 135 179 119 131 117 103 160 325
1558385 at 1553 56 54 + 3 i.¾ 1634 475 4 It, 1630 430 884 1 102
1558489_at 74 2 1 37 3 25 35 39 16 26 34 14 1
1558960_a_3t 81 73 1 1 46 8 67 122 39 55 61 60
1559053_at 86 197 404 87 48 109 112 118 123 163 79 88 137
1559Q54_a_at 277 r.n 863 21 1 192 25 / 212 iM 2 W 3->S 162 224
1559151_at 75 110 1 38 72 33 35 108 112 218 64 99 90
1559166_at iiiiiiiiii liiiiiiiiiiii 35 48 11 M 3? 71 W: :M 49
1559232_a_at 250 178 118 134 189 56 184 284 3 205 59 146 364
1559278_ at liiiiiiiiiiii .V: 4 1 7
1559434 at 2 26 12 2 2 5 3 2 26 1 6 1 39
1559563_at 16 1111111111111 KG 6 44 42 18 34 -1 4 90 1?
1559565_x_at 9 5 32 2 17 14 72 3 66 17 18 5 52
1559770„at 14 III!!!!!!!!!!! 1 !!!!!ll!!!!!!l 4 13 It) I!!!!!!!!!!!!!!! !!!!!l!!!!!!!l !!!!l!!l!!
1560185_at 8 2 34 16 31 56 9 54 11 10 9 50 24
J 5602 30 .-it 85 54 78 63 38 4.1 4 58 95 81 222 -> 188
1560476_at 101 78 69 26 129 16 51 48 76 3 28 86 123
11 64 71 Λ7 78 19 20 72 51 110 10
1561092_at 1014 351 953 475 214 1024 1215 340 774 601 730 1010 1669
1562055_3t 14 I!!!!!!!!!!!! !!!!!ll!!!!!!l J'.i •33 15 !!!!!!l!!!!!!!!l ?K 38 !!!!!l!!!!!!!l !!!!l!!l!!
1562586_at 7 2 4 23 37 30 2 3 40 21 59 35 10
1562642„at 25 65 45 20 l!l!l!ll!l!l!l!ll! 4i¾ 50 !!!!!!l!!!!!!!!l 52 !!!!!!l!!!!!!ll! !!!!!!l!!!!!!l!! 45 !!!!l!!l!!
1562723_at 5 53 40 1 12 60 96 39 6 2 8 16 3
1502-?< :1 111!!!!!!!! 26 44 3 iliiiiiiiiiiiiili !l!l!ll!l!lil 3 !!!!!!l!!!!!!ll! 12 i!i!i!li!i!i!i!ii !!!!!l!!!!!!l! !!!!l!!l!!
1563460_at 4 72 2 23 2 40 5 4 39 4 23 19 14
1563690...at 88 116 85 109 89 144 112 56 136 104 153 161 123
1563958^at 8 40 64 15 1 46 66 3 38 2 22 13 5 l ".o J2 i 449 256 2 1 3 JO? i!i V 666 716 4 ib KS i 924 51 ! H 5J 1010
1564498_at 72 109 56 57 61 65 102 157 62 131 24 64 163
1564545„3„at 6 3 27 I!!!!!!!!!!!! 26 !l!l!ll!l!lil " 55 31 25 !!!!!l!!!!!l!! 7-1 6
1564984_at 2 14 3 44 15 4 3 23 2 31 3 4 27
1565SQl_at 4 38 !!!!!ll!!!!l! ^ 32 -S5 I!!!!!!!!!!!!!!! !!!!!!li!!!!!l!! 52 3
1565845_at 103 7 88 24 3 48 24 2 5 47 98 42 35
1566032. at 76 35 7 58 70 66 46 60 JO 1 2'! ■■.n
1566033_at 89 229 31 1 21 92 41 3 13 4 6 5 41
1566428_3t liiiiiiiiii 78 I!!!!!!!!!!!! 100 !l!l!ll!l!lil 83 63 27 3 !!!!!l!!!!!l!! 15 f;7
1566503_at 5 95 28 1 27 12 2 3 24 5 22 10 24
1566504„at 4 ■U- .18 !!!!!il!!!!l! l!l!l!l!l!l!l!ll! 21 9 21 40 54 !!!!l!!l!!
1566548_at 52 12 2 25 43 34 10 22 20 31 44 40 5
1566549_at 44 30 3 i 32 !l!l!lll!l!l!l!ll I!!!!!!!!!!!!!!! !!!!!!l!!!!!!!!l .17 3S 36 16
1566803_at 3 3 5 2 28 3 5 16 3 7 5 2 2
1567031 at 96 48 % 40 72 4 1 * . 54 80 97 55 51 54
1568780_at 651 248 259 70 209 114 263 228 400 197 159 470 646
1569041_3t 61 85 . 29 77 58 178 57 222 52 52 97
1569405_at 37 22 2 14 6 29 2 1 22 19 3 24 3
15696Q3...at 55 27 4 25 15 B 24
1569981_at 22 3 36 36 3 1 2 1 26 9 15 16 1
1 ·".702 1 :.. III!!!!!!!!!! 1:· 2
201205_at 448 327 492 267 390 274 391 366 144 212 139 255 416
2022 SO .!! 66 51 40 60 49 32 =13 IS >H 69 5 1
203326_x_at 116 13 147 149 201 120 178 180 69 184 232 110 253
2< /S2 27 2b 8 M 71 16 52 37
2O5703^at 54 58 52 80 52 12 38 37 51 5 _6 73 2
205800...a÷ 16 37 21 13 44 29 iiiiiiiiiiiii
2Q7730_x_at 1144 734 686 626 820 1130 1041 621 1277 641 1258 1445 1229 i0(: "/g .,! 1715 2190 1010 1122 1411 1559 1854 1214 2 51 ') 1147 1934 15'.: 5 1423
210723_x_.at 89 3 91 44 31 51 89 50 79 66 21 107 131 .
;
21 U -M » .i! 4 (; 52i", 1 % 166 Vif- 506 606 22'i 186 1.50 219 MS 20S
211878_at 7 12 5 4 26 1 2 22 3 1 3 7 1
51 48 75 65 52 54 44 44 6 ? 5 1
214227_at 50 69 57 7 53 88 51 89 24 32 56 31 62
1 5 6 iiiiiiiiiiiii! 13 9 20 32
214979_at 31 63 5 5 2 30 2 40 3 24 23 6 33
2 13:, K .li 16 liR 27 -'3 2i 5 3S 1 2¾
215675_ at 26 3 79 4 5 4 97 9 12 7 73 15 11
215774_s_at 155 99 222 1 5 234 120 2H2 80 !=!(; 127 S ! 2 /ii 3 W
216249_at 270 109 107 186 137 119 112 112 106 95 166 96 142
2 1G ¾0 J 51 12 ■■10 36 72 64 4 40 2" 17
216318 at 23 91 143 3 45 56 65 45 37 53 9 36 64
10 16 8 9 15 6
216431_at 5 3 36 8 10 29 50 41 17 2 2 30 1
; tc>hs i __.it 44 126 27 2 5 K l 72 58 30 11 -so -,,f'
216739_at 25 46 36 30 6 39 92 20 35 48 8 34 7
21 I Ji 26 si 4 iiiiiiiiiiiii s 34 12 3 IS 2 32 2!
216772_at 2 5 41 2 12 26 26 37 35 7 1 25 26 l ")2 19 !!!i!!!!!!l! III!!!!!!!!!! t>7 41 33
216801_at 53 7 3 2 27 3 45 2 17 51 41 5 4
!lbo-i-l .Λ 5 n--> 7 112 -S3 J Oil 2* " 16
216936_at 38 10 63 10 59 57 2 5 45 40 15 74 47
2i 0( :..ii .M 108 112 199 194 328 "K -.'2') 171 173 118 244 408
217091_at 59 9 2 1 15 33 42 3 29 22 3 12 16
217 LS? ..t 127 249 95 95 (>i; 158 132 78 122 170 124 114 53
217193_x_at 1014 196 500 25 461 1579 710 146 45 257 34 8 101
2173S2 :ii 560ίί 6489 j. Wi 1755 ?;% 4012 3S52 3617 ',52? 35 i-1 J'.(;S 3K 54 5473
217490_at 909 154 493 206 295 397 460 277 415 237 314 425 349
221074_at 47 !»7 ■il 53 8 liiiiiiiiiiiiiiii 5 35
221137_at 34 22 25 13 1 77 7 6 48 34 87 58 49
221138..S..at 27 41 45 46 34 .V) 47 46 28 .10 27 3') 28
221625_at 547 434 415 449 489 522 717 764 1060 803 768 737 834
2?2%K .ii 25550 12798 2 iH "' 1 257 i 17614 17275 215905 18299 19264 18-320 J13¾ 20197 22572
224238_at 1 7 8 24 1 5 9 3 1 20 6 7 1
2- Xil ■■ 163 ! v; 129 154 171 59 22 i 124 70 IDS SO 1.5 23/
226812_at 141 110 202 103 176 106 121 96 88 70 86 161 152
227(>i>J ..i 56 iOO liiiiiiiiiiiiiiii 66 34 -S3 30 26 75 3
230162_s_at 74 4 33 74 3 147 116 141 192 131 39 229 293
2«.lOO.Vl-,f ;- 7 1005 3«S 75 471 M i 413 795 762 856 7ΊΙ 884 c-.52
230461.. t 2053 603 1159 1031 1283 1447 1988 1921 1211 1661 943 1273 3554
230694_at 47 79 19 9 35 23 5
231818_x_at 372 100 38 134 682 122 752 343 271 416 333 210 562
231888„at 21 iiiiiiiiiiii! 30 iiiiiiiiiiii 9 12 31 8 iiiiiiiiiiii
232344_at 347 170 328 133 380 208 205 144 109 386 96 399 266
232f».'b 132 199 .101 8 >A 2)1 72 84 183 HP 90 114 101
232778_at 297 242 387 205 245 400 257 391 285 415 465 514 422
2328¾ί...;ι 16 iiiiiiiiiiiii > 16 4 24 2 20
O :
am T> — :¾:¾¾¾ O : 50 i
m S!fSi StSii ¾ISS
Figure imgf000138_0001
en; aa * r-. ; -:-* -: Mi ¾¾i :¾::C?i::
Figure imgf000138_0002
:;::t0::: :: oo : ¾**5S ami
Figure imgf000138_0003
Figure imgf000139_0001
Figure imgf000140_0001
Figure imgf000141_0001
Figure imgf000142_0001
Figure imgf000143_0001
Table 12GDS2697 RNA expression values of U133 plus 2 probes resembling human crisprs
IPatient number
Probe ID IGSM158 63 1GSM158464 1GSM158465 1GS 158466 GSM158467 1GSM158468 6SM158469 1G5M158470 GSM158471 1GSM158472 GSM158473 1GSM158474 : GS 158475 1GSM158476 1GSM158 77 1GSM158478 1GS 158479 GSM158480 1GSM158481 GSM158482 1G5M158 mm*, ia 14.6*75 - : -' : . -. ■■ : .· -■ ■ -- . - ■ ■ ■
155 108_at 15.251 jio 110 110 10 11,2875 21.062 iio 10 10 13,4538 iio 10 10 iio 110.7465 i 10 13.4482 10 14.3146 11.826
10 illiilll iO iiiillliiiiiiiiiiii 10 iiliiiiiiiiiii iillll! iiiiiiiiiiiiiiii lS55014_x_at :10 116.0537 10 iio 13.785S .. 26.9922 11.0552 10 10 10 :29.8415 113.9712 10 115.3161 Ή.6846 jio 11.8079 144.9972 29.9585 :65.5219
1111111 10 11.8805 1111111 iiiiiliiiili 13 iiiiiiiiiii 14.62ji 23.2737 iiliiiiiiiiiii iiiiiiiiiii iilllliiiii iiiiiiiiiii 11.0103 iiliiiiiiiiiiii !ll!iiii i55652hnt il&084 =21.309 137.9187 121.4342 28.3916 121.8732 19.2096 42.1426 38.7101 124.3411 12.5136 293063 117.4071 15.65 =13.4932 122.4433 119.2216 251691 120.8903 14.4005 21.1875
=■ : ' 179.377 liiiiii iiiitiiiiiii illiilll iilllliiiii liiiiii! iiiiiiiiiii 53.0431 iilllliiiii 12 39 6 2353 iiiiiiiiiii! 110.914 33.4548 !ill!!iii 71304 iillll
15S6S36_at 13.5173 iio =17.0446 i 10 10 iio 10 115.4685 10 10 10 i 11.327 10 10 iio 11.9459 10.1139 14.1809 iio 10 iio
llilll Iiiiiiiiiii 1111111 illiilll iiiiiiii iiiiiiiiiiiiiiii illiilll! liiiii 20.852 2Ϊ51 iillill 25.5741 iillll liiiii ΙΙβΙίΙίΙ llilll ill!! iiillii
1557339 116.3389 119.492 116.7317 135,3213 20.8621 141.0599 22.2216 25,1495 12.9226 118.5433 18.5474 37.9556 126,5117 139.3379 142.7061 135.1607 136.7165 26.3341 116.6688 42.6565 383872
15.6125 llillll 25.8754 illiilll iiiillliiiiiiiiiiii iilllliiiii 14.;i2S iiiiiiiiiiiiiiii III! iiiillliiiiiiiiiiii iiiiiiiiiiiiiiii IIBI! !i iii!! iiiillliiiiiiiiiiii iillll!! 48.4839 •48208
1557539 36.6575 134.1215 3.5262 125.6664 32.8492 124.2981 :26,6734 118.198 29.4885 19.8569 32,3242 ¾.4069 26.944 53,2313 141.436 ΐΐ.6667 141.5139 74.6383 160,8709 71.7934 57.2251
97.0205 llilll liiiiii liiiiii iiilillll 1111111! iiilllil! iiiiiiiiiii! iilllliiiii iiiiiiiiiii !i!li!! Iiiiiiii! iiiiiiiiiii iiiiiiiiiii iiiiiiiiiii iiiiiiii! iillil
1557645 ;21.2405 128.4568 168.7682 143.1646 35.2854 1966889 66.7971 167.9723 117.134 58.5613 133.263 107.317 135.0118 31927 12.1638 142,2612 190.2023 56.8361 138.3771 .38.7984 51.8152
!llii! iiliiiiiiiiiii ".- -· : iiiiiiii iiliiiiiiiiiii llll!!! iiilllil! 35.0325 iiiiiiii! 1£ ill!!!!!! iiliSiiii! iiiiiiii!! i ili i i i i i i i i i i iiiiiiiiiii iiiiljiiiiiiiiiiii iiiiiiiiiiiiii iiiiiiii
1558275 =133.339 1112.491 183.448 1121.115 121.157 181.0759 110.967 109.227 99.2675 105.438 136.38 146.827 1106.712 195.7148 ¾.6496 100.868 177.8282 110.056 1133.699 84.787 135.73
Iilllliiiii 1111111 iiiiiiiiiiiiiiii 39.5094 llilll iiiilllliiiii : ■■:. iiiillliiiiiiiiiiii illiilll illiilll liiiiii 33.6576 llilll! i ill llilll iiiillliiiiiiiiiiii i!li!
1558489 =10 110 no iio 10 iio 22.3727 iio 13.5647 10 22.3937 118.5357 126.7922 12.4282 iio 14.7205 110 24.8739 136.6289 24.3495 133.9027 iissecj is 10 Iiiiiiiiiii ΙΙϋΙΙΙ illiilll iiiiiiiiiiiiiiii 10 10 iiiiiiiiiii iiiiiiiiiiiiiiii
1559053 128.2806 iio 123.6532 In) 11.6104 113.8116 21.1121 389267 30.8625 120.2611 26.0614 21.8832 115,0753 136.5442 125.4439 :40.6266 10,8646 24.5902 138.7866 29.1875 =612302
54.9356 iiiiiiii 111111 ii ill li!! 210.1*9 147.3S2 Iiiiiiiiiii iiillllil! iiiiiiii! iilllliiiii iiiiiiii!! 160.326 iiiiiiii! iiiiiiii! i!iii!iiiiii till
1559151 27.6571 122.5024 110 120.9455 10 i 11.6583 2.778 10 10 12.8861 JZZ... 113.9844 10 iio ' 116.7045 .i26-89........ iio 13.3018 112,8729 21.7691 16.1026
llilll 32.6302 1111111 2S9S9 iiliiiiiiiiiii iiliiiiiiiiiiii iilllliiiii iiiiiliiiili 27.192 21.3304 iiiiiiiiiii 515205 61.4268 iiiiiiii!! iiiiiiiiiii !iliiii!! iiiiiiiiiii! iillll
1559232 77.1941 100.889 173.3336 1131.077 99.4607 47.5254 43.6982 148.4036 53.5687 ;S0.8809 73.3291 171.0874 160.2204 124.727 1110852 135.785 134.035 141.84 1149.037 122.125 194.1511
1111111 illiilll llll!!!! llilll ii ΙΙΒΙ! llilll iiiillliiiiiiiiiiii iiiiiiiiiiiiiiii llll llilll 111!!! llilll -¾ 7255 iiiilllliiiii llilll llll!!!! llll!
1559434 !IO iio 110 114.4067 10 iio 10 12.264 15.2232 iio 11.9131 10 10.5588 iio i 11.4235 iio i 10 21.8104 124.7231 13.2473 166723 l|||i|l|i|||| lilllilil iiiiiiii llillll i 3i5S illiilll llilll iiillllil! iilllliiiii 70.2186 57.4=589 iiiilliliiii iiiillliiiiiiiiiiii iiiliiiiiiiiiii 111! iiiliiiiiiiiiii iiiillliiiiiiiiiiii 547504
1559565_x :33.7856 152,2043 ■37.3227 148.41 76.1778 49.0918 51.5068 ¾.3429 52.6455 :44,6949 43,2292 130.1972 147.0893 :49.8291 146,1008 127.1796 ■ 46.8981 41.2389 146,9598 136.2672 127.143
14.92' 25.9676 ill!!!! 1111111 ; iilllliiiii iiiiiiiiiii llilll!! iiiil!iiii liBI! iiiiiiiiiii iiiiiiiiiii iiilliiiiiiii iiiiiiii!! iiiiiiiiiii !illiiil iiiiiiiiiii! iillil
15601S5 Ϊ8.2531 .8691 31.8096 135.3016 43.1296 1184735 23.8771 =22.4174 26.7123 21.1363 30.6349 33.3834 130.521 122.8153 147.6307 421869 134.7012 27.5949 148,6062 331943 51.377
iiliiiiiiiiiii 16.1393 iiliiiiiiiiiii ]£ iiiiiiiiiii iiliiiiiiiiiiii iiliiiiiiiiiii ]£ iiiliiiiiiiiiii iiliiiiiiiiiii Ii!!!!!! i ili i i i i i i i i i i ii ili i i i i i i i i i i iiiiljiiiiiiiiiiii iiiiiiiiiiiiii Iiiiiiii
1560476jt ¾6263 :43.8826 158.9756 161.2021 60.6092 140.4099 45.855 131.895 .40.9074 133.7505 34.253 ;33.8295 134.8407 136.94 1211.935 129.805 1149343 143.206 i 177.542 179.908 344.274 li|||||||||| 299585 illiilll 1111111! iiiillliiiiiiiiiiii illiilll iiiillliiiiiiiiiiiiii iiiillliiiiiiiiiiii iiiillliiiiiiiiiiii iiiiiiiiiiiiiiii : : ■- iiiilllliiiii liiiiii 33.9051 iiii!lilil Hill 11=111! illiilll! 111!
I561092 1213123 110 =10 115.7025 16.9675 123.5731 20.4695 156.3892 13.7843 10 10 117.8904 10 15.0024 122.1651 iio i 10.588 10 iio 10.2407 iio l£52055_at 92.4536 llilll : : iii=illiiiiiiiiiii 111!!! iiiilllliiiii 135 «24 lill!l! iiiillliiiiiiiiiiii i llll !!!!ll!l iiiillliiiiiiiiiiii iiiiiiiiiiiiiiii iilllliiiii iiii iiiiiiiiiii iiiiiiii! llll
1562586 125.5692 155.8674 iio 127,7075 34.8713 121.8915 40.8492 115,3071 21.4742 132.8847 45.8716 137.0048 126,0711 121.1594 124.9893 133.1449 133,1118 26.4477 143.2853 28.4553 123,5715
§11111 lie! 25.5334 iiiiiiiiilliiiiiii Ilillll !!!fiii iiiiiliiii iiiiiiiiiiiii iiiiiiii iiiiiiiiiliiiii iiiiiiiiiiiiiiii iiiiiiiiiiiiiiii iiiiiiiiiiiiii iiiiiiiiii iiiiii ilil ll 4:3635 Iiii iii 44822 illlilli
156.72._at :S2.74S3 101.508 154.852 117.629 109.447 186.6669 40.2822 :58.?327 83.4798 ;95.9011 62.1891 :84.1983 i 50.8808 183.0753 i 127.519 :40.2847 70.9047 36.2074 152.0978 34.725 39.0004
B525 i_3t !lll!! ΙΙΙΙΙΙΙ!! ΙΙίΙϋΙΙ lliiil iiiiiiiilllliiii -- : ■■: ;-■ iiiiiiiiilliiiiiii iiiiiiiiiiiii §!!!! iiiiiiiiilliiiiiii ■ -V 34.557 4: : ■ lliiil iiiiiiiiiliiiii iiiiiiiiilliiiiiii iiiiiiiiiiiiiiii iiiiiiiiiiiiiiii
1553460_at 10 10 10 iio 10 10 10.1743 10 J 10 10 10 i 10.3749 10 10 iio io 10 10 10 10 lliiil Ilillll 1111111 Ilillll iiiiiiiiiiiii lliiil iiiiliiiiiiiii • 87; iiiiliiiiiiiii iiiiiliiii 11111 iiiiiiii iiiiliiiiiiiii i I iiiiiiiiiiiii! iiiiiiiiiiiii iiiiliiiiiiiii iiiiiliiii iiiiiiiiiiiii 28.2842 iiiiiiii
1563958_at 27.69i≤ :2S.4376 iio 13.4715 14.2876 12.7924 32.3107 12.6253 10 iio 11.357 19.896 13,3955 17.7153 iio 14.5707 121.716 31.8522 123474 12.6842 17.3755 lliiil iiiii 19.8919 III!!!! 38,4022 iiiii!lll iiiiiiii!! iiiiiiii iiiiiliiii illl!l ;s.si5i iiiilllllii iiiiiiiiiii iiiiillii! 24.6:65 iiiiiiii iiiiiiiiiliiiii iiiiiiiiiii
1564498jt 108.278 :91.8756 J67.3229 i 128.454 107.135 ...i.84.191 104.16 106.378 107.797 128.352 117.643 97.098 113,983 :67.2346 J97.483 111.487 Ϊ9 6275 119138 ...i.98.5442 82,105 ;88.3259
29.1752 31.9575 iiiiiiiiiiiii lliiil i!!ili!!! iiiiiiiiliiiiiiiiii iiiiiiiiilliiiiiii iiiiiiii iiiiiiii iiiiiiililiiiiiii iiiiiiiiiiiiiiii 420326 iiiiiiiiiiiiiiii iiiiiiiiilliiiiiii iiiiiiiiiiiiiiii ΙΙϋΙΙΙ 2 1157 iiiiiiiiliiiiiiiiii iiiiiiiiiii
1564 84_at ¾5.507 i304.165 1317.621 :583.625 336.722 183.872 297.313 :286.8Q2 247,456 176143 358.838 1321.476 i 287.6 :294.649 i334.364 1271.033 i266.424 273,355 254.83 269.068 i318.896 lliiil iiiliii iiiiiiiiiiiii 39.6013 33.S3B 14.4355 iiiiiiiiilliiiiiii iiiiiiililiiiiiii lliiil iiiiiii! iiiiiii iiiiiiiiiii «.967 iiiiiiiiliiiiiiiiii iiiiiiiiiii iiiiiiiiilliiiiiii iiiiiiiiiii iiiiiiill iiil!lll iiiiiiiiiiiii 31.24.0S
1565845_at ;88.4858 128.836 180.593 141.817 166.375 i 130,571 140.267 ill8.25 102.385 ;96.5161 162.738 1177.129 i 243.841 162.246 i 166.05 155.488 175.908 184.068 i 170.013 180.776 ϋϋϋΙ ΙϋϋΙΙ iiiiiiililiiiiiii i!!i!l!! 111111 iiiiiiililiiiiiii iiiiiiililiiiiiii iiiiiiiiilliiiiiii iiiiiiiiiiiiiiii iiiiiiiiiiiii §!!!! iiiiiiiiilliiiiiii iiiiiiiiiiiiiiii iiiiiiiiilliiiiiii iiiiiiiiiliiiii iiiii iiiiiiiiiliiiii iiiiiiiiliiliiiiii iiiiiiiiiiiiiiii !!lll!ii! iiiliilii
1566033_at 117.7303 iio 12.4266 il3,6153 10.6079 23.2227 17.8083 15,6745 10 12.1551 10 10 i 10.923 iio 121.1322 15.3405 ill! 23.5755 17.6528 21.0724 21,6012 lliiil IIIII 111!!!! Iiiiiiiiiii !!!!!!!!! iiiiiiiiiiiii! 10 10 ill!! iiiiliiiiiiiiii 116331 iiiiiiiiii iiiiiiiiiii iiiiiliiii iiiiiiii iiiiiiii 23.6627 21,6485
1566503_at ilO 12.5349 iio i 10 10 iio 10 10 15.1485 iio 10 10 i 10 iio 10.2338 il3.3485 iio 10.7192 i 19.956 13.3485 10 lliiil 115.057 iiiiiiiil!lliiii liiiill iiiiiliiii iiiiiiii! 585176 liiiill i!iilll!! I!!!!!! :\ iiiii iiiiiiiiilliiiiiii i¾,2£ iiiiiiiiliiiiiiiiii 157.561 iiiiiiiiilliiiiiii iiiiiiiiii iiiiiiiiilliiiiiii iiiiiiiiiiiiiiii iiiiiiii
1566548_at 10 152.7097 18.6273 18.6369 20.6187 13.4125 10 :36.5665 11.7003 10 10 10 11.2788 10 Ϊ34.3593 121.8736 iio 21.9529 139.3681 11.6797 165215 lllllii 1111111 iiiiiliiii iiiiiiii iiiiiiii iiiiiiiiiiiii iiiiiiiiiiiii iiiiiii! iiilll iiiiiiiiiii iiiiiiiiii iiiilllllii iiiiiliiii iiiiiiill iiiiiiill iiiiiiill iiiiiliiii iiiiiii
1566SG3_at 10 iio :48.3964 i 13.6341 10 ; 523603 10 i39.37U 123.325 10 10 i23.4099 i 56.7246 :29.2915 125.5243 iio : 65.293 10 123.0884 24.4529 11.6017 lSS703i_3l iiilliiiiiiiii 29,9759 31.5133 iiiiiiiiilliiiiiii iiiiiiililiiiiiii . Ilillll iiiiiiiiiiiii iiiiiiiiiii lliiil !!iilB!i iiiiiiiiiiiiiiii iiiiiiiiliiiiiiiiii liiiill iiiiiiiiilliiiiiii iiiiiiiiiiiii
1568780_at Ώ.7452 «.9967 :37.8623 183.0057 37.605 i 27.8914 52.5079 ■ma. 28.1643 148.4945 20.2508 49.3107 : 50.8734 67.5178 143.461 1154.397 i 133.45 226.777 i 123.715 165.088 511.459 lliiil 1111111 iiiiiiiiiiiii !lilll iiiiiiii! iiiiiiiiiiiii! iiiiiliiii 141454 lliii iiilll •7.3028 i III iiiiiiiiiii iiiiiiiiii iiiiliiiiiiiii iiiiiii iiiiiiill iiiiiiii! iiiiiiii
1569405_at ilO 10 15.4821 i 14.2753 12.2656 iio ■4.;43< 10 13.7069 iio 16.6302 118728 iio 14.8218 i 11.0204 16.4644 i 14.447 14.9053 15.7079 18.0902 14.1557 lliiil iiillllliiiii iiiiiiililiiiiiii liiiill iiiii iiiiiii iiiiiiiiilliiiiiii lliiil iiiiiiiiliiiiiiiiii :: . ; iiiiiiiiiliiiii iiiiiiiiiii iiiiiiiiilliiiiiii :i : -■■ iiiiiliiii iiiiiiiiliiiiiiiiii iiiiiiiiliiiiiiiiii iiiiiiililiiiiiii iiiiiiiiilliiiiiii iiiiiiiiiiiiiiii iiiiiiiiilliiiiiii iiiiiiiii iiii
1569981_at 10 j 10 iio iio 10 iio 10 10 10 10 10.1185 10 iio 10 13.9907 iio i 10 10 iio 10 10 iliiiliii iiililiiiiii iiiiiίΐι iiilliiiiiii Hill! iiiiiiiiiiiii 111!! iiiiiiiiiiiii iiiiiiiiilliiiiiii iiiiiiiiilliiiiiii lliiil iiiiiiiiilliiiiiii iiiiiiililiiiiiii iiiiiiiillliiiiiiiiiii iiiiiiiiliiiiiiiiii i ill
201205_at :S0.4928 154.55 ί 7ι8.4ι74ι1ιι lllii!l iiiiii
109.233 142,302 i60,3041 109.888 109.477 ιιΐ 79.4ϋ006ΐι :73,7888 113.96 107.93 i 87.3317 105,279 128.109 109.815 100.413 104.051 i 132.56 83.7874 146.101 iiHiil 11!!!! iiiiiiiiiiiii llillill ill!!!!! iiiiiiii 10 iiiiiiiiiiiii! iiiiliiiiiiiii iiiiiiiiiiiii Iiilll U6035 iiiiiiiiiiiii Ilillll
203326j_at 16.5177 j 24.9967 iio jiolll 11.714 iio 10 12.5166 19.2048 18.5269 iio J 23.7772 ]ioV........ 10 15.085 V J.IO.......... ..J.......... i 18.7002 10 ...iio....... iiililiiiiii 113.857 1G2L1S3 iiiiiiiiilliiiiiii iiiii iiiiiii lliiil iiiiiiiiilliiiiiii iiiiiiiiilliiiiiii iiiiiiiillliiiiiiiiiii iiiiiiiiiiiii iiiiiiiiiii iiiiiiiiiiiiiiii iiiiiiiiiiiiiiii 101.777 iiiiiiililiiiiiii 12 797 iiiiiiiiiliiiii iiiiiiiiilliiiiiii 115.515 lliiil iiiiiiiiiiiii
205703 β iio I32.4&3S iio ill 2221 11.4275 i 13.747 16.1784 10 10 iio 18.9932 108452 iio i25.7298 16.7907 19.1485 i20,1226 13.0671 18.2742 19.2928 12,402ϋϋΐιιι IIIII 16.6819 iiiiiiill i!ill!! iiiiiiililiiiiiii iiiiliiiiiiiii iiiiiliiii
6 4051.26 111!!!!! III!!! iiiiiiiiii 15.1316 iiiiiiiiiiiii iiiiiiiiiii iiiiiiiiii iiiiiiiiilliiiiiii iiiiiii 29.3153 23.8133 iiiiiiiiilliiiiiii iiiiiiiiiiiii
207730_x_at :3945.05 ;3237.13 :3279.7 i4078.2 "¾3Ϊ' " 3523.07 4428.69 4312.11 14217.45 3802.89 397131 i 3791.56 i3636.97 i3728.03 ¾5121 " 3783.5 3578.78 i3238.39 3293.63 13774.07 iiilll iiiiiiiiiiiii iiiiiiililiiiiiii 635.76 4655.71 iiiiiiililiiiiiii ιΐϋϋΐι iiiiiiiiHiliiiiii iiilll!! ; .- 4640.54 iiiiiiiiilliiiiiii iiiiiiill - iiiiiiiiiiiiii iiiiiiiiiiiii iiiiiiiiliiiiiiiiii 443173
210723_xjt :516951 149.6377 m0654 i 51.1604 69.907 : 51.4008 59.8511 ¾2128 50.3047 921073 103.661 62.5734 :57.6O03 587152 :50.1O86 ¾.9091 ifrO.267 44.4548 155.2808 79.9228 8.9927
21ic33_x_K 45.7469 34.9927 Ilillll iiiiiliiii! 51.9903 lliiil 13.6632 iiiiliiiiiiiiii iiiiiiiiiii illilil! iiiiiiiiiiiii iiiiiiiiii iiiiliiiiiiiii iiiiiiiiiiiiii iiiiiiii
211878_at 10 iio 18.5115 111.4744 10 iio 18.1902 iio 10 15.007 14.6509 iio 10.1592 12.655 iio 10.6884 103473 10 iio 10.2409 iio iiililiiiiii iiiiiiiiiiiii iiiiiiililiiiiiii iiiiiiiiilliiiiiii ill!!! iiiiiiiiilliiiiiii iiiiiiii!!! lllllii iiiiiiii iiiii 18.2874 iiiiiiililiiiiiii iiiiiii iiiiiiiiiiiii 45.32S7 ,· ..··: iiiiiiiiiiiii ? .i S7 iiiiiiiiiiiiiiii iiiii
214227.at 143.0641 175.914 17.6614 i29.401 65.4733 i 17.9165 29.8645 36.9292 11.4169 i29.565 24.503 44.321 i 52.2895 191.0698 i62.786 ilOO.782 i80.4O15 83.1095 190.183 76.586 88.8761
illllill li ill lliill liilllii ΐϋϋΐι iiiililll iiiiiiiiiiliiiii iiiiiiiiiiliiiii iiiiiiii iiiiiiii iiiiiiiiiiiiii iiiiiiiililiiiiiii iiiiiiiiiiiiii iiiiiiiilliiiiiiiii iiiiiiililiii iiiiiiiiiiiiii iiiiiiiiiliiiii iiiiiiiililiiiiiii iiiililll
214979_at 174955 120.644? 10 ¾.6808 25.4905 :10 18.1152 12.6075 10,187 15.2611 19,8575 30.2389 12.3491 263303 122.9528 121.3745 =26.6=329 26,1506 132,8271 15.4372 131.761
■· : . - llllil 11111111 j. :: liilllii lliilil 337 4 iiliiillll iiiiiiii liiill 111111 iiiiiiiiiiii iiiiillii 23.8602 iiiiiiiiiiii iiiillliii lliifllll llllli
215675_at 3181 19.9488 127.9005 121.518 27.6829 17,0985 20,4861 :il.00O3 22.4694 15,4201 3i 024 13.683 20.1947 14.574 16,8892 11.8198 15,11 30.5938 129.5013 21.8248 14,5105
2!57K s 3i llllil lllll liilllii iiiiiiii lliilil 11111111 iiiiii iiiililll iiiiiiiiiiii 40.3273 iiiiiiiiiiii 33.4724 iiiiiiiililiiiiiii iiiiiiiii iiiiiiiililiiiiiii iiiillliii 16,8016 iiiiillii
21624 .at =25.8517 47.0384 126.5045 =38.90=99 31.0884 1167522 59.1792 =24,517 18,6471 31.2463 27.5128 134.1855 : 30.7376 =54.8788 J41.3701 131,7558 134,0995 33.5818 143.448 35,5288 54,652 liiill iiiiiiii 45.8032 65.2967 iiiiii! 54.701* ιιιιιιιι 4= 4336 iiiiiiiiiiii iiiiiiiiiiii iiiiiiiiiiii iiiiiiilllliiiiiii lllillll iiiillliii iiiiiiiililiiiiiii lliillll iiiiiiiililiiiiiii iiiiiiiiiiiiii iiiiiiililiii iiiiiiiii iiiiiiiiiiii
216318_at m :70.8045 :48.5681 147.8207 40,0074 1384251 50.7345 413831 41.8172 57.3083 49.0362 =34.8638 :37,2046 19.3333 :20.5942 19,5668 127,151 27,9275 129.3461 33.1422 27,345 ilillll ιιιιιιι 1 1325 lllillll :=■ :- iiiiii! iiiiii iiiililll ΙΙΙϋΙΙ iiiiiiiililiiiiiii illliiiiii iiiiiiiililiiiiiii 10 iiiiiiiiiiiiii 10 iiiiiiiilliiiiiiiii
216431_at 115.6195 137.3884 15.0234 123,9956 27.8632 120.3329 26,8464 22,4141 22.1688 15.1006 14.2071 297041 :28,6525 K.9089 153.7757 60,9551 148,524 74.2252 165.2553 65,3197 168,8033 lliilli 24.1424 lllillll lliilil lllillll lliilli lllillll lllillll •33919 10 21.0983 iiiiiiii •3.7639 10 32.3703
..... iiiililll iiiiiiiiiiii iiiiiiii iiiiiilll iiiiiiiii iiiiiiiii 719834
216739 jt ¾5.3094 191.774 103,469 168.909 142,78 182,2843 186.0639 90.5273 184.5783 129,544 115.074 163.383 127.034 18,507 109.449 104,461 117.425 125.403 111,882 iiiiii lllillll .....
21.0391 iiiiiiii lllillll llllil llllil 11111111 iiiiiiiiiiliiiii 23.3254 iiiiiiiililiiiiiii ii.;o7i iiiiiiiililiiiiiii iiiiiiilllliiiiiii iiiiiiii iliiiiiii iiiiiiiililiiiiiii iiiililll liil! iiiiiiiiiiliiiii iiiiiiiiiiii
216772 A 41.1817 14.0449 iS2.2031 =64.8648 10 10.4489 13,018 =14.2189 50.503 10 26.7395 183.8309 1100313 120.4038 134.4276 122,5 33 =35.2424 35,0946 158.4439 32,0552 29.174
:: lliilli -:■ Iiiillliii a . . ■.■ iiiiii Iiiiii am 121341 12,35? iiiiiiiililiiiiiii iiiiiiiililiiiiiii iiiiiiiililiiiiiii a iiiiiiiiiiiiii iiiiiiiilliiiiiiiii iiiiiiiililiiiiiii iiiiiiililiii 24,487* iiiiiiiii ii
216801_at 1309316 :30.1999 134.2512 1246165 39.4416 123,7377 10 :28.3008 24.3386 =31.9951 24,8112 ¾8386 i 20.1726 19.8017 128,0042 28.5288 131.2895 27.5575 134,0036 28,1537 ¾1085 llllil lliilil lllillll iiiiii lllillll 1 111 i 10 lllll Iliill 10 iiiiiiiiiiiiii i
216936_at 272428 149,515? ¾,7525 =32.6312 28.8199 132,2574 31.4442 =28.8766 42,8117 149,3486 34,4137 38.8304 i 45.4838 22.2821 133,9245 =45.9323 =27.3834 34,0933 152,9399 23.8398 151.008 lliilil lllillll i liiiiii lliilil lliill iiiillHil iiiiiiiiiiii lllll 14.2749 iiiiiiiiiiii iiiillliii iiiillliii 28.6389 iiiiiiiiiiiiii 29,0411
217091_at 10 10 10 10 10 10 13.0304 10 10 12,3343 10 10 10 15.9056 10 ilO 13,3992 10 10 10 11,5609
23.3518 llllil lllillll lllillll iiiiiiii iiiiiiii iiiiiii iliill iiiiiiiililiiiiiii iiiiiiii iiiiillii iiiiiiiilliiiiiiiiiiiiiii ;7.444I 311734 iiiiiiiiiiliiiii iiiiiiiiiiii
217133_x_at 13.7822 19.9621 191559 130.5766 22.6317 10 29.2649 16,9616 22.4789 27.7432 15.2425 i221857 i 23.2846 22,0901 i 10.4023 121.559 11,8543 10 10 10 19,3136 m iiiiii lllillll 2S 3¾7 Iiiililll 111 iiiiiiilllliiiiiii iiiiiiiililiiiiiii iiiiiiiililiiiiiii 38.0679 :: 4. 63,507 ■& ΙΙΙΙΙΙΙΙ iiiiiiilllliiiiiii iiiiiiiilliiiiiiiii iiiiiiiililiiiiiii lliill lliill iiiiiiiiiiii
217490_at ©.7907 =33.658 =24.7631 128.371 29,8877 1180123 26.1508 14,7529 10 23.2322 31.1143 =25.2331 i 3,7461 =53.7206 36.2485 162,048 148,2103 51,0929 187.0277 74.7201 194,4995 liil llllil lliilil llllil lllillll lllillll Hill iiiiiiiilliiiiiiiiiiiiiii iiiiiiiililiiiiiii illliiiiii iiiiiiiililiiiiiii 10 illllill i liil iiiiiiililiii iiiiii
221137_at 137.9854 ;23.9553 128.0547 129,6218 35.6891 : 38.4885 42,9428 279048 40.0623 :S4.S366 41.5757 1367904 i 30.0133 183.239 178.7141 127,066 185,6537 116.344 105,927 136,019 131.428
1111111 llllil lllillll lllillll liilllii : :: 2 6246 llllil iliill lllillll iiiililll iiiiiiiiiiii iiiililll lllillll liiill 26.603; j- .:=■ 31,9231 iiiiillii
221625 jt 137.8123 131.7993 136.9532 ;30.5337 29.0452 j 50.8061 63.1498 61.6113 39,0289 162,635 40.1315 ;44,5451 : 28,5295 195.1075 197.4371 =98,2976 122.692 137,883 160.882 74.256
222968,3! lllll lllillll llllil 140379 17044 lllll llllil llllil 10 iiiiiiiiiiii 241698 iiiiiiii lllll llllil iiiiiiiiiiiiii iiiiiiiii :; ;· 111111 iiiiiiiiiiii
224238 A 10 "iio 16.3905 i 14.155 28,675 ji 10 10 .10 10 11.1759 10 10 14.3709 14.4436 =10,0615 ilO 12.1546 12,9408 10 122.3882
:. \. .. lliilil lllillll Iiiililll 58.3241 liilllii 114,322 illllill 97.7591 iiiiiiiililiiiiiii ■ ii iiiiiiiii iiiiiiiililiiiiiii 117.454 iiiiiiiililiiiiiii 56.258 - -: iiiiiiiilliiiiiiiii lliill 166123 iiiiiiiilliiiiiiiii
226812 jt 152.9029 139735 =130.102 1146.023 157,692 J 80.3066 831423 ■: .: . 80.9008 138.5353 126.183 132.288 : 123.325 111.856 111513 146.27 1150.37 113,539 112.566 131.166 150433 lillll lliilil ιΐϋϋΐι -: liil llliill iiiiiilllliiiii iiiiiiilllliiiiiii iiiiiiiililiiiiiii iiiiiiiiiiii 1 liil iiiiiiiiiiii iiiiiiiililiiiiiii iiiiiiiililiiiiiii iiiiiiiililiiiiiii 2SC-¾3 iiiiiiiiiiliiiii iiiiiiiililiiiiiii iiiiiiiilliiiiiiiii iiiiiiiiiiliiiii iiiiiiiiiiiiii
230162_sjt 1419491 ;52:8398 137.219 ...1451143... 49.8857 129.3882 66,627 =285231 34.8052 =46.8102 19.2569 15.0549 J38.8615 46113 145,7328 142.2972 134.091 30.4822 411761 32,8778 «.4808
ZiOiOOjJt llllil lllillll 1111111 llllil lliilil 111111 iiiiiiiiiiii iiiiillii iliill iiiiiiiiiiii llllil iiiillliii iiiiiiiiiiiiii 55.0914 42,242 iiiiiiiii iiiiiiiii Iiiiiiii
230461_sji 114.2358 12.6448 13.5402 124.7424 16,2032 11,6382 36.5959 121.0061 24,0018 10 111903 132.4915 i 30.2128 24605 17,0484 19.1984 128.8173 18,8592 113,3219 19.2033 :30.3803 iiiiii .= .■.. iiiiiiii iiiiiiilllliiiiiii iiiiiiiliii 24,2834 liil lllll iiiiiiii iiiillliii iiiililll iiiiiiiililiiiiiii iiiiillii iiiiiiiililiiiiiii iiiiiiii
231818_¾_at 157.3387 159.3842 134.1893 «,2962 31.7383 137,9518 25.4254 17,8969 47.8058 140.7901 23.9973 15.9225 15.6918 35,27 1221224 126.6906 156,3153 32.0225 40.3341 30,4074 123,8626 lliilil llllil iiiiii 46.71S7 43,4618 iiiiiiililiii iiiiiiiiiiliiiii iiiiiiiililiiiiiii 38,2467 iiiiiiiiiiii iillliiiii ίΐίΐϋΐιι 38,25 lliill iiiiiiiililiiiiiii iiiiiiiililiiiiiii 36.9773 iiiiiiiii 40:4677 46.8667 iiiiiiiiiiii
232344 at il06.242 181.249 148.6705 1134.645 110.686 154.3197 61,1647 is0,7B 80.9232 161.3959 115,01 104.417 : 99.871 196.3921 Ϊ9Ζ0098 112.182 197,7752 135.45 1113.929 116,386 145.604
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Table 14 GDS4843 RNA expression values of U133 plus 2 probes resembling human crisprs
Patient number
Probe ID 6SM1050271 GSM 1050273 GSM 1050270 GSM1050274 GSM1050272 GSM1050260 GSM1050263 GSM1050261 GSM1050265 GSM 1050264 GSM1050262 GSM1050266
1554007_3t -0.177221 -0.143961 0.22.1073 -0.280409 0 0 0 0 0 0.20 -Μ ί
1554108_at 0.0686769 0.172031 0.104472 1.21022 0 0 0.0739002 0 0 0 0 0
1554723. . at! 0 1 0 0.834989 0 0 0 !!ll!l!l!l!l!l!l!l!l!! 0 ϋϋΐϋϋϋϋϋϋϋ!!!!!!!!!!!!!!!!!!!!!!!!!!! !ll!l!l!l!l!l!l!l!l!l!!
1555014_x_at 1.03: 526 1.35253 0 0 1.72207 0 0 0 o 0 o o
1556520_at OJ. 5 V". 0.22.'. i 33 0 -0.0103555 !!§!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 0.826115 0.2-10073 0.190927 o 0 0 0
1556521_a_at 0 0 0 0 o 1.36319 0 1.04257 0 0 1.30905 0
1556701_at n i 0 !!!l!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! o 0 111!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 0 0 Iiilililililil 0 0
1556836_at 0 0 o 0 0 o 0 0 0 0 0
1556S37_a_at! 0 0 ΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙ 0 0 I!!!!!!!!!!!! !llililililililil! iiilililililil 0 0 0
1557339_at 0 0 0 0 0 0 0 0 0 0 0
1557341.x.3t! 0 0 0 0 !lll!l!l!l!l!l!l!l!l!l!l!l ill!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 0 0 0 0
1557539_at 0.54f 5921 0.847764 1.05167 1.08162 0.846006 0.00589085 -0.00589037 -0.39728 -0.336243 0.152154 0 -0.0160546
1557555_at 0.775902 -0.181836 0.2 M- 506 0.1 7iiJ S 5 0.56561 0 0.426097 0.00125027 72 , '7'i 7 -0.364096 0.195626 0
1557645_at 0 0.309139 0 1.54312 0 0 0.338195 0.0412817 0.193428 0.769556 -0.0706463 -0.104097
1557807_a_ati 0 i 0 0 !!§!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! 0 0 0 0 I1I|I|I|I|I|I|I! 0
1558275_at 0 0 0 0 o 0 0 0 0 0 0 0
15 -,f ¾8 :1 1.49156 1 28733 2 :. Ώ·1(; -0.0536213 t 7b"Si. -0.314437 0.342531 -0.247491 n.b<it> 5 -> iilililililili! ϋϋΐϋϋϋϋϋϋϋ!!!!!!!!!!!!!!!!!!!!!!!!!!! -1.82558
1558489_at 0 0 0 0 0 0 0 0 0 0 o 0
J .V^'JGO.. i...fi! 1.91855 0 !!ll!l!l!l!l!l!l!!!l!l!l! 0 0 0 0 !!ll!l!l!l!l!l!l!l!l!! 0 ϋϋΐϋϋϋϋϋϋϋ!!!!!!!!!!!!!!!!!!!!!!!!!!! !ll!l!l!l!l!l!l!l!l!l!!
Figure imgf000153_0001
1559151_at -0.63 1429 0 0 0.190144 0 0 0 0 0 0 o o
1559166_at 0 0 0 0 0 0 I!!!!!!!!!!!! !llililililililil! iiilililililil 0 !|i||||||||||||lll
1559232_a_at 0.76: L557 0.247^ t85 1.16884 0.175316 0.96792 -0.262558 -0.0439177 -1.20083 0 0 -0.851443 0
1559278..at 0 0 0 0 0 !lll!l!l!l!l!l!l!l!l!l!l!l ll!l!l!l!l!l!l!l!l!l!l!l 0 0
1559434 at 0 0 0 0 0 0 o o 0 0 0 0
1559563_at 0 0 0 o 0 0 0 o 0 0
1559565_x_at 0 0 0 0 0 0 0 0 0 0 0 0
1559770„at 0.171918 1.15826 1.01257 !!!l!!!!!!!!!!!!!!!!!!lll o 0 0 o 111!!!!!!!!!!!!!!!!!!!! 0 0
1560185_at 0 0 0 0 0 0 0 0 0 0 0 0
J %0230 .-it 1.7182 2 1 S2-12 1.30256 .1 3717it 2.19114 -0.054196i -0.157971 1.00341 0.0541973 0 1.01337 0
1560476_at 0 0 -0.352846 0 0 0 0 0 0 0 0 0.65289
0 I!!!!!!!!!!!!!!!!!!!!!!!!!! 0 l!!!l!!!!!!!!!!!!!!!!!!l! 0 I!!!!!!!!!!!!!!!!!!!!!! 0 I!!!!!!!!!!!!!!!!!!!!!!!!! 0 0
1561092_at 0 o 0 o 0 0 0 0 0 o 0 0
1562055_3t 0.126782 C 5 J -JS 0 0 0 ,?b7¾ 0 0 !!!!!l!!!!!!!!!!!!!!!!!!!i 0
1562586_at 0 0 0 0 0 1.80285 0 0 0 0 0 0
1562642„at iiiiiiiiiiiiii !!!!l!!!!!!!!!!!!!!!!!!! o !!!!l!!!!!!!!!!!!!!!!!!!!!i !!!!!l!!!!!!!!!!!!!lll 0.0858412 o D.GK'.S.IJ ; 0 C! ¾585 i 0.54002
1562723_at 0 0 0 0.655876 0 0 0.127296 0 0.140468 0 -0.274148 0.677993
1502 < :1 I!!!!!!!!!!!!!! !illililililililili 0 0 iiiiiiiiiiiiiii!!i 0 iliiiiiiiiiiiiii 0 lillilililililil!!i ΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙ!! !!!!!l!!!!!!!!!!!!!!!!!!!! 0
1563460_at 0 0.00571156 1.32821 1.6443 0.78467 0 0 0 0 0 0 0
1563690...at !!!ll!!!!!!!!!!!!!!!!!!l! 0 !!!!l!!!!!!!!!!!!!!!!!!!!!! o 0 0 o !!!!!l!!!!!!!!!!!!!!!!!!!l! !!!!!l!!!!!!!!!!!!!!!!!!!! !!!!il!!!!!!!!!!!!!l!
1563958 ^rt o 0 0 0 0 0 0 0 0 o 0 0
1 ".<>-U i 0.0587502 0. ;i524:, I K 78 ii 0.796983 0.341 17 0 2ί¾¾.?3·3 -0.0587502 -0.335124 -0.640462 2 v, , -0.13183 ; I.¾S-J:>
1564498_at 0.444904 0 1.35047 0.402971 0 0 0 0 0 0 0 0.286547
1564545„3„at 0 I!!!!!!!!!!!!!!!!!!!!!!!!! o 0 0 0 lillilililililil!!i 111!!!!!!!!!!!!!!!!!!!! 0 0
1564984_at 0 0 0 0 0 0 0 0 0 0 0 1.05452
1565SQl_at 0.00545495 iiiiiiiiiiiiii 0 lilililililililili 0 0 0 o lillilililililili!! 0 0
1565845_at 0 0 0 0 0 0 0 0 0 0 0 0
1566032. at .U2 C-. ill!!!!!!!!!!!!!!!!!!!!!! 10710 ¾ 0.284908 l!!!l!!!!!!!!!!!!!!!!!!l! 0 I!!!!!!!!!!!!!!!!!!!!!! 0 I!!!!!!!!!!!!!!!!!!!!!!!!! 0.419906 0 0
1566033_at 0 o 0 0 0 0 0 0 0 0 0 0
1566428_3t 0 ||l|||||||||||||||i 0 I!!!!!!!!!!!!!!!!!!!!!!!!! 0 o lill!lililililil!!i 0 !!!!!l!!!!!!!!!!!!!!!!!!!i 0
1566503_at 0 0 0 0 0 0 0 0 0 0 0 0
1566504„at !!!!l!!!!!!!!!!!!!!!!!!!!!!! !!!!l!!!!!!!!!!!!!!!!!!! o !!!!l!!!!!!!!!!!!!!!!!!!!!i !!!!!l!!!!!!!!!!!!!lll 0 o !!!!!l!!!!!!!!!!!!!!!!!!!!i! 0 !!!!l!!!!!!!!!!!!!!!!!!!! 0
1566548_at 0 0 0 0 0 0 0 0 0 0 0 0
1566549_at 2i- lK2-J 0.48799 0 44S W O.C"V,S )09 (· .¾;' ¾■■, -S2 0 0. lf»92 i ¾ -0.255215 0.439319 -0.858042
1566803_at 0 0 0 0 0 0 0 0 0 0 0 0
1567031 at 0 0 0 0 0 0 o 0 !!!!!l!!!!!!!!!!!!!!!!!!!! 0
1568780_at 0 0 0.199863 0 0 0.566215 0.307853 0.0488949 0 -0.24334 -0.453582 -0.206691
1569041_3t 1.50292 1.535 J..K0 I I .2H40 I 1.76816 -ϊ/ί > -0.411511 -0.55553 -0.485429 ■J 0 744 J 12 ¾ 7
1569405_at 0 0 0 1.50128 0 0 0 0.78148 0 0 o 0
15696Q3...at -0.180721 -0.0189729 0.426549 0 10 102 : 0.43718 0 01S;l/.M 0 7 UM 0 0 0.697351 0
1569981_at 0 0 0 0 0 0 0 0 0 0 0 0 .iW U. liillililllliililllllillil o 0 0 0 0 0 0
201205_ at 0 0 1.20097 0.859789 0 0 0 -0.110336 0 0 0 0.110336
2021 SO .!· 0 o 0 iliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 0 0 0
203326_x_at 0 0 0 0 0 0 0 0 0 0 0 0
/S2 .Λ 0 1111111111111 0 0 0 0
205703 at 0 0 0 0 0 0 o o o 0 0 0
205800...a÷ iiiiiiiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii o o iiiiiiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 0 0 0 0 0 0 0
2Q7730_x_at 0.0191145 0.165817 -0.0558872 0.390528 0.981818 0.390369 -0.0191145 -0.414841 -0.779483 -2.17766 -0.481512 -2.28736
0 I 2 A ; 0 Χ 7 ΪΜ :>:> i i;t? 0.86038 0.623249 O. f iW 0.ΜΛ297 O.S53 57K -1.46708 -0.387064 -1.2663
210723_x_.at 0.275185 0.304955 0.414231 -0.216646 0.583345 0.0322957 0.293317 -1.15117 -0.0486946 0.10425 -0.0322957 -0.305144
21 U -M » .is ΙΐΛΐΙΙΙΙΙΙΙΙΙΙΙί 0 0 0 0 0 0 0 0 0
211878_at 0 0 0 0 0 0 0 0 0 0 0 0
2 ) ? 0 o 0 i!!!!!!!!!!!!!!!!!!!!!!fififif 0 0 0
214227_at 0 0 0 0 0 0 0 0 0 _o o o 148^ ,;l o iiiiiiiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii iiiiilliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii iiiiiiiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 0 liliiililililil 0 0 0
214979_at 0.000278 0 0 0.107597 0 0.481594 0 0.763124 0.58839 -0.558032 0 0
.J l .W.K .li liillililllliililllllillil 1.01215 0 0 0 1 005-Ki 0 0 0
215675_ at 0 0 2.43708 0 0 0 0 0 0 0 0 0
215774_s_at 0 o 0 0 0 0
216249_at 0 0 0 0 0 0 0 0 0 0 0 0
2 lb V) i .Λ 0.0531521 -0.0531521 -0.449098 v ,-\>- n2 0 0 0 0
216318 at 0 1.47044 1.32197 0 2.36676 0 0 0 0 0 0 0
21 (,.ν.' 7. . li iiiiiiiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 0 o iiiiiiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 0 0 0 0 0 0 0
216431_at 0 0 0 0 0 0 0 0 0 0 0 0
; tc>hsi __.it o o 0 ΙΐΛΐΙΙΙΙΙΙΙΙΙΙΙΙ 0 0 0 0
216739_at -0.47608 0 -0.761995 0 0 0.540121 0.116718 -0.590622 0.497046 0.594631 0.835455 0
Ί> , / \ illll 0 0 0.18225y 0 0 0 0.943042 0 0 0
216772. 0 0 0 0 1.66628 0 0 0 Q 0 0 0
1.- -52 o 0 !lll!ll!l!l!l!l 0 111!!!!!!!!! 111!!!!!!!!!!! iiiliiiiiiillilili i!l!!!!!!!!!!!!!l 0 0
216801. .at 0 0 0 0 0 0 0 0 0 0 0 0
' WW . ..l 0 9 lOOir. iiiiiiiiiiiiii 0 I i if,.' liiiiiiiiiiiiiiiiii 0 0 liiiiiiiiiiiiiiiiii ilil!li!i!i!iilil !!l!!!!!!!!!!!!l! 0 0
216936. _at 0 0 0 0 0 0 0 0 0 0 0 0
.?ι «(.-: . .at 0 Q l!ll!!!!!!!l! 0 0 Q !!ll!!!!!!!l! o e
217091. .a 0 0 0 2.21762 0 0 0 2.11706 0 0 2.80642 0 m¾2. 0.237782 0.663517 0 0.477244 1.13676 0 0.348974 C ?¾<)0'<4 •0.44541 1 0 -0.488235
217193. _x_at 0 0 0 -0.540083 0 0 0.319296 0 0 0 0 0 17 3S2 ,Bt 0.281033 0.290308 .'15f¾Q i:i 0.137208 0 O.S2.1 7-1 -0.137208 0.314348 -0.196936 l!i!!!!!!!!!!!l!! -1.60631
217490. _at 0 0 0 0 0 0 0 0 0 0 0 0
22107 at ilillililililililii 0 0 iliiiiiiiiiiiiiiili 0 liiiiiiiiiiiiiii III!!!!!!!!!!! Q 111!!!!!!!!! o 0
221137. .at 0 0 0 0 0 0 0 0 0 0 0 0
221138. .s. at o 1.12391 0.538232 0 0 o.¾v.3<> 0 !!l!!l!!!!ll!
221625. _at 0 0 0 0 0 0 0 0 0 o 0 0
Π ?.' '■.#, _ Λ'- 1.29415 I!il!l!l!l!ll 0 111!!!!!!!!!!! o 0 o 0
Figure imgf000156_0001
226812. .at 1.18913 0 0 0 0 0 0 0 0 0 0 0
.'27 -. i it 0 iiiiiiiiiiiiii 0 0 0 0 0 o 0 0 0 0
230162. _s_at 0 0 0 0 0 0 0 0 0 0 0 0
2 «.100 ..s...at 0 0 0 l!ll!!!!!!!ll 0 l!l!l!l!l!l! 0 0 0 0
230461. _s_at 0.866686 -0.563119 0.598194 0.923498 0.182642 0.145009 -0.948363 -0.552279 -0.0754175 0.0754175 -0.279367 -0.580801
.at 0 0 o l!!!!!!!!ll 0 0 !!l!!!!!!!!!!!!i!i
231818. _x_at 0.739627 0.995526 0.170051 0.944313 0.579336 0.116967 0 -0.10483 -0.668369 -0.132463 0.282405 -0.746424 "; iss;; .at 0 il!ll!l!l!l!l!l 0 o 0 0 !!i!!!!!!!!!!!l!! 0
232344. .at -9.35E-05 9.25E-05 0.167056 0.36436 0.0368967 0.705882 -0.0152988 -0.619175 -1.30958 0 0.0542488 -1.25341
2326 , .1- 0.771571 1.0=. u« n « n 0 !!!!!!!!!!!! 0 0
232778. .at -0.181981 0.391916 0.763914 1.12496 1.10535 0.181981 0.372055 -0.463783 0 0 0 0
232840. 0 0 0 0 111!!!!!!!!!!!! 0 0 0 0 0 0 0
232947. _at 0 0 0 0 0 0 0 0 0 0 0 0 Ώ \α at J =>7H7 ¾ 0.3(λ'Γ. ί7 1.00537 t i:r>;t>9 2!-2 -,f..' o.o<; .¾■■¾!,¾ in 0 0
233266. .at 0 0 0 0 o 0 o 0 o 0 0 0
233382. 0 0 iiiiiiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 0 0 0 111 0 111!!!!!!!!!!!
233390, .at 0 0 0 0 0 0 0 0 0 0 0 0
.at liilttillliilliillllilll lliil^liilllllilliillil 0 111 0 0
233629. .at 0 0 0 0 0 0 0 0 0 0 0 0
2 } \\>ϊ, . 0 0 0 0 !i 0 0
233674. .at 0.543115 1.02674 0.357329 -0.00636292 0.96158 0 0 0 0 0 0 0 num . 0.538061 iiiiiiiiiiiii 0 l!lll!l!l!l! 111 0 0
233706. .at 0 0 0 0 o 0 0 0 0 0 0 0
0 li!ili!i!i!i!i!i!i!i 0 iiiiiiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii iiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 0 ΙΙΙΙΙΙΙίΙίΙΙΙΙΙίΙί llll!!!!!!!!l 111 0 0
233717. _x_at 0 2.01395 0 0 0 0 0 0 0 0 0 0
; -i s;--<9 .at 0 0 0 0 111 0 0
233853. .at 0 0 0.807104 0.779406 0 0.363459 0 -0.0182433 0 0 0 0
,at !i!!li!i!i!i!i!i!i 0 III!!!!!!!!!!! 111 iliillliilllllillilll 0
233921. _s_at 1.05883 0.304647 1.68541 1.10311 1.60423 -0.410674 0 -0.0354896 -0.0201311 0 -0.599205 0
at 0. -,2r.b0J 0.684577 iiiiiiiiiiiii 0.0716867 1!!!!!!!!!!! 0 04 000 ! ill 0 0
234214. .at 0 0 0 0 0 0 0 0 o 0 0 0
234439. 0 !!!!li!!!!!!!!!!!!!!!l! 0 iiiiiiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 0 0 0 !!ll!!!!!!!l! 111 0
234454. .at 0 0 0 0 0 0 0 0 0.625457 0 0 0
2. W .at liilttillliilliillllilll -0.000372 0.5 1 W8 2" }.?f: 0 -0.168325 l!l!l!l!l!l!l!l!li 0. Hi 0 256185 0
234574. .at 0 0 0 0.360667 0 0.765191 0 0.547155 1.48636 0 0 0 J -n . 0 1.39045 0 0 0 !lll!l!l!l!l!l!lil !i 0 0
234707. _x_at 0 0 0 0 0 0 0 0 0 0 0 0
III!!!!!!!!! 0 111 0 0
238183. .at 0 0 0 0 o 1.31834 0 0 0 0 0 0
238305. 0 iiiiiiiiiiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 0 iiiiiiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii iiiiiliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii 0 ΙίΙίΙίΙίΙίΙίΙίΙίΙίΙΙΙί llll!!!!!!!!l 111 0 0
239815. .at 0.49341 0.664218 0.903991 -0.174168 0.707451 -0.147393 0.0153227 -0.0153227 0 0 0 0
241468. .at 0 0 0 0 111!!!!!!!!!! 111 0 0
242575. .at 0 0 0 0 0 0 0 0 0 0 0 0
Figure imgf000158_0001
d to
o ;
oo :
d i
ΓΜ O m d o ;¾©:: d :¾ d
Table 15 GDS5408 RNA expression values of U133 plus 2 probes resembling human
crisprs
Sample number
Probe ID GSM1309417 GSM 1309418 GS 1309419 GSM 1309420 GSM1309421 GSM1309422 GSM 1309423 GSM1309424
1554007 ..at 10107.1 10264.4 3479.1 3585.81 r u5.22 800 Ϊ 5 .v.-.f-.s.-t.1 1622.05
1554108. .at 18.827 25.0834 93.4315 83.7125 24.5681 36.5627 57.5494 109.709 i' -i;.- j. _x_at 2. 1 •1.9-1.',66 9.--3 W7 If !.¾!>:(; 0.fc,V7i22 0.536406 4..J4N2 562639
1555014, _x_at 46.636 59.6926 42.9535 27.9417 41.6103 58.761 71.0827 67.7114
1556520, .at 20.8081 39.0051 26.6241 j7.SHf) W. il 26 U21
1556521, _a_at 9.37817 3.33041 11.4702 11.0124 17.4859 8.39058 7.854 3.029
15567Ql_at 17.5886 71.1589 11.158 30.6716 10.73(>S J 272><5 70.5742 '■> ,'507'j
1556836. .at 1.20287 2.35312 4.49548 9.23199 10.3049 1.50473 3.48428 5.25122
1556837. .·».. -'i 1.87552 3.61941 8.19522 .1. >..3 :>(>¾/ 1.93881 ΐ 5U.¾6 7 Oi^J.i
1557339 .at 65.4333 44.6339 17.3394 34.1857 79.3141 46.2748 27.034 15.7328
155734 l_X_3t 62.5431 113.459 21.9507 3J.fi 122 115 shS :-i.f;¾o; 2(: '102:' 30.9402
1557539 .at 69.3906 54.0205 73.7029 44.5242 76.7909 72.2745 76.9929 77.3301
1557555. .at ;o.so.5<i 36.1555 24.6251 27.32', K. iV.i SO. i46S IS 1SSI 54.1903
1557645. .at 25.0907 10.2627 10.2369 1.68897 11.6939 14.501 24.9936 14.3318
1557807. 3_a' 2·'; .'11 Ϊ 2. ¾<■.■(<■ i 241 9 1330VJ V.-SJ >7 10.621 J.65CS3
1558275. .at 101.31 104.448 195.198 171.616 79.7419 91.097 194.025 198.777
1558385 ..at 71.8807 29.8187 23. Ml] 27.0 ; c> 36.16"·} ;v j-w 54.2039 24.5013
1558489. .at 2.7061 3.63113 1.35137 1.84351 3.52216 5.29764 7.48521 0.582836
1558960. A. -i¾ 90.8969 80.6125 63.6177 12*3. *38 114.135 84.4027 76.07 if:
1559053. .at 20.7328 14.1426 21.0525 20.8649 15.928 35.1223 18.4927 26.4501
1559054. ,a_at 73■)■!>' 76.2689 Sb.SS.lS ttf) 38 ί 34.6091 72.73.. 84..¾>=13 98.3073
1559151. .at 36.4521 22.2429 60.9683 49.1014 34.2005 22.0171 48.2016 45.2705
1559166_at 6.46331 ■1. 093b 8.40152. 10.942 7 ii'3¾ ! / 1,240/ 7.4352? J 96 if.
1559232. _a_at 38.7032 42.8863 36.8997 48.0165 24.5303 29.5371 84.7965 75.1119
1559278. .·■' 22.1333 4,52391 1 ΐ 57 2Ϊ 047 6.42994 31.9795 27,1184
1559434 at 7.04163 12.5613 7.46421 1.05822 1.28444 2.60359 5.71553 1.66527
1559563 4,75857 5.47007 ■■ 5-J!i2n ". 5-J -13 18.7997 5.72504 3.54658
1559565, _x_at 5.57597 6.36376 7.69635 7.28994 8.77103 7.2365 5.33682 8.82157
1559770, -3t 23 iV S i 5 5C! J- 1 3.63') 7 J. liJ'V)-, 17.4589 24.8178 20.3903
1560185. _at 2.52064 1.69253 3.91557 9.75478 13.8219 1.11468 2.02426 16.081
J 560230 .-it 3.06889 16.2874 n 72« 3 9.142.89 1.3777 * i' 5 5./G2S?
1560476. .at 46.4729 50.6561 49.7359 61.5574 76.1186 47.3695 53.5283 84.8055
I 5(,0.1'.V. .·■' 2.31452 ¾.'- ¾706 ;· woo 7 Ml, V I 5.11321 6.02377 5.19728
1561092. 32.7144 38.4281 16.8643 34.8598 8.91944 50.2423 48.7996 32.6503
1562055_3t 59.0844 79.4772 73.8549 SK.H'-l I J 47.577 45.998 76.386 wmmm
1562586. _at 17.961 8.28608 4.8022 6.782 9.14365 7.49895 3.49587 2.88533
]■;(.1(:M .at 10.4859 57 ? 19.2953 2f S 54 2K.'tK i; ■;3 677 i 36.0695 19.0758
1562723. ,at 40.8219 60.6701 58.2159 38.8158 45.9701 41.5272 38.0364 37.577
1502·?<·7 27.5933 -,:..t.¾0 ¾ 37 7164 3?; 9 i 74 36.5054 3 ! . ¾(>■? ;' 39.6221
1563460. _at 18.9732 7.63461 9.52457 1.05987 2.18537 1.31949 6.07046 5.13483
1563690. ..at 11.0891 2.96488 5.85561 1 •.'■■')«f-. to. r/fi-i 1.10037 4.68764 1.0436
1563958. .at 1.41878 1.04828 4.03866 3.78122 2.74074 4.366 11.8141 4.56617 i5. ; . f: 45.144 2 Hi> lii ■;0.K28 68 5.J -5 35.679 48.5664
1564498. .at 87.323 116.617 133.685 119.207 107.253 127.384 111.771 80.0313
1564545. , 3 „at ', 'LSI.', 11.8512 .. ι -n i 13.554 12.2744 .5.6j ii:13 wmmm
1564984. _at 47.2409 56.8793 10.4087 14.0972 17.6672 49.3026 10.0179 28.2703
1565SGl_at 14.6816 ^ !·.2 2.5.1508 21.2701 κ.;«ί·. 25 U Ί ° 15.2.755 22.7523
1565845. .at 54.8489 114.925 69.6134 123.851 103.42 119.036 88.0684 77.2043
1566032. .·■' 32 i.'V 57 '!.¾.¾') J,2.fic-.5 l 5 .^1 38.6208 32.8049 46.9607 38.8033
1566033. 10.8914 15.2527 4.09365 12.2613 4.51385 45.0451 4.59854 26.8025
1566428_3t 0.868676 1.27606 6.7640 s 8.13 8.280-3 6.78991 8.6'V; V.J S.7S755
1566503. _at 8.51204 19.8453 32.3158 28.7281 14.3285 25.104 25.0129 5.57446
1566504. .at 64.7441 91.0981 f, 3 7 U 1 63.2401 89.1767 VS ',1 1 3 <>2 7S3;! 63.4123
1566548. 4.91655 11.9849 8.49975 12.3717 5.1681 4.31809 4.51274 2.99306
1566549. 3t 62.1613 52 30K7 60 1 143 J,- 32K 32 H 72.6339
1566803. _at 1.95856 30.4832 7.08174 5.10388 22.6862 8.75169 5.56698 4.15246
1567031. ..at 2.1 W S i J .?:-. 16.762 51.6126 32 0161 32.7595 wmmm
1568780_at 915.587 782.37 458.876 461.763 334.519 446.449 701.218 728.56
1569041_3t :.1.292" W.71.-K. 504 U 27.7577 41.1527 85.6611 99.3296
1569405_at 1.87972 14.2411 16.4092 24.6358 16.2434 15.139 18.7277 19.6121
1569603 at ri."'t 2 30 /»¾: 21.7248 l').001V 2ti.7rf -i o.m:.-2i 35.498 45.4718
1569981_at 6.59435 0.598602 0.404845 3.08671 1.24245 14.0824 1.01698 1.08386
I'.W.T.. 3,71326 10.9745 7.G 8:. iy.?4K8 ..¾i>91 :,.K27 33.8173 22.2875
201205_at 84.5914 95.6171 105.871 101.023 108.22 85.7914 92.9614 92.1121
2022 SO .!! > 2c,<u 3.17816 2.520H2 4.28021 6.38099 2.20312 2.01018 2.3548
203326_x_at 5.48358 13.0374 8.0628 11.5398 11.987 8.81143 6.5705 8.28628
2i' /S2 .Λ 175.813 J9,->.2.>J 171.389 108.876 197.04 164.948 Ί Ώ 2i-.3 122.962
205703^at 30.5506 8.9654 4.35994 4.5472 2.04392 8.67544 11.9223 3.95171
205800...at I.13833 2.87643 ΐ« Μ 1,0414 >..V-,Vi, 1.44621 14.0983 mmmm
2Q7730_x_at 1109.58 1268.39 1280.33 1552.55 883.864 976.103 1651.88 1553.65 i0(:"/g .,! 7 J 5 ¾ (•.!?. Ί ¾ 767.825 730.151 306.479 611.676 1057 mmmmm
210723_x_.at 78.0885 63.6784 75.4721 100.723 81.7777 121.309 116.361 88.3809 21U-M » .i! 4.13652 5.26629 7.07025 12.4->',3 V rW7s 5.3119 25.5014 2.86019 211878_at II.7887 0.958391 9.72383 4.2304 5.40559 4.14711 2.53234 6.03541
7.V<r,¾-» Ι','Λ.ίί. 27 ) -,<;■.' 2 3'- !7 6.11549 7.55037
214227_at 3.86399 41.8273 5.39115 19.8321 34.9804 29.8724 15.803 12.1304
-5.32.101 Wil: 30.8787 Irf.l20'i ■ '■· I'f'rt".? 19.6511 6.2<>/s_> 10.992 214979_at 29.3791 34.9476 62.7038 39.822 42.2221 37.3531 47.7762 50.9005 ^l. .-'.K .li 19.5142 23.7708 4.41308 ?y.i Li" i¾2:, 2 J.wiRS
215675_at 2.14968 7.56472 9.5371 4.26137 3.33064 3.99302 9.57726 6.05325 215774_s_at 27.9018 b ».«)■/(, 7 34.% 12 41.089 1. -18S7 48.2808 216249_at 61.1919 38.2933 36.5074 57.2958 43.9866 44.5115 38.5107 38.2943
21G¾0J .Λ 61.1597 ',ί·.2 -^ 115.864 Kj. 5iS "Ί A7 ) « !"!(> ¾ 100.924 53.2725
216318 at 22.4964 47.5607 64.7185 36.5827 93.4569 60.263 55.1471 55.4267
18.5196 A.Q2.V:2 2.79537 3.40047 24 '/Hi. 2.64898 216431_at 5.28602 5.24015 25.9091 6.75538 5.48624 4.75522 2.16211 4.69434
}m*i ..t 11.2898 20W?7 2*. 1.33164 2.32112 4.03141 13.1536 w m
216739_at 70.61 79.5484 73.1564 71.757 48.8887 79.1181 61.1707 73.6625
216771_at 20.4827 281925 27,3368 17.6354 2.L.80-53 ! i M34 45.1368 6.88695 216772_at 20.1022 13.2528 25.8674 30.8099 34.5112 19.0794 11.7823 25.937 216792_at 46.0926 2f,.7¾4} 61.2152 71.8679 54.217 39.7403 18.4917 64.8707 216801_at 50.2691 61.3152 85.0203 98.8631 61.6995 51.9549 10.3011 42.067 216934j3t ■ .03=. V) !> (52 40«J2"J 10.8316 4··.1722 19.4771 7,37775 216936_at 3.19458 22.8377 29.5343 9.54266 6.69833 7.57817 5.14501 31.3739 217065_at 15.5022 40.0017 (> 65 ^8 ΛΙ 5Ϊ05 30.5871 27 S.127
21 091.a! 15.1074 11.4162 0.477302 9.09624 5.92696 9.46445 23.1847 4.04613
118.796 94.6918 i ¾.;t'-i 18f-; ΪΠ 109 1 7 97.4916 173.663 192.836
217193_x.at 53.9883 23.0828 34.2538 35.5414 66.7133 54.9884 29.3484 16.195
217382 :31 b-l. J84 ■>2 ',(-2 ? 106.249 51,¾83 63.9764 67.0083 ao.i%2 83.4564
217490_at 43.2704 59.555 17.6561 69.4822 35.6431 48.8933 78.6377 56.7338
221074..,!! 5.60175 3 !-.f9R JO.3561 i.-MV18 7.Ϊ1ΜΚ 2.21901 4.80182
221137_at 26.9131 25.5491 25.2384 55.208 54.7824 37.1371 27.9419 37.0794
221138..s„at 10.5747 17.0865 20.0562 6.10071 UUW-t 19.2537 8.193S4 11.6888
221625_at 61.6348 77.4822 43.4876 57.16 38.5143 34.5686 47.1415 27.6672
222968_3t ?'K- 08-1 592.971 :,; r;¾2 351.941 .¾¾K.702 :s 7. ; 337.934 405.729
224238_at 6.5043 3.98174 1.40532 2.87034 1.89044 1.78967 2.47598 2.19527
226061_s_at 59.4971 t>fi.H271 49.7082 3-5 y;t>.< 76.9153 : ^ :ί:3¾?
226812_at 19.6391 24.92 10.9431 23.1545 35.9359 40.7508 10.4105 56.1295
227661„at 3.51573 7.13058 5.15767 3,99131 477052 9J 351 ;:;:;:j£ )::: ι¾i
230162_s_at 25.5212 57.7108 26.6818 32.9869 35.0031 23.0859 40.1906 28.6094 W400 - 6.1.028 66.1452 ;7.SC-..19 65 1723 59.7016 ¾K 711> /.52K¾ 59,2856
230461_s_at 45.1898 69.9973 110.903 103.594 22.1136 42.7841 84.9635 96.0762
230frJ4...!! 17.1019 ; or 7¾?2 4.8652 20242 6.703 I t 10.2255 :.669.-;9 4.39315
231818_x_at 128.398 85.3721 110.904 82.9364 167.1 69.3378 117.387 108.088 3188.S .il 12,4701 ■ί.ί Ι « 10.15/4 10.3011 40.1939 174832 U 7116 17.4354
232344_at 82.0758 63.2757 166.889 217.578 65.7245 67.7958 206.162 227.717
232fi2f»..,i! 6.40255 7.23016 30.3 24.2719 31.7665 26.3473 wm mmm
232778_at 56.6446 49.8624 47.7398 29.7827 36.9628 29.4927 50.1094 55.0327
2.32840. ji 6.29935 18.4737 3.40847 11.7987 728 0 2.05054 340 9 19.0991
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Figure imgf000164_0001
Table 16 GDS48S5 RNA expression values of U133 plus 2 probes resembling human crisprs
Sample numbers
Probe ID GSM1179364 GSM 1179365 GSM1179366 GSM 1179367 GSM1179368 GSM1179369 GSM 1179370 GSM1179371 GSM 1179372 GSM1179373 GSM1179374 GSM11793
1554007, at !i-V>5J 65.535 58.5246 19.2181 ! 30^91 14.2402 .920K5 17.8864 1572)9 ! 33 r.'» 89.2318 I09.2K7
1554108, _at 55.7087 69.0439 63.486 27.0538 35.8555 27.7405 27.5521 47.3519 32.9266 65.2135 79.5277 56.5973
1554723 .*..<!' 33 6.Ή95 26.176 252^f>7 18.6861 >,;. ;i75(. ■57.0007 31,1313 29.8603 14.463 2ί· « :i« -1. ');.?
1555014. _x_at 39.7167 44.6765 40.361 35.978 61.3966 51.9574 59.3534 62.4169 51.3385 56.1382 46.9549 58.5477
1556520. 181G92 39.0811 39.3311 -52.3092 36.0261 4.?.i»i;v (;0.0t>:,2 15 5055 44.8602 62.0378 48.6759 ■".1.8(1-1 i
1556521 _a_at 4.72545 7.41744 9.89421 11.3432 7.81916 9.96385 16.0819 9.72778 12.2698 13.7957 14.0224 10.4997
1556701 -3t (:5.H-U4 54.6709 50.4638 •■b.l'K)* 56.9949 iiS.7713 62.6346 7.5i ~> '.■S8 I5 66.1615 70.3593 84.9182
1556836. .at 21.9045 25.4193 40.1954 17.906 31.5975 25.3475 31.1487 33.6263 24.2362 22.483 27.6499 32.7032
1556S37_a_at 5.S20f.;¾ 6.58457 i> H ¾05 7.7907 5.91 Jf, Ί 1ί'78ί·. ■-..«J!.Wi (..201,30 6.86S81 4.i'0J -! 5 5 5
1557339. .at 8.12859 9.787 16.2133 14.6849 8.90081 12.7921 16.0487 16.2589 12.8444 9.61242 8.87405 11.4322
1557341. 20.0714 25.5715 2GH5I') 15.0794 18.3957 20.3195 16,8685 .?G. ¾,f, 23.04 19.5129 28.9695 '88 27
1557539 .at 24.7085 17.1831 14.2152 22.9488 16.648 19.1931 30.1264 20.9319 17.0715 28.3282 18.8699 24.7153
1557555_at ; .i;i-,v 22.1714 a,.:, J ¾f: 21.6355 19.1085 21.4498 2.J 6695 24.894 28.7045 22755.J 28.2118
1557645. .at 10.5963 13.1224 8.35008 10.4165 11.9708 15.1539 16.5345 24.4087 17.9488 13.7072 9.0797 15.4878
1557807. _a„ai 9.97915 3 'V=)7t> 14.345 6.51905 5 :S ?¾0(; 10.7165 10.2769 '5.2-177', ;.5L 1K 9.0684 5.9915 11.322;
1558275. .at 37.9001 36.842 42.2846 36.4954 33.7497 40.3283 45.5769 46.8048 40.1532 36.703 39.6121 38.8046 at -il/.OJn 21.6161 3.Μ ·»·· 31.7i«. 46.5 i'-i .'t 3371 3 .S-1M 25 t,505 Π 5557 28.527 200001
1558489. .at 3.15407 4.03662 2.32602 3.75019 1.56069 3.24107 6.25564 0.00952643 1.80078 0.0247972 6.15682 6.16288
1558960. . A- <).':■,>.--: 30.9926 39.128 29.9033 27.7706 ■52.7287 30 (.101 21.7553 30.1 -Hi.- 33.1077 rf.:;«5
1559053. .at 50.2143 48.3603 42.9406 34.1951 32.9126 39.0921 34.2464 31.7201 41.1736 49.8603 48.3349 55.5379
1559054. A. -i¾ 117.885 108. S 97.9945 77.6073 75.2499 K9.0801 65.5241 7·-.2C,.;'j 76.1817 13 K 5 115.547 1 4. -558
1559151 .at 15.8428 11.4645 12.8822 5.14632 2.62477 9.65971 11.7209 9.74485 9.2854 19.3995 9.58016 10.8013
1559166, .at 2-UK77 23535', 19.3281 18.708 16.9941 2t!.',t!;S 18.6772 15.874 16.6599 18.2544 18.9008 22.154
1559232. _a_at 1.94869 1.39907 5.29529 2.39786 1.57816 7.84088 10.4908 12.4094 8.06044 9.2003 6.64132 0.507478
1559278_.at ■!. 3() ί J -i ¾ί·632 n 5!,/ , 2.96004 7.07972 6.50192 4.88708 3.38471 8.40836 7.1 383 8.41685 5.77215
1559434. .at 1.4631 0.173067 2.24227 3.17034 0.00305431 4.17267 4.14489 0.0415983 1.11495 1.71803 1.08408 0.00553963
1559563.at 30Gf-7 15.5454 15.9664 20.849'- 14.4025 13.5698 9.50029 16.9825 16.6417 Ί.32715 10 «49
1559565_x_at 12.0088 10.984 11.9255 8.35567 15.2129 10.3481 8.52756 15.4692 12.4487 15.1351 5.87771 11.3135
1559770_3t 2i.J<\"2 19.8695 33.5076 14.02) 221 53 AK.!»681 . .-.22.' 18.8697 18,4304 2« 8 If 21.6372 2(: iOV)
1560185 nt 5.25074 9.11702 7.20211 5.24415 6.40714 10.1121 3.86946 8.48692 6.60611 6.44258 3.99768 8.71563
Jf:tt .?W. it 10.2 \!i.Ml>2 11.513 14.2581 11.0916 17.3 13.5385 15,648 16.8878 *.7!v-.S-> «.::->'.-.76 S-H72
1560476_at 23.8788 22.9535 28.3375 24.231 23.8279 23.8196 27.9314 25.6205 32.8549 19.1248 15.3701 14.8442
1560498_at ■1. 66S5 6.81716 ';. V,04:.. 3.4419 /.¾.?:; J 7.73276 6.72785 9.42038 7.21673 . -'t 7 ' ' 5.57177 3 K.'_I 8
1561092.at 15.312 18.9128 29.557 34.2915 26.2315 24.2292 18.0594 23.8006 32.7336 31.7123 16.15 24.4609
1562055_at 44.4446 49.441 4¾.biOS ■JS.SCJJi ■>1.0,K'.-S ¾i 1Ί ί O'.C ir; 58.1764 51.4626 47.7248
1562586_at 25.7238 23.6146 23.0458 20.0126 21.5046 25.025 34.5594 43.3798 23.9151 31.3252 31.6483 32.9933
1562642_.at -1.(7Γ> <M 01; 11 3i.?;78.l 36.9201 -!n.b 2 ■J2.C:8K 2ί:.1¾Ί U057 34.8064 2ΆΛ"1<)
1562723_at 49.5376 47.6312 51.5414 57.5274 45.7703 54.6951 71.9208 72.5294 58.6625 44.1551 45.0417 71.3053
1.6')f.-5 n (. Ώ7 30.5509 20. 0 13.4934 26.4848 23,8376 2S/-..127 18.8938 41.3885 41.6106 48.5806
1563460_at 0.0021818 0.00357007 3.69512 8.55882 0.113908 0.00435978 2.49667 5.87833 1.77337 2.9304 0.00232375 1.01967
1563690_3t 4.25035 2. ^9 -!2 2 ' -.i-i?. 2.')7K-is ;i f,S5l7 3.77995 2.23811 5.17879 2.40731 5.06691 3.91468 ;-'i ;:·<>¾
1563958_at 13.3234 13.0318 10.7505 23.2303 29.6282 18.229 22.5184 19.2643 21.698 16.2384 13.0351 12.5375
1564424_at 19.2509 2.i.;r,?s 26.4985 22 tyl*l ?S.?t>0? 2 ¾ j>?tyl 22.0ί JO m,< 19.6632 W22U2 l*i.«77S
1564498_at 80.3955 81.7582 81.3438 81.1744 96.6531 86.5051 85.4803 94.054 98.1874 106.724 92.7607 101.757
1564545_3_at f.5:t7¾, .¾.6ibK'.-, 5.91769 7 jhli? b 0ί,9 6.17391 7,40995 24--. 23 8.72098 -, i V ii t 6.58847
1564984_at 60.7804 60.2624 84.4923 117.793 154.973 141.224 140.965 146.649 143.209 41.5988 38.3286 67.3576
1565801. at 10.4581 12.5776 12 "V¾: 21.0633 11.2381 11.9164 15.3387 15,0277 13.6396 14.0856 16.8493
1565845_at 150 164.856 176.055 170.013 155.885 184.319 158.326 175.923 170.508 167.228 173.745 170.003
1 '".oiiO J.? 14.9156 13.171 K.oK IKS) 6.04654 20.2107 16.0.? 72 15.7456 15.805 11.9834 13.0448 i .y:,i.i» H .77C; 566033..at 12.524 6.70975 15.0423 27.6239 29.065 36.2157 16.5874 29.9338 25.5574 12.1209 6.66292 10.6327
1566428„at 0.421306 1.53918 2.02784 025/157 2. l'if." 0.681162 2.0 ->■■>! ί o ;sf58v,' ■ ϊ-,.η.5 t!..50r,.'ii,i 0.00677865 7.0<:/<)7
1566503_at 27.1161 22.1556 28.3219 24.2787 27.3809 25.3689 27.3882 27.6355 25.2845 25.5883 23.1749 30.4464
15665Q4_at .'2 2 < ii . N 7f, Ώ !>15(> 37.16 37.9181 -!3."K/ J I !"!b><2 (Ι,'Μό 2f,.J03-, <> 7¾25 .'tOi,
1566548_at 100.177 94.1903 97.0285 137.928 134.138 137.408 134.358 133.247 124.663 55.051 81.0488 60.8672
1566549..at 60.8461 L-f.(.t0¾ 59.8012 46.2106 .15 tt 0 '.i 5 \-\ 44.6908 u 7 . 7¾ '!02« 80.415 7b >b7i.
1566803_at 50.3172 54.8154 42.8146 72.5853 68.7516 93.307 66.687 73.7015 62.6525 43.6892 49.7661 48.212
1567031_at 11.6313 1 ¾ s;¾¾ 17.2ΠΚ 16.0011 Ιν -112 12.588 14.1826 14.8107 14.7426 16.0966 V ?.i72
1568780_at 13.7211 13.8071 16.5688 12.7984 13.5267 12.9952 16.5097 11.464 11.9026 18.7253 16.5172 20.2677
1569041_at 10.3928 1 . J 1 S3 14.1959 15.744 15 S-1S3 18.8169 J4.3K;i 11.1947 15.7798 15,3182 ί\,.ι>\,ί!¾ 12.0148
1569405_at 4.67564 8.23887 3.33101 10.073 5.50314 1.25673 3.80362 4.67757 7.82148 8.30197 2.76707 3.6863
1569603„3t _UKS2 Γ, ί2Κΐ. ! S.S 17 6.13122 10.5102 8.02227 10.9649 11.481 JC 2I-1 i ;.j-n<> 11.3018 10»
1569981_at 5.52051 1.58248 5.68799 4.67523 0.477375 6.16184 4.5451 5.53425 3.18615 5.44659 4.75299 3.8477
1570215_at 67.5807 !·.-!. 5·".:-. 1! X >. (>S.¾.?2 .">2 S.-..20¾S 85.0536 81.4364 40.6542 52.1154 v<.< ¾S
201205. _at 144.461 135.606 124.956 146.585 170.147 183,129 171.846 175.76 166.849 110.225 118.121 126.687 0 ASO 5.5785 i.9.1(.2:-. 0,0040852 ').7Ο; 3.37241 j ½ 5i. 7.15416 6.14384 2./ I '.':?. i a- > 0.0408117
203326, _x_at 366.814 298.926 284.679 232.665 178.258 171.614 339.09 285.783 244.573 389.639 289.431 349.596
.at - .1W Sj¾2!3 66.1591 4At>¾¾ 48.0844 225s75 ?r> is7(: 40.411 63.1941 91.7599 84.9251
205703, .at 3.81098 6.08755 4.47167 3.9198 8.32175 9.0067 7.59866 2.12808 2.84616 5.4312 6.54227 6.82989
20-A00 ,at 3.10041 (· s=)n 5 J 3207 3.5969 5.49892 .l.Sj,.fi 4.1249 0.00250634 4.2249 1.31391 0.00370975 0.412518
207730. _x._at 675.975 709.001 742.821 822.766 791.359 940.743 858.482 1052.34 840.101 682.922 648.65 600.511 n Of.7·». X_3t U07.'-i Jf-C77* 887.351 1159.55 1058.42 .Π 2 h 1169.42 1403.19 1119.84 Ί 02-5.8" '-!<;·.>. lb 944.552
210723. _x_at 744.383 727.606 729.59 768.58 805.482 796.756 825.193 744.709 735.026 604.593 582.943 573.415
: H- . A.at 19,5679 24.185 26.765 2" <).¾.¾t; 2il.t,').¾f, ■,.>, - - 28^178 ij >Wi 24.1791 20.7752 18.0541
211878. _at 0.0183598 1.17012 0.000784805 0.250939 6.38937 0.00692468 0.0101142 2.24311 5.33907 0.00439099 0.00074115 0.00281671
214 ΚΛ _3t S.3S029 5.25566 9.57129 11.218 9.K.?S03 11.5619 11.2319 11 S--JK 7 f :<>.¾<> 6.11327 7. *?.*!<> 9.92609
Figure imgf000167_0001
214979. .at 31.9223 40.2237 35.4915 45.2535 58.9119 43.8152 48.0545 50.4125 46.0629 27.7742 35.0961 35.5546
..l 7.272Π-Ϊ 15.22(>f. 15.1996 15.8647 13.209 i J 6797 17.503.! 14.7586 10.6607 19.9683 V,«1?..\ lx.77/2
215675. _at 148.036 142.884 162.34 145.046 270.925 174,264 240.52 156.914 129.83 93.465 168.897 141.591
.!1'7/1, ..s.at 11.114 11.0877 8.41007 13.9038 7.0«971 16.72;'··; 11,9718 11.1755 Lvs r- ·).«,» ;Ή; 7,93868 7.77071
216249. .at 23.2687 35.9469 43.3664 24.8991 40.8098 16.9676 30.4987 30.2322 27.2614 18.3617 15.3284 14.5276 ic i .at 93.1721 66.9367 7L 2216 105.506 70.2231 101.527 W>W 82 S3S 1 r,\:: 523 92.1169
216318. .at 57.4831 41.2842 47.3163 51.9977 49.1214 37.8294 51.2285 45.0774 42.548 56.7545 53.8223 44.3839 1f;.J 7 ,at 12.9451 11.7603 16 S02S 11.1218 10.9701 5.5241 12.2539 18.1489 13.9907 12.0429 13 (XM 10.727S
216431. .at 3.01235 7.55862 9.00053 5.5382 9.5824 5.38651 5.36766 3.36079 5.13953 8.8512 6.74617 8.11422 at 1.73035 6.46691 8.82012 ¾ ^t. 0 /.^t. 5 (■ ( ' 50 i:.fi027 ■J 0 40<;(b; χ.'ΐ 9;'4 8.86352 I W¾
216739. .at 37.932 41.3425 45.9812 34.4255 40.3334 41.7503 42.5399 38.6149 43.4791 41.6006 49.3247 55.9452
? 16771. 20.8142 .M.0fl¾ 19.7517 18.1385 21.1915 22 '-87; 245/ 21.5802 19.3103 25.5647
216772. _at 1.32284 13.2371 11.6779 7.97413 6.70513 11.8877 0.00463109 5.73188 3.05215 12.3568 14.7218 9.2355 1 C79 28.295 15.3415 2.1.90 7 15.4001 15.8019 20.3945 .' t 35 19.37 16.4143 2.0.0178 2 -U.ii.54 1 .3094
216801. .at 18.8382 23.7292 22.8412 38.0743 54.3633 48.5937 42.2334 51.2086 49.3276 19.1734 18.056 20.0473 llllli 3 1.493 W 7 i 3 ! 7065 39.9795 33.763.1 32.8419 28. t'H'i 32 3548 30.6401 VI .8261 28.3613 26.3 32
216936. -3t 24.8582 26.198 29.2743 29.3709 20.8265 32.4635 45.7832 37.0324 38.4869 31.8245 30.0153 34.1137
21 7005 2 ! '.18'.'? 75.0453 25 27 51 31.5008 37 770.J 29. 5 =3 i.6.379 19.634 25.9668 33 :, J2 17.8068 1 1.7328
217091. _at 4.38528 6.57755 9.72772 23.0897 33.471 12.0204 13.938 10.351 14.1102 12.4508 16.9122 8.41335 1715 .!! 7.88504 ] 3 !i SS 14.0447 3.06899 8.48996 9.16695 2 ->.3 1.½ 10.8466 1 . 759K 13.9548 V 3.507
217193. A-3t 23.8705 18.6202 31.5804 11.682 23.8236 13.445 12.6586 24.0981 18.26 20.9009 17.7691 18.5008
..I 16.683 19.6339 16.2897 17.7865 13.9735 11.0889 13.32.14 J 8. 53H4 20.362.3 16.8358 17.1026 2 1 1789
217490. 19.8577 20.3418 19.3458 19.6477 23.2482 21.0941 20.2943 14.9076 11.0622 18.3695 17.8814 24.3225
22107 t ..at 29.9626 22.460; •12 02r: 20.8·.) V, 53 6 17 1 1 .706 26.9265 2 >..2. 8b 22.4501 5.3 67'M 52. 551 40,1348
221137. _at 36.6261 17.3134 15.6217 20.8274 25.9274 8.03163 13.1562 15.2536 10.6809 24.8309 25.9478 23.8665
7 1 138. _s_at 6.632.14 8.91634 5 34165 : .0-1006 2.04577 7.61335 l l .Gs/ l 3.55'.' 57 i.3%8 H.2 47 O.'.U lSi"; 4. 1819
221625. .at 5.54269 4.8118 6.24882 0.610014 1.625 6.85186 2.55666 3.70536 0.0676444 10.2565 3.76466 10.4787
2?2' « n . .at 29.4283 34.7239 53 1205 24.7964 22.501 27 37 i2 22.4326 16,2544 26.6524 2«i..377S 48.3365 32.6383
224238. _at 4.40953 2.8284 2.07245 4.24918 2.46901 0.615852 10.0108 4.44743 6.19939 7.51827 2.59564 7.59308
2260( 1 _s_at 20 260- ! 227 5 2 .K :!5 19.0388 /A 5299 ■■' 6 H82 21.8685 16.1927 20 205 11.6577 25.739 I .WM-
226812. _at 6.7615 11.2247 7.29068 6.62365 7.25653 4.56267 6.58308 6.61724 6.77419 8.0643 8.9135 4.4078
-.'27f f-.1. 20 902 / 12.6452 12.6206 2.7250,3 2.292 5.88871 0 0200155 0.0 ^706 1.6797 2.94448 1.36109
230162. s_at 29.4038 15.2602 25.617 16.7912 27.2735 30.0205 25.9113 23.2384 25.1663 9.44262 26.5312 19.9081
23040 _s_at 18.1815 19.9186 16.4421 32.K Si 3 25.08 50.8 336 .¾ i. lKiSJ 20.1032 20.0875 ..'0 9847 19.6966 21.693
230461. s at 14.9813 40.8124 26.9176 19.776 33.1399 16.8688 41.4285 34.4858 36.7444 49.0961 40.5681 50.9449
2 3<V).'i 3 =162 J 5 =l.i ,-3->2 4.75501 .•K720J -> O.V; M 4.89706 5 Ί 304 13.08 i ;5 ->'l 5...52-l-> 8.56139 6.84599
231818. _x_at 105.856 109.92 109.145 127.992 118.399 99.1485 102.982 147.611 124.097 97.3183 95.9194 104.693
231888J .at 16.3129 19.8738 22 j.l'i 44.054S 35.416 y>. \ ■!.>.74'V 39.1601 * 3 0314 H 39 i > 505-15 0,011215:
232344. .at 5.62526 23.6642 24.4799 33.597 34.6284 37.1858 46.4903 54.4129 50.4776 34.5252 8.2763 30.1506
232626 : at 11.8265 12.5952. 13.9632 11.4845 4.40056 .12.8758 6.11432 4 816*2 4813 7.31556 7.01347 8.17301
232778. _at 25.3704 31.287 28.2875 26.2877 43.5852 36.8966 37.3437 42.2672 35.6075 25.6013 19.9532 23.8694
732'.: 10 .at 8.54087 15.7148 '.: K'.: I K 16,8841 5.03658 7726; S.29766 23.3473 11.6634 2 72 J V) 2.665 2.59543
232947. .at 20.9647 13.8519 17.9158 18.531 22.0509 15.3419 15.4646 20.6536 14.0694 15.0866 15.648 12.3216
_3t 3.54621 5.75237 :,.y>i.i,s 20.6263 17 1·λί»321 i 1.0478 . 51t>:, 11.1659 .?.i'i;2i 4.7750 i 5.66843
233266. 64.6048 66.6097 73.7083 58.841 68.0103 71.9929 77.3974 75.9528 71.0986 56.7125 63.7586 68.655
23 ¾; 2 M.2(;S 18.3696 21.9095 .. V/20'1 3.23014 12.1706 5.12641 \>Λ7Υϊ 13.1116 j 7.37/5 20.6117
233390. _at 0.00549778 7.26944 5.66441 0.00143522 0.00235812 0.00244596 0.00247948 6.84315 11.3369 0.00279578 0.00248864 0.00154379
2MV) ..l J 5.75589 5.47788 o.t> - bi J.2(>1L>¾ .S5247 .■-.;·<* t ■-..=.112'.;. 4.13384 1.6808 2 U7«S
233629. _at 13.1416 10.2634 13.5982 10.3293 13.472 11.99 11.5058 13.2189 14.8857 16.592 10.6623 8.46897 W:. 0« 722 -S3 ·.' y*; 2.1,^32 I ')fif}S0 3.43659 1 386 J 2 3.66988 ■s iii ;> or//-- 3.91902 2 S0.1C/: 3.33272
233674 _at 25.9862 32.1929 30.0664 38.7892 42.0502 29.7196 28.5561 42.3202 30.7081 32.6859 38.0926 35.7575
.at 8.24164 S.72?4<> 7.16685 2.71326 2.63894 2.10998 .O s f.V,' 5 on?:: ;.;i,"-V8 2.01123 10.1763 8.16179
233706, .at 0.00276547 0.00559189 2.1793 0.00674945 0.00229225 0.00141319 6.96615 5.84431 0.945617 0.00348065 4.46946 4.85492 3 /0:·; ,at 22.3511 19.6636 40.1563 17.3891 16.4194 15■>■/*>; 23.ΐ)-ι Ϊ2 10.7024 10.3267 29.1668 25.0053 31.1497
233717. _x._at 114.583 148.747 142.653 238.184 202.423 295.549 202.873 257.97 247.774 112.028 106.243 101.866 at 0.85468 4.01851 0.631488 0.000998158 >..! % 0.0010188 1.59217 1.32S23 3.02 Hi 00001:81 2.7505.'
233853. .at 7.22021 17.0107 18.037 14.6698 17.6038 16.2874 13.4153 17.1265 21.2186 12.0568 15.3318 16.1086
233920. '■ 58 7.61483 13.0385 13.3756 16.0617 H.-.12V2 11. J -J 7253 17.8123 16.04 11.0041 10.403
233921, _s_at 4.94368 4.31132 4.63639 8.0118 4.8066 7.88407 2.684 9.9996 7.4434 8.80755 6.71029 2.22846
1148K5 5.31123 .W58 1 :>.I;2.J 14.2945 6.05185 1 5·.2:,(; 10.0115 7.93705 8.f!.1C.K > ■:■ nwi
234214. _at 17.5546 18.2127 18.5983 22.3074 28.1141 23.0225 25.7286 20.0734 23.8506 22.2325 17.0344 18.4088 J -H1. 20.5267 22.1525 17.4254 13.954 13.9 13.9139 13.1626 14.2284 10.0646 22 ΟΛΊ 1 JS.8t>H» 22.i;.i<m
234454. _at 24.6656 17.0802 23.3396 16.9402 32.1469 20.1874 24.8688 26.6268 21.2352 19.4597 24.5307 10.5187
2 ..l 22.2901 17.8776 2-ί Ι,'ιΆ, Ί8.29.1Κ 22 J I Γ/.^ "> ί J o.i<n 12.8111 14.7857 ?.\.V/H 23.'.'0/
234574, _at 51.316 52.0082 54.4016 20.6932 36.8631 28.8024 35.1828 42.6117 34.9813 83.1318 65.6466 71.4353
. 5M .-:! 39.3416 38.12.1 41.6449 41.7631 40.3111 r:3.32;--i 66,8086 52.1661 372757 44.635 38.9627 .126127
234707 _x__at 42.1368 41.4296 38.4737 38.2195 44.6769 39.5951 32.9155 30.8686 33.9012 44.1854 40.0147 39.986
2-iC O _at 3-n.;i':n 51"). ¾.½ 349.781 1 2.822 237.954 \7') V:- >.bCb }?.?.<MZ 209.758 402.193 380.215 410.544
238183. .at 6.34043 7.51541 4.91386 2.23734 2.01683 6.13656 0.014064 0.346122 0.00606603 1.1596 0.485291 1.8163 -!Ki j, ,at 2. MM),' 1.64032 1.66047 4.09643 ■'■ 3?¾Γ,1 2 1.1619 5.16647 4.00217 37'"ΙΚ7"
239815. .at 27.9327 28.8666 42.2866 32.9179 28.8318 34.9358 34.627 38.9921 30.1954 46.9591 46.7916 40.1615
241 :8 at 13378<J 151.978 ! 2.1 104.7M> 105.27 "7.77 114.175 110.045 117.488 2.10.043 0 .KJH 198.651
242575. .at 31.3923 34.4255 34.1247 33.5396 40.8559 34.8938 29.9481 32.3142 36.1812 49.0341 20.3701 40.3482
2 t2«.M. 10.6351 b ;·ί.ιη¾ 6.04935 4.91174 Ϊ 3.S70rf.4 5.98621 4.31734 i.bb-:.-b 7.7«0;12 T. bi -5. 2
243147_x_at 362.172 344.871 368.409 335.573 350.03 382.738 374.801 470.517 358.334 366.005 343.677 349.93
Figure imgf000170_0001
Table 17 226 Mitranscriptome transcripts resembling or overlapping a human CRISPR that are differentially expressed in 11 different cancers.
1 2 3 4 5 6 SEC¾ 1 D
Transcri tJD logFC AveExpr P.Value Adj.P.Value Cancer.type 7
Figure imgf000171_0001
Lung adenocarcinoma
T002820 0.928864961 1.34803238 7.7635E-11 1.69616E-09 " „. ,, 68
(509T vs 57N)
Kidney chromophobe
T002825 -1.222000274 0.48084286 4.7142E-29 5.92223E-27 ,e ,_ 68
(64T vs 25N)
Kidnev chromophobe
T009250 -0.660140521 0.49289643 6.5425E-22 3.13106E-20 ,,ΛΤ 181
(64T vs 25N)
Bladder u othelial
T009267 -0.628175871 0.39166666 0.00025586 0.005025114 . ,. T 182 carcinoma (122Tvs 16N)
Gastric carcinoma
T011801 -0.623041841 0.1047345 2.6543E-20 2.66757E-17 ,- e .T 226
(164T s 24N)
Kidnev chromophobe
T011928 - UNC01135 -0.875168217 0.6162543 6.7502E-17 1.79233E-15 ,e>(T ,e M, 229
(64T vs 25N)
Thyroid carcinoma
TO11928 - LINC01135 -0.652404051 0.85373797 5.5945E-19 1.44166E-17 C OM, 229
(456T s 58N)
Kidnev chromophobe
T011929 - UNCOH35 -0.528390302 0.45842222 1.1036E-10 1.36925E-09 ,e>(T ,e M, 228
(64T vs 25N)
Thyroid carcinoma
TO11929 - LINC01135 -0.629660662 0.62490336 9.2902E-26 3.73465E-24 C OM, 228
(456T s 58N)
Bladder urothelial
T013953 0.60296135 0.67326853 0.00074971 0.012990681 . ,. ^Ύ £..η 313 carcinoma (122Tvs 16N)
Head neck squamous eel!
T013953 0.75065764 1.12693204 1.07E-06 1.43374E-05 carcinoma (298T vs 34N) 313
Kidney chromophobe
T013953 -0.505687154 0.56229012 3.0285E-07 2.28849E-06 , (· ,f->4„■,1■ Λ vs 2 -„S-»N,·). 313
Lung squamous cell
T013953 0.992468466 0.99271853 1.4203E-12 1.34664E-11 , ,„-,T .a.., 313 carcinoma (377T vs 43N)
Thyroid carcinoma
T013953 -0.666243566 0.41373496 1.4164E-43 1.77941E-41 (456T vs 5gN) 313
Breast carcinoma
T015716 -1.638312504 0.52165545 3.1274E-90 1.74615E-88 ,„„,,. l nc.,, 356
(8921 vs 105 )
Breast carcinoma
T015720 -0.594264811 0.13167341 4.6036E-67 1.32188E-65 (g92T vs l05N) 357
Kidney chromophobe
T016083 -0.627685776 0.30086996 6.0688E-19 2.25893E-17 {64T vs 25N) 374
Thyroid carcinoma
T017904 1.685646149 1.69044185 1.2898E-28 5.636E-27 (456T vs 5gN) 425
Head neck squamous cell
T030812 0.853702025 0.83782516 4.5926E-05 0.000394494 carcinoma (298T vs 34N) 683
™-„ Λ , „„Λ-„ Λ , ^ ΑΓ Lung adenocarcinoma
Τ030998 0.518100098 0.79092431 2.3377Ε-05 0.000202532 . ' _ 691
(509Τ vs 57Ν)
Breast carcinoma
T031018 0.626877824 0.56335381 4.905E-24 6.31986E-23 ,ΟΛ-τ 693 Gastric card noma
TO31018 0.543714478 0.57956421 0.00114946 0.019917341 ,.1 C .T . .... 693
( 164T vs 24N)
Kidney carcinoma
T031097 -0.568962252 0.78585815 1.8606E-28 3.0159E-27 „-o m- 698
(539T vs 95N)
idnev chromophobe
T031097 -1.109057564 1.32476557 1.1883E-15 2.48792E- 14 ..... 698
{64T vs 25N)
Lung squamous ceil
T036220 - AKR1C2 0.610727511 0.69546797 1.8815E-05 8.22143E-05 5585 carcinoma (377T vs 43N)
T040500 - L1 C00839 -0.505213702 0.13101868 2.3676E-40 5.80344E-39 ^χ^ ^^^ 5759
Kidney chromophobe
T040500 - LI C00839 -1.256217726 0.44736466 5.6939E-13 8.67029E-12 ,C .T 5759
(64T vs 25N)
Kidney chromophobe
TO44664 - UNC00856 0.541108661 0.39734939 8.2768E-06 4.78055E-05 ,, ,T 5867
(64T vs 25N)
Kidney carcinoma
T049586 -1.267368396 0.26404266 1.2921E-82 1.36769E-80 „-o m- 5995
(539T vs 95N)
Lung squamous ce!!
T049676 -0.570574483 0.10460665 3.846E-47 1.24684E-45 carcinoma 5999
(377T vs 43N)
Bladder urothelial
T050959 - LI C00959 -0.832114159 1.08291955 8.203E-07 2.94427E-05 ca rcin oma (122T vs 16N) 6024
Head neck squamous cell
T050959 - U C00959 -0.780904696 1.13060439 9.3207E-11 2.2303E-09 carcinoma {298T vs 34N) 6024
Kidney carcinoma
T050959 - LINC00959 -0.910709785 1.2651067 6.6882E-35 1.26824E-33 (539T vs g5 N) 6024
Kidney chromophobe
T050959 - UNC00959 -0.868397874 2.54519487 1.5325E-08 1.43943E-07 ,, .T „. .. 6024
{bAJ vs 25N)
Lun squamous cell
T050959 - LINC00959 -0.628821974 1.09537849 3.9046E-08 2.62747E-07 ca rcjnoma {377T vs 43N) 6024
Kidney chromophobe
T052162 0.582414008 1.00884062 1.843E-06 1.19497E-05 ί£;ΛΤ 6072
{bAJ vs 25N)
Kidney chromophobe
T055286 -0.770034134 0.22156555 1.1321E-10 1.38607E-09 ,C .T ...... 6129
(64T vs 25N)
Kidney carcinoma
T055287 -1.119885783 0.1703154 4.S75E-112 1.633E-109 (539/ν, 95 Ν) 6129
Kidney chromophobe
T055287 -1.774714371 0.50077929 1.2461E-22 6.26185E-21 ,C .T 6129
(64T vs 25N)
Kidney carcinoma
T055290 -0.780014502 0.153185 5.4143E-83 7.77341E-81 (539/vs 95 N) 6129
Kidney chromophobe
T055290 -1.131043729 0.35194167 3.6094E-17 1.00762E-15 6129
(64T vs 25N)
Kidney carcinoma
T055291 -0.8598315 0.13768751 9.3928E-65 4.96828E-63 (539T vs 95 N) 6129
Kidney chromophobe
T055291 -1.429073455 0.42533685 1.2831E-14 2.47976E-13 , 6129
(64T vs 25N)
Head neck squamous cell
T056308 0.534338636 0.80030093 5.2642E-06 6.22416E-05 carcinoma (298T vs 34N) 5155
Lung squamous cell
T056308 0.652626857 0.59722582 8.5501E-11 7.34433E-10 ca rcin oma ( 377T vs 43 N) 6155
Head neck squamous cell
T056311 1.090241309 1.42415137 8.0555E-11 2.07585E-09 carcinoma {298T vs 34N) 6155 Lung squamous cell
T056311 1.33891029 1.2451478 3.3299E-18 4.52241E-17 carcinoma 6155
(377Tvs 43N)
Breast carcinoma
Γ060449 - Cllorf95 -0.527365977 2.4132932 1.5861E-15 1.56279E-14 {gg2T vs l0SN) 6256
Gastric carcinoma
T060449 - Cllorf95 0.774775295 2.1811671 2.7327E-05 0.001787733 ,1 C .T , ..η 6256
(1641 VS 24l\l)
Kidney carcinoma
Γ060449 - Cllorf95 -0.714112431 2.59140876 1.046E-15 9.82497E-15 {¾39Τ vs g5N) 6256
Head neck squannous cell
T062903 0.597296643 0.7148912 0.00020335 0.001439225 carcinoma (298T vs 34N) 6284
Breast carcinoma
T063471 -0.856390664 0.19194544 4.104E-190 4.1244E-187 6299
(fc>92 [ vs 105NJ
Kidney chromophobe
T063471 -0.549961874 0.52774971 3.2279E-12 4.70155E-11 (6 T vs 25N) 6299
Kidney carcinoma
T072402 -0.648088023 0.47007671 4.7171E-21 5.57733E-20 {539T yc g5N) 6499
Kidney chromophobe
T072402 0.984528808 2.48126535 8.9574E-06 5.11486E-05 (6 T vs 25N) 6499
Lung adenocarcinoma
T072402 0.742066392 1.34937107 4.S761E-06 5.05322E-05 , „... 6499
(509 [ vs 57N)
Liver hepatocellular
T073281 0.919268899 0.85983949 6.8215E-05 0.002980709 . ,CQT ,1 M, 6510 carcinonna (68T vs 31N)
Lung squamous ceii
T073831 1.42091282 1.51665382 8.7125E-15 9.622E-14 carcinoma 6520
(377T VS 43N)
Lung squamous cell
T073832 0.926002052 0.92270724 4.5395E-14 4.80232E-13 carcinoma (377T vs 43N) 6520
Kidney carcinoma
T075536 -0.716304505 0.75513603 1.7273E-35 3.47185E-34 {539T vs 95Nj 6577
Kidney chromophobe
T075536 -1.037552062 0.95251152 2.1894E-15 4.49055E-14 (64T vs 25N) 6577
Kidney chromophobe
T076619 0.766311093 0.71627659 1.1192E-06 7.4493E-06 {6 T s 2rj|S1) 6619
Head neck squannous cell
T079881 0.705799307 0.66202731 0.00031288 0.002096292 carcinoma (298T vs 34N) 6667
Lung sauarnous ceii
T079881 0.574102337 0.53316974 0.00023125 0.000832988 ?τ■ .· 6667 carcinoma (377f 43N)
Lung adenocarcinoma
T082900 -1.576313769 0.59780384 6.6107E-61 6.03973E-59 (509T vs 57N) 6748
Lung sauarnous ceii
T082900 -2.21924802 0.38220373 8.492E-123 8.5344E-120 „, " nrn^ ,.™T . c 6748 carcinoma (377f 43N)
Lung squamous cell
T087049 0.995972556 0.91173217 8.6896E-05 0.000334601 carcjnoma (377T vs 43N) 6851
Kidney chromophobe
T087523 0.508018395 1.04033972 0.0060444 0.020384641 {64T .s 25N} 6866
Kidney chromophobe
T095819 1.226442095 0.9250939 0.00010967 0.000519918 (64T vs 25N) 7126
Kidney carcinoma
T096279 -0.583142134 0.13000678 4.1637E-83 6.97425E-81 {539T ,s 35Nj 7147
Kidney chromophobe
T096279 -0.868609043 0.78823474 8.5274E-12 1.17397E-10 /εΛΧ ' ,CM. 7147 Bladder urothelial
T0982Q9 o W OK is 1.18090814 0.00142405 0.021589034 72 52 carcinoma {122T vs 16N)
Kidney carcinoma
TQ98209 -0.690993818 0.64257378 1.195E-49 4.14119E-48 (539Tvs 95N) 7232
Kidney chromophobe
T0982Q9 -0.564609204 1.7651178 4.9342E-05 0.000250447 72 5
(64T s 25N)
Lung adenocarcinoma
TQ98209 0.714812074 0.90886329 4.2565E-14 1.18828E-12 (509Tvs 57N) 7232
Lung squamous cell
T0982Q9 0.98709S689 1.3399564 3.5309E-17 4.38091E-16 72 5 carcinoma {377T vs 43N)
Bladder urothelial 7317, 7316, T100138 1.034127076 1.20430641 0.00017422 0.003647796
carcinoma (122T vs 16N) 7319, 7318
Gastric card noma 7317, 7316, T100138 0.838014824 0.86847122 3.5195E-07 7.07412E-05 (164T V5 24N) 7319, 7318
Head neck squamous cell
T100138 0.778974868 0.89534141 2.9244E-08 5.4427E-07 carcinoma (298T vs 34N) 7317, 7316,
7319, 7318
Kidney carcinorro 7317, 7316,
T100138 0.538032639 0.62848086 9.7914E-16 9.37178E-15 {539T VS 95N) 7319.. 7318
Liver hepatocellular 7317, 7316, T100138 0.514910154 0.39074698 7.7594E-06 0.000557012
carcinoma (68T vs 31N) 7319, 7318 Lung squamous ceff 7317, 7316, T100138 0.683367546 0.96203818 1.3042E-07 7.94384E-07
carcinoma (377T vs 43N) 7319.. 7318 Kidney chromophobe
T101157 -0.52231613 0.23086988 2.8374E-27 2.85163E-25 (64T vs 25N) 7330
Breast carcinoma
T103470 0.576052298 0.57898256 2.3264E-11 1.75793E-10 73Sf'
(892T S 105N)
Breast carcinoma
T103486 0.957697435 1.02125879 3.8668E-13 3.26564E-12 (892T vs 105N) 7389
Gastric carcinoma
T103645 0 73850.767 0.00178302 0.026440044 (164T VS 24N) 7394
Head neck squamous cell
T103645 2.731783617 3.74803321 2.285E-29 1.14819E-26 carcinoma (298T vs 34N) 7394
Lung squamous ceil
T103645 1.636166591 2.15840456 1.1832E-12 1.13252E-11 7394 carcinoma (377Tvs 3N)
Lung squamous cell
T104965 0.542901027 0.57106658 8.537E-10 7.09064E-09 carcinoma (377T vs 43N) 7425
Kidney chromophobe
T105361 0.927483907 0.86462811 6.7265E-10 7.5957E-09 7442
(64T vs 25N)
Kidney carcinoma
T107637 -0.874375294 0.13387913 7.808E-112 1.9617E-109 (539T vs 95N) 7481
Kidney chromophobe
T107637 -1.53692.3318 0.50788808 6.777E-17 1.79233E-15 (64T vs 25N) 7481
Kidney chromophobe
T111645 -0.807583806 0.77893879 9.1702E-05 0.000440958 7575
(64T vs 25N)
Lung adenocarcinoma
T112050 0.700446938 0.94068753 1.1849E-06 1.56689E-05 7585
(5Q9Tv 57N)
Head neck squamous cell
T112299 -0.737350294 0.49039843 1.3205E-15 4.73978E-14 carcinoma (298T vs 34N) 7594
Kidney chromophobe
T112299 -0.696405246 0.94084031 2.0877E-07 1.60165E-06 7594
(64T VS 25N) Lung squamous cell
T115171 -0.636539161 0.60449239 7.0256E-18 8.97839E-17 7668 carcinoma (377T vs 43N)
Head neck squamous cell
U17J07 0.842961675 0-82976703 2.7131E-09
7703
Lung adenocarcinoma
T120429 -1.085184998 0.36793095 4.075E-47 2.40907E-45 7765
(509T vs 57N)
Lung squamous cell
T120429 -1.753424841 0.35420414 6.6552E-93 2.2295E-90 7765 carcinoma (3771" vs 3N)
Kidney chromophobe
T122676 - LINC01197 -0.800082231 0.54252875 1.1888E-16 2.98675E-15 7811
(64T vs 25N)
T122806 - NR2F2- Kidney chromophobe
-1.225890114 0.43963355 ¾.2-Vi iL .52 1.06431E-29 3 AS1 (64T VS 25N)
T125427 - IR940, Lung adenocarcinoma
-0.52135989 0.19126807 2.4697E-45 1.30636E-43 7859 MIR3677, MIR4717 (509T vs 57N)
T125427 - MI 940, Lung squamous cell
-0.846409023 0.17249446 1.4307E-71 1.30713E-69
MfR3677, IR4717 carcinoma (3771" vs 3N)
Kidney chromophobe
T127555 -0.703229439 0.76504155 8.0456E-06 4.67387E-05 7898
(64T vs 25N)
Kidney chromophobe
T127575 0.627494896 0.45411574 7.5175E-05 0.00037035 7900
(64T VS 25N)
Kidney chromophobe
T127635 1.018974422 1.06867178 2.7391E-06 1.69928E-05 7901
(64T vs 25N)
Lung squamous cell
T127635 -0.586563554 0.166456 3.8653E-43 1.10989E-41 7901 carcinoma (3771" vs 3N)
Breast carcinoma
T127636 -0.551093446 0.15907014 4.415E-131 1.1092E-128 7901
(892T vs 105IM)
Kidney chromophobe
T127636 1.346417141 1.49558307 2.4772E-06 1.54631E-05 7901
(64T VS 25N)
Lung squamous cell
T127636 -1.079220301 0.27672053 1.9249E-53 7.16503E-52 7901 carcinoma (377T vs 43N)
Kidney carcinoma
T132564 -0.746045812 0.25608034 5.9878E-70 4.29839E-68 7976
(539T VS 95N)
Kidney chromophobe
T132564 1.244127842 1.89252309 1.0107E-06 6.81719E-06 7976
(64T vs 25N)
Head neck squamous cell
0.866105684 1.72386108 0.00051431 0.003058473 carcinoma (2981" vs 34N) 8005
Lung squamous ceil
T133789 0.663862288 0.93093697 0.00011041 0.000415573 8005 carcinoma (377T vs 43N)
T139444 - MIR22, Bladder urothelial
-1.516759944 2.61660892 1.8357E-07 7.Λ7'¾ ϊ7ι: Ob 8151 IR22HG carcinoma {122T s 16N)
T139444 - MIR22, Breast carcinoma
-1.044237522 2.04918462 1.1832E-40 1.88742E-39 8151 MIR22HG (892Tvs 105N)
T139444 - MIR22, Gastric card noma
-0.894875115 1.9511018 6.4177E-06 0.00064498 8151 IR22HG (164T V5 24N)
Head neck squamous cell
T139444 - MIR22,
-0.871938348 3.10722612 1.2178E-06 1.58945E-05 carcinoma (298T vs 34N) 8151 MIR22HG
T139444 - fR22, Kidney carcinoma
-1.430603567 2.59494524 7.8218E-40 1.87165 E-38 8151 IR22HG (539T 95N)
T139444 - MIR22, Lung adenocarcinoma
-0.821204496 2.49857226 1.057E-09 2.08301E-08 8151 MIR22HG (509T vs 57N)
Figure imgf000176_0001
T139444 - MIR22, Prostate adenocarcinoma
-0.955489298 2.2059134 1.6586E-10 5.74805E-09 8151
MIR22HG (183T vs 43N)
T139444 - MIR22, Thyroid carcinoma
-1.341603266 3.12231515 2.4329E-19 6.79192E-18 8151 IR22HG (456T VS 58N)
T139445 - MIR22, Bladder urothelial
-0.541410793 0.50243762 5.4499E-05 0.001369292
MIR22HG carcinoma (122T vs 16N) 8151 T139445 - M!R22, Kidney carcinoma
-0.5775931S8 0-49563464 9.2513E-3Q 1.57585E-28
IR22HG (539Tvs 5N) 8151 T139445 - MIR22, Lung squamous cell
-0.633923924 0.47517163 1.1478E-19 1.7217E-18
MIR22HG carcinoma (377T vs 43N) 8151 T139445 - M!R22, Thyroid carcinoma
-0-55430166 0-55823115 4.3568E-17 9.31623E-16 8151 IR22HG (456T VS 58N)
Kidney carcinoma
T142346 -0.606400856 0.98394204 4.9887E-22 6.1897E-21 (539T vs 95N) 8188
Kidney chromophobe
Π42346 -0.842059223 1.5509082 9.6586E-08 8.02227E-07 (64T vs 25N) 8188
Lung squamous cell
T142346 -0.697156465 0.69039034 5.4007E-18 7.04902E-17 carcinoma (377T vs 43N) 8188
Lung adenocarcinoma
Π53012 0.593935399 0.6306667 2.3653E-12 6.25563E-11 3-i 3.7
(509T VS 57N)
Kidney chromophobe
T161706 0.583578421 0.49959466 1.8143E-07 1.40258E-06 (64T vs 25N) 8534
Kidney chromophobe
Π65338 -1.419371149 0-61783573 3.2856E-18 1.06518E-16 (64T vs 25N) So/ ¾
Kidney chromophobe
T165339 -0.648145419 0.32403529 1.5173E-13 2.49977E-12 (64T vs 25N) 8673
Prostate adenocarcinoma
Π71327 0.617467353 0-92431256 0.00100823 0.006495355 8760
(183T VS 43N)
Thyroid carcinoma
T171327 -1.015682034 0.31184067 2.4731E-45 4.97092E-43 (456T vs 58N) 8760
Kidney carcinoma
Π71355 -0.560796144 1.01102464 5.4081E-15 4.60608E-14 (539Tvs 5N) 8761
Thyroid carcinoma
T171355 -0.814989659 1.28210056 4.9665E-14 7.79895E-13 (456T vs 58N) 8761
Kidney chromophobe
Π79285 0.778505164 1.02946073 4.813E-09 4.S6469E-08 (64T vs 25N) 8856
Kidney chromophobe
T180296 -0.660434188 1.69169356 7.7819E-07 5.54671E-06 (64T vs 25N) 8862
Thyroid carcinoma
Π83157 -0.739420592 0-33974856 6.1152E-19 1.53643E-17 (456T VS 58N) 848, 849
Kidney carcinoma
T187550 0.748387301 0.70980475 1.171E-14 9.88933E-14 (539T vs 95N) 959
Kidney carcinoma 960, 959, Π87556 -0.525953867 0-99025367 3.1897E-09 1.69612E-08 (539Tvs 5N) 961
Kidney chromophobe 960, 959, T187556 -1.915811874 0.68550721 7.8189E-31 1.12257E-28 (64T vs 25N) 961
Kidney carcinoma
Π87561 0.987690907 1.81434045 1.0757E-13 8.25245E-13 (539Tvs 5N) 960, 61
Kidney chromophobe
T187561 -1.35854834 0.47531673 1.9609E-18 6.79549E-17 (64T vs 25N) 960, 961
Kidney carcinoma
1 187563 0.761561497 0-72653605 4.3925E-12 3.0656E-11 (539Tvs 5N) 960 Kidney carcinoma
T187565 1.375094542 1.90297523 1.3997E-29 2.34454E-28 961
(539T vs 95N)
Kidney chromophobe
T187565 -1.126971157 0.38071535 S.8479E-24 5 2.;0i>(">f 22 961
(64T vs 25N)
Kidney chromophobe
T187566 -2.772856161 1.11500223 1.1278E-33 1.13348E-30 961
(64T vs 25N)
Kidney carcinoma
T187568 0.737349272 0.67493526 1.1284E-10 6.95734E -10 961
(539T vs 95N)
Head neck squamous eel!
T188105 - SLC8A1-
-0.642651301 0.07576167 1.5215E-21 1.91139E-19 carcinoma (298T vs 34N) 984 AS1
Head neck squamous cell
T194Q30. -1.217052346 0.22960296 4.6941E-45 4.71754E-42 carcinoma (2981" vs 34N) 1119
Kidney carcinoma
T194030 -0.936473753 0.3408321 6.8938E-55 2.6647E-53 1119
(539T vs 95N)
"Π 9 *5 7 - W ii m Gastric card noma
>(>2 .1 7 ϊ:·.5¾. ¾.t>. U Of. 0.000440823 1157.. 1158
Figure imgf000177_0001
T196778 - MIR4435- Gastric carcinoma
0.803326989 0.90924389 1.7882E-07 4.49286E-05 1157, 1158 2HG (164T s 24N)
T196778 - MIR4435- Kidney carcinoma
0.725492124 0-95260074 2.8177E-24 3.67766E-23 1157, 1158 2.HG (539T vs 5N)
T196778 - MIR4435- Lung squamous cell
0.592817366 0.84777584 7.5147E-07 4.12692E-06 1157, 1158 2HG carcinoma (377T vs 43N)
Head neck squamous cell n 96812 0.701555447 0.92548343 4.1351E-11 1.09364E-09 carcinoma {298T vs 34N) 1158
Kidney carcinoma
T196812 0.617090293 0.68793601 1.6773E-23 2.13376E-22 1158
(539T VS 95N)
Liver hepatocellular
T200S14 - TEX41 0.779423248 0.53706413 3.1743E-05 0.001595086 1248 carcinoma {68T vs 31N)
Kidney chromophobe
T201771 -0.86161752 0.80430176 6.9866E-12 9.84573E-11 1287
(64T vs 25N)
Kidney carcinoma
T203610 -0.549660678 0.23494582 7.4164E-65 4.1408E-63 1338
(539T vs 95N)
Kidney chromophobe
T203610 -0.620579995 0.29233996 7.0452E-11 8.96252E-10 1338
(64T vs 25N)
Prostate adenocarcinoma
T203963 0.652290867 0.75076929 6.7902E-05 0.000561668 1349
(183T VS 43N)
Prostate adenocarcinoma
T203988 0.714056417 0.65392432 0.00011049 0.000860777 1349
(1S3T vs 43N)
Bladder urothelial
T2062S7 -0.555625994 1.41660125 4.3126E-05 0.001171402 1429 carcinoma {122T s l6N}
Head neck squamous cell
T206257 -0.866793484 1.50323498 3.4273E-12 9.56783E-11 carcinoma {298T vs 34N) 1429
Kidney carcinoma
T206257 -1.044959311 2.19911618 2.9206E-35 5.6446E-34 1429
{539T VS 95N) Head neck squamous eel!
T206467 0.607796444 0.7152436 6.5631E-06 7.41116E-05 carcinoma (298T vs 34N) 1434
Figure imgf000178_0001
MIR99AHG, (892T vs 105N)
-0.937878086 0.67437488 3.1455E-66 8.78132E-65 9157 MIRLET7C,
IR125B2, IR99A T223700 - Head neck squamoi s cell MI 99AHG, carcinoma {298T V5 34N)
-0.933570979 0.68222219 1.0666E-16 5.4445 -Jh lb 9157 IRLtfVC,
Figure imgf000179_0001
MIR125B2, MIR99A
T223707 - Kidney carcinoma
IR99AHG, (539Tvs 5N)
-1.00964259 0.78590953 2.S982E-S6 1.16508E-54 9157 MIRLET7C,
IR12582, I 99A
T223707 - Kidney chromophobe
MIR99AHG, (64T s 25N)
MIRLET7C,
Figure imgf000179_0002
Breast carcinoma
T233871 -1.020159348 2.31355157 1.3228E-21 1.54588E-20 9377
(892T vs 105N)
Kidney carcinoma
T2.33.S71 1.293399305 3.09498326 1.1188E-24 1.51947E-23 9377
(539T vs 95N) Kidney chromophobe
T233871 -1.382780907 1.30966912 1.0417E-09 1.11368E-08 9377
(64T vs 25N)
Prostate adenocarcinoma
T233871 -1.820491493 2.60213017 1.0655E-25 1.07085E-22 9377
(183Tvs 43 N)
Bladder urothelial
T239482 0.51311333 0.85635833 0.0008014 0.013650913 1652 carcinoma (122T vs 16N)
Lung squamous cell
17 WA 0.554352629 1.05143716 2.1695E-05 '•'.27Sf. n=. 1652 carcinoma (377Tv 3N)
Kidney chromophobe
T240613 - MYRIP -0.539995469 0.52617203 9.8307E-14 1.64665E-12 1733
(64T vs 25N)
Kidnev chromophobe
T243120 -0.670192614 0.45007903 1.6697E-14 3.16617E-13 17 ¾
(64T vs 25N)
Kidney carcinoma
T244322 0.517916891 0.44452359 1.5865E-09 8.61829E-09 1749
(539T vs 95N)
1744623 - ADAMTS9- Bladder u othelial
η:.?Λ¾7.ι 0.09686609 !... 2°; 25 1.78983E-22 1762, 1763 AS2, MIR548A2 carcinoma (122Tvs 16N)
Τ244623 - ADAMTS9- Kidney carcinoma
-0.507921097 0.60870905 8.6173E-19 9.41345E-18 1762., 1763 AS2, IR548A2 (539T vs 95N)
1744623 - ADAMTS9- Kidnev chromophobe
-1.619165837 0.53473713 1.7628E-32. 4.42897E-30 1762, 1763 AS2, MIR548A2 (64T vs 25N)
Τ244667 - ADAMTS9- Kidney carcinoma 1762, 1763,
-0.555022836 0.5489444 2.8516E-15 2.49207E-14
AS2, IR548A2 (539T vs 95N) 1764
1744667 - ADAMTS9- Kidnev chromophobe 1762, 1763,
-1.701999805 0.53936436 1.3037E-21 5.95562E-20
AS2, MIR548A2 (64T vs 25N) 1764
Τ244675 - ADAMTS9- Kidney chromophobe
-1.030212721 0.31154641 3.4514E-28 3.85408E-26 1762, 1763 AS2, IR548A2 (64T vs 25N)
Kidnev chromophobe 1762, 1763,
Τ244678 -0.582196058 0 20:».'267t! •1..OW. 27 7.70554E-25
(64T vs 25N) 1764 Kidney chromophobe
T249192 -0.51939233 0.88381119 4.0225E-08 3.48501E-07 1925
(64T vs 25N)
Kidnev chromophobe
Τ252309 1.386436387 1.46.358885 1.0239E-07 8.43464E-07 2009
(64T vs 25N)
Lung squamous cell
Τ255234 0.714871163 0.64501122 4.4918E-10 3.76189E-09 2115, 2116 carcinoma (377T vs 43N)
Lung squamous ceii
Τ255252 1.011439418 0.912.43816 2.0299E-14 2.17024E-13 2116 carcinoma (377Tv 3N)
Head neck squamous eel!
Τ255253 0.565029805 0.74160346 3.083E-05 0.000281675 carcinoma (298T vs 34N) 2116
Lung squamous cell
1.305325579 1.18323972 7.1812E-17 8.80129E-16 2116 carcinoma (3771" vs 3N)
Lung squamous cell
Τ255259 0.50813041 0.45784617 1.347E-08 1.00277E-07 2116 carcinoma (377T vs 43N)
Lung squamous cell
Τ255669 0.:, MAhJ.7-\2 0 4S72 M2rj S ?.ii ¾ 5.39306E-07 2 125 carcinoma (3771" vs 3N)
Head neck squamous cell
Τ256375 0.616617267 0.69235891 0.00062574 0.003573141 carcinoma (298T vs 34N) 2133
Lung squamous cell
t , 7 1.507635049 1.44269605 6.9829E-08 4.55704E-07
carcinoma {377T vs 43N) a Kidney chromophobe
T256469 -0.58229372 0.21794643 1.9816E-06 1.26045E-05 2134
(64T s 25N)
Kidney carcinoma
-0.559766913 0.0867815 3.072E-119 1.5439E-116 2. H I
(539T vs 95N) Kidney chromophobe
T256497 -1.120236557 0.37054263 9.4364E-17 2.4317E-15 ,,ΛΤ 2134
(64T vs 25N)
Kidnev carcinoma
T256631 0.658496767 0.69962169 9.2866E-13 6.71444E-12 2136
(539Tvs 9¾N)
Kidney chromophobe
T256631 3.120819848 2.58273791 6.639E-12 9.53177E-11 ,, .τ 2136
(64T vs 25N)
Kidnev carcinoma
T257541 0.524754364 0.46419725 1.2506E-20 1.46147E-19 2166, 2167
(539Tvs 9¾N)
Kidney carcinoma
T258141 -1.214299327 0.19041853 2.984E-144 2.9993E-141 „-.., 2184
(539T vs 95N)
Kidnev chromophobe
T25S141 -2.211575085 0.64069247 4.9758E-33 1.78497E-30 ,e ._ --M( 2184
(64T vs 25N)
Kidney carcinoma
T258261 - LINC00885 -0.641190824 0.15368165 7.7556E-78 5.99566E-76 lc. ' 2190
(539T vs 95N)
Kidnev chromophobe
T25S261 - UNC00885 0.856404365 1.96614897 0.000.30611 0.001.373378 ,e ._ * M1 2190
(64T vs 25N)
Lung squamous cell
T258261 - LINC00885 0.790974063 1.07537814 2.0259E-08 1.45432E-07 carcInoma {377T vs 43N) 21 0
Kidnev chromophobe
T260466 -0.627587123 0.232.16957 7.8841E-11 9.904.38E-10 ,e ._ --M( 22.50
(64T vs 25N)
Kidney chromophobe
T262095 -0.580798218 0.16314557 2.2775E-06 1.43956E-05 ,,ΛΤ 2312
(64T vs 25N)
Kidnev chromophobe
T264872. 0.536300566 0.41709227 7.02E-08 5.92862E-07 ,e ,_ 2413
(64T vs 25N)
Kidney chromophobe
T265047 -0.711490867 0.666242 2.3055E-12 3.40743E-11 ,, .τ 2417
(64T vs 25N)
Lung sauamous cefi
T265047 -1.005491394 0.50829575 3.7752E-42. 9.98443E-41 1 2417 carcinoma (377Tvs 3N)
Lung adenocarcinoma
T266617 0.823005917 1.10810816 9.9563E-09 1.69595E-07 ',. 2478
(509T vs 57N)
Lung sauamous cefi
T266617 1.806536244 2.17423046 2.0223E-18 2.78414E-17 . 1 2478 carcinoma (377Tvs 3N)
Prostate adenocarcinoma
T266617 -0.954211073 1.3075106 1.3086E-09 3.38527E-08 ,, 00, 2478
(183T vs 43N)
Lung sauamous ceff
T266618 0.552055553 0.5428182 5.6139E-07 3.13443E-06 car -10rn3 (377T vs 43N) 2478
Lung squamous cell
T267813 0.596001819 0.54569638 3.1662E-10 2.69661E-09 ..... 2527 carcinoma (377T vs 43N)
Head neck squamous cell
1267826 0.879911024 0-82174649 7.0674E-09 1.42055E-07 carcinoma (298Tvs 34N) 2527
Lung squamous cell
T267826 0.858258855 0.78642656 1.3065E-09 1.05887E-08 ; ,™T 2527 carcinoma (377T vs 43N)
Head neck squamous cell
T267827 0.568718287 0.55666909 4.S407E-05 0.000412279 carcinoma (2981" vs 34N) 2527
Lung squamous ceil
T267827 0.798925454 0.72395096 2.492E-08 1.75134E-07 2527 carcinoma (377T vs 43N) siadder urothelial
T268443 - STPG2 0.549594397 0.90139765 0.00091113 0.01501118 . l r . 2556 carcinoma {122T s 16N)
Head neck squamous cell
T268443 - STPG2 0.74686957 1.19251395 5.618E-08 1.00823E-06 carcinoma (298T vs 34N) 2556 Lung squamous cell
68443 - STPG2 1.362642811 1.50247465 3.0137E-19 4.32679E-18 carcinoma 2556
(377T VS 43N)
Kidney chromophobe
T270578 -0.78554579 0.2328534 2.5638E-23 1.35613E-21 2633
(64T vs 25N)
Kidney chromophobe
12705S6 -1.4714S9755 0.4341281 5 3 1.78497E-30 2o i¾
(64T vs 25N)
Thyroid carcinoma
T272154 -0.563115969 0.36792428 1.3127E-44 2.19873E-42 2701
(456T vs 58N)
Kidney chromophobe 2724, 2725, V273101 1.306775632 0-99133795 9.2228E-07 6.39239E-06
(64T vs 25N) 27.';.
Prostate adenocarcinoma
T274230 0.553143953 0.46305116 0.00044585 0.003133418
(183T vs 43N) 2780
Prostate adenocarcinoma
V274234 1.441095058 1.2S445561 3.1808E-06 3.9465E-05 (183T VS 43N) 2780
Head neck squamous cell
T275252 1.797769486 2.60707913 5.9377E-09 1.21783E-07 carcinoma (298T vs 34N) 2854
Lung squamous cell
T2752S2 1.103046329 0.99767503 6.8S6E-08 4.50999E-07
carcinoma {377T vs 3N)
Head neck squamous cell
T275255 1.552801943 2.40064662 9.2053E-08 1.59506E-06 carcinoma {298T vs 34N) 2854
Lung squamous cell
1.097290853 0.99097326 4.Q37E-08 2854 carcinoma {377T vs 43N)
Kidney chromophobe
T276533 -0.953646061 2.64887552 8.3716E-05 0.000405977 2890
(64T s 25N)
Lung squamous cell
f .V 0-> --, ¾ -0.656087157 1.17790171 3.9216E-G8 W, 7i -Q)
carcinoma {377T vs 43N) 2890 Kidney carcinoma
T277645 0.906358174 0.87126452 1.5036E-25 2.09875E-24 2931
(539Tvs 95N)
Lung squamous cell
[ 2782-14 0.640790927 0.57715771 4.5231E-09 3.47001E-08 :>«)¾.'
carcinoma {377T vs 43N)
T278748 - Gastric carcinoma
MIR4458HG, -0.951099649 0.35455537 1.4078E-14 7.07425E-12 (164Tvs 24N) 2967 MIR4458
Kidney chromophobe
T283698 -1.132559631 0.41056757 3.3589E-27 3.06883E-25 3144
(64T VS 25N)
Kidney chromophobe
T285164 -0.890951558 0.28944607 2.4175E-24 1.61969E-22 3197
(64T vs 25N)
Kidney carcinoma 3 .Ό ,?. >. T285969 1.011543097 1.10539017 8.9993E-16 8.6964E-15
(539T VS 95N) .5221
Kidney chromophobe 3220, 3222, T285969 -0.520931096 0.19559988 8.3259E-07 5.89263E-06
(64T vs 25N) 3221
Lung squamous cell
T28S925 0.605949966 0.57531605 4.S674E-13 4.84329E-12 Π08 carcinoma (3771" vs 43N)
Kidney chromophobe
T287748 -0.501722878 0.16815961 5.2675E-24 3.30864E-22 3308
(64T vs 25N)
Liver hepatocellular
T292277 -0.527950419 0 f- \$1 biV) 1.6516E-05 0.000922168 ¼i 5 carcinoma (68T vs 31N)
Thyroid carcinoma
T294686 -0.88570401 0.41805071 1.3401E-42 1.49645E-40 3472
(456T vs 58N)
Lung squamous cell
T29S895 -0.781757564 0.09783415 7 ΊΓ,ΛΗί: <S2 1.85041 £-89
carcinoma (3771" vs 43N) Lung squamous cell
T296898 -0.545743071 0.06299538 5.0443E-72 5.06956E-70 3533 carcinoma (377T vs 43N) Kidney chromophobe
1 2'.v.7295 -0.741832806 0.912.40408 3.8555E-18 1.21088E-16 3542
(64T vs 25N)
Lung squamous cell
T298139 -0.533312623 0.92759706 9.82 E- 10 8.08942E-09 3558 carcinoma (377T vs 43N)
Thyroid carcinoma
T29S139 -0.506151637 1.48992.49 2.1494E-10 2.40015E-09 3558
(456Tvs 58N)
Kidney chromophobe
T300038 -0.550444884 0.27034035 3.6238E-16 7.91725E-15 3595
(64T vs 25N)
Kidney chromophobe
T301548 -0.678563993 0.39687338 1.4348E-09 1.50202E-0S 3611
(64T vs 25N)
Kidney chromophobe
T301549 -0.720413842 0.37657789 7.0537E-12 9.84573E-11 3611
(64T vs 25N)
Breast carcinoma
T302165 -0.597140899 3.2562094 1.3696E-10 9.90225E-10 3618
(892Tvs l05N)
Gastric carcinoma
T302165 0.773956092 3.22232866 0.00018027 0.005489891 3618
(164T vs 24N)
Head neck squamous cell
1302165 -0.750979692 3.15835187 1.0482E-05 0.000110889 carcinoma (298Tvs 34N) 3618
Kidney carcinoma
T302165 -1.307936359 3.28862115 2.5675E-26 3.68616E-25 3618
(539T vs 95N)
Kidney chromophobe
T302165 -0.880597645 4.27432999 0.00015982 0.000740168 3618
(64T VS 25N)
Lung squamous cell
T302165 -0.844179944 2.89506975 7.4426E-08 4.79532E-07 3618 carcinoma (377T vs 43N) Thyroid carcinoma
T302165 -0.71318044 3.61720108 6.1022E-06 3.62881E-05 3618
(456T VS 58N)
Bladder urothelial
T302167 -0.650788959 0.95573622 0.00087569 0.014667805 3618 carcinoma (122T vs 16N) Thyroid carcinoma
T302167 0.50294435 1.91580183 0.00319718 0.011813099 3618
(456T VS 58N)
Lung squamous cell
T302404 -0.889826308 0.19169286 2.0993E-83 3.01393E-81 3624 carcinoma (377T vs 43N) Thyroid carcinoma
T302404 -1.283234557 1.32552484 S :-: ?-._ Ml 7.14595E-36 3624
(456T VS 58N)
Kidney carcinoma
T304269 0.903847686 0.77915437 8.6191E-13 6.27695E-12 3651
(539T vs 95N)
Kidney carcinoma
T304271 0.52128642 0.45273063 4.698E-08 2.11381E-07 3651
(539T VS 95N)
Breast carcinoma
T304646 -0.604552159 0.30728044 5.1568E-66 1.40069E-64 3657
(892T vs 105N)
T309007 - Kidney carcinoma
0.583048816 6.6457E-14 5.21795E-13 .5,- H LOC100422737 (539T VS 95N)
Lung squamous cell
T309951 0.604808125 0.57281574 5.7346E-09 4.33331E-08 3884 carcinoma (377T vs 43N) Head neck squamous cell T309958 0.732086819 1.20888541 9.9262E-07 1.38553E-05 carcinoma (2981" vs 34N)
Lung squamous ceil
T309958 1.393267143 1.26510145 1.8202E-14 1.96701E-13 3884 carcinoma (377T vs 43N) Head neck squamous cell
"(309960 0.646079809 0.73263069 3.4466E-G8 6.29793E-07 carcinoma {298T vs 34N) 3884
Lung squamous cell
T309960 0.741775107 0.75654964 1.4S82E-09 1.18704E-08 3884 carcinoma (377T vs 43N) Lung adenocarcinoma
T310468 -0.605642931 0.40519926 7.5703E-26 2.92623E-24 3909
(509T 57N)
Lung squamous cell
T310468 -1.192116168 0.27905992 4.948E-99 2.48634E-96 3909 carcinoma (377T vs 43N) Lung squamous ceff
T311570 0.697125223 0.62689707 2.5336E-09 2.00494E-08 3948 carcinoma (377T vs 43N) Kidney carcinoma
T311917 - LI C00271 -1.033460415 0.59323683 1.3609E-82 1.36769E-80 3957
(539T vs 95N)
Kidney chromophobe
T311917 - LI C00271 -2.072118382 0.96913278 6.6934E-31 1.12115E-28 X'S ;
(64T vs 25N)
Thyroid carcinoma
T311917 - LI C00271 -0.553641559 1.3577822 1.331E-10 1.53753E-09 3957
(456T vs 58N)
Breast carcinoma
ι.ίΐ ,ί.ν· , -0.551110086 0.40537713 1.3954E-56 2.9838E-55 3977
(892T VS 105N)
Lung squamous cell
Τ314343 -0.69147266 0.63164851 4.3081E-18 5.69694E-17 4013 carcinoma (377T vs 43N) Thyroid carcinoma
T314343 -0.547316081 0.78068367 3.1153E-19 8.23916E-18 4013
(456T 58N)
Kidney carcinoma
T317967 -0.55202774 1.38030033 2.5048E-15 2.22775E-14 4121
(539T vs 95N)
Liver hepatoceiiular
T317967 1.174303994 1.05509696 7.1116E-11 3.21205E-08 4121 carcinoma {6ST vs 31N)
Head neck squamous cell
T318841 1.914485813 2.31985337 8.0253E-26 2.68847E-23 carcinoma (298T vs 34N) 4146
Lung squamous ceii
T31S841 1.169565203 1.4518033S 1.8219E-11 1.62036E-10 4146 carcinoma (377Tvs 3N) Head neck squamous eel!
Τ318849 2.279221078 2.49928967 6.7419E-17 3.76425E-15 carcinoma (298T vs 34N) 4147
Lung squamous ce!!
T318849 1.927445324 1.7522091 1.1751E-11 1.0639E-10 4147 carcinoma (3771" vs 43N)
Kidney chromophobe
T319605 -2.410422753 2.0226496 1.3213E-16 3.2388E-15 4167
(64T vs 25N)
Lung squamous ce!!
Τ319605 0.840792465 1.34213453 7.4126E-06 3.53067E-05 4167 carcinoma (3771" vs 43N)
T320415 - Kidney carcinoma
-0.647083616 0.90281879 1.0195E-18 1.10168E-17 4183 LOC441204 (539T vs 95N)
T320415 - Kidney chromophobe
-1.043797358 1.7626454 1.3937E-06 9.15443E-06 4183 LOC441204 (64T VS 25N)
T320415 - Lung squamous cell
-0.818923911 0.27309203 2.4703E-56 1.12848E-54 4183 LOC441204 carcinoma (377T vs 43N)
Kidney chromophobe
T322119 -0.545324107 0.24665498 2.8583E-11 3.77976E-10 42 3
(64T VS 25N)
Kidney chromophobe
T322579 - LINC00957 1.689837392 4.64367347 1.2163E-12 1.82442E-11 4233
(64T vs 25N)
Lung squamous ce!!
T322579 - U C00957 -0.559776751 1.09110913 7.-.32i. OS 4.79532E-07 42.Π carcinoma (3771" vs 43N) T323004 - SNHG15, Gastric carcinoma
0.58901704 1.87368974 0.0001608 0.005177467 4237 SNORA9 (164T 24N)
T323004 - SNHG15, i|ig !¾!|8a§iiiiiiiiiiiii
0.599797585 1.96548299 1.8204E-05 0.000164819 ■ij y?
T323004 - SNHG15, Thyroid carcinoma
-0.518087555 1.59880666 6.7288E-08 5.12304E-07 4237 SNORA9 (456T vs 58N)
Kidney carcinoma
T32S104 1 .083789656 0.96127438 5.1957E-23 6 52706? ?7 4406
|||ll|||l||!||||||||!!!
T330930 - SLC26A4- Kidney chromophobe
0.510180482 0.40632269 4.6739E-05 0.000239656 4484 AS1 (64T vs 25N)
T !WHP si ^GA-l- Thyroid carcinoma
-1.935329546 2 4 1 >>.>¾■-> ; 1.3258E-14 2.18 27E-13 4484
T330940 - SLC26A4- Kidney chromophobe
1.155202661 1.01373408 8.353E-06 4.79701E-05 4484 AS1 (64T vs 25N)
T Htm ¾i c., c,A.-i- Thyroid carcinoma
-2.73879393 4.31444266 2.9692E-16 5.52593E-15 4484
AS1
Gastric carcinoma
T334872 0.663060586 1.81354981 4.2622E-05 0.002141745 4599
(164T s 24N)
T334872 -1 115250373 3 j 'F.S M*1, 1.1894E-05 o j aftf. n:. 4599
Liver hepatocellular
carcinoma (68T vs 31N)
Figure imgf000185_0001
T345216 - RRS1-AS1! -0.651507911 0.19212038 6.D516E-80 5.06825E-78 4935
(53ST vs 95N)
Bladder urothelial
T346167 1.075477276 2.18473516 0.00243012 0.033455742 4957 carcinoma (122T vs 16N)
Gastric carcinoma
T346167 1.1462696S2 ! 1.51170322 1. /80"i. O 0.0D14S9703 495? Head neck squamous eel!
T346167 2.4990218 2.59289604 5.4753E-17 3.23688E-15 carcinoma (298T vs 34N) 4957 ιιιιιιι Kidney chromophobe
-0.537206399 0.3679048 0.00303449 0.010930698 (64T VS 25N)
Liver hepatocellular
T346167 1.011811121 0.90996396 0.00038463 0.009396412 carcinoma (68T vs 31N) 4957
Lung adenocarcinoma
0.869297497 0.86371117 2.626E-07 3.82489E-06 495
(509T VS 5 N)
Lung squamous cell
T346167 2.885293912 2.66452929 3.7759E-33 8.07397E-32 carcinoma (377T vs 43N) 4957
Head neck squamous cell
T34617.1 0,77282396 0.76612111 2.6517E-10 5.92224E-09 carcinoma (298T vs 34N) 4958
Lung squamous ceil
T346171 0.855755024 0.77338537 2.7386E-17 3.44032E-16 4958 carcinoma (377T vs 43N)
Kidney chromophobe
T347140 0.546328471 0.84258426 6.9403E-06 4.07895E-05 (64T vs 25IM) 4987
Breast carcinoma
T349596 -0.839743491 0.12599346 3.717E-126 7.4711E-124
(892Tvs 105N) 5069
Kidney chromophobe
T351G96 -0.646244919 0.95181058 1.6211E-07 1.27279E-06 (64T vs 25IM) 5116
T353045 - Bladder urothelial
0.775053484 1.25530801 0.00160844 0.023427206 5193 LOC100288181 carcinoma (122T vs 16N)
Head neck squamous cell
T353045 -
1.468739081 2.15240777 1.9412E-13 6.0967E-12 carcinoma {298T vs 34N) 5193 L.OC100288181
T353045 - Kidney chromophobe
-0.507585076 0.80528375 0.00832575 0.026483041
LOC100288181 (64T s 25N) 5193
T353045 - Lung adenocarcinoma
0.608274508 0.65134275 1.7651E-06 2.19004E-05 5193 LOC100288181 (509T 57N)
T353045 - Lung squamous cell
1.188764617 1.22550993 1.2487E-11 1.12048E-10
LOC100288181 carcinoma (377T vs 43N) 5193
Kidney chromophobe
T354826 0.794566598 0.73190716 1.7448E-07 1.35935E-06 (64T vs 25N) 5218, 5219
Kidney chromophobe
T354851 0.588757373 0.54220544 8.8703E-07 6.19072E-06 (64T s 25N) 5219
T356436 - fFNE, Thyroid carcinoma
1.341115254 1.60921924 1.888E-16 3.72047E-15 5273 MIR31, MfRSlHG (456T 58N)
Head neck squamous cell
T356437 - IFNE,
0.601430464 1.48500803 0.00774223 0.029142091 carcinoma (298T vs 34N) 5273 MIR31, MIR31HG
Ϊ >56 Π ? :> tit.. Kidney chromophobe
-0.810221552 0.61092223 4.9734E-06 3.01927E-05 52.73
MIR31, MfR31HG (64T vs 25N)
T356437 - IFNE, Thyroid carcinoma
0.666627826 0.87974807 1.0304E-08 9.16411E-08
MIR31, MIR31HG (456T VS 58N) 5273
Prostate adenocarcinoma
T359194 -0.505262.026 0.28577993 1.3353E-21 6.71012E-19 ', 03
(183T vs 43 N)
Prostate adenocarcinoma
T360691 - PCA3 2.873239655 3.01686974 9.8371E-19 2.47156E-16 (183T vs 43N) 5362
Prostate adenocarcinoma
T360692 - PCA3 2.081818283 2.06775409 2.5659E-16 2.57877E-14
(183T vs 43 N) ¾ 46
Kidney carcinoma
T362204 0.561811213 2.06949516 7.8781E-06 2.79771E-05 (539T vs 95N) 5400 Kidney chromophobe
-1.613969761 1.23003999 9.4603E-Q9 9.05483Ε-08 5400
(64T vs 25IM)
Thyroid carcinoma
T362204 -1.076012301 1.35950501 5.3641E-23 1.79698E-21 5400
(456Tvs 58N)
Head neck squamous cell
T375351 -0.527780546 0.97346337 1.2541E-G7 2.10054E-06 carcinoma 9605
(298T VS 34N)
Kidney chromophobe
T375351 -1.139100445 1.60682954 3.0925E-21 1.35129E-19 9605
(64T vs 25N)
Kidney carcinoma
T380237 -0.641280925 0.67964047 1.4952E-47 4.69572E-46 9802
(539T vs 95N)
Kidney chromophobe
T380237 -0.69221316 1.40728465 3.7S18E-08 3.30495E-07 9802
(64T vs 25N)
Prostate adenocarcinoma
T383413 -TTTY15 0.532774248 1.59586202 5.8683E-05 0.000506024 9927
(183T vs 43N)
Prostate adenocarcinoma
T3S3417 - TTTY15 0.628055448 0.99593549 5.0005E-08 8.66461E-07 9927
(183T vs 43N)
πκ5ί· ί7 um. Gastric carcinoma
-0.63059702 0.45077032 3.2869E-05 0.001835194 9956, 9957
TT7Y14 (164T vs 24N)
Head neck squamous cell
Τ383637 - CD24,
-1.225321513 0.559815 1.466E-19 1.33943E-17 carcinoma 9956, 9957 TTTY14 (298T VS 34N)
Τ383637 - D24, Kidney carcinoma
-0.928147218 0.5855595 1.6886E-27 2.57126E-26 9956, 9957
TTTY14 (539Tvs 95N)
Lung squamous cell
Τ383637 - CD24,
-0.537306181 0.4523842 3.4762E-08 2.37661E-07 carcinoma 9956, 9957 TTTY14
(377T VS 43N)
transcript identification number as obtained from the MiTranscriptome datasets (http://www.nature.com/articles/ng.3192)
2 LogFc value indicates whether the cancer transcripts were up or down reguated compaed to the tissue controls
3 AveExpr is the average expression value in the tumor tissue as obtained from the MiTranscriptome datasets
4 P-value that the expression in the cancer datasets is significant different as compared to the normal tissue controls
5 Adj._P. Value is the adjusted P-value after stringent filtering
6 shows the cancer type that can be diagnosed and reveals the number of cancer patients (T) versus normal controls (N) in which the transcript is identified
' unique patent ID that correspond to the 'transcript or overlaps with the transcript
Table 18 Summary of MiTranscriptome cancer cohorts
Type1 Cancer2 Metastatic3 Normal4
Bladder urothelial carcinoma L22 0 16
Breast carcinoma 892 8 105
Gastric carcinoma 164 0 24
Head neck squamous cell carcinom 298 0 34
Kidney carcinoma 539 0 95
Kidney chromophobe 64 0 25
Liver hepatocellular carcinoma 68 0 31
Lung adenocarcinoma 509 6 57
Lung squamous ceil carcinoma 377 0 43
Prostate adenocarcinoma 183 1 43 Thyroid carcinoma 456 7 58
1 type of cancer related to the patient cohort
2 number of cancer patients in the cohort
3 number of metatstatic cancer patients in the cohort
4 number of healthy patients in the cohort
Table 19 123 unique Mitranscriptome transcripts resembling or overlapping a human CRISPR that can be used as diagnostic markers for 11 different cancers.
SEQ ID
Transcript ID1 logFC2 AveExpr3 P.Value4 adj.P.Value5 Cancer_type6
NO7
:Ι1Ιβ1 Kidney chromophobe
0.480842862 4.7142E-29 5.9222E-27
1.222000274 (64T vs 25N) !!Ili
Kidney chromophobe
T009250 0.492896428 6.5425E-22 3.1311E-20 181
0.660140521 (64T vs 25N)
Bladder urothelial
T0092G7 0.39 J 66666 0.00025586 0.00502511 182
0.628175871 carcinoma (122T vs 16N)
Gastric carcinoma
T011801 0.104734502 2.6543E-20 2.6676E-17 226
0.623041841 (164T vs 24 N)
Breast carcinoma
TO 15716 0.521655453 3.1274E-90 1.7Λ62Ε-8β 356
638312504 (892T v¾ 105N)
Breast carcinoma
T015720 0.131673409 4.6036E-67 1.3219E-65 357
0.594264811 (892T vs 105N)
Kidney chromophobe
T016083 0.300869962 6.0688E-19 2.2589E-17 374
0.627685776 (647 vs 25N)
Thyroid carcinoma
T017904 1.685646149 1.690441849 1.2898E-28 5.636E-27 425
(456T vs 58 N)
Head neck squamous cell
T030812 0,853702025 0.837S25156 4.5926E-05 0.00039449 |||s3.
carcinoma (298T vs 34N)
Lung adenocarcinoma
T030998 0.518100098 0.790924314 2.3377E-05 0.00020253 691
(509T vs 57N)
T036220 - Lung squamous cell
0.610727511 0.695467974 1.881SE-05 8.2214E-05
AKR1C2 carcinoma (377T vs 43N) UN5
T044664 - Kidney chromophobe
0.541108661 0.397349394 8.2768E-06 4.7806E-05 5867 LI C00856 (64T vs 25N)
11311111 Kidney carcinoma
0.264042658 1.2921E-82 1.3677E-S0 5995
1.267368396 (539T v¾ 95N)
Figure imgf000189_0001
Kidney chromophobe
T055286
0.770034134 °·22156555 ^1Έ-10 1.3861E-09 6129
(64T vs 25N)
Head neck squamous cell
T062903 0.597296643 0.714S91197 0.00020335 0.00143922 6284 carcinoma (298T vs 34 )
Liver hepatocellular
T073281 0.919268899 0.859839486 6.8215E-05 0.00298071 6510 carcinoma (68T vs 31N)
Lung squamous cell
T073831 1.42091282 1.516653819 8.7125E-15 9.622E-14
carcinoma (377T vs 43 N)
Figure imgf000190_0001
T122676 - Kidney chromophobe
0.542528751 1.1888E-16 2.9868E-15 7811 LINC01197 0.800082231 (64T vs 25N)
T122806 · Kidney chromophobe
0.439633549 5.2951E-32 1.0643E-29 7813 N 2F2-ASJ 1.225890114 (647 vs 25N)
Figure imgf000190_0002
Kidney chromophobe
T165338 0.617835728 3.2856E-18 1.0652E-16 8673
1.419371149 (64T vs 25N) Kidney chromophobe
T165339 0.324035292 1.5173E- 2.4998E-12 8673
0.6481*5419 ΪΙ (6*T v 25N)
Kidney chromophobe
T179285 0.778505164 1.029460728 4.813E-09 4.8647Ε-08 8856
(64T vs 25N)
Kidney chromophobe
Τ:ΐ 80296 1.69:1693563 7.7819E-07 5.5467Ε-06 8862
Figure imgf000191_0001
Kidney carcinoma
T187563 0.761561497 0.726536051 4.3925E-12 3.0656E-11 960
(539T vs 95N)
Kidney chromophobe
T187566 1.115002227 1.1278E-33 U335E-30 1
Figure imgf000191_0002
Kidney chromophobe
T206475 0.759495405 0.562248365 1.534E-09 1.5731E-08 1434
(64T vs 25N)
Lung squamous cell 9039, T219106 0.560292635 0.504283943 3.6168E-05 0.00014958
Figure imgf000191_0003
Kidney chromophobe
T225820
0.609563878 °·649869215 5·7459Ε"14 9.7876E-13 9226
(64T vs 25N)
Prostate adenoT227Q58 0.768055292 0.696200189 2.3237Ε-06 3.0329Ε-05
carcinoma (183T vs 43IM) llllil T240613 - Kidney chromophobe
0.526172026 9.8307E-14 1.6466E-12
MYRIP 1733
0.539995469 (64T vs 25 N)
Kidney chromophobe
T243120 0.45007903 1.6697E-14 3.1662E-13 1733
Figure imgf000192_0001
Kidney chromophobe
T252309 1.386436387 1.46358885 1.0239E-07 8.4346E-07 2009
(64T VS 25N)
Lung squamous celf
T255234 0.714871163 0.645011219 4.49I8E-10 3.7619E-Q9 11115, carcinoma (377T vs 43N 2116
Lung squamous cell
T255252 1.011439418 0.912438164 2.0299E-14 2.1702E-13 2116 carcinoma (377T vs 43N)
Lung squamous cell
T255259 0.50813041 0,457846173 1.347E-OS 1.0028E-07 llllli
Figure imgf000192_0002
Kidney carcinoma
T257541 2166,
0.524754364 0.464197249 1.2506E-20 1.4615E-19
(539T vs 95 N) 2167
Kidney chromophobe
T260466 0.232169567 88UE II 9.9044E-10 2250
(64T vs 25N)
Figure imgf000192_0003
Lung squamous cell
T266618 0.552055553 0.542818204 5.6139E-07 3.1344E-06 2478 carcinoma (377T vs 43N)
Lung squamous cell
T2678I3 0.596001819 0.545696378 3.1662E-10 2.69&6E-09 2527 carcinoma (377T vs 43N)
Kidney chromophobe
T270578 -0.78554579 0.232853401 2.5638E-23 1.3561E-21 2633
(64T vs 25N)
Kidney chromophobe
7270586 0.434128096 53283E-33 1.785E-30
1.471489755 ! (64T vs 25N} 11Ϊ33-
Figure imgf000193_0001
Prostate adeno¬
T274230 0.553143953 0.463051161 0.00044585 0.00313342 2780 carcinoma (183T vs 43N)
Prostate adeno¬
T274234 1.441095058 1.284455609 3.1808E-06 3.9465E-05 2780 carcinoma (183T v¾ 43N)
Kidney carcinoma
T277645 0.906358174 0.871264519 1.5036E-25 2.0988E-24 2931
(539T vs 95N)
Lung squamous cell
T278244 0.640790927 0.577157709 4.5231E-09 3.47E-0S 2952 carcinoma (377T vs 3N)
T278748 -
Gastric carcinoma
IR4458HG, 0.35455537 1.4078E-14 7.0742E-12 2967
0.951099649 (164T vs 24N) MIR4458
Kidney chromophobe
T283698 0.4 10567572 3.358 9E-27 3.068SE-25 3144
1.1325596.31 (64T vs 25N)
Kidney chromophobe
T285164 0.289446066 2.4175E-24 1.6197E-22 3197
0.890951558 (64T vs 25N)
111911111 Lung squamous cell 3261, T286925 0.575316048 4.8674E 13 4.S433E-12
carcinoma (377T vs 43N) 3262
Kidney chromophobe
T287748 0.168159613 5.2675E-24 3.3086E-22 3308
0.501722878 (64T vs 25 N)
Liver hepatocellular
T292277 0.618236891 1.6516E-05 0.00092217 3413
0.527 95< m carcinoma (68T vs 3 IN)
Thyroid carcinoma
T294686 -0.88570401 0.418050713 1.3401E-42 1.4964E-40 3472
(456T vs 58 N)
Lung squamous cell
T296895 0.09783415 7.3648E-92 1.8504E-89
0.781757564 carcinoma (377 vs 43N !!!li!
Lung squamous cell
T296898 0.062995384 5.0443E-72 5.0696E-70 3533
0.545743071 carcinoma (377T vs 43N)
Kidney chromophobe
T297295 0.912404076 3.8555E-18 1.2109E-16 3543
0.741832S06 (64T v 25N)
Figure imgf000193_0002
Kidney carcinoma
T304271 0.52128642 0.452730634 4.698E-08 2.1138E-07 3651
(539T vs 95N) Br a t carcinoma ΐ30< f. 0 3 0 728(V' 41 6 1.4007E-64 3657
0 o if 5521 § 5· is 68 E-6
(892T vs 105N)
T309007 Kidney carcinoma
0.583048816 0.826042393 6.6457E-14 5.218E-13 3849
LOC100422737 (539T vs 95N)
Lung squamous cell
T309951 0.604808125 0.572815736 5.7346E-09 4.3333E-08 3884 carcinoma (377T vs 43N)
Lung squamous cell
T311570 0.697125223 0.626897066 2.5336E-09 2.0049E-08 3948 carcinoma (377T vs 43N)
Breast carcinoma
T312843 0.405377131 1.3954E-56 2.9838E-55 3977
0.551110086 (892T v¾ 105N)
Kidney chromophobe
T322119 0.246654977 2.8583E-11 3.7798E-10 4223
0.545324107 (64T vs 25N)
Kidney carcinoma
T32S104 1.083789656 0.961274384 5.1957E-23 6.5271E-22 4406
(539T vs 5N)
T337599 - Thyroid carcinoma 4702,
-50 2.1287E-47
Figure imgf000194_0001
T345216 - Kidney carcinoma
0.192120382 6.0516E-80 5.0682E-78 4935 RRS1-AS1 0.651507911 (539T vs 95 N)
Kidney chromophobe
T347140 0.546328471 0.842584261 6.9403E-06 4.0789E-05 4987
(64T vs 25N)
Breast carcinoma
T349596 0 83974349! 0-125993463 3.717E-126 7.471E-124 5069
(892T vs 105N)
Kidney chromophobe
T351096 0.951810579 1.6211E-07 1.272SE-06 5116
0.646244919 (64T vs 25N)
Kidney chromophobe 5218,
T354826 0.794566598 0.731907164 1.7448E-07 1.3593E-06
(64T s 25N) 5219
Kidney chromophobe
T354851 0.588757373 0.542205444 8.8703E-07 6.1907E-06 5219
(64T vs 25N)
T356436 -
Thyroid carcinoma
IFNE, MIR31, 1.341115254 1.609219236 1.888E-16 3.7205E-15 5273
(456T vs 58N)
MIR31HG
Prostate adeno¬
T359194 0.285779926 1.3353E-21 G.7101E-19 5333
0.5L6262026 carcinoma (183T 3N)
T360691 - Prostate adeno¬
2.873239655 3.01686974 9.8371E-19 2.4716E-16 5362 PCA3 carcinoma (183T vs 43N)
T360692 - Prostate adeno¬
2.081838283 2.067754094 2.5659E-16 2.5788E-14 5362 PCA3 carcinoma (183T v 43 )
T383413 - Prostate adeno¬
0.532774248 1.59586202 5.8683E-05 0.00050602 9927 TTTY15 carcinoma (183T vs 43N)
T383 17 - Prostate adeno¬
0.628055448 0.99593549J 5.0005E-0S 8.6646E-07 9927 TTTY15 carcinoma (1S3T vs 43 N) transcript identification number as obtained from the MiTranscriptome datasets (http://www. nature.com/articles/ng.3192)
2 LogFc value indicates whether the cancer transcripts were up or down reguated compaed to the tissue controls
3 AveExpr is the average expression value in the tumor tissue as obtained from the MiTranscriptome datasets
P-value that the expression in the cancer datasets is significant different as compared to the normal tissue controls
5 Adj_P.Value is the adjusted P-value after stringent filtering
6 shows the cancer type that can be diagnosed and reveals the number of cancer patients (T) versus normal controls (N) in which the transcript is identified
7 unique patent ID that correspond to the transcript or overlaps with the transcript
Table 20 unique human CRISPR transcripts that enable the detection of 11 different cancers
Mitranscriptome chromosome position and cancer ID Human CRISPR position
SEQ ID
Chromosome1 Start2 end3 Transcript ID4 Chromosome5 Start6 end7 NO)8 chrl 9739289 9747644 T002825 chrl 9741915 9741994 68 chrl 43296694 43312200 T009250 chrl 43302481 43302574 181 chrl 43381744 i i342 j T009267 chrl3 43382271 !S2 V/4 182 chrl 58035865 58118389 T011801 chrl 58060759 58060855 226 chrl 95975646 95984063 T015716 chrl 95979144 95979235 550 chrl 96004137 96273390 T015720 chrl 96022952 96023024 357 chrl 100723713 100731716 5 L OK3 chrl 100730025 100730097 r/A chrl 116048012 116087217 T017904 chrl 116061896 116061970 425 chrl 22063 V/f-2 220640055 T030812 chrl 220638075 2206 ½2 i l 683 chrl 222007847 222238146 T030998 chrl 222151222 222151312 692 chrl 2220;)7H47 2222 W 14(. T030998 chrl 222140244 222 14 538 691 chrl 222007847 222238146 T030998 chrl 222223605 222223762 693 chr2 ΓΛ3292 1570841 T183157 chr2 1561906 1562048 fAA chr2 1553292 1570841 T183157 c r2 1562322 1562479 849 chr2 34787040 34919833 T187550 chr2 34870808 34870900 959 chr2 34918863 34921257 T187563 chr2 34920022 34920105 960 chr2 34947487 34962431 T187566 chr2 34961718 34961840 961 chr2 34960681 34962458 T187568 c r2 34961718 34961840 961 chr2 40136324 40485789 T188105 chr2 40481625 40481704 "8 chr2 145425482 145621541 T200514 chr2 145504807 145504933 1248 chr2 160458222 160476003 T201771 chr2 160461506 160461600 .1287 chr2 181376453 181786091 T203963 c r2 181745328 181745422 1349 chr2 181557127 181764445 i 2 3°SS chr2 181745328 181745422 1349 chr2 208104587 208394514 T206467 chr2 208141892 208141988 1434 chr2 208125068 208149792 T206472 chr2 208141892 208141988 chr2 208141256 208149792 T206475 c r2 208141892 208141988 1434 chr3 40215468 40343037 T240613 chf3 402 '123 40235006 1702 chr3 51760588 51788624 T243120 chr3 51777879 51777988 1733 chr3 59800302 T244322 chr3 59702584 59702706 1749 chr3 64670572 64900928 T244675 c r3 64866726 64866820 1762 chr3 64670572 64900928 T244675 chf3 04H73t>V 0487 777 1763 chr3 64862009 64974696 T244678 chr3 64866726 64866820 1762 chr3 64862009 G4«74iW(- T244678 chr3 64873670 (j S i77 J t> 5 chr3 64862009 64974696 T244678 c r3 64973192 64973295 1764 chr3 1221 i4H'> 122156106 T249192 chf3 122154466 122154589 1925 chr3 149756876 149958210 T252309 chr3 149773516 149773609 2009 chr3 178241979 j V.r,7fi.?S2 i 25':2 J.4 chr3 178339165 178339323 2115 chr3 178241979 178578282 T255234 c r3 178575621 178575699 2116 chr3 178446848 178578282 T255252 chf3 178575621 178575699 2116 chr3 178462491 178578282 T255259 chr3 178575621 178575699 2116 chr3 182012991 182129947 T255669 chr3 182059088 182059184 2125 chr3 186307935 186382019 T256469 c r3 186381144 186381220 2134 chr3 193981568 194004369 T257541 chf3 193987073 193987162 2166 chr3 193981568 194004369 T257541 chr3 194003477 194003630 2167 chr4 19799418 19855509 T262095 chr4 19829543 19829619 2312 chr4 55618670 55650836 T264872 c r4 55649675 55649759 2413 chr4 76006962 76052398 T266618 chr4 76022159 76022300 2478 chr4 88487847 88631663 T267813 chr4 88618696 88618793 2527 chr4 122 532 )41 122437110 T270578 chr4 1 23Κ9ί·4·¾ 26 -: 5 chr4 122370868 122447075 T270586 c r4 122389648 122389788 2633 chr4 142253956 142354214 T272154 c r4 142342233 2701 chr4 154731725 155193569 T273101 chr4 154939288 154939468 2724
Chr4 154731725 155193569 i .7751 1 chr4 154947051 154947163 2725 chr4 154731725 155193569 T273101 chr4 155034720 155034834 2726 chr4 169965431 169995585 T.' "/ 1.'. V5 c r4 169995114 169995204 2780 chr4 169965431 169995585 T274230 chr4 169995114 169995204 2780
Chr4 169977737 169995521 i .774 .¾4 chr4 169995114 169995204 2780 chr5 1463911 1474355 T277645 chr5 1472894 1472998 2931 chr5 4520700 4615565 T2 8244 c r5 4607106 4607208 2952 chr5 8457655 8487505 T278748 chr5 8471534 8471614 2967 chr5 68477131 68485325 T28369S chr5 68477934 68478113 3144 chr5 82203639 82296875 T285164 chr5 82245206 82245327 3197 chr5 103415624 103688021 T.'Sol :"> c r5 103610299 103610371 3262 chr5 103415624 103688021 T286925 chr5 103429286 103429386 3261 chr5 Π λ?6052 " 117336359 T28774S chr5 117275508 117275587 iO chr5 159292063 159318322 T292277 chr5 159315835 159315918 3413 chr5 177728740 177744047 c r5 177738451 177738564 3472 chr6 8158403 8326541 T296895 chr6 8224546 8224657 3533 chr6 8158421 S.toOlSfc i .7>J!,8-)S chro 8 25 i > 8224657 35.H chr6 10709997 10723069 T297295 chr6 10719971 10720126 3543 chr& 28952710 28961677 T300038 c r6 28955550 28955804 3595 chr6 32223080 32358963 T301548 chr6 32319480 32319575 3611 chr6 T301549 chro 32319480 32319575 3611 chr6 44011314 44057025 T304269 chr6 44034545 44034646 3651 chr& 44011314 44057025 T304271 c r6 44034545 44034646 3651 chr6 46638073 46644163 T304646 chr6 46639479 46639580 3657 chr6 107152892 L0 ? X>579 i WW/ chro 107163342 107163476 3849 chr6 113936088 113971328 T309951 chr6 113954396 113954498 3884 chr& 133468831 ] > 1970¾« T311570 c r6 133494090 3948 chr6 143515294 143528884 T312843 chr6 143525536 143525639 3977 chr7 40576833 40611760 T322119 chr7 40589781 chr7 90940547 91124062 T328104 chr7 91086041 91086133 4406 chr8 1047827 1087777 c rS 1080833 1080944 4703 chr8 1047827 1087777 T337599 chr8 1076591 1076682 4702 chr8 12051883 12427948 T339210 chr8 12192788 12193018 lo8¾ chr8 12051883 12427948 T339210 chr8 12339566 12339640 4762 chr8 12051883 12427948 r.iw ) chrS 12353544 12353634 4763 chr8 67111200 67344602 T345216 chr8 67220341 67220496 4935 chr8 86394900 86406515 T347140 chrS 86398018 86398101 m chr8 112388836 112555213 T349596 chr8 112484277 112484367 5069 chr8 127569140 127630730 T351096 chrS 127602071 127602151 5116 chr9 1454630 1719413 T354826 chr9 1658457 1658589 5218 chr9 1454630 1719413 i V.58.V> chr9 1715608 1715711 5219 chr9 1701022 1719413 T354851 chr9 1715608 1715711 5219 chr9 21439474 21559853 T356436 c r9 21545333 21545443 527.¾ chr9 66454654 66470824 T359194 chr9 66459361 66459482 5333 chr9 79379167 79413274 T360691 chr9 79 5ii - 79384048 J« chr9 79379167 79413274 T360692 chr9 79383942 79384048 5362 chrlO 5017715 5149708 TOSo. O chrlO 5095161 5585 chrlO 121932092 122097660 T049586 chrlO 122058751 122058833 5995 chrlO 122798470 122836974 T049676 chrlO 122835446 122835548 5999 chrll 449931 458766 T052162 chrll 457929 458019 6072 chrll 15644972 15727227 T055286 chrll 15647631 15647718 6129 chrll 69972328 69988489 T062903 chrll 69980726 69980825 6284 chri2 8940830 8948404 T073281 chrl2 8942407 S-).V.'¾27 6510 chrl2 10514984 10532532 T073831 chrl2 10531650 10531735 6520 chrl2 10516136 10554002 i 073832 Chrl2 10531650 10531735 6520 chrl2 33589183 33847629 T076619 chrl2 33648345 33648441 6619 chrl2 115583006 115608603 T0S7049 chrl2 115599279 115599373 6851 chrl2 119825780 120033360 T087523 chrl2 119841216 119841296 6866
Chrl3 68978608 >''>01235 ? T095S19 chrl3 68980702 68980782 7126 chrl4 23451867 23467729 T101157 chrl4 23452524 23452626 7330 chrl4 43339034 43942369 T 103470 chrl4 43899484 43899592 7 ¾,¾ chrl4 43613830 43942367 T103486 chrl4 43934300 43934376 7389
Chrl4 57579378 T104965 chrl4 57513434 57513531 7425 chrl4 60434868 60470890 T105361 chrl4 60444551 60444639 7442 chrl4 105498953 105544699 T111645 chrl4 105536093 105536202 7575 chrl4 106322273 106343948 T112050 chrl4 106342983 106343084 7585
Chrl5 42184971 42191022 T115171 chrl5 42186057 42186165 7668 chrl5 56311491 56463110 T117107 chrlS 56316527 56316651 7701 chrlS 56311491 56463110 T117107 chrlS 56355199 770.' chrlS 56311491 56463110 T117107 chrl5 56399996 56400092 7703 chrl5 95752049 95870177 i l22lj ?!"> chrlS 95790852 95791055 7811 chrl5 96624114 96872548 T122806 chrlS 96661691 96661767 7813 chrie 13352189 13568500 T127555 chrl6 13539407 13539522 7898 chrl6 13633276 13717419 127575 chrl6 13706093 13706205 7900
Chrl7 66092029 66097644 T153012 chrl7 66095900 66096004 333.7 chrl8 44359581 44373556 T161706 chrl8 44369215 44369295 8534 chrl9 780880 792558 T 165338 chrl9 791821 8673 chrl9 781580 792558 T165339 chrl9 791702 791821 8673 chrl9 51012411 51038098 T179285 chrl9 51024310 51024386 8856 chrl9 53406621 53411614 T180296 chrl9 53407160 53407326 8862 chr20 46463450 46755253 T219106 chr20 46629320 46629559 9040 chr20 46463450 T219106 chr20 46520935 (.'. 1 '.)V3 9039 chr21 29811665 30047170 T224771 chr21 29850167 29850261 9207 chr21 36118005 36159604 T225510 chr21 ¾ H04<H5 3613059.} <52 chr21 38336760 38348108 T225820 chr21 38346894 38346994 9226 chr21 44329709 44346147 T227058 chr21 44335786 .«-! 55K77 9258 chrY 14774162 14804148 T383413 chrY 14799075 14799147 9927 chrY 14774163 14804148 T383417 chrY 14799075 14799147 9927 chromosome in which the IVIitrancriptome transcript was detected
start position of the Mitrancriptome transcript as obtained by RNA sequencing
end position of the Mitrancriptome transcript as obtained by RNA sequencing
specific Mitrancriptome transcript code
chromosome in which the human CRISPR resides
start position of the human CRISPR
end position of the human CRISPR
unique patent ID given to the human CRISPR Table 21 Human CRISPRs that reside in a transcription factor binding site in the Hgl9 genome
Transcription factor binding site Human CRISPR position
Chromosome1 start2 end3 Transcription Chromosomel"* start6 end7 SEQ IP' chrX 39120264 39120528 CTCF chrX 39120253 39120341 9558 chrX 79659020 79659400 CTCF chrX 79659065 79659162 9647 chrX 153219632 153219996 CTCF chrX 153219855 153219980 chr9 17810787 17811369 CTCF chr9 17811295 17811369 5262 chr9 26975645 CTCF chr9 ,:iW i C ..'iW i) ¾.'S« chr9 36008703 36009266 CTCF chr9 36008952 36009049 5319 chr9 38620509 38620839 CTCF rhr 38620511 38620596 ~, \V chr9 72547811 72548211 CTCF chr9 72547913 72547993 5347 chr9 92981798 92982192 CTCF chr9 92982118 ¾:<S2 20 5399 chr9 99983796 99984045 CTCF chr9 99983766 99983852 5428 c r8 29940373 29940737 CTCF chrS 29940717 29940806 4813 chr8 37683981 37684352 CTCF chr8 37684348 37684445 4835 chr8 76169483 76169903 CTCF chrS 76169499 76169615 4957 chr8 101873814 101874198 CTCF chr8 101873814 101873907 5036 chr8 141348708 141349417 CTCF chrS 141349269 141349372 5171 chrS 142416478 142416754 CTCF chrS 142416496 142416596 5177 chr8 l i i i'lWl 143396130 C'l I > chr8 143395966 143396061 5186 chr7 1036964 1037334 CTCF chr7 1037114 1037199 4083 chr7 1126175 1126411 CTCF chr7 1126285 1126387 4086 chr7 1852512 1852796 CTCF chr7 1852792 1852871 4091 chr7 W H . CTCF Chr7 4034971 4035107 4110 chr7 33802129 33802535 CTCF chr7 33802095 33802234 4202 chr7 82799515 82799735 CTCF chr7 82799524 82799650 4364 chr7 102004146 102004546 CTCF chr7 102004049 102004154 4460 chr7 113350346 113350756 CTCF chr7 113350364 113350455 4512 chr7 134063308 134063678 CTCF chr7 134063535 134063629 4571 chr7 143077198 143077631 CTCF chr7 143077464 143077619 4599 chr6 1515640 1515869 CTCF chr6 1515569 1515674 3503 chr6 ?7(-ΥΛ7 2765912 C'l I > chr6 .'70S».¾2 3512 chr6 3849353 3849773 CTCF chr6 3849487 3849596 3520 chr6 3978413 3979016 CTCF chr6 3521 chr6 33479869 33480249 CTCF chr6 33479790 33479889 3614 chr6 33558974 CTCF Chr6 33558691 3615 chr6 37333509 37333917 CTCF chr6 37333901 37333977 3631 chr6 113954330 113554566 CTCF chr6 113554396 113954498 chr6 127817664 127817994 CTCF chr6 127817870 127818005 3933 chr6 S0 5 .5 138024309 CTCF chr6 138024074 138024172 chr6 150030607 150030827 CTCF chr6 150030714 150030806 3991 chr& 166972531 166972887 CTCF chr6 l W:fi WO 166972763 4037 chrS 402655 403025 CTCF chr5 402777 402856 2910 chr5 1641612 1642117 CTCF chr5 1641811 1641910 2937
Figure imgf000199_0001
chr4 189294050 189294405 CTCF chr4 189294176 189294264 2875 chr3 19270576 19270899 CTCF chr3 19270565 19270643 1630 chr3 66623782 66624143 CTCF chr3 66623709 66623817 1766 chr3 72137954 CTCF chr3 72137915 1782 chr3 133943374 133943763 CTCF chr3 133943485 133943564 1958 chr3 153553680 CTCF l iir i 153553661 153553756 2025 chr3 178940314 178940589 CTCF chr3 178940530 178940608 2117 c r3 192507134 192507386 CTCF chr3 192507339 192507446 2161 chr3 195577662 195578219 CTCF chr3 195577893 195577977 2184 chr2 -.'-r.sr. 736171 CTCF chr2 736006 736076 S.iS chr2 2174106 2174286 CTCF chr2 2174057 2174139 859 chr2 aW i CTCF chr2 8573638 857 ¾7<iS 881 chr2 26694953 26695149 CTCF chr2 26695063 26695158 936 chr2 26695157 r,(j<i ¾ π CTCF chr2 26695063 26695158 936 chr2 65566152 65566336 CTCF chr2 65565864 65566156 1037 chr2 235180011 235180301 CTCF chr2 235180163 235180286 1521 chr2 236460543 236460931 CTCF chr2 236460709 236460813 1525 chr2 239313215 CTCF chr?. 239313385 239313492 1534 chr2 240318835 240319205 CTCF chr2 240319204 240319297 1546 chrl 1624231 1624749 CTCF chrl 1624403 1624654 1 chrl 1624231 1624749 CTCF chrl 1624211 1624313 17 chrl 6497084 6497454 CTCF chrl 6496994 6497100 58 chrl 8299015 8299337 CTCF chrl 8299330 8299471 66 chrl 12„> id .i.M 12244704 I I > chrl 12244495 12244576 76 chrl 28286497 28286909 CTCF chrl 28286854 28286948 131 chrl 45964990 45965240 CTCF chrl 45965057 45965152 189 chrl 53435749 53436150 CTCF chrl 53436073 53436169 215 chrl 56844198 56844552 CTCF Chrl 56844529 56844610 2.72 chrl 60554325 60554643 CTCF chrl 60554229 60554345 234 chrl 150521312 150521796 CTCF chrl 150521576 15052.1685 4:».' chrl 152080179 152080375 CTCF chrl 152080245 152080420 455 chrl 154579965 154580188 CTCF chrl 154580161 154580286 464 chrl 156824381 156824770 CTCF chrl 156824354 156824425 470 chrl 206781449 206781887 CTCF chrl .7fSi:7ri l 7«7 206781892 649 chrl 223897334 223897704 CTCF chrl 223897581 223897665 702 ch 22 2.7» Ϊ» IS". 22W<1 O I > chr22 22936417 fi.53i> chr21 38938037 38938393 CTCF chr21 38938279 38938373 9228 chr21 45246013 45246407 CTCF chr21 45246401 45246496 9263 chr20 452014 452234 CTCF chr20 452194 452318 8901
Chr20 7.1Sb , 7486523 CTCF chr20 7486365 7486547 8921 chr20 15899367 15899617 CTCF chr20 15899506 15899611 8942 chr20 25265769 25266125 CTCF chf20 25266067 25266158 8968 chr20 35184866 35185351 CTCF chr20 35185291 35185385 9006 chr20 50481581 50481805 CTCF chr20 50481764 50481860 9052 chr20 53016331 53016527 CTCF chr20 53016187 53016342 9058 chr20 55886203 55886487 CTCF Chr20 55886549 9072 chr20 56730202 56730595 CTCF chr20 56730442 56730524 9075 chr20 60876861 60877254 CTCF chr20 60877210 60877541 <Xib > chrl9 883580 883960 CTCF chrl9 883889 883967 8674 chrl9 3513171 3513561 CTCF chrl9 3513139 3513241 8692 chrig 6769273 6769841 CTCF chrl9 6769652 6769803 8705 c.hrl9 ;BW.»¾ in 38389660 CTCF chrl9 38389624 38389695 8803 chrl9 40349143 40349363 CTCF chrl9 40349294 40349391 8809 chrl9 46513010 46513412 CTCF chrlS 46513048 46513130 ¾4 chrlS 1006369 1006739 CTCF chrl8 1006297 1006436 8418 chrlS 12377566 12377919 CTCF chrlS 12377506 1.7 ΐ 72 8450 chrl? 260803 261173 CTCF chrl7 261087 261183 8133 ch l 7 1073974 1074413 CI I > chrl7 1074238 1074327 8146 chrl7 72797343 72797553 CTCF chrl7 72797525 72797666 8362 chrl7 7303200 ¾ CTCF chrl7 7 56 ¾23 ί7 73632413 H V. : chrl7 75092600 75092936 CTCF chrl7 75092816 75092964 8373 chrl7 79204286 79204671 CTCF chrl7 79204619 79204731 K VJ.i chrl7 79674312 79674632 CTCF chrl7 79674575 79674653 8401
Chrl6 709200 709540 CTCF chrl6 709521 709605 7841 chrl6 1396837 1397287 CTCF chrl6 1396753 1396894 7852 c.hrl6 19566458 19566783 CTCF chrl6 19566661 19566971 7888 chrl6 32993729 32993974 CTCF chrl6 32993799 32994685 10023 chrl6 66517601 66518289 CTCF chrlS 66517581 8007 chrl6 68783446 68783789 CTCF chrl6 68783733 68783806 8014 chrie 81591721 81591925 CTCF chrl6 81591822 81591932 chrl6 89449703 89450108 CTCF chrl6 89450035 89450132 8108 chrl6 89597422 89597656 CTCF chrl6 ί-: ¾5<>ϊί·04 89597694 8112 chrl5 22460931 22462586 CTCF chrl5 22462316 22462420 7597 chrl5 22978992 22979242 CTCF chrl5 229 S92.-S 22979001 10017 chrl5 29149662 29150032 CTCF chrl5 29149824 29149903 7629 chrl5 76350159 CTCF chrlS 76350134 76350217 7757 chrl5 79888280 79888869 CTCF chrl5 79888531 79888665 7768 chrlS 101677761 101678131 CTCF chrl5 101677648 101677779 chrl4 23452500 23452875 CTCF chrl4 23452524 23452626 7330 chrl4 106765041 106765649 CTCF chrl4 106765150 106765547 10014 chrl4 107251661 107252006 CTCF chrl4 107251729 107251888 7587 chrl3 20710889 20711267 I I > chrl3 20711243 20711318 6960 chrl2 40200836 40201252 CTCF chrl2 40200867 40200948 10017 chrl2 68845168 68845452 CTCF chrl2 68845349 r,sm¾44« 6711 chrl2 94823448 94823786 CTCF chrl2 94823551 94823648 6789
Chrl2 131708690 131708940 CTCF chrl2 131708917 131709011 6917 chrl2 133325092 133325342 CTCF chrl2 133325135 133325245 6947 chrll 11178767 11179149 CTCF chrll 11178981 11179068 6118 chrll 35483468 35483881 CTCF chrll 35483545 35483649 6178 chrll 45123939 45124203 CTCF chrll 45124152 45124234 6213 chrll 45952099 45952310 CTCF chrll 45952190 45952271 6216 chrll 68024874 68025252 CTCF chrll 68025191 68025327 6275 chrll 68495327 68495620 CTCF chrll 68495324 68495403 6277 chrl l 89232401 O I > chrl l 89232187 & 2 :·?. '(:< t>. i2 chrll 117009358 117009738 CTCF chrll 117009658 117009785 6431 chrlO 6720148 f»7?.0-i2S CTCF chrlO 6720409 6720538 5639 chrlO 25984923 25985306 CTCF chrlO 25985161 25985282 5694 chrlO 27180222 CTCF chrlO 27180081 27 L80 l«0 5700 chrlO 103817364 103817773 CTCF chrlO 103817609 103817685 5939 chrlO 115079605 119079975 CTCF chrlO 119079968 119080040 chrlO 127318345 127318715 CTCF chrlO 127318416 127318526 6012 chrlO 129041788 129042140 CTCF chrlO 129041729 129041799 6016 chrlO 134257100 134257481 CTCF chrlO 134257406 134257885 5993 chrlO 134457702 134457959 CTCF chrlO 134457867 134457967 6049 chr9 108061775 108062095 Po!2(b} chr9 108062023 108062146 5452 chr9 139834542 1 ί'ιίί 54K'W Pol2(b) rhf 139834466 139834587 r>o;i chr6 159192567 159192907 Pol2(b) chr6 159192600 159192710 4013 chr5 179042989 179043345 Pol2(b) chr5 179043020 179043114 3479 chr4 3307415 3307735 Pol2(b) chr4 3307377 3307483 2230 chrl 1624244 1624611 Pol2{b) chrl 1624403 1624654 1 chrl 1624244 1624611 Pol2(b) chrl 1624211 1624313 17 chrl 1677525 1677881 J*ol2{b) chrl 1677682 1677934 2 chrl 1677525 1677881 Pol2(b) chrl 1677486 1677588 18 chrl 222.. S 22231875 Po!2{b) chrl 22231610 22231744 109 chrl 24743486 24743826 Poi2(b) chrl 24743669 24743756 119 chrl 154580101 154580441 Pol2(b) chrl 154580161 154580286 464 chrl 201566784 201567104 Pol2(b) chrl 201566696 201566793 633 chrl 230262VW 2 i0 63 j J 3 Pol2(b) chrl 230262996 230263096 chr22 19947226 19947582 Po!2(b) chr22 19947316 19947412 9328 chr22 22007958 22008314 Pol2(b) chr22 22008149 22008225 933-, chr21 44515300 44515656 Po!2(b) chr21 44515439 44515519 9259
Chrl7 17109525 17109881 Pol2(b) chrl7 17109779 17109885 8194 chrl7 80048720 80049076 Pol2(b) chrl7 80048928 80049020 8403 chrl6 19566931 19567251 Pol2{b) chrl6 19566661 19566971 7888 chrl6 83847962 83848282 Pol2{b) chrl6 83848024 83848139 8069 chrl6 89571828 S0V,'22¾ Po!2{b) chrlS 89571991 89572097 8110 chrl5 45709785 45710141 Poi2(b) chrl5 45709938 45710050 7679 chrl4 106765150 106765506 Pol2(b) chrl4 106765150 106765547 10014 chrl2 71055589 71055909 Po!2(b} chrl2 71055506 71055592 6720 chrlO 105881244 105881600 Pol2(b) chrlO 105881235 105881318 V 8 chrY 22960195 22960471 GR chrY 22960429 22960517 9962 chrX 71933401 71933697 G chrX 71933490 -. .'3.r. 2 9622 chr9 108061795 108062052 GR chr9 108062023 108062146 5452 chr8 37684090 37684360 R chrS 37684445 4835 chr8 144542881 144543151 GR chr8 144542935 144543046 5199 chr8 144986369 144986639 GR chrS 144986564 144986734 5200 chr7 12700084 12700354 GR chr7 12700231 12700362 4143 chr6 169032339 169032555 GR chr6 169032326 169032432 4055 chr5 33050005 33050275 GR chr5 33049885 33050059 3061 chr5 W0(, i(-7b GR .h: 5 ¾!,37 4 3141 chr4 7650530 7650780 GR chr4 7650500 7650603 2258 chr4 20338957 20339173 GR chr4 20339005 20339116 2 518 chr4 186631377 186631513 GR chr4 186631274 186631385 2865 chr3 106147498 106147714 GR l iir i 106147511 106147661 1884 chr2 236460625 236460841 GR chr2 236460709 236460813 1525 chrl 6042936 6043210 chrl 6043069 6043161 54 chrl 221785511 221785781 GR chrl 221785629 221785736 690 chr21 45768758 45769028 GR chf-21 45768852 45768952 9271 chrlS 11995749 11996019 GR chrl8 11995947 11996057 8449 chrl7 1617864 1618149 GR chrl7 1617853 1617940 8151 chrl7 1884873 1885175 GR chrl7 1884798 1884879 8153 chrl 6 !S7 i W . ¾:.<=; 57334575 GR chrl6 57334258 57334361 7!j :; chrl6 85270020 85270290 GR chrl6 85270118 85270201 8074 chrl6 89571821 89572199 GR chrl6 89571991 89572097 8110 chrl2 680582 680923 GR chrl2 680540 680670 6480
Chrl2 HACK 'S 132021148 GR chrl2 132020937 132021030 ¾' J chrll 952429 952700 GR chrll 952644 952729 6083 chrll 66115467 66115737 GR chrll 66115701 66115785 6263 chrll 68025050 68025320 GR chrll 68025191 68025327 6275 chrlO <rr/sv -, ;' K39 GR chrlO ; 7 i;½7 r 7%-'.c-. i 5746 chrlO 92923743 92924018 GR chrlO 92923953 92924065 5910 chrlO 99478515 99478814 GR chrlO 99478551 W.K chrlO 126770606 126770856 GR chrlO 126770807 126770902 6011 chrlO 134140095 134140394 GR chrlO 134140206 134140319 6046 chrX 1540828 1541138 Pol2 chrX 1540834 1540943 9464 chrX 48659016 48660116 Pol2 chrX 48660039 48660137 9583 chrX 71933455 71933728 Pol2 chrX 71933490 71933592 9622 chrX 113283977 113284154 Po!2 chrX 113284101 113284193 y7 i-> chr9 26975785 26976544 Pol2 chr9 26975670 26975820 5289 chrS 38620373 38621070 Pol2 chr9 38620511 38620596 chr9 108061767 108062392 Pol2 chr9 108062023 108062146 5452 chrS 128463681 128463945 Pol2 chi-9 128463780 12. . ΐί·81 5510 chr9 138799544 138799884 Pol2 chr9 138799480 138799699 5521 chr9 138863780 138864190 o; chr9 138863933 138864042 5551 chr8 29939788 29941070 Pol2 chr8 29940717 29940806 4813 chrS 107297978 107298288 f>:2 chrS 107298106 107298182 5050 chr8 144986621 144986698 Pol2 chr8 144986564 144986734 5200 chr7 1126321 1126893 Pol2 chr7 1126285 1126387 4086 chr7 5518273 5518493 Pol2 chr7 5518333 5518482 4121 chr7 72 W.W 72476437 Po!2 Chr7 J .M 7tj2 >.7 72476370 4318 chr7 101080512 101080752 Pol2 chr7 101080639 101080717 4454 c r7 102004098 102.004548 Pol2 chr7 102.004049 102004154 4460 chr7 143077339 143077684 Pol2 chr7 143077464 143077619 4599 chiv 158655977 158656287 Pol2 chiv 158655912 158656014 4680 chr6 2765533 2766004 Pol2 chr6 2765487 2765632 3512 chr& 2891534 Poi2 chr6 2891226 2891306 3513 chr6 2940527 2941007 Pol2 chr6 2940840 2940933 3514 chr6 3849449 3849899 Pf>:2 chr6 3849596 3520 chr6 10719759 10720023 Pol2 chr6 10719971 10720126 3543 chr6 24663276 24663580 Pol2 chr6 24663501 24663614 3578 chr6 31132739 31133263 Pol2 chr6 31132721 31132835 3606 c r6 31782006 31782829 Pol2 chr6 31782084 31782199 3609 chr6 138350071 138350367 Pol2 chr6 138350360 138350557 3910 chr6 155192561 159192805 Pol2 chr6 159192600 159192710 4013 chr5 435324 435604 Pol2 chr5 435289 435394 2911 chr5 33049929 33050149 Pol2 chr5 33049885 33050059 3061 chr5 33841158 33841483 Pol2 chr5 33841116 33841201 3066 chr5 !,M 77727 68477991 o;2 .h: 5 68478113 3144 chr5 133484815 133485079 Pol2 chr5 133484729 133484836 3351 chr5 176264642 176265052 Pf>:2 chr5 176264742 176264828 3470 chr4 967181 967481 Pol2 chr4 967430 967526 2218 chr4 3388998 i8 HC2 Po!2 chr4 3389099 3389195 22 J2 chr4 93175458 93176613 Pol2 chr4 93176111 93176193 2546 c r4 12.0147226 120147536 Pol2 chr4 120147137 120147255 .'i.2 5 chr4 154409238 154410187 Pol2 chr4 154408899 154409319 2723 chr3 53'542. . : Pol2 chr3 33942080 3 i9 ¾2 1 K7 1679 chr3 67705890 67706340 Pol2 chr3 67705692 67705939 1750 chr3 133144219 133144619 Poi2 chr3 133144614 133144876 1943 chr3 134090814 134090974 Pol2 chr3 134090906 134090983 1960 chr3 183273249 183273898 o;2 .h: 3 183273814 183273928 2 J 27 chr3 194886487 194886751 Pol2 chr3 194886472 194886564 2176 chr3 195577786 195578196 Pol2 chr3 195577893 195577977 2184 chr3 195853626 195854036 Pol2 chr3 195853969 195854074 2189 chr3 196000379 196000683 Po!2 l iir > 196000459 196000554 2192 chr2 55367486 55368118 Pol2 chr2 55368003 55368125 1025 chr2 110872887 110873156 Pol2 chr2 110873085 110873242 1154 chr2 110873186 110873648 Pol2 chr2 110873085 110873242 1154 chr2 220065729 220065993 Pol2 chr2 220065792 220065897 1474 chr2 242036507 242036925 Pol2 chr2 242036568 242036665 1561 chrl 1623777 1624270 Poi2 chrl 1624211 1624313 17 chrl 1624446 1624716 Pol2 chrl 1624403 1624654 1 chrl 1677559 1677819 Pf>:2 chrl 1677682 1677934 2 chrl 1677559 1677819 Pol2 chrl 1677486 1677588 18 chrl 12244507 12244787 Pol2 chrl 12244495 12244576 76 chrl 15761805 15762049 Pol2 chrl 15761835 15761947 93 chrl 222 U -I if, 222 S I 8"-: 4 Pol2 chrl 22231610 22231744 109 chrl 32479850 32480169 Pol2 chrl 32479789 32479871 141 chrl 150521053 150521792 Pol2 chrl 150521576 150521685 4'.2 chrl 151913781 151914127 Pol2 chrl 151913718 151913859 441 chrl 154580219 154581570 Pol2 chrl 154580161 154580286 464 chrl 203650928 203651378 Pol2 chrl 203651242 203651350 642 chrl 228463594 22 4637 /0 o;2 ch l 2 4 37!, 1 22Mi, S!J42 678 chrl 230262626 230263036 Pol2 chrl 230262996 230263096 725 chr22 18008783 18009079 Pf>:2 chr22 18008951 18009037 <' 5? j chr22 19947049 19947395 Pol2 chr22 19947316 19947412 9328
Figure imgf000204_0001
chrl6 81492534 81492754 Pol2 chrl6 81492554 81492676 8057 chrl6 82044882 S20 i:>29 Pol2 chrie S2 if.232 82045319 8061 chrl6 83847968 83848232 Pol2 chrl6 83848024 83848139 8069 chrie 89257439 «■).■ ¾ / 7(5 Ϊ Poi2 chrie H-Ub / V 7 89257631 8103 chrl6 89571894 89572558 Pol2 chrl6 89571991 89572097 8110 chrlS 89768532 89768839 Pf>:2 chrl6 89768460 89768554 8115 chrl6 89831216 89831564 P0I2 chrl6 89831177 89831300 8117 chrl5 204X7S67 20488087 P0I2 chrl5 204K797,--; 20488199 7591 chrl5 43757331 43757641 P0I2 chrl5 43757326 43757412 7671 chrl5 69744235 69744543 P0I2 chrlS (->" ? 54. W 69744482 77 V chrl5 89446131 89446529 P0I2 chrl5 89446088 89446173 7796 chrl4 2 ? 1':25 15 2345277') P0I2 chrl4 23452524 2 W.202& 73 i chrl4 69282164 69282821 P0I2 chrl4 69282279 69282392 7466 chrl4 71698567 71698827 P0I2 chrl4 71698706 71698909 7476 chrl4 93216638 93216928 P0I2 chrl4 93216507 93216641 7534 chrl4 107251643 107251913 Po;2 chrl4 107251729 107251888 75S7 chrl3 100028390 100028654 Pol2 chrl3 100028639 100028716 7227 chrl3 100148801 100149469 Pf>:2 chrl3 100148988 100149109 7228 chrl3 110384343 110384598 P0I2 chrl3 110384570 110384721 7272 chrl3 113808626 113808964 Pol2 chrl3 113808710 113808818 7298 chrl2 680028 680766 Pol2 chrl2 680540 680670 6480
Chrl2 6201552 Po!2 chrl2 6201657 6201737 6498 chrl2 10062905 10063753 Pol2 chrl2 10063027 10063115 6514 c.hrl2 12594915 12595365 Po!2 chrl2 12595125 ! 2ν:·52ίί.' (Λ >(> chrl2 49520208 49521180 Pol2 chrl2 49520317 49520411 6647 chrl2 95831515 95831785 Pol2 chrl2 95831780 95831866 6793 chrl2 116819392 116819637 Pol2 chrl2 116819406 116819500 6857 chrl2 123319887 123320234 Poi2 Chrl2 123319859 123319962 6874 chrll 308965 309275 Pol2 chrll 309226 309317 6070 chrll 815871 816181 Pf>:2 chrll 815881 815967 6077 chrll 952446 952724 Pol2 chrll 952644 952729 6083 chrll 4414589 4415039 Pol2 chrll 4414591 4414685 6098 chrll 5704906 5705555 Pol2 chrll 5704773 5704930 6100 chrll 10066132 10066436 Po!2 chrll 10066059 10066157 6112 chrll 45123879 45124159 Pol2 chrll 45124152 45124234 6213 chrll t. 55293 ? 63'»2<· 6·: Pol2 chrll &3'>2° 52.1 63529412 6256 chrlO 42970874 42971192 Pol2 chrlO 42971024 42971122 5759 chrlO 74086424 74087034 Pol2 chrlO 74086665 74086769 5851 chrlO 92923592 92923959 Pol2 chrlO 92923953 92924065 5910 chrlQ 99477818 fiW8? .7 Po;2 chrlO 99478551 99478665 5928 chrlO 105880458 105882271 Pol2 chrlO 105881235 105881318 5948 chrlO 134965112 134965416 Pf>:2 chrlO 134965042 134965115 6058 chrX 16919722 16919902 USF-1 chrX 16919869 16919946 9512 chr9 98531842 98532115 U5F-1 Chr9 98531894 98531993 5423 chr9 108061799 108062049 USF-1 chr9 108062023 108062146 5452 chr9 138110467 138110671 USF-1 chr9 138110626 138110747 5545 chr8 19372648 19372878 USF-1 chr8 19372672 19372761 4783 chr6 2765520 2765778 USF-1 c r6 2765487 276':032 55 12 chr6 110818733 110818983 USF-1 chr6 110818694 110818788 3865 chr& 166913791 166914021 USF-1 chr6 166913967 166914065 4035 chr5 55544902 55545132 USF-1 chr5 55545074 55545234 3112 chr5 115880652 115880832 USF-1 .h: 5 115880687 115880768 ί .ΐΓΜ chr4 967496 967746 USF-1 chr4 967430 967526 2218 chr4 163842632 163842862 USF-1 chr4 163842700 163842811 2 chr3 195577834 195578084 USF-1 chr3 195577893 195577977 2184 chr2 735868 736098 USF-1 Chr2 7 Jt,.')(V> 736076 838 chr2 64262324 64262574 USF-1 chr2 64262564 64262665 1054 chr2 101507723 101507995 USF-1 c r2 101507790 101507891 1132 chr2 224896167 224896488 USF-1 chr2 224896209 224896412 1486 chrl 12156057 12156395 USF-1 chrl 12156124 12156284 75 chrl 22231583 22231833 USF-1 chrl 22231610 22231744 109 chrl 37209361 37209639 USF-1 chrl 37209400 37209541 162 chrl 230262774 230263010 USF-1 chrl 230262996 230263096 725 chrl 247436367 247 Η(/:'-;7 USF-1 chrl 2471 50 U 5 247436435 816 chrl 247542007 247542257 USF-1 chrl 247542130 247542214 818 chr22 33961519 33961749 USF-1 chr22 33961551 33961650 3M' chr22 37298000 37298250 USF-1 chr22 37298229 37298316 9373 chr22 37736629 37736859 USF-1 chr22 37736608 37736730 937 5 chr22 44849719 44849949 USF-1 chr22 44849805 44849884 9400 chr22 47666290 47666540 USF-1 chr22 47666233 47666375 5411 chrl9 3070558 3070845 USF-1 chrl9 3070667 3070760 8689 chrlS 1?. ΐ Γ/ λ /ϊ 12377787 USF-1 chrlS 12377506 VA?;- n 8450 chrl8 77468379 77468609 USF-1 chrl8 77468462 77468551 8649 chrl 7 17109609 17109953 USF-1 chrl7 17109779 17109885 8194 chrl7 71847842 71848092 USF-1 chrl7 71848088 71848194 8356 chrl7 76250580 76250831 USF-1 chrl7 76250645 76250741 ίί 57': chrl6 14967836 14968065 USF-1 chrl6 14967880 14968000 7906 chrl6 17195538 17195836 USF-1 chrl6 17195660 17195747 7915 chrl6 19566912 19567158 USF-1 chrl6 19566661 19566971 7888
Chrl6 21552513 21552743 U5F-1 chrl6 21552521 21552689 7935 chrl6 86017774 86018004 USF-1 chrl6 86017726 86017805 8079 chrl6 89571883 89572133 USF-1 chrl6 89571991 89572097 8110 chrlS 79888360 79888601 USF-1 chrl5 79888531 79888665 7768 chrl4 USF-1 chrl4 vJ7 i.<01 59743135 7436 chrlS 113358726 113358976 USF-1 chrl3 113358873 113358968 7291 chrl3 113864535 113864805 USF-1 chrl3 113864788 113864905 chrl2 109774450 109774704 USF-1 chrl2 109774558 109774646 6837 chrl2 132830978 132831208 USF-1 chrl2 132831021 132831096 6936 chrll 66115525 66115787 USF-1 chrll 66115701 66115785 6263 chrlO 133622455 133622719 USF-1 chrlO 133622568 133622648 6038 chr9 33221278 33221595 ERalpha_a chr9 33221392 33221473 5311 chr9 140305072 140305348 ERalpha_a chr9 140305319 140305466 5569 chr7 921147 921391 ERalpha_a chr7 921236 921318 4081 chr? 4864695 4864939 ERal h „a chr7 4864733 4864848 4117 chr7 11638618 11638894 ERalpha_a chr7 11638663 11638805 4138 chiv 55809551 55809827 ERalpha_a chiv 55809587 55810067 10094 chr6 2765433 2765693 ERaipha_a chr6 2765487 2765632 3512 chr6 169032281 169032541 ERalpha_a chr6 169032326 169032432 4 55 chrS 143482435 143482679 ERaipha_a chrS 143482612 143482712 3372 chr4 7290634 7290910 ERalp a_a chr4 7290605 7290683 2256 chr4 84205356 84205637 ERalpha_a chr4 84205458 84205558 2509
Chr4 151795620 151795896 ERalpha. 3 Chr4 151795830 151795932 2717 chr3 32130903 32131179 ERalpha_a chr3 32131117 32131257 1668 chr3 106147463 106147739 ERalpha_a chr3 106147511 106147661 1884 chr3 192614874 192615118 ERalpha_a chr3 192614968 192615068 2162 chr2 110873212 110873647 ERalph „a chr2 110873085 110873242 1154 chr2 233428342 233428586 ERalpha_a chr2 233428386 233428474 1518 chr2 236460664 236460978 ERalpha . a chr2 236460709 236460813 1525 chr2 241230819 241231095 ERaipha_a chr2 241230769 241230882 1555 chrl 233217451 i 3 J 769 ERalpha_a chrl i 3 J 75<13 7 Ϊ» chr21 15646137 15646381 ERal ha_a chr21 15646177 15646266 9151 chr21 18873763 18874007 ERalpha_a chr21 18873881 18873961 9161 chrl9 610021 610281 ERalpha_a chrl9 610176 610270 8669
Chrl9 707432 707692 ERalpha. a chrl9 707409 707531 8672 chrl9 2631434 2631710 ERalpha_a chrl9 2631555 2631659 8683 chrl9 50937973 50Ή;·:_· ¾ ERalph „a chrlS 50938230 100.18327 :5¾¾S8S§¾ chrl7 38083808 38084068 ERalpha_a chrl7 38083901 38083979 8235 chrl7 76250562 ϊί 0822 ERalpha_a chrl? 76250741 S.¾ 7¾ chrll 1145484 1145760 ERaipha a chrll 1145612 1145687 6085 chrY 8898009 8898259 FOXAl JC-20) chrY 8898125 8.v-JS,:.H 9917 chrX 77043607 77043705 FOXAl JC-20) chrX 77043627 77043724 9643 chr9 140010715 140010983 FOXAl JC-20) < r<' 140010751 140010868 r><y chr8 11499507 11499767 FOXAl JC-20) chr8 11499580 11499663 4759 chrS 39066440 39066700 FOXA1_{C-20) chrS 39066484 39066639 4839 chr8 103519758 103519911 FOXAl JC-20) chr8 103519699 103519793 5041 chr7 921145 921462 FOXAl JC-20) chr7 921236 921318 4081 chr7 4864666 4864890 FOXAlJC-20) chr7 4864733 4864848 4117 chr7 16964725 16964949 FOXAl JC-20) chr7 16964933 16965023 4159 chr7 70052707 70052967 FOXAl JC-20) chr7 70052718 70052798 4310 chiv 123365000 123365117 FOXAl JC-20) chiv 123365008 123¾5Γ.8 4538 chr6 2765505 2765729 FOXAl JC-20) chr6 2765487 2765632 3512 chr6 .'5^ 5576 2 ¾.V' J 7 FOXAl JC-20) chr6 2 ¾.177 l 25863871 3581 chr6 26145138 26145362 FOXAl JC-20) chr6 26145275 26145355 3582 chr6 111598041 111598265 FOXAl JC-20) chr6 111598099 111598226 3873 chr5 115880446 115880706 FOXAl JC-20) chr5 115880687 115880768 3304 chr5 123430604 123430828 F0XA1_ (C-20) chr5 123430644 L .!.¾50-.'.| 7 .Π24 chr5 134311054 134311314 F0XA1_ (C-20) chr5 134311064 134311151 3354 chr5 178691863 178692123 F0XA1.. (C-20) Chr5 178691893 178691989 3475 chr4 55649633 55649859 F0XA1_ ;c-20) chr4 55649675 55649759 2413 c r4 185784723 185784947 F0XA1_ {C-20} chr4 185784777 185784880 2861 chr3 169877188 169877412 F0XA1_ ;c-20) chr3 169877366 169877443 2081 chr3 172278760 172278984 FQXA1__ ;c-20) chr3 172278855 1 7227S 6-i 2091 chr3 190956200 190956391 F0XA1_. (C-20) chr3 190956192 190956285 2156 chr3 192614845 192615105 F0XA1... (C-20) chr3 192614968 192615068 2162 chr3 195577804 195578028 F0XA1_ C-20) chr3 195577893 195577977 2184 chr2 61672160 61672420 F0XA1„ (C-20) chr2 61672279 61672360 1041 chr2 85151900 85152160 F0XA1_ ;c-20) chr2 85152041 85152146 1107 chr2 114743707 114743893 F0XA1_ (C-20) chr2 114743848 114743923 1165 chr2 167036833 167037093 F0XA1_ (C-20) chr2 167037071 167037175 1304 chr2 169942115 169942339 F0XA1_ (C-20) chr2 169942123 169942203 1317 chr2 212243418 212243642 F0XA1_ ;c-2oj chr2 212243619 212243728 1452 chr2 2 ¾ ί-ΙΛ*-! 23 U284°0 F0XA1_ (C-20) c r2 23 U28WJ 2"! S474 1518 chr2 240225926 240226150 F0XA1_ ;c-20) chr2 240225882 240225968 1545 chrl 1624153 1624353 FQXA1__ (C-20) chrl 1624211 1624313 17 chrl 1677442 1677642 F0XA1_ (C-20) chrl 1677486 1677588 18 chrl 1677767 1678027 . 0ΧΛ 1 (C-20) chrl ] 67.?..,H.' 1677934 ? chrl 100224455 100224715 F0XA1_ ;c-20) chrl 100224633 100224721 373 chrl 235413811 235414013 F0XA1„ (C-20) chrl 2 i¾ U 3K J 235413946 746 chr22 36038557 36038817 F0XA1_ ;c-20) chr22 36038553 36038634 9370
Chr21 18S73771 18874083 F0XA1.. (C-20) chr21 18873881 18873961 9161 chr21 38938250 38938489 F0XA1_ ;c-2o) chr21 38938279 38938373 9228 c.hrl9 57262109 57262.500 F0XA1_ (C-20) chrl9 57262 j -ifi ¾ >2t.22.i.' 8893 chrl7 473789 474049 F0XA1_ ;c-20) chrl7 473883 473979 8135 chrl7 16821855 16822079 F0XA1_ (C-20) chrl7 16821924 16822014 8193 chrl7 38083678 38083938 F0XA1_ ;c-20) chrl7 38083901 38083979 8235
Chrl7 8 -'.C,: ™ 80302659 F0XA1... (C-20) chrl7 80 ¾0.'57ί: 8405 chrl6 4511551 4511648 F0XA1_ C-20) chrl6 4511459 4511603 7866 chrl 6 11904119 11904378 . 0ΧΛ 1 (C-20) chrl6 11904262 11904361 7895 chrl6 83847780 83848040 F0XA1_ ;c-20) chrl6 83848024 83848139 8069 chrl6 87739591 α :·7.Υ)<3?. ·\ F0XA1_ (C-20) chrl6 K -.'7.W: 7b S 73¾:>5 KO-i.i chrl6 89571955 89572082 F0XA1_ (C-20) chrl6 89571991 89572097 8110
Chrl6 90124362 90124622 F0XA1.. (C-20) chrl6 90124299 90124411 8124 chrl5 72267515 72267739 F0XA1_ ;c-2oj chrl5 72267623 72267751 7743 chrl3 41146398 41146523 F0XA1_ (C-20) chfl3 41146460 41146548 7028 chrl3 71865465 71865725 F0XA1_ :c-2o) chrl3 71865441 71865535 7137 chrl3 K2. S ? S2MK ".'72 FQXA1__ ;c-2o) chrl3 7169 chrl3 95097138 95097362 F0XA1_. (C-20) chrl3 95097182 95097302 7209 chrl3 100149004 100149228 F0XA1... (C-20) chrl3 100148988 100149109 72 K chrl3 108956588 108956812 F0XA1_ C-20) chrl3 108956552 108956690 7260 chrll 34643389 34643659 F0XA1„ (C-20) chrll -:.KJ4 M ¾.¾ 546 )3', 70 6176 chrll 90244933 90245157 F0XA1_ ;c-20) chrll 90245087 90245173 6345 chrlO 74848125 74848397 F0XA1_ (C-20) chrlO 74848135 :--Mi M ?.2 ?.
chrlO 92923776 92924036 F0XA1_ (C-20) chrlO 92923953 92924065 5910 chrlO 107753433 j 7 /5 iiVi .i F0XA1_ (C-20) chrlO 107753337 107753438 5954 chrlO 119120816 119121147 F0XA1_ (C-20) chrlO 119120930 119121023 5983 chrX 48655725 48660055 ATF3 chrX 48660039 48660137 9583 chr9 36008884 36009108 ATF3 chr9 36008952 36009049 5319 chiv 4034975 4035199 ATF3 chiv 4034971 4035107 4110 chr3 195577812 195578036 ATF3 chr3 195577893 195577977 2184 chrl 12156077 1 2 1 %W ¾ ATF3 chrl 12156124 12156284 75 chrl 22231447 22231683 ATF3 chrl 22231610 22231744 109 chr21 I .W1K3H 18874042 ATF3 chr21 18873881 18873961 9161 chrl7 17109710 17109914 ATF3 chrl7 17109779 17109885 8194 chrl7 38083791 38084000 ATF3 chrl7 38083901 38083979 K2V, chrl7 76250580 76250784 ATF3 chrl7 76250645 76250741 8375
Chrl6 1 ? l«V>77 17195801 ATB chrl6 17195660 17195747 7915 chrl6 19566934 19567158 ATF3 chrl6 19566661 19566971 7888 chrl5 22462196 224(>2 2h ATF3 chrlS .'2462 2 >2'i20 7597 chrlS 79888417 79888641 ATF3 chrl5 79888531 79888665 7768 chrl4 106765207 106765458 ATF3 chrl4 106765150 106765547 10014 chrlO 133622430 133622654 ATF3 chrlO 133622568 133622648 6038 chrX 87155463 87155586 BAT chrX 87155486 87155585 9675 chr7 33801986 33802202 BATF chr7 33802095 33802234 4202 chr7 112422670 112422926 BATF chr7 112422799 112422895 4508 chr6 2940661 2941014 BATF chr6 2940840 2940933 3514 chr6 6225461 6225677 BATF chr6 622.5 -i 77 6225649 3525 chr6 6440102 6440318 BATF chr6 6440227 6440305 3526 chr6 115319001 115319201 BATF chr6 115319070 115319164 2·Η*? chr5 25569469 25569685 BATF chr5 25569504 25569595 3033 chrS 54868535 54868751 8ATF c rS 54868565 54868672 3128 chr5 114404645 114404784 BATF chr5 114404634 114404729 3301 chr5 156891955 156892105 BATF chr5 156892015 156892109 3408 chr4 37075125 37075341 BATF chr4 37075246 37075337 2369 chr4 133045463 133045588 BATF chr4 133045440 J ¾03 5- 10 2671 chr4 154409293 154409509 BATF chr4 154408899 154409319 2723 chr3 2 «0 70-3 2 5S;J27',.¾ BATF chr3 23802706 23802796 1644 chr3 119419519 119419763 BATF chr3 119419620 119419714 1916 chr3 133943324 133943540 BATF l iir i 133943485 133943564 1958 chr2 242036508 242036734 BATF chr2 242036568 242036665 1561 chrl 236150278 236150494 BATF chrl 236150197 ? & \ Γ>ΐΏ&? 751 chrl8 55093455 55093671 BATF chrl8 55093504 55093689 8565 chrl8 77468548 77468764 BATF chrlS 77468462 77468551 8649 chrl6 90124382 90124598 BATF chrl6 90124299 90124411 8124 chrlS 28984214 28984430 BATF chrl5 ,:<WM2:"> ¾ 28984350 7604 chrl5 83480062 83480126 BATF chrl5 83480014 83480112 7781 chrl 3 71865360 7J ¾!«W? BATF chrl3 71865441 71865535 7137 chrl3 77565610 77565808 BATF chrl3 77565612 77565745 7150 chrl2 X27?. -ii:').V, 127257235 BATF chrl2 127257076 127257168 6895 chrll 66115488 66115704 BATF chrll 66115701 66115785 6263
Chrll 115795821 115796172 BATF chrll 115795944 115796095 6427 chrlO 125312660 125312898 BATF chrlO 125312740 125312814 6003 chrX 87155353 87155589 BCL11A chrX 87155486 87155585 5675 chr9 76908420 76908596 BCL11A chr9 76908522 76908603 5354 chr8 54437118 54437354 BCL11A chrS vM 37 r. ■■:■.■)■■. < :·-'.2.2 4894 chr6 1665545 1665781 BCL11A chr6 1665562 1665705 3505 chr& 2940743 BCL11A chr6 2940840 2940933 3514 chr6 115318963 115319199 BCL11A chr6 115319070 115319164 3892 chr5 114404626 114404862 BCL11A chr5 114404634 114404729 3301 chr3 23802632 23802868 BCL11A chr3 23802706 23802796 1644 chr3 119419565 119419667 8CL11A chr3 119419620 119419714 1916 chr2 62575112 62575348 BCL11A chr2 62575281 62575364 1045 chr2 1>)92 ?f«..Jfj 199236882 BCL11A chr2 199236595 199236679 1411 chr2 242036524 242036667 BCL11A chr2 242036568 242036665 1561 chr22 39906814 39906990 BCL11A chr22 39906714 39906863 9380 chrlS 77580146 77580382 BCL11A chrl8 77580201 77580310 8653 chrlS 83480170 BCL11A chrlS 83480014 83480112 7781 chrl3 100028423 100028659 BCL11A chrl3 100028639 100028716 7227 chrl 2 1 7257020 127257141 BCL11A chrl2 127257076 127257168 t>895 chrll 115795875 115796131 BCL11A chrll 115795944 115796095 6427 chrlO 62111004 62111240 BCL11A chrlO 62110925 62111027 5812 chrlO 125312687 125312923 BCL11A chrlO 125312740 125312814 6003 chrX 87155345 87155585 BC Li chrX 87155486 87155585 9675 chr9 138863891 138864071 BCL3 chr9 138863933 138864042 5551 chr8 37645958 37646198 SC I.5 Chr8 37646017 v/!,-ir. i:!8 4834 chr8 104136132 104136372 BCL3 chr8 104136237 104136356 5044 c r6 2940743 2940983 SCL ? chr6 2940840 2'i'o.m i 3514 chr6 115318957 115319197 BCL3 chr6 115319070 115319164 3892 chr5 114404592 114404832 tX.i.3 chr5 114404634 114404729 3301 chr5 176264719 176264899 BCL3 chr5 176264742 176264828 3470 chr4 123822510 123822690 BO.-i chr4 u> ios 123822521 263" chr4 133045488 133045560 BCL3 chr4 133045440 133045540 2671 chr3 119419549 119419667 1X 13 chr3 119419620 119419714 1916 chr3 133943347 133943587 BCL3 chr3 133943485 133943564 1958 chr3 185635700 185635890 BC Li chr3 185635836 LS ".65:": 37 2 132 chr2 104051651 104051711 BCL3 chr2 104051628 104051750 1135 chr2 1>)92 ΚΗ, ΛΊ 199236879 SCL ? chr?. 199236595 199236679 1411 chr2 242608257 242608497 BCL3 chr2 242608434 242608513 1568 chrl 3034465 3034705 BCL3 chrl 3;n-r,2-\ 3034624 3» chrl 6093194 6093521 BCL3 chrl 6093368 6093478 55 chrl 15761852 i ':.7L :o"J.i tX.i.3 chrl 15761835 15761947 3 chrl 105249611 105249851 BCL3 chrl 105249637 105249736 394 chrl 22 i!J-lHS5 223949046 l. i .j ch l 2 3fi DO.1 223949141 70 S chr21 44804950 44805190 BCL3 chr21 44804845 44805052 9260 chrl8 77557531 ;w: V(-o7 He n chrl8 77557576 77557665 ί-:652 chrl6 24267289 24267469 BCL3 chrl6 24267330 24267430 7943
Chrl6 88959738 88959875 SC I.5 chrl6 88959572 88959883 8054 chrl6 89257385 89257625 BCL3 chrl6 89257507 89257631 8103 c.hrl3 ■j ¾53 i-> 71865575 BQ. S chrl3 71865441 71865535 7137 chrl3 114459366 114459606 BCL3 chrl3 114459421 114459558 7306 chrl2 127257030 127257219 BCL3 chrl2 127257076 127257168 6895 chrl2 133234922 133235162 BCL3 chrl2 133234966 133235064 6944 chrii 722« >09<: BO.-i chrll 72282847 ?.V:829 /1 6299 chrll 115795877 115796175 BCL3 chrll 115795944 115796095 6427 chrl l 128823215 128823336 l. i .j chrl l 128823128 1 .'s \? S ¾ t> l 7 chr3 195577802 195578156 BCLAF1JM33- chr3 195577893 195577977 2184 chr2 242036489 242036 / 39 BCLAF1 J 33- chr2 >.A20K--,hi 242036665 1561 chrl 22231581 22231805 BCLAF1_(M33- chrl 22231610 22231744 109
Chrl9 44598335 44598608 BCLAF1J 33- chrl9 44598400 44598496 8828 chrl7 76250566 76250816 BCLAF1JM33- chrl7 76250645 76250741 8375 chrl6 19566711 19566961 BCLAF1JM33- chrl6 19566661 19566971 7.W chrlS 69744366 69744590 BCLAF1JM33- chrl5 69744385 69744482 7732 chrl4 106765268 106765518 BCLAF1...( 33- chrl4 106765150 106765547 10014 chrX 115127298 115127534 EBFlJC-8) chrX 115127357 115127448 9742 chr8 142416423 142416640 EBFlJC-8) chr8 142416496 142416596 5177 chr7 1126133 1126453 EBF1JC-8) chr7 1126285 1126387 4086 chr7 122830702 122830938 EBFlJC-8) chr7 122830689 122830786 4535 chr6 2940751 2940987 EBFlJC-8) chr6 2940840 2940933 3514 chr6 31132811 31133047 EBFlJC-8) chr6 31132721 31 L 32855 3606 chr6 52161574 52161810 EBFlJC-8) chr6 52161778 52161905 3676 chr6 lvl67.> 46 84672653 EBFlJC-8) chr6 84672604 /8 5 chr6 89435364 89435423 EBFlJC-8) chr6 89435264 89435378 3795 chrS 119793919 119794151 EBFlJC-8) c rS 119794061 119794139 chr4 3388896 3389132 EBFlJC-8) chr4 3389099 3389195 2232 chr4 133045499 EBFlJC-8) chr4 133045440 133045540 2ί-71 chr4 154409275 154409882 EBFlJC-8) chr4 154408899 154409319 2723 chr3 ] s i'j-n.i . 133943578 EBFlJC-8) ch 3 133943485 LI 3'i 3 5 ..,-! 1958 chr2 62575067 62575316 EBFlJC-8) chr2 62575281 62575364 1045 chr2 2420¾¾r> 2420 56771 EBFlJC-8) chr2 242036568 242036665 1561 chr2 242262700 242262936 EBFlJC-8) chr2 242262774 242262909 1565 chrl 15532848 15533063 EBFlJC-8) chrl 15532803 15532924 89 chrl 116777120 116777356 EBF1_(C-S) chrl 116777178 116777262 427
Chr20 60877036 60877272 EBFl JC-8) chr20 60877210 60877541 ¾2 chrl8 2960619 2960855 EBFlJC-8) chrl8 2960595 2960669 8428 hrlS 55093517 55093753 EBFlJC-8) chrlS 55093504 ¾-.η·).ϊΓι¾· chrl7 17109750 17109863 EBFlJC-8) chrl7 17109779 17109885 8194 chrl7 26698504 ji-fWK -.'.'.(; EBFlJC-8) chrl? ½ i-:V)7 26698706 8216 chrl? 29055896 29056132 EBFlJC-8) chrl7 29055786 29055917 8219 chrie 19566576 19566783 EBFlJC-8) chrie 19566661 19566971 7riSK chrl6 89571797 89572033 EBFlJC-8) chrl6 89571991 89572097 8110 chrlS 89831268 89831504 EBFlJC-8) chrl6 89831177 89831300 8117 chrl5 22462185 22462438 EBFlJC-8) chrl5 22462316 22462420 7597 chrl5 28984313 EBFlJC-8) chrl5 28984253 2>¾:'S4.5b 7604 chrl5 83480035 83480150 EBFlJC-8) chrl5 83480014 83480112 7781 chrl5 101602388 101602624 EBFlJC-8) chrlS 101602318 101602415 7825 chrl4 106765378 106765614 EBFlJC-8) chrl4 106765150 106765547 10014 chrl3 77565559 77565795 EBFlJC-8) chfl3 77565612 77565745 7150 chrl3 100028444 100028680 EBFlJC-8) chrl3 100028639 100028716 7227 chrl2 132020978 132021038 EBFlJC-8) chrl2 132020937 132021030 6923 chrll 45952166 45952402 EBFlJC-8) chrll 45952190 45952271 6216 chrl l 115795982 115796277 EBFlJC-8) chrll 115795944 115796095 > 127 chrlO 62110999 62111235 EBFlJC-8) chrlO 62110925 62111027 5812 chrlO V.W4K07 74848310 EBFlJC-8) chrlO 74848135 V4f 3222 ¾5 ¾ chrlO 125312655 125312905 EBF1JC-S) chrlO 125312740 125312814 6003 chrX 48659981 48660157 Egr-1 ChrX 48660039 48660137 chrX 71933445 71933661 Egr-1 chrX 71933490 71933592 9622 chrX 153607260 153607476 Egr-1 chrX 153607264 153607413 y8i? 5 chr9 138404868 138405084 Egr-1 chr9 138404989 138405124 5547 chrS 138799635 138799826 Egr-1 chrS 138799480 138799699 5521 chr9 140128619 140128835 Egr-1 chr9 140128770 140128880 5568 chr8 29940764 W WW. Egr-1 chr8 29940717 29940806 4813 chr8 142386407 142386623 Egr-1 chr8 142386542 142386629 5176 chr7 1126309 1126540 Egr-1 .h: 7 1126285 1126387 4 ¾ chr7 101080570 101080786 Egr-1 chr7 101080639 101080717 4454 chr6 2765390 2765614 Egr-1 chr6 2765487 /i.b6¾? 3512 chr6 3849550 3849726 Egr-1 chr6 3849487 3849596 3520 chr6 H-nr-!?:??. 8 J4 35 IK Egr-1 Chr6 8'M }¾.'»■-. 89435378 3795 chr5 77893233 77893449 Egr-1 chr5 77893174 77893252 3188 chrS 170060534 170060750 Egr-1 chrS 170060476 170060580 U.%7 chr4 967285 967501 Egr-1 chr4 967430 967526 2218 chr3 194003484 194003700 Egr-1 chr3 194003477 194003630 2167 chr3 194714769 194714985 Egr-1 chr3 194714866 194714947 2172 chr3 195577855 195578071 Egr-1 chr3 195577977 2184 chr2 1286354 1286570 Egr- 1 chr2 1286432 1286554 843 chr2 47632183 I u V.VV> Egr-1 chr2 ΐ νυ ¾22ί)ΐ 7ti 52 157 1005 chr2 231521667 231521883 Egr-1 chr2 231521752 231521847 1510 chrl 1624117 .102 133 Ϊ Egr-1 chrl 1624211 1624313 17 chrl 22231540 22231865 Egr-1 chrl 22231610 22231744 109 chrl 2ΒίΤ» »>« ϊ 28053119 Egr-1 chrl 28053114 iO: 0:. 129 chrl 154580204 154580420 Egr-1 chrl 154580161 154580286 464 chrl 228160541 22H [f-()7':7 Egr-1 chrl 228160651 228161912 719 chrl 228463697 228463913 Egr-1 chrl 228463761 228463942 678 chrl 230262924 230263140 Egr-1 chrl i;2i 230263096 725 ch'r22 39906787 39907011 Egr-1 chr22 39906714 39906863 9380 chr21 d.¾2%r-.n Egr-1 chr21 4.;255".! 3 43256095 fi2¾2 chr21 44804636 44804856 Egr-1 chr21 44804845 44805052 9260 chr20 25266154 Egr-1 chr20 25266067 25266158 fvifjH chr20 60849717 60849870 Egr-1 chr20 60849658 60849757 9096 chrl9 903521 903737 Egr-1 chrl9 903465 903545 8675 chrl9 6373360 6373576 Egr-1 chrl9 6373061 6373448 8661
Chrl9 42807124 42807340 Egr-1 chrl9 42807266 42807377 8824 chrl7 17109706 17109985 Egr-1 chrl7 17109779 17109885 8194 c.hrl7 20059073 00V-S2 7 Egr-1 chrl7 20059180 10042 chrl7 29055758 29055974 Egr-1 chrl7 29055786 29055917 8219 chrl7 38083718 Egr-1 chrl? 38083901 38083979 chrl7 76250609 76250785 Egr-1 chrl7 76250645 76250741 8375 chrie 91823 Egr-1 chrl6 91963 92095 10022 chrl6 375089 375265 Egr- 1 chrl6 375060 375159 7837 chrl6 24267351 .J2 75G7 Egr-1 chrl6 2.L7 73 i 24267430 7943 chrl6 89571960 89572136 Egr-1 chrl6 89571991 89572097 8110 chrl6 89768506 ;;-VA-S/ 2 Egr-1 chrl6 89768460 89768554 8115 chrl6 90124324 90124540 Egr-1 chrl6 90124299 90124411 8124 chrl5 20487850 20488066 Egr-1 chrlS 20487978 20488199 7591 chrl5 79888404 79888620 Egr-1 chrl5 79888531 79888665 7768 chrl3 113358682 ] 1 ¾ iWS Egr-1 chrl3 113358873 113358968 7291 chrl3 113808658 113808874 Egr-1 chrl3 113808710 113808818 7298 chrl2 90254947 90255163 Egr-1 chrl2 90254873 90254955 6774 chrll 2465939 2466155 Egr-1 chrll 2465727 2466083 6094 chrl l .'927 16. Egr-1 chrll 2927165 t«i97 chrll 66115507 66115735 Egr-1 chrll 66115701 66115785 6263 chrll 120082901 120083117 Egr-1 chrll 120082929 120083030 6439 chrlO 3185668 3185884 Egr-1 chrlO 3185734 3185819 5613 chrlO 14854271 14854487 Egr-1 chrlO 14854385 14854508 5660 chrlO 134257633 134257849 Egr-1 chrlO 134257406 134257885 5993 chrX 152992899 152.993139 ELFlJSC-631) chrX 152.992934 152993010 ysiiifi chrX 153607046 153607296 ELFlJSC-631) chrX 153607264 153607413 9864 chrS 38620575 ELFlJSC-631) chr9 38620511 38620596 chr9 96337995 96338289 ELFlJSC-631) chr9 96337914 96338024 5413 chr9 99983850 99983960 ELFlJSC-631) chr9 99983766 12« chr9 138799496 138799736 ELFlJSC-631) chr9 138799480 138799699 5521 chrS 142386341 Hi iBir.S l ELFlJSC-631) chr8 142386629 5176 chr8 142416274 142416550 ELFlJSC-631) chr8 142416496 142416596 5177 chr7 102004138 102004373 ELFlJSC-631) chr7 102004049 102004154 4460 chr7 150760446 150760696 ELFlJSC-631) chr7 150760678 150760783 4628 chr6 604573 604823 ELFlJSC-631) Chr6 604752 604853 3498 chr6 2765394 2765762 ELFlJSC-631) chr6 2765487 2765632 3512 chr6 2940687 2940963 ELFlJSC-631) c r6 2940840 w.m ¾
chr6 3849398 3849718 ELFlJSC-631) chr6 3849487 3849596 3520 chr5 176264680 176264930 ELFlJSC-631) chr5 176264742 176264828 3470 chr3 119419402 119419671 ELFl J SC-631) chr3 119419620 119419714 1916 chr3 195577870 195578146 ELFlJSC-631) chr3 195577977 2184 chr3 195872718 195872968 ELFlJSC-631) chr3 195872965 195873074 2190 chr2 55367769 55368019 ELFlJSC-631) chr2 55368003 55368125 1025 chr2 61317571 61317811 ELFlJSC-631) chr2 61317637 61317728 1040 chr2 238569087 ..«!■:&'-).» ELFlJSC-631) chr2 238569151 1532 chrl 1624499 1624749 ELFlJSC-631) chrl 1624403 1624654 1 chrl 1677772 1678022 ELFlJSC-631) chrl 1677682 1677934 2 chrl 22231427 22231656 ELFlJSC-631) chrl 22231610 22231744 109 chrl 228463705 228463955 ELFlJSC-631) chrl 228463761 22S4b V.'42 678 chr22 18008796 18009036 ELFlJSC-631) chr22 18008951 18009037 9321 chr22 18453143 18453393 ELFlJSC-631) chr22 18453056 18453157 'U?A chr22 19947229 19947479 ELFl J SC-631) chr22 19947316 19947412 9328 chr22 36038465 36038705 ELFlJSC-631) chr22 5 r. S5 ". ¾ 9370 chr20 39677622 39677898 ELFlJSC-631) chr20 39677561 39677643 9018 chr20 60876944 60877274 ELFlJSC-631) chr20 60877210 60877541 chrl9 1018403 1018653 ELFlJSC-631) chrl9 1018302 1018411 8676 chrl9 2631440 2631793 ELFlJSC-631) chrl9 2631555 2631659 8683 chrl9 44598348 44598664 ELFlJSC-631) chrl9 44598400 44598496 8828
Chrl9 54975259 54975587 ELFlJSC-631) chrl9 54975046 54975738 chrl8 12377569 12377809 ELFlJSC-631) chrl8 12377506 12377572 8450 hrlS 77468403 77468636 ELFlJSC-631) chrlS 77468462. 77468551 8649 chrl7 1617918 1618158 ELFlJSC-631) chrl7 1617853 1617940 8151 chrl7 17109688 17109964 ELFlJSC-631) chrl? 17109779 17109885 8194 chrl? 20058990 20059191 ELFl J SC-631) chrl7 20059180 20059290 10042 chrl7 29055672 29055820 ELFlJSC-631) chrl7 29055786 29055917 fs2 1 « chrl7 38083780 38084033 ELFlJSC-631) chrl7 38083901 38083979 8235 chrl7 76250565 76250805 ELFlJSC-631) chrl7 76250645 76250741 fi 57': chrl6 375052 375317 ELFlJSC-631) chrl6 375060 375159 7837 chrl6 14967851 14968091 ELFlJSC-631) chrl6 14967880 14968000 7906 chrl6 19566859 19567129 ELFlJSC-631) chrl6 19566661 19566971 7888 chrl6 66517663 66517977 ELFlJSC-631) chrl6 66.517581 66517675 8007 chrl6 89571867 89572176 ELFlJSC-631) chrl6 89571991 89572097 8110 chrl6 89768396 89768708 ELFlJSC-631) chrl6 89768460 89768554 8115 chrl6 90124207 90124447 ELFlJSC-631) chrl6 90124299 90124411 8124 chrlS 22462100 22 R-237 ELFlJSC-631) chrlS 22 i6 -!20 7597 chrl5 79888470 79888710 ELFl J SC-631) chrl5 79888531 79888665 7768 chrl4 .' W S237", . ΐ:;.'? 5 ELFlJSC-631) chrl4 . i:;.'52 3 2 W5.702t> 7.530 chrl4 106765206 106765482 ELFlJSC-631) chrl4 106765150 106765547 10014 chrlS 77565686 77565891 ELFlJSC-631) chrl3 77565612 77565745 7150 chrl2 127257035 127257285 ELFlJSC-631) chrl2 127257076 127257168 6895
Chrll 4414594 4414849 ELFlJSC-631) chrll 4414591 4414685 6098 chrll 66115496 66115772 ELFlJSC-631) chrll 66115701 66115785 6263 chrlO 27179930 27180206 ELFlJSC-631) chrlO 27180081 27180190 5700 chrX 48660040 48660224 ETS1 chrX 48660039 48660137 9583 chrX 1■■. if-()72SCj 153607470 ETS1 chrX 153607264 153607413 .¾4 chr9 138799612 138799852 ETS1 chr9 138799480 138799699 5521 chr9 J iSri-ViSS^ 138864096 ETS1 chr9 H88G ¾« i ¾ 138864042 5551 chr6 2765512 2765752 ETS1 chr6 2765487 2765632 3512 chr5 443568 443808 ETS1 C.h: 5 443593 444175 2903 chr5 176264690 176264930 ETS1 chr5 176264742 176264828 3470 chr4 3307461 Μ :·7 ETS1 chr4 .55 ".'377 3.! 7-iS3 2?. iV chrl 22231557 22231797 ETS1 chrl 22231610 22231744 109 chrl ?. 0?Α-.?.Η Ϊ 230263073 ETSl chrl 230262996 2 i ?.o ifi'Ji, 725 chr22 21405881 21406121 ETS1 chr22 21406112 21406221 9331 chr20 60877141 60877381 ETSl chf20 60877210 60877541 0G2 chrl9 791820 792060 ETSl chrl9 791702 791821 8673 chrlS 2631616 2631800 ETSl chrl9 2631555 2631659 Si-S i chrl9 44598325 44598565 ETSl chrl9 44598400 44598496 8828 chrl7 38083825 38083984 ETSl chrl7 38083901 38083979 z v, chrl7 76250547 76250820 ETSl chrl7 76250645 76250741 8375 chrlS 17195594 17195834 ETSl chrl6 17195660 17195747 7915 chrl6 19566789 19567032 ETSl chrl6 19566661 19566971 7888 chrl6 24267265 24267505 ETSl chrl6 24267330 24267430 7943 chrl6 57334334 57334577 ETSl chrl6 57334258 57334361 7985 chrl5 29150022. ETSl chrlS 29149824 29149903 7629 chrll 66115495 66115735 ETSl chrll 66115701 66115785 6263 chrS 137518404 137518648 GABP chrS 137518528 137518639 55 chr9 138863845 138864117 GABP chr9 138863933 138864042 5551 chr8 29940409 GABP chrS 29940806 4813 chr7 102004101 102004394 GABP chr7 102004049 102004154 4460 chr7 143077659 GAli C.h: 7 143077464 143077619 4599 chr7 156111202 156111472 GABP chr7 156111303 156111403 4649 chr6 (■i)4'j.l2 604812 CiAliP chr6 604752 604853 --:.}■-« chr6 2765385 2765731 GABP chr6 2765487 2765632 3512 chr6 3849416 GABS' chr6 3849487 3849596 3520 chr5 443543 443787 GABP chr5 443593 444175 2903 chr5 176264664 176264941 GASP Chr5 176264742 176264828 M7C chr4 3307456 3307726 GABP chr4 3307377 3307483 2230 c r3 195577790 195578046 GAS chr3 195577893 195577977 2184 chr2 1561812 1562082 GABP chr2 1561906 1562048 848 chrl 1624071 1624341 GABP chrl 1624211 1624313 17 chrl 22231554 22231820 GABP chrl 22231610 22231744 109 chrl 1> ¾0.'.V:8.M .V.C,:CWH GABP chrl .7 -.0,:ί..™«ίι 725 chrl 237392657 237392927 GABP chrl 237392789 237392909 756 chr22 18008806 18009076 GABP chr22 18008951 18009037 « i? J chr20 45501312 45501582 GABP chr20 45501398 45501505 9037 chr20 60849677 60849947 GABS' chr20 60849658 60849757 9096 chrig 2631578 2631848 GABP chrl9 2631555 2631659 8683 c.hrl9 i> v; i776 6374046 AS chrl9 6373587 6373798 Si. 2 chrl9 42807039 42807309 GABP chrl9 42807266 42807377 8824 chrl9 44598354 44598636 GABP chrl9 44598400 44598496 8828 chrlS 77468374 77468610 GABP chrl8 77468462 77468551 8649 chrl7 38083712 38084059 GABP chrl? 38083901 38083979 S235 chrl? 76250565 76250835 GABP chrl7 76250645 76250741 8375 chrl 6 ?.2(-?.-m GABP chrl6 Λ?ι> 7 ·!ί .' 62K 3 7858 chrl6 89571898 89572154 GABP chrl6 89571991 89572097 8110 chrlS 90124221 90124491 GABS' chrl6 90124299 90124411 8124 chrl5 29149735 29150005 GABP chrl5 29149824 29149903 7629
Chrl2 12595073 12595343 GABP ch l2 12595125 12595282 Wi, chrll 4414583 4414853 GABP chrll 4414591 4414685 6098 chrll 66115506 66115786 GAflS' chrll 66115701 66115785 6 3 chr7 102004088 102004358 IRF4JM-17) chr7 102004049 102004154 4460 chr7 112422752 112422890 IRF4JM-17) chr7 112422799 112422895 4508 chr6 1665549 1665819 IRF4JM-17) chr6 1665562 1665705 3505 chr& 2158142 2158412 !RF4.JM-17) chr6 2158404 2158500 3508 chr6 2940729 2940969 IRF4JM-17) chr6 2940840 2940933 3514 chr6 fi.l672.vP! 84672619 IRF4JM-17) chr6 84672604 84672689 S 7 .i chr6 115318973 115319243 IRF4JM-17) chr6 115319070 115319164 3892 chr6 .1503725.17 150322807 IRF4JM-17) chr6 150322548 150322626 3993 chr5 114404570 114404840 IRF4JM-17) chr5 114404634 114404729 3301 chr5 156891911 156892181 1RF4J -17) Chr5 156892015 156892109 3408 chr4 133045321 133045591 IRF4JM-17) chr4 133045440 133045540 2671 chr3 119419525 119419795 IRF4JM-17) c r3 119419620 119419714 1916 chr3 195577816 195578086 IRF4JM-17) chr3 195577893 195577977 2184 chr2 199236647 199236917 IRF4JM-17) chr2 199236595 199236679 1411 chr2 242036538 242036691 IRF4JM-17) chr2 242036568 242036665 1561 chr20 . V ?Aci?. i IRF4 JM-17) chr20 ,: .VM 7,-¾2 23624902 8961 chrl5 22462054 22462324 IRF4JM-17) chrl5 22462316 22462420 7597 chrlS 7¾¾i.}.? 79888696 IRF4JM-17) chrlS 79888531 /■/'.,» chrl4 106765110 106765380 IRF4JM-17) chrl4 106765150 106765547 10014 chrl3 77565691 /■.'■i 5 /f.7 !RF4JM-17) chrl3 ;-.'·;ι·5ί-.ΐ2 77565745 7150 chrl2 127256991 127257156 IRF4JM-17) chrl2 127257076 127257168 6895 chrll 66115481 66115751 1RF4JM-17) chrll 66115701 66115785 6263 chrll 115795940 115796055 IRF4JM-17) chrll 115795944 115796095 6427 chrlO 125312716 125312814 IRF4JM-17) chrlO 125312740 125312814 6003 chrX 87155356 87155612 MEF2A chrX 87155486 87155585 9675 chr6 7i-Vi S 2765754 MEF2A chr6 2765487 2765632 3512 chr6 2940743 2940999 MEF2A chr6 2940840 2940933 3514 chr6 3849391 3849647 EF2A chr6 3849487 3520 chr6 31804260 31804516 MEF2A chr6 31804365 31804470 3610 chr6 52161548 52161804 MEF2A chr6 52161778 52161905 3676 chr5 1641737 1641993 MEF2A chr5 1641811 1641910 2937 chr5 54868581 54868670 MEF2A chr5 54868565 54868672 3128 chr3 119419553 119419809 MEF2A chr3 119419620 119419714 1916 chr2 G?..':f. . ?« 86226494 MEF2A Chr2 86226264 622(".¾i' 1110 chr20 1781574 1781830 MEF2A chr20 1781803 1781887 8905 chrl? 2 0¾02 .'Πθνΐ ', MEF2A chrl7 20059180 2W!.')2'iO 10042 chrl7 38083750 38084006 MEF2A chrl7 38083901 38083979 8235 chrlS 83480176 MEF2A chrlS 83480014 83480112 7781 chrl4 106765178 106765434 MEF2A chrl4 106765150 106765547 10014 chrl3 71865483 71865594 MEF2A chrl3 71865441 7137 chrl2 127256999 127257255 EF2A chrl2 127257076 127257168 6895 chrll 115795893 115796149 EF2A chrll 115795944 115796095 6427 chrlO 62110982 62111238 MEF2A chrlO 62110925 62111027 5812 chrlO 125312681 125312937 MEF2A chrlO 125312740 125312814 6003 chr6 2940742 2940986 MEF2CJSC-13268) chr6 2940840 2940933 3514 chr2 199236647 199236891 MEF2CJSC-13268) chr2 199236595 199236679 1411 chr2 242262682 242262926 MEF2CJSC-13268) chr2 242262774 242262909 1565 chrl9 2631502 2631746 MEF2CJSC-13268) chrlS 2631555 2631659 8683 chrl9 56368673 56368917 MEF2CJSC-13268) chrl9 56368568 56368752 8884 chrl4 106765263 106765507 MEF2CJSC-13268) chrl4 106765150 106765547 10014 chrl3 71865391 71865635 MEF2CJSC-13268) chrl3 71865441 71865535 7137 chrl l 115795982 115796226 MEF2CJSC-13268) chrll 115795944 115796095 t> 127 chr9 138863778 138864185 NRSF chr9 138863933 138864042 5551 chrS 37646011 37646241 NRSF chrS 37646017 576 JH 2K 4834 chr8 103187993 103188247 NRSF chr8 103187967 103188070 5039 chr8 120994818 120995041 NRSF chr8 120994705 120994832 5100 chr8 133376683 133376967 NRSF chr8 133376902 133377014 5136 chrS 144024666 144024870 NRSF chrS 144024811 14402.4891 5196 chr7 5518323 5518553 NRSF chr7 5518333 5518482 4121 chr6 89435102 89435298 NRSF chr6 89435264 89435378 3795 chr6 130113396 130113583 NRSF chr6 130113333 130113455 3939 chr& 166913856 166914086 NRSF chr6 166913967 166914065 4035 chrS 1248066 1248270 NRSF chrS 1248093 1248233 2927 chr5 176264563 176265061 NRSF .h: 5 1 7626- 17 176264828 3470 chr4 3637112 3637331 NRSF chr4 3637316 3637433 2234 chr4 84205464 84205748 NRSF chr4 84205458 84205558 2509 chr2 1286472 1286656 NRSF chr2 1286432 1286554 843 chrl 22231545 2.7231 NRSF chrl 22231610 22231744 109 chrl 32913578 32913774 NRSF chrl 32913603 32913725 142 chrl 201566698 201566954 NRSF chrl 201566696 201566793 chrl 230262940 230263124 NRSF chrl 230262996 230263096 725 chrl9 30581528 30581748 NRSF chrl9 30581505 30581591 chrl9 58812065 58812353 NRSF chrl9 58812005 58812135 8899 chrl7 42237417 42237601 NRSF chrl7 42237391 42237467 S.'.Vi chrl7 76250512 76250696 NRSF chrl7 76250645 76250741 8375 chrlo 24267143 24267566 NRSF chrl6 2.}2 73 i 24267430 7943 chrl6 66517644 66517928 NRSF chrl6 66517581 66517675 8007 chrl6 85285946 NRSF chrl6 ;;5 85¾ 'i2S 8075 chrl3 99612749 99612933 NRSF chrl3 99612767 99612867 7225 chrl2 114277705 114277935 NRSF chrl2 114277822 114277906 6849 chrll 2380955 2381139 NRSF chrll 2381011 2381124 6093 chrll .73070V; 67307229 NRSF chrll 67307086 67307190 6270 chrlO 42970927 42971157 NRSF chrlO 42971024 42971122 5759 chrlO 92923726 92924010 NRSF chrlO 92924065 5910 chr9 128463666 128463890 POU2F2 chr9 128463780 128463881 5510 chr6 2<i Jf. L ¾ (Λ >?.· 2 chr6 3514 chr5 1641729 1641976 POU2F2 chr5 1641811 1641910 2937 chr4 153434182 153434475 i>OU2t chr4 153434331 153434407 2721 chr4 154409254 154409478 POU2F2 chr4 154408899 154409319 2723 chr3 .195577SOr> 195578054 POU2F2 chr3 195577893 195577977 2184 chr2 85151838 85152103 POU2F2 chr2 85152041 85152146 1107 chrl 6093194 6093434 POU2F2 Chrl 6093478 55 chr20 23624756 23624996 POU2F2 chr20 23624782 23624902 8961 c.hrl9 38389412 38389652. POU2.F2 chrl9 38389624 38389695 8803 chrl9 54975009 54975249 POU2F2 chrl9 54975046 54975738 8869 chrl9 54975328 5 1975 6 POM J chrl9 54975046 54975738 8869 chrl7 20059126 20059263 POU2F2 chrl7 20059180 20059290 10042 chrl7 38083991 POU2F2 chrl7 38083901 38083979 K2V, chrl6 84547982 84548206 POU2F2 chrl6 84547966 84548045 8071
Chrl6 89571987 8Τ.7Λ'27 POU2F2 chrl6 89571991 89572097 8110 chrl5 22462149 22462429 POU2F2 chrl5 22462316 22462420 7597 chrl4 106765122 106765346 POU2F2 chrl4 106765150 106765547 10014 chrl4 107251653 107251911 POU2F2 chrl4 107251729 107251888 7587 chrl3 100028472 100028696 POU2F2 chrl3 100028639 100028716 7227 chrlS 115033863 115034103 POU2F2 chrl3 115033968 115034047 7312 chrl l 66115485 66115768 OD.?; chrll 66115701 66115785 oh, < chrY 8898018 8898302 p300 chrY 8898125 8898233 9917 chrX 49558301 49558585 p 500 chrX 49558546 49558790 < ϋΟ chrX 122914367 122914651 p300 chrX 122914371 122914480 9779 chr9 76908453 76908693 p300 chr9 76908522 76908603 .r:Vi chr9 84228031 84228301 p300 chr9 84227929 84228048 5378 c r9 124375761 124376031 i) ; o chr9 124376013 124376103 5493 chr8 39066571 39066657 p300 chr8 39066484 39066639 4839 chr8 142416284 142416508 p300 chr8 142416496 142416596 5177 chr7 921141 921425 p300 chr7 921236 921318 4081 chr7 12700108 12700378 p30O chr7 12700231 12700362 4143 chr7 16964704 16964988 p300 chr7 16964933 16965023 4159 chr7 102003998 102004268 p300 chr7 102004049 102004154 4460 chr6 2765531 2765771 p300 chr6 2765487 2765632 3512 chr6 2940715 2940939 p 500 chr6 2940840 2iJ40<' 53 3514 chr6 25863640 25863924 p300 chr6 25863771 25863871 3581 chr6 111598018 111598302 p300 Chr6 111598099 111598226 *S73 chr5 33049979 33050249 p3Q0 chr5 33049885 33050059 3061 chr5 134311092 134311376 i) ; o chr5 134311064 134311151 chr5 170060464 170060734 p300 chr5 170060476 170060580 3447 chr5 178691876 178692160 p300 chr5 178691893 178691989 Ϊ47¾ chr4 20339002 20339272 p300 chr4 20339005 20339116 2318 chr4 70057616 70057900 p30O chr4 70057691 70057764 ,:4.->0 chr4 152212650 152212920 p300 chr4 152212781 152212901 2721 chr4 154409260 154409484 p 500 chr4 154408899 154409319 7? ¾ chr4 170091817 170092087 p300 chr4 170091880 170091960 2782 chr3 106147360 106147886 p300 chr3 106147511 106147661 1884 chr3 119419523 119419747 p300 chr3 119419620 119419714 1916 chr3 192614817 192615101 p300 l iir i 192614968 192615068 2162 chr3 195577807 195578091 p300 chr3 195577893 195577977 2184 chr2 1286442 1286712 p300 c r2 1286432 1286554 S4 5 chr2 56851320 56851590 p300 chr2 56851482 56851575 1031 chr2 61317618 61317768 p300 chr2 61317637 61317728 1040 chr2 114743652 114743936 p300 chr2 114743848 114743923 1165 chr2 183150035 183150305 p300 chr2 183150154 183150259 1354 chr2 233428297 233428581 p300 chr2 233428386 233428474 1518 chr2 242036503 2420 50727 500 chr2 242036568 242036665 1561 chrl 1624138 1624407 p300 chrl 1624403 1624654 1 chrl 1624138 1624407 p300 chrl 1624211 1624313 17 chrl 1624474 1624719 p300 chrl 1624403 1624654 1 chrl 1677752 1678002 i) ; o chrl 1677682 1677934 i chrl 32913538 32913778 p300 chrl 32913603 32913725 142 chrl S'123-ISM 84235134 p300 chrl 84234920 84234990 .516 chrl 100224562 100224846 p300 chrl 100224633 100224721 373 chrl 2 r i-> - , 221786019 i) ; o chrl 221785629 22 J 7H¾7 5f, 690 chrl 246868703 246868987 p300 chrl 246868695 246868804 809 chr22 19947252 19947536 p300 chr22 19947316 19947412 chr22 36038479 36038763 p300 chr22 36038553 36038634 9370
Chr22 39906773 39907013 p300 chr22 39906714 39906863 9380 chr21 18873773 18874063 p300 chr21 18873881 18873961 9161 chr21 Λ7<1ί,Κ')% p300 chr21 -169 79 22469173 9175 chrl8 26065282 26065421 p300 chrl8 26065344 26065419 8487 chrl7 1617927 1618217 ;■> 500 chrl7 1617853 1617940 8151 chrl7 38083747 38084031 p300 chrl7 38083901 38083979 8235
Chrl6 4511422 4511565 p300 chrl6 4511459 4511603 chrl6 11904043 11904267 p3Q0 chrl6 11904262 11904361 7895 chrl6 87739677 87739826 i) ; o chrl6 87739575 87739930 8053 chrl6 89571935 89572096 p300 chrl6 89571991 89572097 8110 chrlS ,:2-! Γ,? 2 R-2V; p300 chrlS 2.Mfi2-'.20 7597 chrl3 80798653 80798923 p300 chrl3 80798870 80798987 7163 chrl3 8.M SS3S-i 8.'- .8f.^7 p300 chrl3 82448673 7169 chrl3 106936808 106937092 p300 chrl3 106936719 106936831 7248 chrl 3 107928454 107928724 p300 chrl3 107928617 107928715 725 J chrl3 110979231 110979501 p300 chrl3 110979443 110979528 7273 chrl2 104972287 104972557 p300 chrl2 104972523 104972607 6816 chrl2 116784615 116784885 p300 chrl2 116784859 116784973 6856
Chrl2 1.7 ?:">70 ϊ 127257228 p300 chrl2 127257076 127257168 6895 chrll 952524 952808 p3Q0 chrll 952644 952729 6083 chrll 66115489 66115713 p300 chrll 66115701 66115785 6263 chrll 115795823 115796047 p300 chrll 115795944 115796095 6427 chrlO 17030379 17030649 p300 chrlO 17030543 17030643 5½·ι chrlO 24830871 24831155 p300 chrlO 24830811 24830903 5689 chrlQ 101913110 101913235 p300 chrlO 101913010 101913151 5934 chrlO 119120889 119120979 p300 chrlO 119120930 119121023 5983 chrlO 125312694 125312918 ;■> 500 chrlO 125312740 125312814 6003 chr9 6676681 6676905 PAX5-C20 chr9 6676878 6677020 5229 chr7 1126282 1126466 PAX5-C20 chr7 1126285 1126387 4086 chr7 101691877 101692101 PAX5-C20 chr7 101692089 101692197 4458 chr7 155989282 155989506 PAX5-C20 chr7 155989362 155989505 4647 chr6 2765524 2765796 PAX5-C20 chr6 2765487 2765632 3512 chr6 2940779 2941003 PAX5-C20 chr6 2940840 24-KW3 ί chr6 126782339 126782563 PAX5-C20 chr6 126782537 126782628 3928 chr5 176264703 176264927 PAX5-C20 chr5 \ 7i:,:G-V/A?. 176264828 3470 chr4 154409250 154409474 PAX5-C20 chr4 154408899 154409319 2723 chr3 23^0 3 2.¾W? .i, ΡΛΧΰ-tVfl chr3 .5W70 23H0279t> 1644 chr3 38106587 38106811 PAX5-C20 chr3 38106805 38106881 1694 chr3 195577828 195578052 PAX5-C20 chr3 vvirmm 195577977 2184 chr2 199236655 199236879 PAX5-C20 chr2 199236595 199236679 1411 chr2 242036590 242036814 PAX5-C20 Chr2 242036568 242036665 1561 chr2 242262682 242262906 PAX5-C20 chr2 242262774 242262909 1565 chrl 1624541 1624719 PAX5-C20 chrl 1624403 1624654 1 chrl 1677775 1677999 PAX5-C20 chrl 1677682 1677934 2 chrlS 6373584 PAX5-C20 chrl9 6373061 6373448 Si-61 chrl9 44598350 44598574 PAX5-C20 chrl9 44598400 44598496 8828 chr20 61419998 t,J-V:02:'2 PAX5-C20 chr20 61420100 61420192 9106 chrl7 17109575 17110017 PAX5-C20 chrl7 17109779 17109885 8194 chrl7 20059021 20059250 PAX5-C20 chrl7 20059180 20059290 10042 chrl7 38083794 38083978 PAX5-C20 chrl7 38083901 38083979 8235 chrl7 76250611 76250795 PAX5-C20 chrl7 76250645 76250741 ;;y/-> chrl6 19566525 19566715 PAX5-C20 chrl6 19566661 19566971 7888 chrl6 21552489 21552713 PAX5-C20 chrl6 21552521 i -.52i>;-;9 7935 chrl5 22462157 22462381 PAX5-C20 chrl5 22462316 22462420 7597 c.hrl4 103374380 103374604 PAX5-C20 chrl4 103374599 103374686 7568 chrl4 105689672 105689896 PAX5-C20 chrl4 105689753 105689856 7576 chrl4 105765229 106765507 PAX5-C20 chrl4 106765150 106765547 10014 chrl3 100028399 100028648 PAX5-C20 chrl3 100028639 100028716 7227 chrll 45952150 45952334 PAX5-C20 chrll 45952190 45952271 6216 chrll 66115490 66115714 PAX5-C20 chrll 66115701 66115785 6263 chrl l 115795807 115796031 ΡΛΧϋ-CVO chrl l 115795944 115796095 t> 127 chrlO 125312742 125312966 PAX5-C20 chrlO 125312740 125312814 6003 chrS 142416296 142416556 PAX5-N19 chrS 142416496 142416596 5177 chr7 1126254 1126514 PAX5-N19 chr7 1126285 1126387 4086 chr7 155989257 155989517 PAX5-N19 Chr7 155989362 155989505 4647 chr6 2940739 2940977 PAX5-N19 chr6 2940840 2940933 3514 chr4 154409170 154409430 PAX5-N19 chr4 154408899 154409319 .' ^ ¾ chr3 23802612 23802872 PAX5-N19 chr3 23802706 23802796 1644 chr3 133943308 133943568 PAX5-N19 chr3 133943485 133943564 1958 chr2 199236657 199236917 PAX5-N19 chr2 199236595 199236679 1411 chr2 .Μ 2Π3ί>ο¾Ν PAX5-N19 chr2 ?.\ ?.l)ii>V 242036665 1561 chrl 1624480 1624740 PAX5-N19 chrl 1624403 1624654 1 chrl9 44598320 44598580 PAX5-N19 chrl9 44598400 l.i:; M9t> 8828 chrl7 17109571 17110025 PAX5-N19 chrl7 17109779 17109885 8194 chrl7 20058950 20059210 PAX5-N19 chrl7 20059180 20059290 10042 chrl6 21552496 21552756 PAX5-N19 chrl6 21552521 21552689 7935
Chrl4 105689652 105689912 PAX5-N19 chrl4 105689753 105689856 v/!, chrl3 77565564 77565824 PAX5-N19 chrl3 77565612 77565745 7150 chrl3 100028409 100028653 PAX5-N19 chrl3 100028639 100028716 Ί2 Π chrl2 127256977 127257237 PAX5-N19 chrl2 127257076 127257168 6895 chrll 115795813 115796073 PAX5-N19 chrll 1157959-54 115796095 6427 chrlO 62111022 62111282 PAX5-N19 chrlO 62110925 62111027 5812 chrlQ \ ϊ 2 hi ? 125312887 PAX5-N19 chrlO 125312740 125312814 6003 chr6 52161601 52161783 Pbx3 chr6 52161778 52161905 3676 chr2 24 '7Κ254 242° 7K Pbx3 chr2 242° 7K YJ 242978687 10065 chrl 6093204 6093400 Pbx3 chrl 6093368 6093478 55 chrl 15761860 15762056 Pbx3 chrl 15761835 15761947 •1 chrig 54974936 54975098 Pbx3 chrl9 54975046 54975738 8869 chrl? 44087496 44087692 !ix.- chrl7 44087551 44087644 S2-.7 chrl6 88959650 88959846 Pbx3 chrl6 88959572 88959883 8054 chrll 115795847 115795986 Pbx3 chrll 115795944 115796095 6427 chrll 128823221 128823417 Pbx3 chrll 128823128 128823288 6457 chrlO 125312590 125312786 Pbx3 chrlO 125312740 125312814 6003 chrX 1540854 1541110 POI2-4H8 chrX 1540834 1540943 9464 chrX 48659964 48660160 Pol2-4H8 chrX 48660039 48660137 9583 chrX 91359926 91360122 Pol2-4H8 chrX 91359915 91360001 9689 chrX 113284101 113284153 Po!2-4H8 chrX 113284101 113284193 <-· / ¥ chr9 21545326 21545590 Pol2-4H8 chr9 21545333 21545443 5273 chr9 26975808 26976035 Poi2-4H8 Chr9 26975670 b')75S::0 ■¾.?««) chr9 38620417 38620630 Po'l2-4H8 chr9 38620511 38620596 5325 chr9 99983685 99983918 Poi2-4H8 chr9 99983766 99983852 5428 chr9 128463730 128463861 Pol2-4H8 chr9 128463780 128463881 5510 chrS 138799580 138799824 Pol2-4H8 chi-9 138799480 138799699 5521 chr9 138863916 138864042 Pol2-4H8 chr9 138863933 138864042 5551 chr7 2t,-! >'- J 2697175 POI2-4H8 chr7 2696907 2697145 4104 chr7 101080465 101080729 Pol2-4H8 chr7 101080639 101080717 4454 chr7 143077368 143077644 Po!2-4H8 chr7 143077464 143077619 4599 chr6 604550 604794 Pol2-4H8 chr6 604752 604853 3498 chr6 2765578 2765895 Pol2-4H8 chr6 2765487 2 /1.563? 3512 chr6 2940539 2940954 Pol2-4H8 chr6 2940840 2940933 3514 chr6 3849566 3849850 POI2-4H8 chr6 3849487 3849596 3520 chr6 31132741 31133245 Pol2-4H8 chr6 31132721 31132835 3606 c r6 113954193 113954477 Pof2-4H8 chr6 113954396 113954498 3884 chr6 159192566 159192830 Pol2-4H8 chr6 159192600 159192710 4013 chrS 133485013 Pol2-4H8 chrS ] 3 ¾ J 34724 n sii ti. 3351 chr5 134717912 134718156 Pol2-4H8 chr5 134717838 134717942 3356 chr5 176264678 \ 7i:,:G-\"A?. Po!2-4H8 chr5 \ 7i:,:G-V/A?. 176264828 3470 chr4 93175457 93176613 POI2-4H8 chr4 93176111 93176193 2546 chr4 93364923 Pol2-4H8 chr4 93364740 93364886 25-17 chr3 15202193 15202389 Pol2-4H8 chr3 15202160 15202326 1612 chr3 28092416 28092680 Po!2-4H8 chr3 28092430 28092524 16¾2 chr3 133144147 133144672 Pol2-4H8 chr3 133144614 133144876 1943 chr3 134090905 134091026 Poi2-4H8 l iir i 134090906 134090983 1960 chr3 195577820 195578092 Pol2-4H8 chr3 195577893 195577977 2184 c r3 195872768 195873012 Pof2-4H8 chr3 195872965 195873074 2190 chr3 196370638 196370757 Pol2-4H8 chr3 196370708 196370788 2196 chr2 176885206 176885450 Pol2-4H8 chr2 176885294 176885398 1335 chr2 242036479 242036908 Pol2-4H8 chr2 242036568 242036665 1561 chrl 1677558 1678022 Po!2-4H8 chrl 1677682 1677934 2 chrl 1677558 1678022 Pol2-4H8 chrl 1677486 1677588 18 chrl 3418509 3418637 Pol2-4H8 ch l 3418555 3418652 chrl 6093200 6093495 Pol2-4H8 chrl 6093368 6093478 55 chrl 15761782 15762071 POI2-4H8 chrl 15761835 15761947 ■ i chrl 22231594 22231779 Pol2-4H8 chrl 22231610 22231744 109 chrl 24743440 24743684 Poi2-4H8 Chrl 2 175 sGtV'-i .M 7-i.i ibf. 119 chrl 68154960 68155241 Pol2-4H8 chrl 68155234 68155328 254 chrl 84493148 84493315 Pof2-4H8 chrl 84493164 318 chrl 154580146 154580969 Pol2-4H8 chrl 154580161 154580286 464 chrl 228463561 ?Κ 1ί-.ίΚ.Γ.' Pol2-4H8 chrl 228463761 72.V. - J ! ? &7S chrl 230262963 230263030 POI2-4H8 chrl 230262996 230263096 725 chr22 39906760 39907054 POI2-4H8 chr22 39906714
chr21 44515296 44515552 Pol2-4H8 chr21 44515439 44515519 9259 chr20 60849688 60849932 Po!2-4H8 chr20 60849658 60849757 9096 chr20 60876941 60877268 Pol2-4H8 chr20 60877210 60877541 9062 chrl9 883758 884022 Pol2-4H8 chrl9 883967 8674 chrig 4852139 4852403 Pol2-4H8 chrl9 4852359 4852498 8700 chrl9 40653654 40653897 Poi2-4H8 chrl9 40653886 40653961 8817 chrl9 44598388 44598777 Pol2-4H8 chrl9 44598400 44598496 8828 chrl9 55901218 55901521 Pof2-4H8 chrlS 55901191 55901293 8879 chrl7 17109479 17109808 Pol2-4H8 chrl7 17109779 17109885 8194 chrl7 20058903 20059201 Po!2-4H8 chrl7 20059180 20059290 10042 chrl7 20059203 20059527 POI2-4H8 chrl7 20059180 20059290 10042 ch l 7 38083648 5808 i« > 3 Pol2-4H8 chrl7 38083901 8235 chrl7 42237387 42237631 Pol2-4H8 chrl7 42237391 42237467 8253 chrl7 Vi-250Vi } 76250648 Po!2-4H8 chrl7 76250645 76250741 K 57': chrl6 374880 375136 Pol2-4H8 chrl6 375060 375159 7837
Chrl6 2262463 Poi2-4H8 chrl6 :«7 $8 ,\V>.78 3 7858 chrl6 4511353 4511549 Pol2-4H8 chrl6 4511459 4511603 7866 c.hrl6 19566907 19567192 Poi2-4H8 chrl6 19566661 19566971 7888 chrl6 83847954 83848230 Pol2-4H8 chrl6 83848024 83848139 8069 chrl6 84547885 84548224 Pol2-4H8 chrie 84547966 84548045 SO 71 chrl6 87329043 87329307 Pol2-4H8 chrl6 87329060 87329148 8085 chrie 89571889 a--,:, / . POI2-4H8 chrie 89571991 8110 chrl6 89768535 89768799 Pol2-4H8 chrl6 89768460 89768554 8115 chrlo 89831169 89831445 Po!2-4H8 chrl6 89831177 89831300 8117 chrl5 29149733 29149977 Pol2-4H8 chrl5 29149824 29149903 7629 chrl5 45709888 45710132 Pol2-4H8 chrl5 45709938 45710050 7679 chrl4 38660602 38660798 Pol2-4H8 chrl4 38660753 38660840 7373 chrl4 69282740 Pol2-4H8 chrl4 6-17H 279 692S2.592 7466 chrl4 103374450 103374737 Pol2-4H8 chrl4 103374599 103374686 7568 c.hrl3 77565876 Poi2-4H8 chrl3 77565612. 77565745 7150 chrl3 100028457 100028741 Pol2-4H8 chrl3 100028639 100028716 7227 chrl3 100148867 100149131 Pol2-4H8 chrl3 100148988 100149109 722? chrl3 111954679 111954935 Pol2-4H8 chrl3 111954607 111954699 7280 chrl3 113808647 113808911 Po!2-4H8 chrl3 113808710 113808818 7298 chrl2 8942348 8942448 POI2-4H8 chrl2 8942407 8942527 6510 chrl2 12595090 1 v!53 i 3 Pol2-4H8 chrl2 12595125 i ?.rm ><>.2 t>526 chrl2 27430210 27430486 Pol2-4H8 chrl2 27430288 27430359 6584 chrl2 59721682 59721878 Po!2-4H8 chrl2 59721725 59721823 6687 chrl2 69237430 69237635 Pol2-4H8 chrl2 69237539 69237679 6713
Chrl2 116872595 116872859 Poi2-4H8 chrl2 116872828 116872899 6858 chrl2 123319961 123320164 Pol2-4H8 chrl2 123319859 123319962 6874 c.hrl2 12.3449388 12.3449632 Pof2-4H8 chrl2 12.3449512 123449601 6875 chrl2 131713441 131713685 Pol2-4H8 chrl2 131713564 131713705 6918 chrl2 132863490 i j2Si-.i;:> J Pol2-4H8 chrl2 rj2Si-.il.-Ki) 132863803 6937 chrl2 133234805 133235081 Pol2-4H8 chrl2 133234966 133235064 6944 chrii 60702674 60703567 Po!2-4H8 chrll 60702562 60702681 6248 chrlO 1036805 1037081 Pol2-4H8 chrlO 1036963 1037077 5596 chrlQ 1043132 1043416 Pol2-4H8 chrlO 1043317 1043389 : j7 chrlO 42970915 42971127 Pol2-4H8 chrlO 42971024 42971122 5759 chrlO 74086460 74086712 POI2-4H8 chrlO 74086665 74086769 5851 chrlO 99478556 99478820 Pol2-4H8 chrlO 99478551 99478665 5928
ChrlO 105881245 105881679 Poi2-4H8 chrlO 105881235 105881318 5948 chr9 128463666 128463890 POU2F2 chr9 128463780 128463881 5510 chr6 29407! ? 2940999 POU2F2 c r6 2940840 w.m ¾ chr5 1641729 1641976 POU2F2 chr5 1641811 1641910 2937 chr4 153434182 153434475 POU2F2 chr4 153434331 153434407 2721 chr4 154409254 154409478 POU2F2 chr4 154408899 154409319 2723 chr3 195577805 195578054 OD.?; chr3 195577893 195577977 2184 chr2 85151838 85152103 POU2F2 chr2 85152041 85152146 1107 chrl 6093194 GO0 iJ ί 5 i>OU2t chrl 6093478 v; chr20 23624756 23624996 POU2F2 chr20 23624782 23624902 8961 chrl9 ¾f.«« H .ma ,! POU2F2 chrl9 .<S38 .i 3¾¾.¾S¾f> :-; 8803 chrig 54975009 54975249 POU2F2 chrl9 54975046 54975738 8869 c.hrl9 54975568 POU2.F2 chrl9 54975046 54975738 chrl7 20059126 20059263 POU2F2 chrl7 20059180 20059290 10042 chrl7 38083751 38083991 POU2F2 chrl7 38083901 38083979 chrl6 84547982 84548206 POU2F2 chrl6 84547966 84548045 8071 chrie 89571987 a--,:,/??. ' 7 POU2F2 chrl6 89571991 8110
Chris 22462149 22462429 POU2F2 chrl5 22462316 22462420 7597 chrl4 106765122 106765346 pou.?; chrl4 106765150 106765547 10014 chrl4 107251653 107251911 POU2F2 chrl4 107251729 107251888 7587 chrl3 100028472 100028696 i>OU2t chrl3 100028639 100028716 7227 chrl3 115033863 115034103 POU2F2 chrl3 115033968 115034047 7312
Chrll 66115485 66115768 POU2F2 chrll 66115701 66115785 « 3 chrY 16452812 16453042 U.l chrY 16452759 16452854 9942 chrY 22960508 22960567 U.l chrY 22960429 22960517 chrX 105726834 105727064 U.l chrX 105727001 105727109 9723 chrX 149012074 149012274 PU.l chrX 149012231 149012313 9853 chr9 12307893 12308151 PU.l chr9 12307862 12307952 5251 chr9 i 3221. iS I 33221599 U.l chr9 3327 1392 33221473 5311 chr9 115182847 115183047 PU.l chr9 115182962 115183060 5468 chrS 19372912 U.l chrS 19372672 19372761 4783 chr7 1983548 1983779 PU.l chr7 1983510 1983616 4096 chr7 50728055 PU.l chr7 50727876 50727983 4287 chr7 92794786 92795016 PU.l chr7 92794879 92794990 4414 chr7 115486898 115487114 PU.l chr7 115486795 115486908 4518 chr7 122830708 122830940 PU. l chr7 122830689 122830786 4535 c r7 155989467 155989661 U. l chr7 155989362 155989505 4647 chr6 1665515 1665837 PU. l chr6 1665562 1665705 3505 chr6 2158171 2158412 PU.l c r6 2158404 2158500 550? chr6 2940741 2940992 PU.l chr6 2940840 2940933 3514 chr& 3849629 U.l chr6 3849487 iv1Wi> 3520 chr6 36596732 36596950 PU.l chr6 36596926 36597035 3629 chr6 71807077 71807293 PU.l chr6 71807156 71807247 3738 chr6 115318894 115319130 PU.l chr6 115319070 115319164 3892 chr5 1564262 1564462 U.l chr5 1564323 1564422 2934 chr5 2047734 2047964 PU.l chr5 2047881 2047979 2942 chr5 38194378 38194594 U. l chr5 38194337 38194439 3085 chr5 81445033 81445263 PU. l chr5 81445031 81445115 3194 c r5 '< .;■"* iS2¾ 93938501 PU. l chr5 93938356 . L chr5 134717862 134718062 PU.l chr5 134717838 134717942 3356 chr4 165867435 165867635 PU.l chr4 lfc-.Si-7-i2-1 165867511 2767 chr3 75466695 75466911 PU.l chr3 75466900 75466972 1791 chr3 183273833 183274063 U.l chr3 183273814 183273928 J 2 chr2 735963 736193 PU.l chr2 736006 736076 838 chr2 ?< ?.n -,..>i>,?« PU.l chr2 .?.·! >.').;.,%?: 242036665 1561 chrl 1792173 1792404 PU.l chrl 1792086 1792185 19 chrl 12244268 12244651 PU.l chrl 12244495 12244576 6 chrl 15689332 15689574 PU. l chrl 15689339 15689467 91 chrl 22231475 PU. l Chrl 22231610 22231744 109 chr22 19947207 19947407 PU. l chr22 19947316 19947412 9328 chr22 50732494 50732724 U.l chr22 50732704 5448 chr21 43786095 43786316 PU.l chr21 43786036 43786108 9257 chrlS 2631445 2631813 PU.l chrl9 2631555 2631659 Si-S i chrl9 44598452 44598600 PU.l chrl9 44598400 44598496 8828 chr20 PU.l chr20 ; :■,·., j >>- 3 ΛΝ0 8961 chr20 39677573 39677797 PU.l chr20 39677561 39677643 9018 chrl8 11996024 11996268 PU.l chrl8 11995947 11996057 8449 chrl8 77580109 77580412 PU.l chrl8 77580201 77580310 8653 chrl7 29055615 29055864 PU.l chrl7 29055786 29055917 8219 chrl7 45314678 45314878 PU. l chrl7 45314612 45314721 8265 chrl7 80302631 80302831 PU. l chrl7 80302576 80302655 8405 chrl6 11904075 11904305 PU.l chrl6 11904262 11904361 7895 chrl6 89571876 89572106 U.l chrl6 89571991 89572097 8110 chrl5 83479768 83480187 PU.l chrl5 83480014 83480112 7781 chrl4 <vj,-¾200.™ t,-!3702:><> U.l chrl4 69819962 69820040 7469 chrl 71698513 71698713 PU.l chrl4 71698706 71698909 7476 chrl 3 77565676 7 ? ½5SM > PU.l chrl3 77565612 77%¾ 7 . 7150 chrl3 100028446 100028676 PU.l chrl3 100028639 100028716 7227 chrlO 27179914 27180144 PU.l chrlO 27180081 27180190 5700 chrlO 29852677 29852860 PU.l chrlO 29852786 29852904 5709
ChrlO 62110980 62111210 PU. l chrlO 62110925 62111027 5812 chrlO 125312727 125312980 PU. l chrlO 125312740 125312814 6003 chrX 122914318 122914578 RXRA chrX 122914371 122914480 >7 ?·? chr9 36008877 36009073 RXRA chr9 36008952 36009049 5319 chi-8 .UKK 2232079 iiAiiA chr8 2231969 4718 chr7 1037048 1037244 RXRA chr7 1037114 1037199 4083 chr& 2765544 2765804 RXRA chr6 2765487 2765632 3512 chr6 3849480 3849650 RXRA chr6 3849487 3849596 3520 chr6 11122616 11122876 RXRA chr6 11122694 11122788 3547 chr6 25863633 25863893 RXRA chr6 25863771 25863871 3581 chr6 33558518 .i .s/ 7.--; RXRA chr6 777 3615 chr5 1641795 1641965 RXRA chr5 1641811 1641910 2937 chr5 178691883 178692143 RXRA chr5 178691893 178691989 3475 chr3 195577838 195578037 RXRA chr3 195577893 195577977 2184 chr2 3048773 3049033 R RA chr?. 3048695 3048797 %6 chrl 8320858 8321118 RXRA chrl 8320950 8321039 67 chr22 19947185 19947445 RXRA chr22 19947316 19947412 chr21 18873883 18873961 RXRA chr21 18873881 18873961 9161 chr20 60876991 RXRA chr20 60877210 60877541 9062 chrl7 1617898 1618158 RXRA chrl7 1617853 1617940 8151 chrl 7 38083861 38084031 RXRA chrl7 38083901 8235 chrl6 375068 375238 RXRA chrl6 375060 375159 7837 chrlo 14967836 14968096 RXRA chrl6 14967880 14968000 7906 chrl6 89571821 89572081 RXRA chrl6 89571991 89572097 8110
Chrl4 106765404 106765455 RXRA chrl4 106765150 106765547 10014 chrl2 132366383 132366643 RXRA chrl2 132366615 132366722 6932 chrlO 74848137 74848397 RXRA chrlO 74848135 7484822.2 58.53 chrX 48659915 48660165 Sin3Ak-20 chrX 48660039 48660137 9583 chi-9 138799793 Sin3Ak~20 chi-9 138799480 138799699 5521 chr9 138863878 138864098 Sin3Ak-20 chr9 138863933 138864042 5551 chr& 2765556 2765806 Sin3Ak-20 chr6 2765487 2765632 3512 chr5 443598 443768 Sin3Ak-20 chr5 443593 444175 2903 chr5 176264690 176264936 Sin3Ak-20 C.h: 5 1 7626- 1712 176264828 3470 chrl 32479720 32479890 Sin3Ak-20 chrl 32479789 32479871 141 chr22 39906797 39906997 Sin3Ak-20 chr22 39906714 39906863 9380 chrig 44598235 44598455 Sin3Ak-20 chrl9 44598400 44598496 8828
Chrl9 54974830 54975050 Sin3Ak-20 chrl9 54975046 54975738 8 i,'i chr20 60876939 60877344 Sin3Ak-20 chr20 60877210 60877541 9062 chr20 60877538 60877923 Sin3Ak-20 chr20 60877210 60877541 9062 chrl7 17109690 17110019 Sin3Ak-20 chrl7 17109779 17109885 8194 chrl7 38083919 Sin3Ak~20 chrl? 38083901 38083979 S2.i¾ chrl6 2262639 2262809 Sin3Ak-20 chrl6 2262738 2262823 7858 chrl 6 14967831 14968051 Sin3Ak-20 chrl6 14967880 14968000 7906 chrl6 24267298 24267473 Sin3Ak-20 chrl6 24267330 24267430 7943 chrlo 89571910 89572221 Siri3Ak-20 chrl6 89571991 89572097 8110 chrll 952599 952819 Sin3Ak-20 chrll 952644 952729 6083 chr7 102004047 102004294 SIX5 chr7 102004049 102004154 4460 chr6 2765410 2765756 SIX5 chr6 2765487 2765632 3512 chrl 1624126 1624377 S!X5 chrl 1624211 1624313 17 chrl 1624479 1624703 SIX5 chrl 1624403 1624654 1 chrl 1677767 1677987 5iX5 chrl 1677682 1677934 2 chrl9 44598311 44598603 S!X5 chrl9 44598400 44598496 8828 chrl7 MS8-S ?i>K 38084083 SiX5 chrl7 38083901 38083979 chrl7 76250534 76250837 SIX5 chrl7 76250645 76250741 8375 chrl 6 4511372 4511596 SIX5 chrl6 4511459 4511603 781,6 chrl6 17195631 17195808 SIX5 chrl6 17195660 17195747 7915 chrlo 19566761 19567046 SI 5 chrl6 19566661 19566971 7888 chrY 8898016 8898296 SP1 chrY 8898125 8898233 9917
ChrX 122914294 122914574 SP1 ChrX 122914371 122914480 " 77«) chrX 153607105 153607586 SP1 chrX 153607264 153607413 9864 chr9 76908435 76908699 SP1 chr9 76908522. 76908603 53.54 chr9 138863857 138864121 SP1 chr9 138863933 138864042 5551 chi-8 29940493 29940911 SP1 chr8 2'jn -i( i 7 29940806 4813 chr8 145987757 145988121 SP1 chr8 145987838 145988031 5209 chr7 1126168 1126428 SP1 chr7 1126285 1126387 4086 chr7 74100326 74100590 SP1 chr7 74100404 74100498 4321 chr7 102004001 102004344 SP1 chr7 102004049 102004154 4460 chr7 158655848 158656112 SP1 chr7 158655912 158656014 4680 chr6 2765413 2765749 5P1 chr6 2765487 /i.b6¾? 3512 chr6 2940738 2940998 SPl chr6 2940840 2940933 3514 chr6 10719843 10720233 5P1 chr6 10719971 10720126 .'54.1 chr6 25863664 25863944 SPl chr6 25863771 25863871 3581 c r6 52161530 52161790 SPl chr6 52161778 52161905 3676 chr5 6444721 6444985 SPl chr5 6444783 6444903 2962 chrS 68477747 68478027 SPl c rS 68477934 68478113 chr5 114404525 114404785 SPl chr5 114404634 114404729 3301 chr5 171624827 171625091 SPl chr5 171625038 171625105 3454 chr5 178691880 178692160 SPl chr5 178691893 178691989 3475 chr5 179798313 179798577 SPl C.h: 5 179798429 179798523 5 1 4 chr4 81382604 81382868 SPl chr4 81382520 81382632 2498 chr4 154409229 154409489 SPl chr4 154408899 154409319 ? ¾ chr4 171012870 171013134 SPl chr4 171013015 171013204 2788 chr4 l«OMC 5 }■:> 190690640 SPl Chr4 190690470 LfXV><W 3 2S\)!, chr3 67705815 67705935 SPl chr3 67705692 67705939 1750 c r3 195577765 195578055 SPl chr3 195577893 195577977 2184 chr3 196000497 196000761 SPl chr3 196000459 196000554 2192 chr2 3048785 3049065 SPl chr2 ■JC J½9:-> .<0-!H7 v 866 chr2 61317560 61317840 SPl chr2 61317637 61317728 1040 chr2 85151983 85152247 SPl chr2 85152041 85152146 1107 chr2 114743666 114743946 SPl chr2 114743848 114743923 1165 chr2 135561659 135561899 SPl chr2 135561881 135561982 1225 chr2 199236619 199236879 SPl chr2 199236595 199236679 1411 chr2 220065614 220065894 SPl chr2 >?.Q0b- ') > 220065897 1474 chr2 242036480 242036740 SPl chr2 242036568 242036665 1561 chrl 1624118 1624378 SPl Chrl 1624211 1624313 17 chrl 1624489 1624608 SPl chrl 1624403 1624654 1 chrl 1677769 1678009 SPl chrl 1677682 1677934 2 chrl 12156081 12156377 SPl chrl 12156124 12156284 75 chrl r.'-'.H i-;'8 17482938 SPl chrl 17482788 17482910 96 chrl 24817001 24817241 SPl chrl 24816942 24817046 120 chrl 100224580 100224860 SPl ch l 10022- it> .13 100224721 M i chrl 154580134 154580398 SPl chrl 154580161 154580286 464 chr22 18008853 18009138 SPl chr22 18008951 18009037 '-•M l chr22 19947164 19947444 SPl chr22 19947316 19947412 9328 chr22 30907986 30908226 SPl chr22 30908003 30908098 9349 chr22 36038470 36038750 SPl chr22 36038553 36038634 9370 chr22 39906757 39907021 SPl chr22 39906714 39906863 chr21 18873843 18873990 SPl chr21 18873881 18873961 9161 chr21 38938162 SPl chf21 38938279 389 1S37 5 922? chrl9 6373354 6373614 SPl chrl9 6373061 6373448 8661 chrl9 6373354 6373614 SPl chrl9 i- lW. ) 7 ¾ 7-)3 »(,(, :■ chrl 9 8441377 8441657 SPl chrl9 8441283 8441390 8710 chrl9 °A J?r> 8444465 SPl chrl9 8444097 8444291 8711 chrl9 39559000 39559240 SPl chrl9 39559137 39559229 8807 chrl9 54974899 SPl chrl9 54975046 54975738 8869 chrl9 54975255 54975568 SPl chrl9 54975046 54975738 8869
Chr20 i VJ }-i S-3 SPl chr20 3 i<) 5 < :i$ 9001 chr20 60877007 60877287 SPl chr20 60877210 60877541 9062 chrlS ')» 1 2 Ϊ7.Ϊ 9912637 SPl chrlS 9912497 9912.588 8441 chrl7 576498 576762 SPl chrl7 576670 576775 8138 chrl7 1617879 1618159 SPl chrl? 1617853 1617940 8151 chrl7 17109631 17109911 SPl chrl7 17109779 17109885 8194 chrl7 17536088 17536348 SPl chrl7 1 ?.Vi<" 77 17536443 8200 chrl7 20059035 20059295 SPl chrl7 20059180 20059290 10042 chrl7 38083767 38084027 SPl chrl7 38083901 H.I V: chrl7 79325378 79325658 SPl chrl7 79325544 79325699 10063 chrl6 .175024 SPl chrl6 375060 375 Γ. 7S3 chrl6 11904067 11904347 SP1 chrl6 11904262 11904361 7895 chrl6 17195537 17195801 5P1 chrl6 17195660 17195747 7915 chrl6 19566654 19566918 SP1 chrl6 19566661 19566971 7888 c.hrl6 89571874 89572154 SP1 chrl6 89571991 89572097 8110 chrl6 89768432 89768743 SP1 chrl6 89768460 89768554 8115 chrlS 31518303 31518563 SP1 chrl5 31518461 31518554 ■/(■ ί7 chrl5 40874080 40874357 SP1 chrlS 40874190 40874286 7664 chrl4 106765114 106765374 SP1 chrl4 106765150 106765547 10014 chrlS 71865287 71865547 SP1 chrl3 71865441 71865535 7137 chrl3 7">ί,¾,ί> 7 565^, SP1 chrl3 77565612 7 %573:·. 7150 chrl3 82448404 82448684 SP1 chrl3 82448439 82448673 7169 chrlS 100028460 100028720 SP1 chrl3 100028639 100028716 7227 chrl3 100148941 100149221 SP1 chrl3 100148988 100149109 7228
Chrl2 7792829 7793094 SP1 chrl2 « 935 6504 chrl2 127256941 127257201 SP1 chrl2 127257076 127257168 6895 chrll 952472 "-.;?32 SP1 chrll 952644 952729 6083 chrll 5704854 5705114 SP1 chrll 5704773 5704930 6100 chrll 11879290 11879554 SP1 chrll 11879359 11879542 6119 chrll 115795913 115796173 SP1 chrll 115795944 115796095 6427 chrlO 14854290 14854554 SP1 chrlO 14854385 14854508 5C..)0 chrlO 31876204 31876464 SP1 chrlO 31876432 31876668 5714 chrlQ 119120837 119121117 SP1 chrlO 119120930 119121023 <ίί chrlO 125312722 125312982 SP1 chrlO 125312740 125312814 6003 chr9 36008958 36009122 5RF chr9 36008952 36009049 5319 chr7 38215180 38215415 SRF chr7 38215359 38215533 4217 chr7 66579834 66580057 SRF Chr7 66579940 66580018 ■1272 chr7 72162196 72162376 SRF chr7 72162260 72162337 10106 chr7 158655777 158655941 SRF chr7 158655912 158656014 4680 chr6 2940751 2940892 SRF chr6 2940840 2940933 3514 chr5 55544980 55545160 SRF chr5 55545074 55545234 3112 chr4 4350464 4350693 SRF chr4 4350652 4350794 2242 chr22 45005059 45005269 chr22 45004991 45005113 9401 chr21 38346946 38347126 SRF chr21 38346894 38346994 9226 chrl7 38083997 SRF chrl7 38083901 ί-:.?3·: chrl6 89768499 89768679 SRF chrl6 89768460 89768554 8115 chrl4 106765192 106765483 SRF chrl4 106765150 106765547 10014 chrl2 6616829 6617039 SRF chrl2 6616829 6616944 6501 chrlO ; -is¾-> SRF chrlO 32248883 5 > chrX 48659911 48660225 TAF1 chrX 48660039 48660137 9583 chrS 26975793 TAF1 chrS 26975670 26975820 5289 chr9 38620430 38620650 TAF1 chr9 38620511 38620596 5325 chr9 99983802 99983908 FAF1 chr9 99983766 ¾42Κ chr9 108061819 108062039 TAF1 chr9 108062023 108062146 5452 chr9 138799546 138799876 TAF1 chr9 138799480 138799699 5521 chr8 145987747 145988017 TAF1 chr8 145987838 145988031 5209 chr7 143077340 143077610 TAF1 chr7 143077464 143077619 4599 chr6 604566 604816 TAF1 chr6 604752 604853 3498 chr6 2765530 2765849 TAF1 Chr6 2765487 2?>5^32 3512 chr5 33050011 33050231 TAF1 chr5 33049885 33050059 3061 chr4 967190 967483 TAF1 chr4 967430 967526 2218 chr4 84205532 84205782 TAF1 chr4 84205458 84205558 2509 chr3 195853729 195853979 TAF1 chr3 195853969 195854074 chr3 196000470 196000740 TAF1 chr3 196000459 196000554 2192 chrl 1677727 1677997 FAF1 chrl 1677682 1677934 2 chrl 22231568 22231818 TAF1 chrl 22231610 22231744 109 chrl -P4- 58 247-3 Ϊ7().¾ TAF1 chrl 24743669 24743756 119 chrl 151913840 151914060 TAF1 chrl 151913718 151913859 441 chrl 154580213 154580483 TAF1 chrl 154580161 154580286 464 chrl 197115166 197115841 TAF1 chrl 197115082 197115186 617 chrl 22K Mi.i¾ ;f» 22;vi63H i- TAF1 chrl 228463761 228463942 678 chrl 230262834 230263084 TAF1 chrl 230262996 230263096 725 chr22 19947162 19947426 TAF1 chr22 19947316 19947412 y¾2° chr20 60876999 60877303 TAF1 chr20 60877210 60877541 9062 chrl9 44598205 44598647 TAF1 chrlS 44598400 44598496 8828 chrl9 54974718 54975091 TAF1 chrl9 54975046 54975738 8869 chrl7 20059199 20059539 FAF1 chrl7 20059180 20059290 10042 chrl7 29055550 29055800 TAF1 chrl7 29055786 29055917 8219 chrl 7 38083739 38083979 TAF1 chrl7 38083901 8235 chrl7 76250428 76250692 TAF1 chrl7 76250645 76250741 8375 chrlS 19566813 19567275 TAF1 chrl6 19566661 19566971 7888 chrl6 89571954 89572226 TAF1 chrl6 89571991 89572097 8110
Chrl2 10705867 10706107 TAF1 chrl2 If '705 ? " .": 10705877 6521 chrl2 123319884 123320148 TAF1 chrl2 123319859 123319962 6874 chrlO 105881269 105881633 TAF1 chrlO 105881235 105881318 5948 chrX 48660017 48660108 TCF12 chrX 48660039 48660137 9583 chi-9 76908436 76908674 TCF12 chi-9 76908522 769 860 -, chr9 138863871 138864087 TCF12 chr9 138863933 138864042 5551 chr7 1126180 1126451 FCF12 chr7 1126285 1126387 4086 chr7 25772574 25772790 TCF12 chr7 25772668 25772756 4181 chr6 2765470 TCF12 chr6 .'70S».¾2 3512 chr6 2940750 2940966 TCF12 chr6 2940840 2940933 3514 chr5 176264703 176264919 TCF12 chr5 176264742 176264828 3470 chr3 119419563 119419779 TCF12 chr3 119419620 119419714 1916 chr2 61317684 61317900 TCF12 Chr2 61317637 61317728 1040 chrl 84493117 84493333 TCF12 chrl 84493164 84493266 318 chr22 39906856 39906964 TCF12 chr22 39906714 39906863 9380 chr21 18873814 18874030 TCF12 chr21 18873881 18873961 9161 chrl7 20059031 20059211 TCF12 chrl? 20059180 20059290 10042 chrl7 38083731 38083985 TCF12 chrl7 38083901 38083979 8235 chrl 6 19566594 19566820 TCF12 chrl6 19566661 19566971 7B¾ chrl6 21552474 21552690 TCF12 chrl6 21552521 21552689 7935 chrlS 24267234 24267450 TCF12 chrl6 242673 i 24267430 7943 chrl6 83847930 83848194 TCF12 chrl6 83848024 83848139 8069 chrl4 55141171 55141387 TCF12 chrl4 55141200 55141262 7419 chrl4 106765192 106765408 TCF12 chrl4 106765150 106765547 10014 chrl3 77565517 77565733 TCF12 chrl3 77565612. 77565745 7150 chrll 115796009 115796177 TCF12 chrll 115795944 115796095 6427 chrlO 134257245 134257461 TCF12 chrlO 134257406 134257885 chr9 26975779 26976043 YYlJC-20) chr9 26975670 26975820 5289 chr9 36008816 36009080 YYl .jC-20) chr9 36008952 36009049 ¾.U« chr9 138863842 138864106 YYlJC-20) chr9 138863933 138864042 5551 chrS YYlJC-20) chr8 6278707 (i.? 7*7').j 4738 chr8 145987785 145988049 YYlJC-20) chr8 145987838 145988031 5209 chr7 77 r>:12 V; 84 YYlJC-20) chr7 2r>772f-G-¾ 25772756 4181 chr7 102003995 102004266 YYlJC-20) chr7 102004049 102004154 4460 chr7 143077282 143077532 YY lJC-20) Chr7 143077464 143077619 4599 chr6 2765403 2765658 YYlJC-20) chr6 2765487 2765632 3512 chr5 1641725 1641975 YYlJC-20) chr5 1641811 1641910 .»> 57 chr5 119793848 119794098 YYlJC-20) chr5 119794061 119794139 3314 chr5 U¾.¾.-?8K -.'S 135329142 YYlJC-20) chr5 l .<532rKiS3 3357 chr5 176264677 176264941 YYlJC-20) chr5 176264742 176264828 3470 chr4 7:-. i,: ,7 77512944 YYl .jC-20) chr4 77512766 77512848 2-18-i chr4 93175996 93176260 YYlJC-20) chr4 93176111 93176193 2546 chr3 66623801 66624065 YYlJC-20) chr3 66623709 66623817 1766 chr3 195577811 195578075 YYlJC-20) chr3 195577893 195577977 2184 chr20 61966530 61966852 YYlJC-20) chr20 61966444 61966566 9120 chrl9 44598285 44598594 YYlJC-20) chrl9 44598400 44598496 8828 chrl7 17109562 17109854 YYlJ -20) chrl7 17109779 17109885 8194 chrl7 38083794 38084086 YYlJC-20) chrl7 38083901 38083979 8235 c.hrl7 762505] 76250782. YYlJC-20) chrl7 76250645 7 2:.-VAU 8375 chrl6 375000 375288 YYlJC-20) chrl6 375060 375159 7837 chrl6 19565551 19567189 YYlJC-20) chrl6 19566661 19566971 7.W chrl5 22462151 22462401 YYlJC-20) chrlS 22462316 22462420 7597 chrlS 79888417 79888687 YYlJC-20) chrl5 79888531 ?<W8.NW:¾ 7 ?.">K chrl4 106765207 106765457 YYlJC-20) chrl4 106765150 106765547 10014 chrl2 132020841 132021091 YYlJC-20) chrl2 1 i>.')2 >!.7 132021030 6923 chrll 66115481 66115733 YYlJC-20) chrll 66115701 66115785 6263 chrll v:??■: 95434013 YYlJC-20) chrll •■Vi 5£j(ifj 95434102 t. 562 chrll 115795772 115796022 YYlJC-20) chrll 115795944 115796095 6427 chrlO ,'?1 «S«$ 27180133 YYl...{ -20) chrlO 27180081 27L80l«0 5700 chrlO 105881248 105881642 YYlJC-20) chrlO 105881235 105881318 5948 chrX 48660075 48660223 BU¾ 3 chrX 48660039 48660137 y¾8¾ chrX 153607237 153607550 ZBTB33 chrX 153607264 153607413 9864 chiv -.51 S?tV.' 5518511 chiv 5518333 5518482 4121 chr6 2765561 2765666 ZBTB33 chr6 2765487 2765632 3512 chr& 2940744 ZB7B33 chr6 2940840 2940933 3514 chr6 3849528 3849723 ZBTB33 chr6 3849487 3849596 3520 chrl 6093248 6ffl .vi>!.> ZBTB33 chrl όΓ.<!.ϊ½8 6093478 55 chr20 23624807 23624954 ZBTB33 chr20 23624782 23624902 8961 chrl9 44598424 44598620 ZBTB33 chrl9 44598400 44598496 KS7K chrl7 76250637 76250833 ZBTB33 chrl7 76250645 76250741 8375
Chrl6 21552508 21552752 ΖΒΎΒ33 chrl6 21552521 21552689 7935 chi-16 87739671 87739867 ZBTB33 chrl6 87739575 87739930 8053 chrl4 106765246 106765466 ZiifB3¾ chrl4 106765150 106765547 10014 chrl3 82448414 82448610 ZBTB33 chrl3 82448439 82448673 7169 chi-9 i.Sf-63i:5 j 138864070 ZE81JSC-25388) chi-9 138864042 5551 chr7 1126264 1126488 ZEBlJSC-25388) chr7 1126285 1126387 4086 chr7 2:·.525.'.? 2552604 ZEB1JSC-25388) C.h: 7 > 552 ¾n .'T.2t>J u 4102 chr5 443665 443889 ZEBlJSC-25388) chr5 443593 444175 2903 chr2 231521622 231521846 ZEBlJSC-25388) chr2 231521752 231521847 1510 chr2 242036567 242036791 ZEBlJSC-25388) chr2 242036568 242036665 1561 chrl WWU 28287054 ZEBlJSC-25388) chrl 28286854 8 Si-:>'s;; 131 chrl 32479831 32480055 ZEBlJSC-25388) chrl 32479789 32479871 141 chrl 101643883 101644107 ZEBlJSC-25388} chrl 101643952 101644044 379 chrl9 8594800 8594966 ZEBlJSC-25388) chrl9 8594711 8594915 8714 chrl9 54975468 54975585 ZEBlJSC-25388) chrlS 54975046 54975738 8869 chrl7 38083776 38084000 ZEBlJSC-25388) chrl7 38083901 38083979 8235 chrl7 80309346 80W57C ZEBlJSC-25388) chrl7 80309376 8406 chrl6 19566571 19566795 ZEBlJSC-25388) chrl6 19566661 19566971 7888 chrl6 21552540 2 J 552763 ZEBlJSC-25388) chrl6 J 5525.M 21552689 7') V. chrl6 82045086 82045310 ZEBlJSC-25388) chrl6 82045232 82045319 8061 chrlo 89768382 89768525 ZEBlJSC-25388) chrl6 89768460 89768554 8115 chrl4 106765216 106765280 ZEBlJSC-25388) chrl4 106765150 106765547 10014 chrll 66115529 66115753 ZEBlJSC-25388) chrll 66115701 66115785 « 3 chr7 25772436 25772785 YY1 chr7 25772668 25772756 4181 chr7 102003980 102.004224 YY1 chr7 102.004049 102004154 4460 chr7 143077326 143077656 YY1 chr7 143077464 143077619 4599 chiv 157563669 1 · ?5ί-.ί / 3 YY1 chiv 157563551 1 Γ. ¾ ΐί·7·ι li-63 chr6 2765396 2765720 YY1 chr6 2765487 2765632 3512 chr5 1641770 1641974 YY1 chr5 1641811 1641910 ,:■!¾ chr5 176264678 176264882 YY1 chr5 176264742 176264828 3470 chr3 195577787 195578031 YY1 chr3 vvirmm 195577977 2184 chrl 32479812 32480056 YY1 chrl 32479789 32479871 141 chrl 161748112 161748448 YY1 chrl 161748340 161748443 4ΛΓ: chr22 37297889 37298241 YY1 chr22 37298229 37298316 9373 chrl9 44598338 44598582 YY1 chrl9 44598400 44598496 KS7K chr20 61966533 61966879 YY1 chr20 61966444 61966566 9120 c.hrl7 17109550 17109794 YY1 chrl7 17109779 17109885 8194 chrl7 38083832 38084036 YY1 chrl7 38083901 38083979 8235 chrl7 76250515 76250769 YY1 chrl7 76250645 76250741 S375 chrl6 19566541 19567198 YY1 chrl6 19566661 19566971 7888 chrl4 106765211 106765455 YY1 chrl4 106765150 106765547 10014 chrlS 113808679 113808883 YY1 chrl3 113808710 113808818 7298 chrl2 131588632 131588908 YYl chrl2 1 i lr.8S78.7 131588874 6916 chrll 66115527 66115771 YY1 chrll 66115701 66115785 6263 chrll 95433708 95434044 YYl chrll <'r>4 i 5£j80 95434102 t. 562 chrlO 625275 625611 YYl chrlO 625497 625648 5593 chrX 79659112 79659316 CTCFJSC-5916) ChrX /■J0r-fXV>b 79659162 9647 chr9 36008833 36009092 CTCFJSC-5916) chr9 36008952 36009049 5319 c r9 38620558 CTCFJSC-5916) chr9 38620511 S8 2 v!(-, chr9 72547914 72548118 CTCFJSC-5916) chr9 72547913 72547993 5347 chr8 6343104 6343308 CTCFJSC-5916) chr8 63 1.Ϊ255 63.!.ίΐΜ J , chr8 76169587 76169803 CTCFJSC-5916) chr8 76169499 76169615 4957 chr8 119149277 119149481 CTCFJSC-5916) chr8 119149476 119149561 chr8 141349123 141349346 CTCFJSC-5916) chr8 141349269 141349372 5171 chr7 1037048 10 5725.' CTCFJSC-5916) C.h: 7 1037114 1037199 4083 chr7 4034919 4035186 CTCFJSC-5916) chr7 4034971 4035107 4110 chr7 113350447 113350663 CTCFJSC-5916) chr7 113350364 113350455 4512 chr7 143077317 143077533 CTCFJSC-5916) chr7 143077464 143077619 4599 chr6 2765588 2765804 CTC JSC-5916) Chr6 2765487 2 HAW 3512 chr6 3849413 3849669 CTCFJSC-5916) chr6 3849487 3849596 3520 chr6 3978526 3Ί75Ϊ 79.1 CTCFJSC-5916) c r6 3<)V ",8i-: -WKG ¾ 3521 chr5 1641767 1641987 CTCFJSC-5916) chr5 1641811 1641910 2937 chr5 56.m-:5fcii CTCFJSC-5916) chr5 56378414 56378504 3133 chr5 58663687 58663903 CTCFJSC-5916) chr5 58663657 58663764 3141 chr5 119794041 119794257 CTCFJSC-5916) c.h; 5 119794061 119794139 3314 chr5 179798308 179798512 CTCFJSC-5916) chr5 179798429 179798523 3484 chr4 88976141 88976357 CTCFJSC-5916) chr4 88976195 88976277 r>3'.J chr4 186385457 186385661 CTCFJSC-5916) chr4 186385535 186385616 2864 chr4 189294132 189294348 CTCFJSC-5916) chr4 189294176 LS9 M 2S7-. chr4 189935119 189935323 CTCFJSC-5916) chr4 189935058 189935166 2885 chr3 72137719 72137923 CTCFJSC-5916) chr3 72137915 72138020 178? chr3 133943474 133943678 CTCFJSC-5916) chr3 133943485 133943564 1958 chr3 195577773 195578062 CTCFJSC-5916) c r3 195577893 195577977 2184 chr2 735947 736151 CTCFJSC-5916) chr2 736006 736076 838 chr2 236460625 236460810 CTCFJSC-591&) chr2 236460709 236460813 1525 chrl9 883669 883900 CTCFJSC-5916) chrl9 883889 883967 8674 chrl9 46513063 46513279 CTCFJSC-5916) chrl9 46513048 46513130 8834 chr20 50481597 50481801 CTCFJSC-5916) chr20 50481764 50481860 9052 chr20 56730285 56730489 CTCFJSC-5916) chr20 56730442 56730524 9075
Figure imgf000226_0001
chrl6 68783532 68783736 CTCFJSC-5916) chrl6 68783733 68783806 8014 chrlS 22462101 _V,ILV: VJH CTCFJSC-5916) chrlS _\Μ(.·,: 1 I.?. .?.-'. ?.Q 7597 chrl5 79888435 79888700 CTCFJSC-5916) chrlS 79888531 79888665 7768 chrl4 23452576 23452814 CTCFJSC-591&) chrl4 ,: . 5.>5:> 5 7.H0 chrl4 106765109 106765558 CTCFJSC-5916) chrl4 106765150 106765547 10014 chrl2 40200936 40201083 CTCFJSC-5916) chrl2 40200867 40200948 10010 chrl2 94823492 94823708 CTCFJSC-5916) chrl2 94823551 94823648 6789 chrl2 131708734 131708938 CTCFJSC-5916) chrl2 131708917 131709011 6917 chrll 11178837 11179041 CTCFJSC-5916) chrll 11178981 11179068 6118 chrll 68495574 CrCFJSC-5916) chrll 6S4'.'5.12.i 68495403 6277 chrll 89232146 89232315 CTCFJSC-5916) chrll 89232187 89232269 6342 chrll 117009470 117009674 CTCFJSC-5916) chrll 117009658 117009785 6431 chrlO 6720236 6720452 CTCFJSC-5916) chrlO 6720409 6720538 5639 chrlO 25985052 25985256 CTCFJSC-5916) chrlO 25985161 27)Η'>282 5694 chrlO 27179904 27180120 CTCFJSC-5916) chrlO 27180081 27180190 5700 chrlO 103817485 103817689 CTCFJSC-5916) chrlO 103817609 103817685 n« chrlO 127318406 127318622 CTCFJSC-5916) chrlO 127318416 127318526 6012 chrX 122914351 122914601 HDAC2 JSC-6296) chrX 122914371 122914480 9779 chr9 138863876 138864145 HDAC2JSC-6296) chr9 138863933 138864042 5551 chr7 143077310 143077514 HDAC2JSC-6296) chr7 143077464 143077619 4599 chr6 604588 604792 HDAC2 JSC-6296) chr6 604752 604853 3498 chr6 2765537 2765787 MDAC2 JSC-6296) Chr6 2765487 3512 chr6 25863647 25863897 HDAC2 JSC-6296) chr6 25863771 25863871 3581 chr6 154859145 154859395 HDAC2 JSC-6296) chr6 154859393 154859514 4006 chr5 176264723 176264927 HDAC2 JSC-6296) chr5 176264742 176264828 3470 chr5 178691914 178692164 HDAC2 JSC-6296) chr5 178691893 178691989 chr4 3307443 3307647 HDAC2 JSC-6296) chr4 3307377 3307483 2230 chr4 186631295 186631545 HDAC2JSC-6296) chr4 186631274 186631385 ,:<v>5 chr3 192614924 192615174 HDAC2 JSC-6296) chr3 192614968 192615068 2162 chr3 195577808 195578111 HDAC2 JSC-6296) ch 3 195577893 195577977 2184 chr2 61317568 61317818 HDAC2 JSC-6296) chr2 61317637 61317728 1040 chrl 22231593 22231770 HDAC2 JSC-6296) chrl 22231610 22231744 109 chrl 230262872 230263076 HDAC2 JSC-6296) chrl 230262996 230263096 725
Chr22 19947182 19947555 HDAC2 JSC-6296) chr22 19947316 19947412 « 32Χ chr22 36038504 36038754 HDAC2 JSC-6296) chr22 36038553 36038634 9370 chr22 39906785 39906975 HDAC2 JSC-6296) chr22 39906714 39906863 9380 chr21 18873847 18874006 HDAC2 JSC-6296) chr21 18873881 18873961 9161 chr20 60849672 60849876 HDAC2 JSC-6296) chr20 60849658 60849757 9096 chrl? 1617913 1618163 HDAC2 JSC-6296) chrl7 1617853 1617940 8151 chrl 7 17109723 17109927 HDAC2 JSC-6296) chrl7 17109779 17109885 8194 chrl7 42237364 42237568 HDAC2JSC-6296) chrl7 42237391 42237467 8253 chrlo 24267266 24267470 HDAC2 JSC-6296) chrl6 V--!. i0 24267430 7943 chrl6 57334331 57334581 HDAC2 JSC-6296) chrl6 57334258 57334361 7985 chrl6 S 773%ii ti ■ 7.Y) -> HDAC2 JSC-6296) chrl6 K -.'7.W: 7b S7739:>50 KO-i.i chrl6 89571863 89572113 HDAC2 JSC-6296) chrl6 89571991 89572097 8110 chrl5 29149740 29149944 HDAC2 JSC-6296) chrlS 29149824 29149903 7629 chrlS 45709888 45710092 HDAC2 JSC-6296) chrl5 45709938 45710050 7679 chrl4 2 R:24')i . 4527 In HDAC2 JSC-6296) chrl4 23452524 2 M'.2CJ & 73 i chrl4 55023349 55023599 HDAC2 JSC-6296) chrl4 55023585 55023655 7418 chrl3 8.M SS.1SK 82448638 HDAC2JSC-6296) chrl3 82448673 7169 chrl3 113358738 113358942 HDAC2 JSC-6296) chrl3 113358873 113358968 7291 chrl l F'". J4.; 952688 HDAC2 JSC-6296) chrl l 952644 95.'7.'9 .^ f chrll 66115574 66115824 HDAC2 JSC-6296) chrll 66115701 66115785 6263 chrlO V.W4K H 74848398 HDAC2 JSC-6296) chrlO 74848135 748 53222 ¾5 ί chrlO 119121013 119121263 HDAC2 JSC-6296) chrlO 119120930 119121023 5983 ch Y 16452653 16452913 JunD ChrY 16452759 16452854 9942 chrX 22481145 22481405 JunD chrX 22481183 22481287 9523 chrX 122914392 122914504 JunD chrX 122.914371 122914480 9779 chr9 33619615 33619905 JunD chr9 33619736 33619812 5312 chi-9 36008819 36009109 JunD chi-9 36008952 36009049 5319 chr9 76908532 76908582 JunD chr9 76908522 76908603 5354 chr9 137518599 137518889 JunD chr9 137518528 137518639 5538 chr9 138863951 138864127 JunD chr9 138863933 138864042 5551 chrS 13733872 13734048 JunD chrS j 57 ί 1002 13734114 4770 chr8 145987767 145988110 JunD chr8 145987838 145988031 5209 chr7 12700123 12700303 JunD chr7 12700231 12700362 4143 chr6 2765519 2765695 JunD chr6 2765487 2765632 3512 chr6 2940743 2940999 JunO chr6 2940840 2940933 3514 chr6 31671746 31672036 JunD chr6 31671813 31671911 3608 c r6 ■■A27S X 77 50273737 JunD chr6 50273478 5027.iv! l 3674 chr6 71184551 71184727 JunD chr6 71184707 71184788 3735 chr6 100298789 100299049 JunD c r6 100298972 100299056 3819 chr5 1641695 1641985 JunD chr5 1641811 1641910 2937 chr5 S2:">7,: ? 7 ■-,::, / ¥.!■,?. JunD chr5 52Γ,7.\ν12 525 .>J iS 3122 chr5 114404551 114404811 JunD chr5 114404634 114404729 3301 chr5 ] i : 132377858 JunD eh; 5 132377611 132377694 chr5 176264730 176264906 JunD chr5 176264742 176264828 3470 chr5 17 V1H J.IC 179798520 JunD chr5 179798429 179798523 3484 chr4 36332383 36332673 JunD chr4 36332560 36332655 2367 chr4 93176144 93176320 JunD Chr4 93176111 93176193 2546 chr4 177822270 177822560 JunD chr4 177822159 177822279 2825 c r4 1782 178225589 JunD chr4 178225515 178225619 chr4 190690420 190690596 JunD chr4 190690470 190690574 2896 chr3 28092364 ϊ>· 926· .·ΐ JunD chr3 . W TO 28092524 1652 chr3 106147443 106147814 JunD chr3 106147511 106147661 1884 chr3 188719427 188719717 JunD chr3 188719492 188719585 2142 chr3 192614870 192615130 JunD chr3 192614968 192615068 2162 chr3 195577781 195578071 JunD eh; -5 195577893 195577977 2184 chr2 36145110 36145370 JunD chr2 36145102 36145215 966 chr2 43934497 43934640 JunD chr2 43934408 43934523 ■ chr2 61317564 61317824 JunD chr2 61317637 61317728 1040 chr2 104051675 104051778 JunD Chr2 104051628 104051750 1135 chr2 240225943 240226199 JunD chr2 240225882 240225968 1545 chr2 242036457 242036713 JunD c r2 242036568 242036665 1561 chrl 1624192 1624339 JunD chrl 1624211 1624313 17 chrl 1624504 1624585 JunD chrl 1624403 1624654 1 chrl 1677761 1678016 JunD chrl 1677682 1677934 2 chrl 32913576 ri\ . IT; ? JunD chrl 32913603 .;2>U 372:". 142 chrl 84493151 84493327 JunD chrl 84493164 84493266 318 chrl 155668172 155668432 JunD chrl 155668068 155668190 469 chrl 189586047 189586337 JunD chrl 189586194 189586297 585 chrl 246868755 246869045 JunD chrl 246868695 246868804 809 chr22 39906856 39906958 JunD chr22 39906714 39906863 9380 chr21 1 BW84S 18874032 JunD chr21 18873881 18873961 9161 chr21 38346814 38347074 JunD chr21 38346894 38346994 9226 chrl9 SS V/20 884016 JunD chrlS 883889 883967 8674 chr20 44731705 44731804 JunD chr20 44731744 44731853 9032 chr20 60876930 f,037/.V,2 JunD chr20 60877210 60877541 9062 chrl7 4233183 4233523 JunD chrl7 4233309 4233406 8163 ch l 7 20059039 2 592 I JunD chrl7 20059180 20059290 10042 chrl7 38083878 38084138 JunD chrl7 38083901 38083979 8235 chrl7 77915849 77916089 JunD chrl7 77915753 77915861 fi 5S': chrl6 4511427 4511586 JunD chrl6 4511459 4511603 7866
Chrl6 19566588 19566878 JunD chrl6 19566661 19566971 7888 chrl6 24267272 24267448 JunD chrl6 24267330 24267430 7943 chrlfi 83847787 83848077 JunD chrl6 83848024 83848139 8069 chrl6 89056683 89056943 JunD chrl6 89056847 89056941 8100 chrl6 89571826 S'JS7/: rj7 JunD chrie 89571991 89572097 8110 chrl4 55023367 55023627 JunD chrl4 55023585 55023655 7418 chrl4 106765256 106765516 JunD chrl4 106765150 106765547 10014 chrl2 71055563 71055853 JunD chrl2 71055506 71055592 6720 chrl2 116784603 116784893 JunD chrl2 116784859 116784973 6856 chrl2 127256942 127257236 JunD chrl2 127257076 127257168 6895 chrl2 132863471 132863761 JunD chrl2 132863686 132863803 6- i 7 chrll 66115585 66115875 JunD chrll 66115701 66115785 6263 chrll 115795793 115796049 JunD chrll 115795944 115796095 6427 chrlO 89500105 89500363 JunD chrlO 89500173 89500294 5893 chrlO 103986847 103987137 JunD chrlO 103986947 103987039 5942 chrlO 127318365 127318655 JunD chrlO 127318416 127318526 6012 chrY 16002447 16002657 NANOG.JSC- chrY 16002360 16002461 9940
Figure imgf000229_0001
chr9 76908501 76908597 POU5F1JSC-9081) chr9 76908522 76908603 5354 chrS 2 31839 ?.2.Q0.Y) PQU5F1JSC~9081) chrS 2231969 22.52086 4718 chr8 53512407 53512607 POU5F1JSC-9081) chr8 53512484 53512564 4885 chr7 25772703 25772 POU5F1JSC-9081) Chr7 25772(" ! >F, 25772756 4181 chr5 1641712 1641912 POU5F1JSC-9081) chr5 1641811 1641910 2937 chrl 84493119 84493319 POU5F1JSC-9081) chrl 84493164 318 chr22 39906796 39906996 POU5F1JSC-9081) chr22 39906714 39906863 9380 chrl3 62848758 62848958 POU5F1JSC-9081) chrl3 62848694 62848789 7098 chrX 113283990 113284194 TAF7JSQ-8) chrX 113284101 113284193 9735 chr9 26975773 26975977 TAF7JSQ-8} chr9 26975670 26975820 W) chr9 99983715 99983919 TAF7JSQ-8) chr9 99983766 99983852 5428 chr9 138863887 138864104 TAF7JSQ-8) ( r<' 1 J. 138864042 5551 chr8 141349143 141349347 TAF7JSQ-8) chr8 141349269 141349372 5171 chr6 2765551 2765755 TAF7JSQ-8) chr6 2765487 2 /6563? 3512 chrS 176264700 176264904 TAF7JSQ-8) chrS 176264742 176264828 3470 chr3 195577796 195578051 TAF7JSQ-8) chr3 195577893 195577977 2184 chr21 38938320 38938524 TAF7JSQ-8) chr21 38938279 38938373 9228 chrl7 20055013 20 5°21 7 TAF7JSQ-8) chrl7 20059180 20059290 10042 chrl6 24267288 24267492 TAF7JSQ-8) chrl6 24267330 24267430 7943 chrl4 106765220 106765424 TAF7..(SQ-8} chrl4 106765150 106765547 10014 chrll 66115508 66115712 TAF7JSQ-8) chrll 66115701 66115785 6263 chrl l 67388921 67389125 TAF7JSQ-8) chrll 67389071 67389187 6271 chr9 38620506 38620696 BHLHE40 chr9 38620511 38620596 5325 chrl8 12 i f 7422 12377612 BHLHE40 chrl8 12377506 12377572 ί-:.}5'.) chrl7 17109706 17109896 BHLHE40 chrl7 17109779 17109885 8194 c Y 16452824 16452883 FOSL2 ChrY 16452759 16452854 9942 chrY 16456919 16457155 FOSL2 chrY 16456906 16457053 9943 chr9 138863883 138864119 > OS!.2 chr9 138864042 55.51 chr7 12700092 12700328 FOSL2 chr7 12700231 12700362 4143 chr5 1564196 1564432 FOSL2 chr5 1564323 1564422 03-1 chr5 114404637 114404767 FOSL2 chr5 114404634 114404729 3301 chr5 115880680 115880812 FOSL2 chr5 115880687 115880768 3304 chrS 176264685 176264921 FOSL2 chr5 176264742 176264828 3470 chr3 119419561 119419635 FOSL2 chr3 119419620 119419714 1916 chr2 53844470 53844706 FOSL2 chr2 53844563 53844652 1024 chr2 22006,">5 ¾ 220065820 FOSL2 chr2 2 06·; 792 220065897 1474 chr21 18873830 18874065 F0SL2 chr21 18873881 18873961 9161 chrl6 19566658 19566796 F0SL2 chrl6 19566661 19566971 7888 chrl6 83847842 83848056 F0SL2 chrl6 83848024 83848139 8069 chrl6 89571902 89572094 > OS!.2 chrl6 89571991 89572097 8110 chrl3 71865335 71865571 F0SL2 chrl3 71865441 71865535 7137 chrl2 127256992 127257228 F0SL2 chrl2 127257076 127257168 6895 chrll 952530 952766 F0SL2 chrll 952644 952729 6083 chrll 66115520 66115756 F0SL2 chrll 66115701 66115785 chrlO 92923723 92923969 F0SL2 chrlO 92923953 92924065 5910 chrY 8898036 8898245 F0XA1JSC- chrY 8898125 8?ί»*2.ΐ¾ 9917 chrX 77043522 77043792 FOXA1JSC- chrX 77043627 77043724 9643 chr9 140010751 140011021 FOXA1JSC- ( r<' 140010751 140010868 ' >( : chr7 123365021 123365116 FOXA1JSC- chr7 123365008 123365158 4538 chr6 25863665 25863914 FOXA1JSC- Chr6 25863771 25863871 3581 chr5 134311054 134311324 FOXAIJSC- chr5 134311064 134311151 3354 c r5 178691S74 178692144 FQXA1JSC- chr5 178691893 178691989 3475 chr4 55649641 55649813 FOXA1JSC- chr4 55649675 55649759 2413 chr4 186631359 186631629 FOXAl JSC- chr4 186631274 186631385 chr3 28092450 28092720 FOXA1JSC- chr3 28092430 28092524 1652 chr3 190956267 190956340 FOXA1 JSC- chr3 190956192 190956285 2156 chr2 85151963 85152233 FOX AIJSC- chr2 85152041 85152146 1107 chr2 236460668 .7 i64 >!.^: FOXA1JSC- chr2 236460813 1525 chrl 100224440 100224710 FOXA1JSC- chrl 100224633 100224721 373 chrl 202971206 202971476 FOXA1JSC- chrl 2029 -.'l.iV- 202971440 f»3K chrl 235413845 235414001 FOXAIJSC- chrl 235413848 235413946 746
Chr22 35038509 toll 58 7 ϊ« FOXA1JSC- chr22 36038553 360 i&yU "370 chr21 18873774 18874073 FOXAIJSC- chr21 18873881 18873961 9161 chr21 "!Sr> ½2'>2 FOXA1JSC- chf21 38938279 389 1S37 5 922? chr20 60876941 60877211 FOXAljSC- chr20 60877210 60877541 9062 chrlS 57262177 57262301 . ΟΧΛ 1 (SC chrl9 57262148 57262242 Si^ i chrl? 473772 474042 FOXA1JSC- chrl7 473883 473979 8135 chrl 7 80 i02 '.j-i 80302634 FOXA1 JSC- chrl7 80302576 8f. 076V". 8405 chrl6 4511498 4511768 FOX AIJSC- chrl6 4511459 4511603 7866 chrl6 11904128 11904382 FOXAIJSC- chrl6 11904262 11904361 7895 chrl6 83847767 83848037 FOXA1JSC- chrl6 83848024 83848139 8069 chrl6 87739595 K-.'7.WJ. 7 FOXA1JSC- chrl6 K-.'7.W:7b S7739:>50 KO-i.i chrl6 89571921 89572047 FOXAIJSC- chrl6 89571991 89572097 8110 chrl6 90124364 90124634 FOXA1JSC- chrl6 90124299 90124411 8124 chrl3 41146310 41146580 FOXA1JSC- chrl3 41146460 41146548 7028 chrl3 H24-1S3 V. S2-WH7'iH FOXAl JSC- chrl3 « 4;U <) 82448673 7169 chrl3 95097147 95097417 FOXAljSC- chrl3 95097182 95097302 7209 chrl3 100148955 100149225 . ΟΧΛ 1 (SC chrl3 100148988 100149109 7 7Κ chrlO 74848147 74848352 FOXAIJSC- chrlO 74848135 74848222 5853 chrlQ 0.7" J7u2 92924032 FOXA1JSC- chrlO fi292.V'".3 92924065 5910 chrlO 119120834 119121102 FOXAIJSC- chrlO 119120930 119121023 5983 chrY 8898065 FOXA2JSC-6554) chrY 125 wis! 9917 chrX 77043549 77043773 FOXA2JSC-6554) chrX 77043627 77043724 9643 chr9 140010761 140010985 FOXA2 JSC-6554) Chr9 140010751 140010868 5565 chr8 11499555 11499779 FOXA2JSC-6554) chr8 11499580 11499663 4759 chr8 103519750 103519974 FOXA2JSC-6554] chr8 103519699 103519793 5041 chr7 70052763 70052987 FOXA2JSC-6554) chr7 70052718 70052798 4310 chr6 25863742 _".-.Χΐ.·.«£).ί FOXA2JSC-6554) chr6 25863771 25863871 3581 chr5 134311071 134311295 FOXA2 J SC-6554) chr5 134311064 134311151 3354 chr4 55649656 55649794 FOXA2JSC-6554) chr4 55649675 55649759 2413 chr3 28092498 28092722 FOXA2JSC-6554) chr3 28092430 28092524 1652 chr3 169877169 169877393 FOXA2JSC-6554) chr3 169877366 169877443 2081 chr3 190956205 190956429 FOXA2JSC-6554) chr3 190956192 190956285 2156 chr3 192614835 192615059 FQXA2JSC-6554) chr3 192614968 192615068 2162 chr2 85151929 85152153 FOXA2JSC-6554) chr2 85152041 85152146 1107 chr2 114743724 114743882 FQXA2.JSC-6554) chr2 114743848 114743923 1165 chrl 235413795 235414019 FOXA2JSC-6554) chrl 235413848 235413946 746 chr21 18873778 18874092 FOXA2JSC-6554) chr21 18873881 18873961 9161 chr21 38938239 38938478 FOXA2JSC-6554) chr21 38938279 38938373 9228 chrl9 57262110 FOXA2JSC-6554) chrlS 57262148 57262242 8893 chrl7 38083721 38083945 F0XA2J SC-6554) chrl7 38083901 38083979 8235 chrl7 8 -'.C,: .«35 f50¾o.>r-.n<) FOXA2J5C-6554) chrl7 S ¾0.>¾7i: 8405 chrl6 4511536 4511760 F0XA2J SC-6554) chrl6 4511459 4511603 7866 chrl 6 11904140 11904365 F0XA2J SC-6554) chrl6 11904262 11904361 7895 chrl6 83847806 83848030 FOXA2JSC-6554) chrl6 83848024 83848139 8069 chrl6 87739572 87740025 FOXA2JSC-6554) chrl6 87739930 K05 ¾ chrl6 89571970 89572052 FOXA2JSC-6554) chrl6 89571991 89572097 8110
Chrl6 90124379 90124603 FOXA2.JSC-6554) chrl6 90124299 90124411 8124 chrl3 82448342 82448732 FOXA2JSC-6554) chrl3 82448439 82448673 7169 c.hrl3 95097201 9 0'.v.M25 FOXA2JSC-6554) chrl3 95097302 7209 chrl3 100149077 100149155 FOXA2JSC-6554) chrl3 100148988 100149109 7228 chrl2 121156992 121157216 FOXA2JSC-6554) chrl2 121156987 121157100 6868 chrll 34643408 34643632 F0XA2J SC-6554) chrll 34643438 34643570 6176 chrlO 74848140 7.18.18ΪΝ: FOXA2..(SC-6554) chrlO 74848135 ■ K-IM'2,: 5853 chrlO 119120827 119121094 FOXA2JSC-6554) chrlO 119120930 119121023 5983 chrX 77043723 77043953 HEY1 chrX 77043724 9643 chr9 38620423 38620596 HEY1 chr9 38620511 38620596 5325 chr9 138799620 138799763 HEY1 chr9 138799480 138799699 5521 chr7 143077367 143077607 HEY1 chr7 143077464 143077619 4599 chr6 33558616 33558846 HEY1 Chr6 33558691 3 ^58 -/ / 3615 chr5 68477754 68477984 HEY1 chr5 68477934 68478113 3144 chrS 158547031 158547271 ΗΕΥΊ c rS 158546651 158547055 ί-1'52 chr4 967212 967442 HEY1 chr4 967430 967526 2218 chr4 967521 967761 ΗΕΥΊ chr4 967430 967526 2218 chr3 171760467 171760697 HEY1 chr3 171760690 171760794 2089 chr2 85152133 K515.' 36 ¾ HEY1 chr2 85152041 85152146 1107 chrl 1677582 1677673 HEY1 chrl 1677486 1677588 18 chrl 150521538 150521685 HEY1 chrl 150521576 150521685 452 chrl 154579932 154580162 HEY1 chrl 154580161 154580286 464 chr22 22008172 22008412 HEY1 chr22 22008149 22008225 933-,
Figure imgf000231_0001
chrl5 20487837 20488077 HEY1 chrl5 20487978 20488199 7591 chrlS 69744275 69744505 HEY1 chrlS 69744385 69744482 7732 chrl3 100148773 100148990 HEY1 chrl3 100148988 100149109 7228
Chrl3 113808766 113808841 HEY1 chrlS 113808710 113808818 λ?9Κ chrl2 37961047 37961277 HEY1 chrl2 37961269 37961361 10005 c.hrl2 123319945 123320206 HEY1 chrl2 123319859 123319962 6874 chrll 952511 952695 HEY1 chrll 952644 952729 6083 chrlO 74086564 74086687 HEY1 chrlO 74086665 74086769 5851 chrY 8898005 8898245 HNF4AJH-171) chrY 8898125 8898233 9917 chrX 122914380 122914519 HNF4A ..(H-171) chrX 122914371 122914480 r;. ? /■-.> chr6 11122746 11122840 HNF4AJH-171) chr6 11122694 11122788 3547 chr6 24663486 24663726 HNF4AJH-171) chr6 24663501 24663614 r>7K chr6 25863644 25863884 HNF4AJH-171) chr6 25863771 25863871 3581 chr6 150030608 150030848 HNF4A_(H-171) chr6 150030714 150030806 3991 chr6 154859207 154859394 HNF4A. JH-171) chr6 154859393 154859514 4006 chr5 134311126 134311366 HNF A. .(H-171) chr5 134311064 134311151 .i i-i chr5 138884381 138884621 HNF4A JH-171) chr5 138884471 138884576 3362 c r5 17(",;ί(.- 37 176264970 HNF A. JH-171) chr5 176264742 176264828 3470 chr5 178691881 178692127 HNF4A. JH-171) chr5 178691893 178691989 3475 chr4 70057706 70057891 HNF4A, JH-171) chr4 70057691 70057764 2460 chr4 159841828 159842068 HNF4A, JH-171) chr4 159841875 159842002 2732 chr3 15661453 15661693 HNF4A ..(H-171) chr3 15661477 15661581 1616 chr3 28092486 28092726 H F4A. JH-171) chr3 28092430 28092524 1652 chr3 1926148S8 192615138 HNF4A, JH-171) chr3 192614968 192615068 2162 chr2 61317669 61317773 H F4A. JH-171) chr2 61317637 61317728 1040 chr2 114743707 114743901 HNF4A. JH-171) chr2 114743848 114743923 1165 chrl 8299394 8299634 H F4A. JH-171) chrl 8299330 8299471 66 chrl 100224614 100224737 HNF4A .(H-171) Chrl 100224633 100224721 m chrl 202971226 202971466 HNF4A. JH-171) chrl 202971355 202971440 638 chr22 19947242 19947424 HNF A. JH-171) chr22 19947316 19947412 W> chr22 36038500 36038691 H F4A. JH-171) chr22 36038553 36038634 9370 chr21 18873879 18873969 HNF A. JH-171) chr21 18873881 18873961 9161 chr20 60877015 60877255 HNF4A, JH-171) chr20 60877210 60877541 9062 chrl9 44598198 44598438 HNF4A ..(H-171) chrl9 44598400 44598496 Sri2K chrl7 38083685 38083925 H F4A. JH-171) chrl7 38083901 38083979 8235 chrl 7 76250550 7 2:>07'iri HNF4A, JH-171) chrl7 7w!;oi«i 76250741 8375 chrl6 89571860 89572099 H F4A. JH-171) chrl6 89571991 89572097 8110 chrl3 82448478 HNF A. JH-171) chrl3 82448673 7169 chrlO 5185460 5185601 H F4A JH-171) chrlO 5185469 5185567 5626 chrlO 119120876 119120969 HNF4A .(H-171) chrlO 119120930 119121023 5983 chrX 49558338 49558588 HNF4G_ SC-6558) chrX 49558546 49558790 9560 chrX 122914401 122914502 HNF4G_ SC-6558) chrX 122914371 122914480 9779 chr6 11122668 11122918 H F4G_ SC-6558) chr6 11122694 11122788 3547 chr6 24663520 24663770 HNF4G_. SC-6558) chr6 24663501 24663614 ΐ'.-.78 chr5 77892930 77893180 HNF4G_. SC-6558) chr5 77893174 77893252 3188 chr5 178691874 178692124 HNF4G_ SC-6558) chr5 178691893 178691989 Π 7", chr4 70057652 70057902 HNF4G_ SC-6558) chr4 70057691 70057764 2460 chr3 192614865 192615115 HNF4G„ SC-6558) chr3 192614968 192615068 2162 chr2 3048752 3049002 HNF4G_ SC-6558) chr2 3048695 3048797 866 chr2 61317686 61317749 HNF4G._ SC-6558) chr2 61317637 61317728 1040 chr2 114743635 114743885 HNF4G_ SC-6558) chr2 114743848 114743923 1165 chrl H »>" J2B 82.99678 HNF46_ SC-6558) chrl 82.99330 8299471 i; chrl 100224635 100224716 H F4G_ SC-6558) chrl 100224633 100224721 373 chrl 147770034 147770284 HNF4G„ SC-6558) chrl 147770073 147770172 450 chrl 202971252 202971502 HNF4G_ SC-6558) chrl 202971355 202971440 638 chr22 19947151 19947401 HNF46... SC-6558) chr22 19947316 19947412 '■I?.?. chr22 36038459 36038709 HNF4G_. SC-6558) chr22 36038553 36038634 9370 chr21 18873805 18874055 HNF4G_ SC-6558) chr21 18873881 18873961 9161 chr21 38938170 38938420 HNF4G_ SC-6558) chr21 38938279 38938373 9228 chrl7 1617915 1618126 HNF4G„ SC-6558) chrl7 1617853 1617940 8151 chrl7 38083727 38083977 HNF4G_ SC-6558) chrl7 38083901 38083979 8235
Chrl7 76250559 76250809 HNF4G ¾ G3b8J chrl7 76250645 76250741 sv chrl6 57334327 57334577 H F4G_ SC-6558) chrl6 57334258 57334361 7985 chrl6 89571912 S"-.72i}fj7 HNF46_ SC-6558) chrl6 89571991 89572097 8110 chrl3 82448472 82448722 H F4G_ SC-6558) chrl3 82448439 82448673 7169 chrlO 5185388 5185638 HNF4G_. SC-6558) chrlO 5185469 5185567 i-?.L- chr9 36008864 36009024 CTCFLJSC-98982) chr9 36008952 36009049 5319 chr7 4035142 CTCFL J5C-98982) chr7 4034971 4035107 4110 chr7 143077353 143077513 CTCFLJSC-98982) chr7 143077464 143077619 4599 chr6 .? 765623 2765771 CTCFLJSC-98982) chr6 271 4Η7 270V. 5? 3512 chr6 3849521 3849592 CTCFLJSC-98982) chr6 3849487 3849596 3520 chr5 1641811 1641971 CTCFL_iSC-98982) chr5 1641811 1641910 -r chr3 195577859 195578019 CTCFLJSC-98982) chr3 195577893 195577977 2184 chr2 236 IMW..5 2.504607S.1 CTCFLJSC-98982) chr2 236460709 236460813 1525 chrl 150521627 150521787 CTCFLJSC-98982) chrl 150521576 150521685 452 c.hrl9 46513100 46.513260 CTCFLJSC-98982} chrl9 46.513048 46513130 SH i 5 chrl7 76250623 76250783 CTCFLJSC-98982) chrl7 76250645 76250741 8375 chrl4 105765193 106765353 CTCFLJSC-98982) chrl4 106765150 106765547 10014 chrll 89232134 89232294 CTCFLJSC-98982) chrll 89232187 89232269 6342 chrlO 6720277 i-7,:0-\ i > Cl"CFL...(SC-98982) chrlO i^7,:040l< -720533 chrlO 27179922 27180082 CTCFLJSC-98982) chrlO 27180081 27180190 5700 chrX 48660014 48660214 E2F6JH-50) chrX 48660039 48660137 9583 chrX 71389055 71389255 E2F6JH-50) chrX 71389028 71389120 9621 chr9 99983811 99984011 E2F6JH-50) ( r<' 99983766 1.12H chr9 138799636 138799723 E2F6JH-50) chr9 138799480 138799699 5521 chr9 140128598 140128798 E2F6JH-50) Chr9 140128770 140128880 >bK chr7 25772502 25772702 E2F6JH-50) chr7 25772668 25772756 4181 chr7 2712.7700 27127900 E2F6JH-50) chr7 .'71 277 J 27127841 4186 chr6 1515660 1515885 E2F6JH-50) chr6 1515569 1515674 3503 chr6 2765575 2765876 E2F6JH-50) chr6 2765487 2765632 3512 chr5 443550 443750 E2F6JH-50) chr5 443593 444175 2903 chr4 1172149 1172349 E2F6 JH-50) chr4 1172139 1172242 220 chr4 84205540 84205767 E2F6JH-50) chr4 84205458 84205558 2509 chr3 195577877 195578077 E2F6JH-50) chr3 195577893 195.577977 2184 chr2 224896154 224896354 E2F6JH-50) chr2 224896209 224896412 1486 chr2 231521636 2.5 ! :": 1H3f- E2F6JH-50) chr2 2.5 1 521 752 231521847 1510 chrl 3712440 3712640 E2F6JH-50) chrl 3712553 3712650 41 chrl 2C. Vj » 3% 26333556 E2F6JH-50) Chrl 26333300 124 chrl 150521361 150521776 E2F6JH-50) chrl 150521576 150521685 452 chrl 230262818 2 92 LS E2F6JH-50) chrl 230262996 230263096 725 chrl 247542113 247542241 E2F6JH-50) chrl 247542130 247542214 818 chr21 46831857 ΐί·χΐ/:ο· 7 E2F6JH-50) chr21 46831891 46831984 28 chrl9 6373478 6373678 E2F6JH-50) chrl9 6373587 6373798 8662 chr20 60877465 E2F6JH-50) chr20 t> S7 .? ] 0 60877.541 chr20 61347770 61347970 E2F6JH-50) chr20 61347860 61347967 9105 chrl7 17109479 17110007 E2F6JH-50) chrl7 17109779 17109885 8194 chrl7 42237388 42237588 E2F6JH-50) chrl7 42237391 42237467 8253 chrl6 19566612 19566812 E2F6JH-50) chrl6 19566661 19566971 7888 chrl6 24267414 24267614 E2F6JH-50) chrl6 24267330 24267430 7943 chrl6 S8376618 88376818 E2F6JH-50) chrl6 88376641 88376739 8092 chrl6 89768384 89768487 E2F6JH-50) chrl6 89768460 89768554 8115 chrl3 113358729 113358929 E2F6JH-50) chfl3 113358873 113358968 7291 chrl3 113808741 113808837 E2F6JH-50) chrl3 113808710 113808818 7298 chrlO 42970975 42971175 E2F6 JH-50) chrlO 42971024 42971122 5 chr4 3307454 3307670 FOSLlJSC-183') chr4 3307377 3307483 2230 chr2 43934494 43934710 FOSLlJSC-183) chr2 43934408 nOJ"..? S chrl 22231494 22231710 FOSLlJSC-183) chrl 22231610 22231744 109 chrl9 42807116 12S;JV3 ¾.? FOSLlJSC-183) chrl9 42807266 42807377 8824 chrl6 19566584 19566800 FOSLlJSC-183) chrl6 19566661 19566971 7888
Chrl6 90124093 90124309 FOSLlJSC-183) chrl6 90124299 90124411 8124 chrl2 116784676 116784892 FOSLlJSC-183) chrl2 116784859 116784973 6856 chrl2 12.7257003 j 2725771 '; FOSLlJSC-183) chrl2 j 7757076 127257168 6895 chrlO 92923742 92923958 FOSLlJSC-183) chrlO 92923953 92924065 5910 chi-9 33619654 33619884 GATA2JCG2-96) chi-9 Ϊ361 .'¾ 33619812 5312 chr6 3978664 3978894 GATA2JCG2-96) chr6 3978588 3978673 3521 chr5 134717931 134718161 GATA2 (CG2-96) chr5 134717838 134717942 3356 chr4 3307440 3307670 GATA2JCG2-96) chr4 3307377 3307483 2230 chr2 176885206 176885436 GATA2JCG2-96) chr2 176885294 j■/(■* ', 5'->K j 53': chrl 22231593 22231769 GATA2JCG2-96) chrl 22231610 22231744 109 chrl 51186744 51186974 GATA2JCG2-96) chrl 51186859 51186947 207 chr22 18453111 18453341 GATA2JCG2-96) chr22 18453056 18453157 9323 chr20 3725203 L .Γ.7 _ν.ί> ! GATA2JCG2-96) chr20 37232184 r.'.n >?.').< 9013 chr20 39677636 39677866 GATA2JCG2-96) chr20 39677561 39677643 9018 c.hrl9 791795 792025 GATA2JCG2-96) chrl9 791702 791821 8673 chrl7 42237398 42237628 GATA2JCG2-96) chrl7 42237391 42237467 8253 chrl6 90124073 90124 if) ¾ GATA2JCG2-96) chrl6 90124299 90124411 8124 chrl5 29149710 29149940 GATA2JCG2-96) chrlS 29149824 29149903 7629 chrlS 45709874 45710104 GATA2 (CG2-96) chrl5 45709938 45710050 7679 chrl4 23923072 23923302 GATA2JCG2-96) chrl4 23922972 23923082 7332 chrl 2 12595145 12595375 6ATA2JCG2-96) chrl2 12595125 12:m >°.2 t>526 chrl2 123449411 123449641 GATA2JCG2-96) chrl2 123449512 123449601 6875 chrll 62528316 62528546 GATA2JCG2-96) chrll i..?!;2S28fi 62528400 6250 chrll 71449482 71449712 GATA2JCG2-96) chrll 71449410 71449506 6294 chrl 1677798 1677982 ■f HAPl... (SC-98174) chrl 1677682 1677934 llllill chrl6 19566537 19566721 THAPlJSC-98174) chrl6 19566661 19566971 7888 c.hrl6 19566822 ."'>(>?-)2r> THAP1JSC.-98174) chrl6 19566661 19566971 7888 chrll 66115534 66115718 THAPlJSC-98174) chrll 66115701 66115785 6263 chr9 138863898 rwsi-i i r-s ZBTB7AJSC- chi-9 138864042 5551 chr7 143077385 143077595 ZBTB7AJSC- chr7 143077464 143077619 4599 chr& 604544 604754 ZBTB7AJSC- chr6 604752 604853 3498 chr4 967334 967544 ZBTB7AJSC- chr4 967430 967526 2218 chr3 195577841 195578051 ZBTB7AJSC- chr3 195577893 195577977 2184 chr2 231521593 231521803 ZBTB7AJSC- chr2 231521752 231521847 1510 chrl 12 ¾\<578 12291038 ZBTB7AJSC- chrl 12290753 12290885 77 chrl 28052908 28053118 ZBTB7AJSC- chrl 28053114 28053203 129 chrl 32479731 32479941 ZBTB7AJSC- chrl >.M 7'} ?S« 32479871 141 chrl 150521668 150521803 ZBTB7AJSC- chrl 150521576 150521685 452 chrl 154579964 154580174 ZSTB7AJSC- chrl 154580161 154580286 464 chrl 228463840 228464050 ZBTB7A_.(SC- chrl 228463761 228463942 678 chrl 230262818 ZBTB7AJSC- chrl 2-J(i2i-.rWf) 230263096 725 chrl9 791768 791978 ZBTB7AJSC- chrl9 791702 791821 8673 chrl9 (, i « Ϊ7Λ ΙΗ » ZBTB7AJSC- chrl9 ¾7.;:.it> L !>373d lS 8661 chrl9 6373756 6373966 ZBTB7AJSC- chrl9 6373587 6373798 8662 chrl9 55510293 55510503 ZBTB7AJSC- chrl9 55510396 55510499 8874 chr20 60877131 60877341 ZBTB7A_(SC- chr20 60877210 60877541 9062 chrl7 90b:":S38 29056048 ZBTB7A_{SC- chrl7 29055786 29055917 8219 chrl7 76250530 76250740 ZBTB7AJSC- chrl7 76250645 76250741 8375 chrl6 19566507 19566717 ZBTB7A„(SC- chrl6 19566661 19566971 7888 chrl6 24267307 24267517 ZBTB7AJSC- chrl6 24267330 24267430 7943 chrlS 29149717 29149927 ZBTB7A...(SC- chfl5 2'· L4AS2.1 29149903 7629 chrll 4414556 4414766 ZBTB7A_.(SC- chrll 4414591 4414685 6098 chrll 66115563 66115773 ZBTB7AJSC- chrll 66115701 66115785 chrlO 92923820 92924030 ZBTB7AJSC- chrlO 92923953 92924065 5910 chrlO ] W2S7.'T. 1 i i257.i(,rj ZBTB7AJSC- chrlO 134257406 1 .■S4.> 78S=; 5993 chr9 17811088 17811310 Rad21 chr9 17811295 17811369 5262 chr9 iyW. 2 Rad21 < r<' 26975670 .?ij«7W20 5289 chr9 36008813 36009096 Rad21 chr9 36008952 36009049 5319 chr9 » 62 7 Rad21 Chr9 38620511
chr9 72547862 72548110 Rad21 chr9 72547913 72547993 5347 chr9 92981876 92982123 Rad21 chr9 92982118 9298222.0 5399 chr9 137518595 137518815 Rad21 chr9 137518528 137518639 5538 chrS 6343093 Rad21 chrS 631.Ϊ 55 6 .. i- l chr8 24812270 24812480 Rad21 chr8 24812274 24812388 4800 chr8 76169574 76169824 Rad21 chr8 76169499 76169615 4957 chr8 119149260 119149496 Rad21 chr8 119149476 119149561 5092 chr7 1037034 1037270 Rad21 chr7 1037114 1037199 4083 chr7 4035035 4035104 Rad21 chr7 4034971 4035107 4110 chr7 33802223 33802433 Rad21 chr7 33802095 4202 chr7 93601779 93601989 Rad21 chr7 93601975 93602085 4419 chr7 113350403 113350666 Rad21 chr7 113350364 113350455 4512 chr7 143077274 143077534 Rad21 chr7 143077464 143077619 4599 c r6 3849426 3849670 Rad?.l chr6 3849487 3849596 > >o chr6 3978480 3978836 Rad21 chr6 3978588 3978673 3521 chr6 }■;½(■'>■/ ;3'>¾8r> 7 Rad21 c r6 33558691 3 i5-:S777 3615 chr5 1641737 1642007 Rad21 chr5 1641811 1641910 2937 chr5 i VSr-i) ¾K 33050248 Rad21 chr5 33049885 33050059 3061 chr5 56378345 56378585 Rad21 chr5 56378414 56378504 3133 chr5 Rad21 C.h: 5 ¾!,37 4 3141 chr5 119793978 119794272 Rad21 chr5 119794061 119794139 3314 chr5 1 7 718 34 179798520 Rad21 chr5 179798429 179798523 3484 chr4 88976124 88976361 Rad21 chr4 88976195 88976277 2530 chr4 186385426 186385662 Rad21 chr4 186385535 186385616 chr4 189294116 189294362 Rad21 chr4 189294176 189294264 2875 c r3 72137739 72137975 Rad?.l chr3 72137915 7213802.0 1782 chr3 105365931 105366141 Rad21 chr3 105365824 105365932 1882 chr3 106147483 106147703 Rad21 chr3 106147511 106147661 1884 chr3 133943532 133943587 Rad21 chr3 133943485 133943564 1958 chr3 177632109 177632345 Rad21 chr3 177632001 2113 chr3 192507110 192507346 Rad21 chr3 192507339 192507446 2161 chr3 195577759 195578059 Rad21 ch 3 195577893 195577977 2184 chr2 8573644 8573884 Rad21 chr2 8573638 8573785 881 chr2 236460609 236460845 Rad21 chr2 236460709 236460813 1525 chrl 28286621 28286863 Rad21 chrl 28286854 28286948 131 chrl ?. W) 7 1W 223897609 Rad21 chrl 223897581 702 chr20 452029 452239 Rad21 chr20 452194 452318 8901 chr20 50481605 50481841 Rad21 chf20 50481764 50481860 ¾T>2 chr20 56730277 56730513 Rad21 chr20 56730442 56730524 9075 chrlS 46513060 46513296 Rad21 chrl9 46513048 46513130 chrlS 1006415 1006631 Rad21 chrl8 1006297 1006436 8418 chrl 7 260865 261130 Rad21 chrl7 261087 261183 8133 chrl7 1074120 1074330 Rad21 chrl7 1074238 1074327 8146 chrl7 751/1 642 75092878 Rad21 chrl7 75092816 75092964 fi 57 ¾ chrl6 19566517 19566796 Rad21 chrl6 19566661 19566971 7888 chrl6 68783509 68783756 Rad21 chrl6 6S783 /.55 68783806 8014 chrl6 89449810 89450050 Rad21 chrl6 89450035 89450132 8108 chrl5 11·? 79888721 Rad?.l chrlS 79888531 79888665 7768 chrl4 23452531 23452821 Rad21 chrl4 23452524 23452626 7330 chrl4 106765095 106765347 Rad21 chrl4 106765150 106765547 10014 chrl2 40200926 40201179 Rad21 chrl2 40200867 40200948 10010 chrl2 44870544 44870784 Rad21 Chrl2 44870489 44870601 6637 chrl2 94823442 94823733 Rad21 chrl2 94823551 94823648 6789 chrl 2 131708696 1 ir,W>!. 2 Rad21 chrl2 131708917 131709011 6917 chrll 11178798 11179060 Rad21 chrll 11178981 11179068 6118 chrll 68495350 68495586 Rad21 chrll 68495324 68495403 6277 chrll 89232091 89232327 Rad21 chrll 89232187 89232269 6342
Chrll 117009443 117009683 Rad21 chrll 117009658 117009785 6431 chrlO 6720207 6720467 Rad21 chrlO 6720409 6720538 5639 chrlO 25985021 W'.W Rad?.l chrlO 25985161 25985282 5694 chrlO 27179886 27180127 Rad21 chrlO 27180081 27180190 5700 chrlO 103817470 103817706 Rad21 chrlO 103817609 103817685 chrlO 127318405 127318652 Rad21 chrlO 127318416 127318526 6012 chrlO 134257172 134257422 Rad21 chrlO 134257406 134257885 v)o-i chrX 16919700 16919920 USF1JSC-8983) chrX 16919869 16919946 9512 chr9 124375819 124376039 USF1JSC-8983) < r<' 124376013 124376103 5493 chr6 2765521 2765741 USF1JSC-8983) chr6 2765487 2765632 3512 chr6 110818727 110818947 USFl_{SC-8983) chr6 110818694 110818788 3865 chr6 166913783 166914001 USFlJSC-8983) chr6 166913967 166914065 4035 chr4 967486 967706 USFlJSC-8983) chr4 967430 967526 2218 chr2 224896177 224896397 USFlJSC-8983) chr2 224896209 224896412 1486 chrl 1624149 1624369 USFlJSC-8983) chrl 1624211 1624313 17 chrl 1624498 1624718 USFlJSC-8983) chrl 1624403 1624654 1 chrl 1677787 1678007 USFlJSC-8983) chrl 1677682 1677934 2 chrl 12156190 12156299 USFlJSC-8983) chrl 12156124 12156284 75 chr22 44849809 44849866 USF1 JSC-89S3) chr22 44849805 44849884 9400 chr22 47666305 47666525 USFlJSC-8983) chr22 47666233 47666375 9411 chrl9 3070602 i07.V,'H. USFlJSC-8983) chrl9 3070760 8689 chrl9 44598332 44598552 USFlJSC-8983) chrl9 44598400 44598496 8828 chr20 61578329 61578480 USFlJSC-8983) chr20 61578471 61578585 9109 chrl8 12377397 12377607 USFlJSC-8983) chrl8 12377506 12377572 8450
Chrl7 17109591 17109956 USFlJSC-8983) chrl7 17109779 17109885 8194 chrl7 38083782 38084002 USFlJSC-8983) chrl7 38083901 38083979 8235 chrl? 76250669 76250745 USFlJSC-8983) chrl7 76250645 7ύ?·:-Υ, \ [ 8375 chrl6 17195571 17195819 USFlJSC-8983) chrl6 17195660 17195747 7915 chrl6 19566912 19567169 USFlJSC-8983) chrl6 19566661 19566971 VPSK chrl6 88946035 88946255 USFlJSC-8983) chrl6 88945968 88946056 8098 chrlS 79888396 79888540 USF1 JSC-89S3) chrl5 79888531 ™R8.NW:¾ 7 chrl4 59743049 59743269 USFlJSC-8983) chrl4 59743054 59743135 7436 chrl 2 109774484 109774704 USFlJSC-8983) chrl2 109774558 109774646 »B¾7 chrl2 132658558 132658778 USFlJSC-8983) chrl2 132658517 132658619 6934 chrl2 132831003 1.52;; 3122.1 USFlJSC-8983) chrl2 132831021 132831096 6936 chrlO 42970950 42971181 USFlJSC-8983) chrlO 42971024 42971122 5759 chrlO 133622547 133622644 USFlJSC-8983) chrlO 133622568 133622648 6038 chr8 76169572 76169832 GATA3 JSC-268) chr8 76169499 76169615 4957 chr8 143851359 143851619 GATA3JSC-268) chr8 143851543 143851627 5195 chr7 921114 921374 GATA3 JSC-268) chr7 921236 921318 4081 chiv 16964727 16964987 6ATA3 JSC-268) chiv 16964933 16965023 4159 chr7 70052701 70052961 GATA3 JSC-268) chr7 70052718 70052798 4310 chr6 25¾.^ ' ¾ GATA3 JSC-268) chr6 2'.i¾. 77 1 25863871 3581 chr6 26145156 26145416 GATA3 JSC-268) chr6 26145275 26145355 3582 chr6 111597997 111598257 GATA3 JSC-268) chr6 111598099 111598226 3873 chr5 76517068 76517328 GATA3 JSC-268) chr5 76517296 76517383 3183 chr5 176264664 176264924 GATA3 JSC-268) chr5 176264742 176264828 3470 chr3 172278773 172279033 GATA3 JSC-268) chr3 172278855 172278964 2091 chr3 192614840 192615100 6ATA3 JSC-268) chr3 192614968 192615068 .".62 chr3 195577820 195578080 GATA3 JSC-268) chr3 195577893 195577977 2184 chr2 212243364 21 24 ii .2 » GATA3 JSC-268) chr2 212243619 212243728 1452 chr2 233428324 233428553 GATA3 JSC-268) chr2 233428386 233428474 1518 chr2 240226155 GA I A WSC Mi chr2 2-102.'5«82 M :>25-!.,K 1545 chrl 171490699 171490959 GATA3 JSC-268) chrl 171490936 171491034 512 chrl 215560154 215560414 GATA3 JSC-268) chrl 215560328 215560443 a(>7 chrl 221785644 221785764 GATA3 JSC-268) chrl 221785629 221785736 690 chrl 24ι.8ϋ87¾0 246868905 GATA3 JSC-268) chrl 246868695 246868804 <ίΟ<· chr21 18873874 18873991 GATA3 JSC-268) chr21 18873881 18873961 9161
Chrl7 .'017 V. iii, 26973286 GATA3 JSC-268) chrl7 26973011 10055 chrl7 38083898 38084158 GAT A3 JSC-268) chrl7 38083901 38083979 8235 chrl5 722i>/¾-> ?;> >(>?-<.v-> 6ATA3 JSC-268) chrlS /22676 ϊ 72267751 7743 chrl4 26165442 26165702 GATA3 JSC-268) chrl4 26165684 26165780 7338 chrl4 56048171 56048431 6ATA3 JSC-268) chrl4 56048179 56048283 7422 chrl3 57685593 57685853 GATA3 JSC-268) chrl3 57685712 57685821 7075 chrl3 82.1 583.Vi GA I A WSC Mi chrl3 S. 18 H') 82448673 7169 chrll 90244915 90245175 GATA3 JSC-268) chrll 90245087 90245173 6345 chrlO 55G r>?': r>(, ' V!*!i GATA3 JSC-268) chrlO r>02 )f-o.? 35624731 rn? chrX 48659985 48660195 c- yc chrX 48660039 48660137 9583 chrX 71933449 71933659 c-Myc chrX 71933490 -. .' i.iW. 9622 chr9 38620550 38620783 c-Myc chr9 38620511 38620596 5325 chr9 115615538 115615748 chr9 11S615745 115615842 5471 chr9 124375800 124376030 c-Myc chr9 124376013 124376103 5493 chr9 138863922 138864136 ΙΙΙΙΙϊΙ ΙΙΙΙΙΙΙΙ chr9 138863933 138864042 chr8 103188033 103188249 c-Myc chr8 103187967 103188070 5039 chr? 4864703 4864913 chr? 4864733 4864848 4117 chr7 101080530 101080740 c-Myc chr7 101080639 101080717 4454 chr7 102 X341: 102fi -Vi83 c-Myc chr7 102004049 102004154 lliii chr7 148761968 148762178 c-Myc chr? 148762028 148762124 4617 chr6 ?7W>?7 c-Myc chr6 >7<> A- ? .'70S».¾2 5512 chr6 3849519 3849729 c-Myc chr6 3849487 3849596 3520 chr6 101448287 101448517 chr6 101448301 101448403 3829
Figure imgf000237_0001
chr2 242597462 242597672 c-Myc chr2 242597622 242597724 1567 chrl ,;: 12244438 12244668 chrl 172 WV6 76
Figure imgf000237_0002
chrl5 101677579 101677809 c-Myc chrl5 101677648 101677779 7827 chrl3 113808651 113808861 c-Myc chrl3 113808710 113808818 7298 chrl2 94823407 94823617 c-Myc chrl2 94823551 94823648 6789 c.hrl2 131708776 131708986 c-Myc chrl2 131708917 131709011 6917 chrll 45123993 45124223 c-Myc chrll 45124152 45124234 6213 chrll 66115507 66115717 c-Myc chrll 66115701 66115785 6263 chrll 68024954 68025363 c-Myc chrll 68025191 68025327 6275
ChrlG W ¾,:48 593458 c-Myc chrlO w; chrlO 27179988 27180198 c-Myc chrlO 27180081 27180190 5700 chrlQ .15 >d 72 4 35624933 c-Myc chrlO 35624602 35624731 5737 chrlO 99478572 99478832 c-Myc chrlO 99478551 99478665 5928 chrY 15664315 15664615 NFKB chrY 15664499 15664605 chrX 87155272 87155642 NFKB chrX 87155486 87155585 9675 chr8 29940405 29940734 F B Chr8 29940717 4813 chr8 129389882 129390207 NFKB chr8 129389913 129390010 5125 chr8 142416250 142416621 NFKB chr8 142.416496 142416596 5177 chr7 92794849 92795187 NFKB chr7 92794879 92794990 4414 chiv 102004137 102004437 NFKB chiv 102004049 102004154 4460 chr7 106436268 106436621 NFKB chr7 106436432 106436526 4481 chrfc 2158145 2158445 NFKB chr6 2158404 2158500 3508 chr6 2940682 2941015 NFKB chr6 2940840 2940933 3514 chr6 52161481 52161806 NFKB chr6 52161778 52161905 3676 chr6 84672323 84672667 NFKB chr6 84672604 84672689 3784 chr6 89435181 ;-Μ4.ί · 2 NFKB chr6 ;M-1352f.'i 89435378 3795 chr6 115318862 115319267 NFKB chr6 115319070 115319164 3892 chr6 15032 5 ?ϊ 150322799 NFKB chr6 150322548 150322626 >J 5 chr5 1641752 1642028 NFKB chr5 1641811 1641910 2937 chrS 114404554 114404906 NFKB c rS 114404634 114404729 530 i chr5 161715602 161715930 NFKB chr5 161715519 161715654 3423 chr4 37075132 37075475 NFKB chr4 ; /:> -!6 37075337 369 chr4 133045351 133045700 NFKB chr4 133045440 133045540 2671 chr3 .' 3fi0 1 -. NFKB chr3 .5W70 3H0 79t> 1644 chr3 119419400 119419730 NFKB chr3 119419620 119419714 1916 chr3 195577748 195578124 NFKB chr3 vvirmm 195577977 2184
Figure imgf000238_0001
chrl9 42807101 42807401 NFKB chrlS 42807266 -12?07377 chrl9 44598220 44598559 NFKB chrl9 44598400 44598496 8828 chrl9 54974762 NFKB chrl9 54975046 5. -> 5 ¾i5 chr20 745005 745305 NFKB chr20 745076 745163 8902 chrl 8 77580110 77580469 NFKB chrlS 77580201 77580310 8653 chrl7 17109625 17109901 NFKB chrl7 17109779 17109885 8194 chrl7 2 O¾ 776 20059234 NFKB chrl7 20059180 20059290 10042
Figure imgf000238_0002
chrl5 22462100 22462376 NFKB chrlS 22462316 22462420 7597 chrlS 79888482 79888771 NFKB chrl5 79888531 7 ? ,Κ chrl5 83479922 83480254 NFKB chrl5 83480014 83480112 7781 chrl4 38576445 38576765 NFKB chrl4 38576575 iSV/i-GCiK 75 /2 chrl4 106765118 106765440 NFKB chrl4 106765150 106765547 10014 chrl3 71865354 71865696 NFKB chrl3 71865441 71865535 7137 chrl2 127256956 127257272 NFKB chrl2 127257076 127257168 6895 chrll 66115478 66115785 NFK8 chrll 66115701 66115785 6263 chrll 115795724 115796218 NFKB chrll 115795944 115796095 6427 chrlO 62110981 62111401 NFKB chrlO 62110925 6211102.7 5812 chrlO 74848116 74848416 NFKB chrlO 74848135 74848222 5853 chrlO 105881313 105881673 NFKB chrlO 105881235 105881318 5948 chrlO 125312614 125312937 NFKB chrlO 125312740 125312814 6003 chrX 48660029 48660285 BRCAlJC-1863) chrX 48660039 48660137 9583 chrX 153607172 153607593 BRCAlJC-1863) chrX 153607264 153607413 9864 chr9 38620490 58..J 0 -.0 BRCAlJC- 1863) chr9 38620511 .;¾.'(i ".9t> 5.525 chr6 3849502 3849762 BRCA1JC-1863) chr6 3849487 3849596 3520 chr3 195577791 195578051 BRCAlJC-1863) chr3 vvirmm 195577977 2184 chrl 1624529 1624596 BRCAlJC-1863) chrl 1624403 1624654 1
Chrl7 4233171 11' i VI 51 BRCAlJC-1863) chrl7 4233406 8163 chrl7 38083762 38084022 BRCAlJC-1863) chrl7 38083901 38083979 8235 chrl6 57334324 57 i l'i^i BRCAlJC-1863) chrl6 57 i 12^fi 57334361 7985 chrlS 69744344 69744604 BRCAlJC-1863) chrl5 69744385 69744482 7732 chrll 66115527 66115787 BRCAlJC-1863) chrll 66115701 66115785 6263 chrX 42806156 42806500 c-Fos chrX 42806148 42806234 9568 chr8 i VSi:¾ J ¾0 33065474 c-Fos chr8 33065139 ¾oo->:>i.-t, 4822 chr7 12700096 12700326 c-Fos chr7 12700231 12700362 4143 chr7 39648823 39649091 c-Fos C.h: 7 39649054 39649163 4219 chr7 158655901 158656015 c-Fos chr7 158655912 158656014 4680 chr6 3978568 397S912 c-Fos chr6 397.¾-.' 3 3521 chr6 10719873 10720123 c-Fos chr6 10719971 10720126 3543 chr5 1564191 1564535 C-Fos ChrS 1564323 1564422 2934 chr5 33049980 33050324 c-Fos chr5 33049885 33050059 3061 chrS 77893119 77893463 c-Fos chrS 77893174 7?0 ?2':2 3188 chr5 83313588 83313932 c-Fos chr5 83313547 83313706 3202 chr5 169565217 169565561 c-Fos chr5 169565459 169565563 3445 chr4 3307390 3307734 c-Fos chr4 3307377 3307483 2230 chr4 152212610 152212954 c-Fos chr4 152212781 152212901 2721 chr3 23141208 23141552 c-Fos chr3 23141420 23141517 1641 chr3 31987800 31988144 c-Fos chr3 31987827 31987945 1666 chr3 32156625 32156875 c-Fos chr3 32156701 32156841 1669 chr3 37745204 .¾ -.' /.·; c-Fos chr3 37745401 37745505 1692 chr3 64866610 64866954 c-Fos chr3 64866726 64866820 1762 chr3 106147485 106147829 c-Fos chr3 106147511 106147661 1884 chr3 119419399 119419743 c-Fos chr3 119419620 119419714 1916 chr3 188719460 188719676 c-Fos chrS 188719492 188719585 21 2 chr3 190956175 190956519 c-Fos chr3 190956192 190956285 2156 chr2 43934406 43934750 c-Fos chr2 43934408 3" ? 1523 9'>5 chr2 85151978 85152228 c-Fos chr2 85152041 85152146 1107 chr2 99011059 99011403 c-Fos chr2 99011046 99011142 1127 chr2 128944593 128944937 c-Fos chr2 128944529 128944661 1204 chr2 190213243 190213587 c-Fos chr2 190213137 190213259 1375 chr2 224896191 224896441 c-Fos chr2 224896209 224896412 1486 chr2 > j 237736919 C-Fos Chr2 : 3 4 237736654 1529 chrl 12156120 12156328 c-Fos chrl 12156124 12156284 75 chrl 22 U 38 S ?;> > . -<?.7 c-Fos chrl 22231610 22231744 109 chrl 72643404 72643748 c-Fos chrl 72643385 72643496 273 chrl 179744228 179744478 c-Fos chrl 179744343 179744438 •j.Vi chrl 196264909 196265253 c-Fos chrl 196264864 196264944 615 chrl 200175494 20 1 ?:>K is c-Fos chrl 200175619 200175695 i-?.a chrl 231526622 231526966 c-Fos chrl 231526800 231526901 729 chrl 236150132 236150476 c-Fos chrl 236150197 236150282 751 chr22 22936529 22936873 c-Fos chr22 22936417 22936532 9336 chr22 47666256 47666506 c-Fos chr22 47666375 9411 chrl9 3070594 3070844 c-Fos chrl9 3070667 3070760 8689 chrl9 8444093 8444343 c-Fas chrl9 8444097 8444291 8711 chr20 33933801 33934051 c-Fos chr20 33933835 33933928 9001 chr20 60833883 c-Fos chr20 60833658 60833747 9095 chrl8 9912397 9912647 c-Fos chrl8 9912497 9912588 8441 chrl8 12377551 12377895 c-Fos chrlS 12377506 12377572 8450 chrl7 4233103 4233447 c-Fos chrl7 4233309 4233406 8163 chrl7 17109686 17109936 c-Fos chrl7 17109779 17109885 8194 chrl7 17536079 17536329 c-Fos chrl7 17536277 17536443 8200 chrl6 19566573 19566917 c-Fos chrl6 19566661 19566971 7B¾ chrl6 83847807 83848151 c-Fos chrl6 83848024 83848139 8069 c rlo 89571836 89572180 c-Fos chrl6 89571991 89572097 8110 chrl5 40874106 40874356 c-Fos chrl5 40874190 40874286 7664
Chrl3 ■i3 " : 1.720 43754470 C-Fos chrlS 43754220 43754410 iOtl, chrl3 80798662 80799006 c-Fos chrl3 80798870 80798987 7163 c.hrl3 100148946 100149196 c-Fos chrl3 100148988 100149109 7228 chrl3 106936677 106937021 c-Fos chrl3 106936719 106936831 7248 chrl3 111903960 111904304 c-Fos chrl3 111904122 111904228 7278 chrl2 5404350 5404694 c-Fos chrl2 5404663 5404776 6496 chrl2 31619772 31620116 c-Fos Chrl2 31620005 31620129 6605 chrl2 116784577 116784921 c-Fos chrl2 116784859 116784973 6856 chrl2 ] ? 725697 i 1272572. ' 3 c-Fos chrl2 127257076 127257168 OB ; chrl2 132863491 132863721 c-Fos chrl2 132863686 132863803 6937 chrll 19637046 19637390 c-Fos chrll 19637066 19637186 132 chrlO 92923677 92924021 c-Fos chrlO 92923953 92924065 5910 chrlO 126301647 126301991 C-Fos chrlO 126301954 126302057 6006 chrX 8769311 8769595 CHD2JN-1250) chrX 8769241 8769354 9492 chrX 48660011 48660307 CHD2JN-125Q) chrX 48660039 48660137 9583 chrX 153607131 153607632 CHD2JN-1250) chrX 153607264 153607413 9864 chi-9 38620578 CHD2J N-1250) chi-9 38620511 38620596 5325 chrS 29940426 29940742 CHD2JN-1250) chrS 29940717 29940806 4813 chr7 1126201 1126517 C.HD2JN-1250) C.h: 7 1126285 1126387 4 ¾ chr6 2765206 2765727 CHD2JN-1250) chr6 2765487 2765632 3512 chr6 3849551 3849630 CHD2JIM-1250) chr6 3849596 3520 chrl 22231615 22231899 CHD2JN-1250) chrl 22231610 22231744 109 chr22 19947130 19947420 CHD2JN-1250) chr22 19947316 19947412 937H chrig 44598374 44598690 CHD2JN-1250) chrl9 44598400 44598496 8828 chrl? 38083728 38084051 CHD2JN-1250) chrl7 38083901 38083979 S2 i-> chrl7 76250543 76250835 CHD2JN-1250) chrl7 76250645 76250741 8375 chrl6 19566777 19567093 CHD2JN-125Q) chrl6 19566661 19566971 7.W chrll 66115478 66115762 CHD2JN-1250) chrll 66115701 66115785 6263 chrlO 28980295 ,:<W:05 9 CHD2JN-1250) chrlO 2ri<lKOH2 28980559 5705 chrlO 134072841 134073125 CHD2JN-1250) chrlO 134072918 134073049 6044 chr9 26975716 26975916 t. i C > C 20! chr9 26975670 26975820 W) chr9 36008856 36009028 CTCFJC-20) chr9 36008952 36009049 5319 chr9 Y4C20V.,'. 38620765 CTCFJC-20) < r<' 38620511 38620596 ~, \V chr9 72547893 72548093 CTCFJC-20) chr9 72547913 72547993 5347 chr8 142416521 142416721 CTCF ..(C-2Q) chr8 142416496 142416596 5177 chr7 143077329 143077514 CTCFJC-20) chr7 143077464 143077619 4599 chr6 3849485 3849635 CTCFJC-20) chr6 3849487 3849596 chr6 3978561 3978669 CTCFJC-20) chr6 3978588 3978673 3521 chr6 SO.MO V; 138024237 CTCFJC-20) chr6 138024074 138024172 chr5 1641745 1642001 CTCFJC-20) chr5 1641811 1641910 2937 chr5 V^i.-S i 5<v>o i ii CTCFJC-20) chr5 58663657 5So 7i.-.J 3141 chrS 119794051 119794251 CTCFJC-20) chr5 119794061 119794139 3314 chr4 88976147 88976347 CTCFJC-20) chr4 88976195 88976277 r>3'.J chr3 133943475 133943675 CTCFJC-20) chr3 133943485 133943564 1958 chr3 .19::5777¾7 195578064 CTCFJC-20) chr3 195577893 195577977 2184 chr2 735930 736130 CTCFJC-20) chr2 736006 736076 838 chrl 12244417 12244617 CTCFJC-20) chrl 12244495 12244576 6 chrig 46513088 46513253 CTCFJC-20) chrl9 46513048 46513130 8834 chrl? 1074123 1074323 CTCFJC-20] chrl7 1074238 1074327 8146 chrl7 75092653 75092829 CTCFJC-20) chrl7 75092816 75092964 8373 chrl6 19565540 19566727 CTCFJC-20) chrl6 19566661 19566971 7.W chrl5 22462051 22462461 CTCFJC-20) chrlS 22462316 22462420 7597 chrlS 79888447 79888699 CTCFJC-20) chrl5 79888531 7 chrl 23452610 23452736 CTCFJC-20) chrl4 23452524 23452626 7330 chrl4 106765091 106765606 i C > [C >0i chrl4 106765150 106765547 10014 chrl4 107251719 107251919 CTCFJC-20) chrl4 107251729 107251888 7587 chrll 11178847 11179047 CTCFJC-20) chrll 11178981 11179068 6118 chrll 45952136 45952336 CTCFJC-20) chrll 45952190 45952271 6216
Chrll 89232095 8 J2 3,\"i5 CTCF ..(C-2Q) chrll 89232187 M 5Λ?υι< i> 1 chrll 117009469 117009669 CTCFJC-20) chrll 117009658 117009785 6431 chrlO 6720266 6720414 CTCFJC-20) chrlO 67.O40'i 6720538 5639 chrlO 27179901 27180101 CTCFJC-20) chrlO 27180081 27180190 5700 chrlO 127318426 127318626 CTCFJC-20) chrlO 127318416 127318526 6012 chrlO 134257215 134257415 CTCFJC-20) chrlO 134257406 134257885 5993 chrX 115127268 115127532 chrX 115127357 115127448 9742 chr8 142416388 142416652 EBF chr8 142416496 142416596 5177 chr7 1126113 1126449 .h: 7 1126285 1126387 chr6 2940905 2941015 EBF chr6 2940840 2940933 3514 chr6 84672599 84672667 EBF chr6 84672604 S4i /2.f.;-;9 .Γ.'8-i chr6 89435269 89435533 EBF chr6 89435264 89435378 3795 chr5 1102769 1103033 f. Br chrS 1102995 1103077 2925 chr5 42467732 42467996 EBF chr5 42467123 42467818 3102 chrS 115793889 119794153 L lif- c rS 119794061 119794139 chr4 133045229 133045493 EBF chr4 133045440 133045540 2671 chr4 154408774 154409038 Ϊ 3!- chr4 154408899 154409319 2723 chr2 735754 736018 EBF chr2 736006 736076 838 chr2 62575116 t>2¾75.?'i6 ΐ Μ chr2 t>2¾75.?fi l 625 /5 iiV! 1045 chr2 82605616 82605880 EBF chr2 82605727 82605880 1095 chr2 231521498 231521762 EBF chr2 231521752 231521847 1510 chr2 242036453 242036717 EBF chr2 242036568 242036665 1561 chrl 15532883 15533015 EBF chrl 15532803 15532924 89 chrl 116777213 116777302 EBF chrl 116777178 116777262 427 chrl 235116932 235117196 F. Bf- chrl 235117168 235117249 745 chr22 21406108 21406372 EBF chr22 21406112 21406221 9331 chr22 50732481 SO 732 ■¥ L lif- chr22 50732704 5448 chr21 34785903 34786167 EBF chr21 34785932 34786030 9222
Chrl7 26698437 ,:(-..->'¾ vm V HV chrl7 ,: 7¾W 7 26698706 8216 chrl6 375099 375363 EBF chrl6 375060 375159 7837 chrl 6 5779t> ¾5 57796319 ΐ Μ chrl6 57795958 577 i:062 7'.)S7 chrl5 23207015 23207279 EBF chrl5 23207107 23207205 10020 chrlS 28984169 2K'">S -m EBF chrlS 28984253 28984350 7604 chrl5 83479922 83480186 EBF chrl5 83480014 83480112 7781
Chrl5 101602378 101602642 r. Bi- chrl5 101602318 101602415 chrl4 59743053 59743317 EBF chrl4 59743054 59743135 7436 chrl3 100028459 100028723 F. iif- chrl3 100028639 10002.8716 J 237 chrl2 40953742 40954006 EBF chrl2 40953847 40953932 6626 chrll 45952103 i'.-.n¾ : ¾ 7 Ϊ 3!- chrll 45952190 45952271 6216 chrlO 74848039 74848303 EBF chrlO 74848135 74848222 5853 chrlO 125312717 125312848 V HV chrlO 125312740 125312814 6003 chr7 102003948 102004224 IRF3 chr7 102004049 102004154 4460 chrlS S7 i.?K fi 32¾2 IRF3 chrl6 ίί 7320000 87329148 8085 chrl4 24105268 24105498 IRF3 chrl4 24105224 24105380 7333 chrX 48660002 48660238 Max chrX 48660039 48660137 9583 chr9 38620511 38620799 Max chr9 38620511 38620596 5325 chr9 124375805 124376015 Max chr9 124376013 124376103 5493 chr9 138863843 138864119 Max chr9 138863933 138864042 5551 c r9 140128571 140128807 Max chr9 140128770 140128880 5568 chr8 76169582 76169818 Max chr8 76169499 76169615 4957 chr? 5518262 5518498 Max chr? 5518333 5518482 4121 chr7 27127663 27127939 Max chr7 27127739 27127841 4186 chr7 50727656 ¾ "/".' /.v-J2 Max chr7 ¾ "/".' /. /i: 50727983 ■J.'S7 chr7 67974636 67974846 Max chr7 67974608 67974687 4280 chr7 102004114 102004415 Max .h: 7 102004049 102004154 4460 chr7 157360797 157361033 Max chr7 157360912 157361008 4659 chr6 2765550 2765796 Max chr6 2?ιΛΛΚ7 27051. 5? 3512 chr6 101448271 101448507 Max chr6 101448301 101448403 3829 chr5 443513 443749 Max Chr5 443593 444175 ? MO 3 chr5 1641754 1642035 Max chr5 1641811 1641910 2937 c r5 150594805 150595041 Max chr5 150594761 150594868 chr5 176264696 176264906 Max chr5 176264742 176264828 3470 chr4 9597171 9597407 Max chr4 9597276 9597415 2273 chr4 189294230 189294360 Max chr4 189294176 189294264 2875 chr3 195577777 195578049 Max chr3 195577977 2184 chr2 735842 736118 Max chr2 736006 736076 838 chr2 224896215 224896491 Max chr2 224896412 1486 chrl 12156065 12156344 Max chrl 12156124 12156284 75 chrl 12612177 12612421 Max chrl 12612417 12612513 80 chrl 22231449 22231799 Max chrl 22231610 22231744 109 chrl 154580253 154580517 Max Chrl 154580161 154580286 464 chrl 230262772 230263016 Max chrl 230262996 230263096 725 chr22 37297971 37298231 Max chr22 37298229 372°S i G 9373 chr21 46549434 46549698 Max chr21 46549585 46549671 9283 chrlS ; , ·ι,: .' bX/tf>i7 Max chrl9 6373061 6373448 Si-61 chrl9 6373427 6373637 Max chrl9 6373587 6373798 8662 chr2Q 55992173 55992409 Max chr20 5¾>!9.? 7 i 9073 chrl8 12377369 12377637 Max chrlS 12377506 12377572 8450 chrl8 77580155 77580391 Max chrl8 77580201 77580310 fi.v; ¾ chrl7 1617923 1618209 Max chrl7 1617853 1617940 8151 chrl7 17109613 17109959 Max chrl7 17109779 17109885 8194 chrl7 29055683 29055919 Max chrl7 29055786 29055917 8219 chrl7 ■6250572 76250782 Max chrl7 76250645 7 2:.-VAU 8375 chrl6 17195526 17195809 Max chrl6 17195660 17195747 7915 chrl6 21552504 21552764 Max chrl6 21552521 21552689 - ¾5 chrl6 24267238 24267474 Max chrl6 24267330 24267430 7943 chrie 89571878 89572142 Max chrl6 89571991 8110 chrl6 89768297 89768533 Max chrl6 89768460 89768554 8115 chrlS 798S8339 79888682 Max chrl5 79888531 79888665 7768 chrl5 101677572 101677808 Max chrl5 101677648 101677779 7827 chrll 66115526 66115790 Max chrll 66115701 66115785 6263 chrll 68024969 68025315 Max chrll 68025191 68025327 6275
Chrll 69980654 69980890 Max chrll 69980726 6284 chrll 72282816 72283080 Max chrll 72282847 72282971 6299 chrlO 99478571 99478835 Max chrlO 99478551 99478665 5928 chrlO 133622453 133622689 Max chrlO 133622568 133622648 6038 chrl7 17109689 17109925 NF-E2JH-230) chrl? 17109779 17109885 8194 chr9 138799466 138799720 Nrfl chr9 138799480 138799699 5521 chr4 967242 967499 Nffl chr4 ■! ,7.130 ΛΊΚ chrl 230262816 230263056 Nrfl chrl 230262996 230263096 725 chrl9 46512968 46513208 Nrfl chrl9 46513048 46513130 chrl7 26698450 26698680 Nrfl chrl7 26698597 26698706 8216 chrl7 WW)?. 38084022 Nrfl chrl7 38083901 38083979 chrl7 76250605 76250835 Nrfl chrl7 76250645 76250741 8375 chrl6 89768311 89768541 Nrfl chrl6 89768460 89768554 8115 chrl5 29149684 29149924 Nrfl chrl5 29149824 29149903 7629 c r9 ;■,(, ! <■»■. & 33619914 p300_{N-15) chr9 33619736 3 ';■-: ! .' 5312 chr9 137518568 137518852 p300_(N-15) chr9 137518528 137518639 5538 chr? 12700104 12700388 P300JN-15) chr7 12700231 12700362 4143 chr7 39648836 39649120 p300JN-15) chr7 39649054 39649163 4219 chr& 46604985 ■JGiiOW) p30 ..(N-15) chr6 46604921 46605015 3655 chr6 137561363 137561647 p300jN-15) chr6 137561589 137561678 3963 chr3 .'?!()« . iS 1 28fJ').'(;0S p300JN-15) chr3 S >!M iO 2W.7".74 1652 chr3 106147453 106147721 p300JN-15) chr3 106147511 106147661 1884 chrl 189586107 189586391 p300_(N-15) chrl 189586194 189586297 '.SI chrl 246868776 246868851 P300JN-15) chrl 246868695 246868804 809
Chrl6 57334354 57334624 p300..{N-15) chrl6 57334258 57334361 7985 chrl4 55023356 55023640 P300JN-15) chrl4 55023585 55023655 7418 chrlO S9500129 89500296 p300_{N-15) chrlO 89500173 89500294 5893 chrlO 99478512 99478796 P300JN-15) chrlO 99478551 99478665 5928 chrlO 103986855 103987139 p300_(N-15) chrlO 103986947 103987039 O I ? chrl6 57334299 57334623 Pol3 chrl6 57334258 57334361 7985 chrX 153607224 153607682 RFX5.JN-494) chrX 153607264 153607413 9864 chr9 36008771 36009027 RFX5JN-494) chr9 36008952 36009049 5319 chr8 29940476 29940758 RFX5JN-494) chr8 29940717 29940806 4813 chr8 145987767 145988037 RFX5JN-494) chr8 145987838 145988031 5209 chr6 2765812 RFX5JN-494) chr6 2765487 6563? 3512 chr6 3849367 3849623 RFX5_(N-494) chr6 3849487 3849596 3520 chr5 1641749 1642005 RFX5JN-494) chrS 1641811 1641910 2937 chr5 178104496 178104756 RFX5JN-494) chr5 178104665 178104770 3473 chr3 192614862 192615122 RFX5JN-494) chrS 192614968 192615068 21 62 chr3 195577830 195578015 RFX5JN-494) chr3 195577893 195577977 2184 chr2 61317702 61317962 RFX5JN-494) chr2 61317637 61317728 1040 chr2 85151903 85152179 RFX5J -494) chr2 85152041 85152146 1107 chr2 203534711 20 ¾:"..v !fi7 RFX5JN-494) chr2 2035. i7 L 3 203534830 1421 chrl 151913607 151913867 RFX5J -494) chrl 151913718 151913859 441 chrl 24t.KiKiVM 246868996 RFX5JN-494) chrl 246868695 246868804 <ίΟ<· chr22 37297970 37298246 RFX5JN-494) chr22 37298229 37298316 9373 chr21 46787642 46787902 RFX5JN-494) chr21 46787875 46787969 9285 chr20 7486343 7486603 RFX5_(N-494) chr20 7486365 7486547 8921 chrl? 31553025 31553321 RFX5JN-494) chrl7 31553161 3 J V 2i>:. 827-. chrl7 38083833 38084093 RFX5JN-494) chrl7 38083901 38083979 8235 chrl6 57334794 RFX5J -494) chrl6 57334258 57334361 r-A'i chrl6 89571905 89572161 RFX5JN-494) chrl6 89571991 89572097 8110 chrlS 79888471 79888727 RFX5.JN-494) chrl5 79888531 7 chrl4 70784157 70784417 RFX5J -494) chrl4 70784135 70784266 7474 chrl 3 100148926 100149186 RFX5JN-494) chrl3 100148988 100149109 77.28 chrlO 89500070 89500326 RFX5JN-494) chrlO 89500173 89500294 5893 chr9 17811073 17811338 S C3Jab9263) ( hr<' 17811295 17811369 ■>.ιω. chr9 26975700 26975936 SMC3_(ab9263) chr9 26975670 26975820 5289 chr9 35008831 36009098 S C3..(ab9263) Chr9 36008952 36009049 5319 chr9 38620568 38620804 SMC3Jab9263) chr9 38620511 38620596 5325 chr9 72547888 7254S124 S C3Jab9263) chr9 72547913 72547993 5347 chr9 92981853 92982121 SMC3Jab9263) chr9 92982118 92982220 5399 chr9 137518596 137518670 S C3_{ab9263) chi-9 l .r. iSi-.W 553 chr8 76169567 76169807 SMC3Jab9263) chr8 76169499 76169615 4957 chr7 113350416 113350676 5 C3..(ab9263) chr7 113350364 113350455 4512 chr7 143077248 143077689 S C3_{ab9263) chr7 143077464 143077619 4599 chr6 2765544 27t >7i½ S C3Jab9263) chr6 27t >4K7 2 7G5t. 57 3512 chr6 3849339 3849712 SMC3Jab9263) chr6 3849487 3849596 3520 chr6 .5 7S7 7 SMC3Jab9263) chr6 .{97S-i8S 397.¾-.' 3 3521 chr5 1641737 1641995 SMC3_(ab9263) chr5 1641811 1641910 2937 chr5 56378428 56378511 SMC3Jab9263) chr5 56378414 56378504 .U 33 chr5 58663692 58663937 SMC3jab9263) chr5 58663657 58663764 3141 c r5 119794021 119794274 S C3j3b9263) chr5 119794061 119794139 3314 chr5 176264694 176264930 SMC3Jab9263) chr5 176264742 176264828 3470 chr4 88975105 88976345 S C3Jab9263) chr4 88976195 88976277 2 HO chr4 189294158 189294223 SMC3Jab9263) chr4 189294176 189294264 2875 chr3 133943456 133943696 5 C3..(ab9263) chr3 133943485 133943564 1958 chr3 195577798 195578051 SMC3Jab9263) chr3 195577893 195577977 2184 chr2 .7 iMMH.'?: S C3Jab9263) chr2 236460813 1525 chrl9 883669 883905 SMC3Jab9263) chrl9 883889 883967 8674 chrl9 Κ3ΗΉ· K S C3Jab9263) chrl9 ":83fi'";f-24 38389695 8803 chrl9 46513026 46513297 SMC3Jab9263) chrl9 46513048 46513130 8834
Chrl7 75092625 75092876 S C3 ..(ab9263) chrl7 75092816 75092964 8 / 5 chrl6 68783507 68783743 SMC3Jab9263) chrl6 68783733 68783806 8014 chrl6 89571813 89572049 S C3Jab9263) chrl6 89571991 89572097 8110 chrlS 22462103 22462343 SMC3Jab9263) chrl5 22462316 22462420 7597 chrlS 79888459 79888711 S C3Jab9263) chrlS 7 8,¾:5 Π 7768 chrl4 23452540 23452809 SMC3Jab9263) chrl4 23452524 23452626 7330 chrl4 106765168 106765408 5 C3..(ab9263) chrl4 106765150 106765547 10014 chrll 11178785 11179052 SMC3Jab9263) chrll 11178981 11179068 6118 chrl l 68024921 68025210 S C3Jab92fi3) chrl l 68025191 V7 t>275 chrlO 6720218 6720465 SMC3Jab9263) chrlO 6720409 6720538 5639 chrlO 27179875 27180125 SMC3Jab9263) chrlO 27180081 27180190 5700 chrlO 103986891 103987127 SMC3jab9263) chrlO 103986947 103987039 5942
ChrlO 125312741 125312981 S C3 ..(ab9263) chrlO 125312740 125312814 6003 chrlO 127318398 127318647 SMC3Jab9263) chrlO 127318416 127318526 6012 chrlO 134257189 134257425 S C3Jab9263) chrlO 134257406 134257885 chr7 102003984 102004214 SPT20 chr7 102004049 102004154 4460 chr9 . .'.!i Mns 2 t- -J. Vbii STAT1 chi-9 27462477 27462590 52^? chr9 108061691 108062051 STAT1 chr9 108062023 108062146 5452 chr7 102004058 102004207 STAT1 .h: 7 102004049 102004154 4460 chr6 11122742 11123102 STAT1 chr6 11122694 11122788 3547 chr5 83313669 K i3 J 5* 77 STAT1 chr5 a m 55 7 83313706 3202 chr5 175824000 175824360 STAT1 chr5 175824293 175824425 3466 chr5 176264606 176264966 STAT1 chr5 176264742 176264828 3470 chrl 22231590 22231860 STAT1 chrl 22231610 22231744 109 chrl 2 »Ύ.>. ύ?»ίΐ 230263127 STAT1 chrl 230262996 ? l: 2hXW> 725 chrl9 44598230 44598590 STAT1 chrl9 44598400 44598496 8828 chrl6 S i2°438 STAT1 chrl6 S7 WOUi) 87329148 8085 chrl5 79888401 79888761 STAT1 chrlS 79888531 79888665 7768 chrll 4414682 4415078 SW1 chrll 4414591 4414685 6098 chrX 42806110 42806394 STAT3 chrX 42806148 42806234 9568 chr9 90084632 90084942 STAT3 chr9 90084791 90084885 5391 chr9 104637881 104638125 STAT3 chr9 104638124 104638245 5444 chr9 12K.Hj ¾V.r> 128463959 STATS < hr<' 128463780 128463881 5510 chr9 140377667 140377917 STAT3 chr9 140377663 140377754 5571 chr8 29940734 29941018 STAT3 chr8 29940717 .7>J«M S0f. 4813 chr8 30859303 30859587 STAT3 chr8 30859306 30859367 4817 chr8 107297973 107298308 STAT3 chr8 107298106 107298182 5050 chr7 126024575 126024819 STAT3 chr7 126024692 126024788 4547 chr6 46604920 46605226 STAT3 chr6 46604921 46605015 ii-r>5 chr6 101448293 101448577 STAT3 chr6 101448301 101448403 3829 chr& 137561301 137561618 SVAV3 chr6 137561589 137561678 3963 chr6 138350131 138350361 STAT3 chr6 138350360 138350557 3910 chr5 91848750 91849034 STATS chr5 91848879 91848982 3220 chr5 135329019 135329270 STAT3 chr5 135328983 135329083 3357 chr5 175893443 STAT3 chr5 175893727 175893826 3467 chr4 95383729 95384051 STAT3 chr4 95383654 95383764 2550 chr4 186631333 186631594 STAT3 chr4 186631274 186631385 2S > chr3 28092372 28092656 STAT3 chr3 28092430 28092524 1652 c r3 106147448 106147816 STAT3 chr3 106147511 106147661 1884 chr3 153599101 153599359 STAT3 chr3 153599357 153599465 2026 chr2 222865106 222865390 STAT3 c r2 222865027 222865183 1482 chrl 200175557 200175818 STAT3 chrl 200175619 200175695 628 chrl 202413939 202414183 SVAV3 chrl 202413918 202413996 636 chrl 230262775 230263030 STAT3 chrl 230262996 230263096 725 chrl 246869055 STAT3 ch l .Μί,Κ ¾9 246868804 809 chrl9 54974813 54975766 STAT3 chrl9 54975046 54975738 8869 chrl9 55297520 55297741 STATS chrl9 55297456 'Λ:.·ΪΓ>4~, chrl8 22726162 22726406 STAT3 chrl8 22726248 22726353 8476
Chrl7 4233184 ΙΙ' ί VI 8 STAT3 chrl7 \ : u ic<) 4233406 8163 chrl6 19566532 19566797 STAT3 chrl6 19566661 19566971 7888 chrl5 43757389 43757679 STAT3 chi-15 43757326 43757412 7671 chrl4 62000272 62000516 STAT3 chrl4 62000319 62000391 7452 chrl3 76181678 76181928 STAT3 chrl3 76181845 76181957 7147 chrl3 106936761 106937011 STAT3 chrl3 106936719 106936831 7248 chrl2 680638 680888 SVAV3 Chrl2 680540 680670 6480 chrl2 127092595 127092879 STAT3 chrl2 127092601 127092680 6893 chrl l 66115468 66115758 STAT3 chrll 66115701 66115785 oh, < chrll 133895187 133895556 STAT3 chrll 133895228 133895364 6471 chrlO 2814317 2814601 STAT3 chrlO 2814276 5611 chrlO 87303168 87303412 STAT3 chrlO 87303147 87303237 5888
ChrlO 89500067 8T.Cit.iV/ STAT3 chrlO 89500173 89500294 WJ } chrlO 99478480 99478825 STAT3 chrlO 99478551 99478665 5928 chrS 26975655 TBP chrS 26975670 26975820 5289 chr9 38620408 38620708 TBP chr9 38620511 38620596 5325 chrS 97060530 97060800 TBP chi-9 97060762 97060846 5416 chr9 108061754 108062054 TBP chr9 108062023 108062146 5452 chr9 128463638 128464008 TBP chr9 128463780 128463881 5510 chr9 137518542 137518842 TBP chr9 137518528 137518639 5538 chr9 138799560 138799830 TBP rhf 138799480 138799699 5521 chr8 29940412 29940738 TBP chr8 29940717 29940806 4813 chrS 33490909 33491179 TBP chrS 33491051 33491160 4825 chr7 92794848 92795158 TBP chr7 92794879 92794990 4414 chr6 2765539 27(,¾n<S TBP chr6 27654 '7 2?6%S/ chr6 10719776 10720076 TBP chr6 10719971 10720126 3543 chr6 28916974 28917290 TBP c r6 28917254 28917326 55'54 chr5 33049998 33050298 TBP chr5 33049885 33050059 3061 chr5 68477725 68478025 TBP chr5 68477934 68478113 3144 chr4 143486988 143487298 TBP chr4 143487163 143487286 2704 chr3 67705923 t>770!,.? i 3 TBP chr3 67705692 67705939 1750 chr3 119419357 119419667 TBP chr3 119419620 119419714 1916 chr3 195577796 195578066 TBP chr3 195577977 2184 chr2 242036382 242036692 TBP chr2 242036568 242036665 1561 chrl 22231503 Λ7231 ? /·· TBP Chrl 22231610 22231744 109 chrl 24743453 24743723 TBP chrl 24743669 24743756 119 chrl 150521573 150522046 TBP chrl 150521576 150521685 45.' chr22 19947198 19947498 TBP chr22 19947316 19947412 9328 ch 21 38938121 38938429 TBP chr21 .¾S9.<S3/i 228 chrl9 44598189 44598479 TBP chrl9 44598400 44598496 8828 chrl9 54974779 5 0 / , 72 TBP chrl9 54975046 5· - ν
chr20 60876945 60877262 TBP chr20 60877210 60877541 9062 chrl7 20059014 20059528 TBP chrl7 20059180 20059290 10042 chrl7 29055572 29055842 TBP chrl7 29055786 29055917 8219 chrl7 38083992 TBP chrl7 38083901 38083979 ;;23-> chrl7 42237285 42237555 TBP chrl7 42237391 42237467 8253 chrl7 7f..-? PViL 76250757 TBP chrl7 76250645 76250741 ;;y/-> chrl6 11904060 11904360 TBP chrl6 11904262 11904361 7895 c.hrl6 19566475 19567123 TBP chrl6 19566661 19566971 7888 chrl6 24267178 24267468 TBP chrl6 24267330 24267430 7943 chrl6 ■\7 U24 57334706 TBP chrl6 57334258 57334361 r:-A'i chrl6 89571905 89572263 TBP chrl6 89571991 89572097 8110 chrie 89768818 TBP chrl6 89768460 89768554 8115 chrl5 31518174 31518484 TBP chrl5 31518461 31518554 7637 chrlS ■i¾?v;.; -i TBP chrl5 43757412 7671 chrl5 69744200 69744500 TBP chrl5 69744385 69744482 7732 chrl4 WW 2 \V:≥7AH TBP chrl4 2 W': 524 23.3S20 753'.)
Figure imgf000246_0001
chrlO 74086520 74086824 TR4 chrlO 74086665 74086769 5851 chr9 975" if, USF2 chr9 26975670 26975820 W) chr9 124375764 124376028 USF2 chr9 124376013 124376103 5493 chr9 138110475 138110725 USF2 rhr 138110626 138110747 ',',Λ'. chr7 67203315 67203389 USF2 chr7 67203296 67203390 4276 chr3 106147563 106147827 USF2 chr3 106147511 106147661 1884 chr2 735830 736086 USF2 chr2 736006 736076 838 chr2 224896182 224896519 USF2 chr?. 224896209 2.1^! -l]2 1486 chrl 12156087 12156364 USF2 chrl 12156124 12156284 75 chrl 230262727 2 '.)2 020 USF2 chrl 230262996 230263096 725 chr22 33961505 33961761 USF2 chr22 33961551 33961650 9360 chr22 ■i?.™82:".5 USF2 Chr22 ■j ?2'¾2:>9 37298316 9373
Ch l9 3070558 3070832 USF2 chrl9 3070667 3070760 8689 chrl8 12 i77.ii,-! 12377634 USF2 chrlS 1 377506 12377572 8450 chrl7 17109684 17109928 USF2 chrl7 17109779 17109885 8194 chrlo 17195575 17195844 USF2 chrl6 17195660 17195747 7915 chrl6 19566904 19567180 USF2 chrl6 19566661 19566971 7888
Chrl6 88946013 88946257 USF2 chrl6 88946056 8098 chrl6 89571857 89572121 USF2 chrl6 89571991 89572097 8110 chrl5 70087627 70087891 USF2 chrlS 70087822. 70087901 775 Ϊ chrlS 79888327 79888633 USF2 chrl5 79888531 79888665 7768 chrl4 59742992 .< -!8 USF2 chrl4 59743135 7436 chrl3 100028410 100028666 USF2 chrl3 100028639 100028716 7227 chrl3 113864531 113864798 USF2 chrl3 113864788 113864905 72™ chrll 66115559 66115823 USF2 chrll 66115701 66115785 6263 chrlO 99478579 99478843 USF2 chrlO 99478551 99478665 V.8 chrlO 133622461 133622725 USF2 chrlO 133622568 133622648 6038 chr3 195577720 195578000 WHIP chr3 195577893 195577977 2184 chr2 242036496 242036776 WHIP chr2 242036568 242036665 1561 chrl 154580076 154580356 WHIP chrl 154580161 154580286 464 chrl4 69282302 69282582 WHIP chrl4 69282279 69282392 7466 c r9 36008826 36009030 Znfl43_ ,16618-1- chr9 36008952. 36009049 5319 chr8 76169602 76169806 Znfl43_ 16618-1- chr8 76169499 76169615 4957 chr? 102004077 102004216 Znfl43.. (16618-1- chr? 102004049 102004154 4460 chr7 113350443 113350647 Znfl43_ 16618-1- chr7 113350364 113350455 4512 chr7 143077346 143077550 Znfl43_ [16618-1- chr7 143077464 143077619 4599 chr6 2765415 2765744 Znfl43_ 16618-1- chr6 2765487 2765632 3512 chr6 3849468 wis? Znfl43_ '16618-1- chr6 3849487 3520 chr6 3978539 3978743 Znfl43_ 16618-1- chr6 3978588 3978673 3521 chr5 1641753 1641957 Znfl43... '16618-1- chr5 1641811 1641910 2937 chr5 176264701 176264905 Znfl43_ 16618-1- chr5 176264742 176264828 3470 chr3 l«V> 78 M 195577948 Znfl43_ ,16618-1- l iir i 195577893 195577977 2184 chrl9 44598303 44598588 Znfl43_ 16618-1- chrl9 44598400 44598496 8828 c.hrl9 46513076 46513280 Znfl43_ ,16618-1- chrl9 46513048 46513130 SH i 5 chrl7 20059072 20059276 Znfl43_ (16618-1- chrl7 20059180 20059290 10042 chrl7 38083782 38084078 Znfl43.. (16618-1- chrl? 38083901 38083979 chrl7 75092655 75092859 Znfl43_ 16618-1- chrl7 75092816 75092964 8373 chrl7 76250536 76250832 Zn l43m (16618-1- chrl7 76250645 76250741 s /b chrl6 17195618 17195822 Znfl43_ 16618-1- chrl6 17195660 17195747 7915 chrl 6 19566530 19566734 Znfl43_ '16618-1- chrl6 19566661 19566971 7B¾ chrl6 19566841 19567045 Znfl43._ (16618-1- chrl6 19566661 19566971 7888 chrl6 24267278 24267482 Znfl43... '16618-1- chrl6 24267330 24267430 7943 chrl5 22462118 22462322 Znfl43_ (16618-1- chrl5 22462316 22462420 7597
Chrl5 79888489 79888693 Znfl43_ ,16618-1- chrl5 79888531 79888665 7kX chrl4 106765172 106765304 Znfl43_ 16618-1- chrl4 106765150 106765547 10014 chrlO 6720236 6720440 Znfl43_ ,16618-1- chrlO 6720409 6720538 5639 chr7 33801870 33802134 ZZZ3 chr7 33802095 33802234 4202 chrl4 74711587 74711851 m ■ i chrl4 74711573 74711671 7478 chrX 22481162 22481432 c- )un chrX 22481183 22481287 9523 chrX 42806181 42806457 c- lun chrX 42806148 42806234 9568 chr9 27462446 27462710 c- Jun chr9 27462477 27462590 5292 chr9 137518563 137518859 iun < r<' 137518528 137518639 r>3K chr8 13733807 13734031 c- Jun chr8 13734002 13734114 4770 chrS 39066471 39066741 c- iun chrS 39066484 39066639 4839 chr7 12700064 12700360 c- Jun chr7 12700231 12700362 4143 chr7 39648864 c- Jun chr7 39649054 39649163 4219 chr7 109797747 109798043 c- Jun chr7 109797646 109797749 4498 chr6 50273427 c- iun chr6 S02 -U7K 50273591 5ί· ?4 chr5 19854035 19854331 c- Jun chr5 19854200 19854301 3013 chr5 33049975 33050291 c- lun chr5 33049885 33050059 3061 chr5 77893201 77893477 c- Jun chr5 77893174 77893252 3188 chr4 ϊ= Ϊ J 36332687 c- lun chr4 5 3 ^ 60 .;.., β.?όν·. 2.;..J7 chr3 28092349 28092645 c- Jun chr3 28092430 28092524 1652 chr3 10" 56·:¾ ί 105366228 lun chr3 105365824 105365932 1882 chr3 106147494 106147747 c- Jun chr3 106147511 106147661 1884 chr3 188719377 188719694 c- Jun l iir > 188719492 188719585 2142 chr3 192614857 192615127 c- Jun chr3 192614968 192615068 2162 chr?. 43934426 43934728 c- Jun chr?. 43934408 995 chr2 55367745 55368029 c- Jun chr2 55368003 55368125 1025 chr2 99011109 99011385 c- Jun chr2 99011046 99011142 1127 chr2 101507873 101508143 c- Jun chr2 101507790 101507891 1132 chr2 104051530 104051800 c- lun chr2 104051628 104051750 1135 chr2 176885265 176885571 c- Jun chr2 176885294 176885398 1335 chr2 2 ; v¾S30 2 i f 7 56812 iun chr2 H77 V.,'.2-l 237736654 1529 chrl 22231445 22231750 c- Jun chrl 22231610 22231744 109 chrl 189586032 189586328 c- Jun chrl 189586194 LS¾R»A62'J 7 chrl 201566766 201567042 c-Jun chrl 201566696 201566793 633 chrl 25026 S/K 230263134 c-Jun chrl 230262996 230263096 725 chrl 231526674 231526950 c-Jun chrl 231526800 231526901 729 chrl 2-i(,H *723 246869019 c-Jun chrl 246868695 246868804 809 chr22 39906820 39907044 c-Jun chr22 39906714 39906863 9380 chr21 18873838 18874108 c-Jun chf-21 18873881 18873961 5161 chr21 38346809 38347079 c-Jun chr21 38346894 38346994 9226 chr20 44731643 44731913 c-Jun chr20 44731744 44731853 9032 chrl7 4233134 4233462 c-Jun chrl7 4233309 4233406 8163 chrl 6 19566576 19566853 c-Jun chrl6 19566661 19566971 7B¾ chrl6 83847791 83848097 c-Jun chrl6 83848024 83848139 8069 chrlo 89571814 89572155 c-Ju chrl6 89571991 89572097 8110 chrl5 45709772 45710075 c-Jun chrl5 45709938 45710050 7679
Chrl4 55 :; *372 c-Jun chrl4 55023585 7418 chrl3 80798710 80798986 c-Jun chrl3 80798870 80798987 7163 chrl3 107928626 107928902 c-Jun chrl3 107928617 10792.8715 7253 chrl2 71055562 71055901 c-Jun chrl2 71055506 71055592 6720 chrl2 116784634 116784910 c-Jun chrl2 116784859 116784973 6856 chrl2 127256920 127257241 c-Jun chrl2 127257076 127257168 6895 chrl2 132863468 132863764 c-Jun chrl2 132863686 132863803 6937 chrlO 89500119 89500311 c-Jun chrlO 89500173 89500294 5893 chrlQ 0.7»2 5 92923984 c-Jun chrlO 9292.V".3 92924065 5910 chr9 138863776 138864172 CtBP2 chr9 138863933 138864042 5551 chrS 145987743 145988139 Cl B^ chrS 145987838 145988031 5209 chr3 66623685 66624081 CtBP2 chr3 66623709 66623817 1766
Chrl6 19566544 19566940 O BP2 chrl6 19566661 19566971 7888 chr5 529278 529562 SUZ12 chr5 529311 529412 2914 chr2 26694935 26695185 5UZ12 c r2 26695063 26695158 936 chr2 238038159 238038409 SUZ12 chr2 238038177 238039981 1531 chr2 ?.;so.«Koe> 238040056 SUZ12 chr2 238038177 238039981 1531 chrl 3034528 3034778 SUZ12 chrl 3034525 3034624 30 chrl 6093299 0f!<i.iS-i« SUZ12 chrl 09.5308 6093478 55 chrl 32238054 32238359 SUZ12 chrl 32238142 32238225 140 chrl 152080708 152080992 SUZ12 chrl 152080869 152080996 456 chrl 152083363 152083647 SUZ12 chrl 152083626 152084811 439 chr20 5 /429317 57429601 SUZ12 chr20 57429515 S7 9061 chrl6 21552592 21552842 SUZ12 chrl6 21552521 21552689 7935 c.hrl3 114175549 114175799 SUZ12 chrl3 114175455 114175568 7302 chrl3 114175549 114175799 SUZ12 chrl3 114175662 114175751 7303 chrY 8897969 8K98 TCF4 chrY SHW L2': ;-:s s23 i f.U chr9 138863845 138864155 TCF4 chr9 138863933 138864042 5551 chr8 29940490 29940800 TCF4 chr8 29940717 29940806 4813 chrS 39066324 39066708 TCF4 chrS 39066484 39066639 4839 chr7 12700176 12700300 TCF4 .h: 7 12700231 J 270 if,2 4143 chr6 2765414 2765724 TCF4 chr6 2765487 2765632 3512 chr6 2WC.T.W 25863918 TCF4 chr6 25863771 WW] 3581 chr6 154859177 154859561 TCF4 chr6 154859393 154859514 4006 chr4 53058698 53059082 TCF4 chr4 53058914 2408 chr4 186631341 186631725 TCF4 chr4 186631274 186631385 2865 chr2 61317533 61317917 TC.F4 chr?. 61317637 6131772.8 1040 chrl 1624288 1624598 TCF4 chrl 1624403 1624654 1 chrl 1624288 1624598 TCF4 chrl 1624211 1624313 17 chrl 1677538 1678054 TCF4 chrl 1677682 1677934 2 chrl 1677538 1678054 TCF4 chrl 1677486 1677588 18 chrl 8320941 8321189 TCF4 chrl 8320950 8321039 67 chrl 100224387 100224973 TCF4 chrl 100224633 100224721 m chrl 151913660 151913970 TCF4 chrl 151913718 151913859 441 chr21 18873477 18874288 TCF4 chr21 18873881 18873961 9161 chrl7 17109487 17109797 TCF4 chrl7 17109779 17109885 8194 chrl7 26698598 26 -.'S9 ;-; TCF4 chrl7 26698597 26698706 8216 chrl6 4511596 4511980 TCF4 chrl6 4511459 4511603 7866 c.hrl6 14967821 14968408 TC.F4 chrl6 14967880 14968000 7906 chrl6 57334308 57334692 TCF4 chrl6 57334258 57334361 7985 chrl6 i»S7H 5242 68783830 TCF4 chrl6 G.W! 73 i ί·8?;·: is 8014 chrl6 89571820 89572204 TCF4 chrl6 89571991 89572097 8110 chrl4 62000221 62000531 TCF4 chrl4 62000319 62000391 7452 chrlS 82448237 82448597 TCF4 chrl3 82448439 82448673 7169 chrl2 12 .27 3 TCF4 chrl2 12 .26S3 1 2562 /υό t>SS5 chrll 47907400 47907784 TCF4 chrll 47907458 47907520 6219 chrlO 103817545 103818029 TCF4 chrlO 103817609 103817685 chrlO 119120789 119121180 TCF4 chrlO 119120930 119121023 5983
Chr9 137518322 137518887 EL 4 Chr9 137518528 137518639 5538 chr7 102004086 102004450 ELK4 chr7 102004049 102004154 4460 c r6 3849329 3849693 EL 4 chr6 3849487 3849596 chrl9 54975239 54975623 ELK4 chrl9 54975046 54975738 8869
Figure imgf000249_0001
chrll 4414624 4414988 ELK4 chrll 4414591 4414685 6098 chrll 68025401 ELK4 chrll 68025191 68025327 6275 chrX 1540639 1541291 KAP1 chrX 1540834 1540943 9464 chrX 44838131 44838581 AP1 chrX 44838476 ΜΗ2.?Γ, 7(> 9574 chr9 94126977 94127427 KAP1 chr9 94127157 94127266 5403 chr9 101864026 101864476 AP1 chr9 101864054 101864170 5431 chr8 11499535 11500107 KAP1 chr8 11499580 11499663 4759 chr8 39724206 Π7 ·ΐ65υ AP1 chr8 39724123 39724211 4846 chr8 145987651 145988158 KAP1 chr8 145987838 145988031 5209 chr7 39921732 39922182 KAP1 chr7 r."52 1 /22 39921846 5222 chr7 133639952 133640402 AP1 chr7 133640066 133640163 4569 chr6 3849140 ■JS J'JVJO KAP1 chr6 ■JS WIK ; .<. .:i J6 3520 chr6 112650022 112650677 AP1 chr6 112650659 112650781 3878 chr6 116176040 116176490 AP1 chr6 116176001 116176101 5897 chr6 133493821 133494271 KAP1 chr6 133493929 133494090 3948 chr5 104393022 104393472 AP1 chr5 104393268 104393363 3266 chr5 175893393 175893817 KAP1 chr5 175893727 175893826 3467 chr4 0.55;; ".'3 20339420 AP1 chr4 20339005 20339116 2318 chr4 163842337 163842787 KAP1 chr4 163842700 163842811 2752 chr3 15661572 156622V. KAP1 chr3 15661477 15661581 1616 chr3 133205536 133205986 AP1 chr3 133205749 133205848 1956 chr2 45768581 45769031 KAP1 c r2 45768726 45768821 1003 chr2 109486536 109486986 AP1 chr2 109486485 109486596 1148 chr2 112803085 112803535 AP1 chr2 112803264 112803415 1160 chrl 21362258 21362708 AP1 chrl 21362636 21362729 108 chrl 2 7^1 36 22791986 AP1 chrl 22791670 227« 1 ί¾ ϊ2 113 chrl 33689737 33690187 KAP1 chrl 33690165 33690290 151 chrl 40960900 40961550 AP1 chrl 40961020 40961463 173 chrl 151913597 151914117 KAP1 chrl 151913718 151913859 441 chrl 152080096 152080790 AP1 chrl 152080245 152080420 Ϊ55 chrl 194388850 194389300 AP1 chrl 194389130 194389293 607 chrl 22.1785680 221786130 KAP1 chrl 221785629 22 j 7857 if, 690 chr22 34730896 34731346 AP1 chr22 34730966 34731056 9363 chr22 49014086 49014536 KAP1 chr22 49014366 49014470 9423 chr21 46456561 46457011 AP1 chr21 46456582 46456673 9281 chrl9 2853130 285. HO- AP1 chrl9 2853105 2.V. ¾,:2S SG87 chrl9 7082866 7083842 AP1 chrl9 7083049 7083177 8708 chrl9 9491902 <54< ? 3': 7 AP1 chrl9 9491833 W2', U 8664 chrl9 44598160 44598610 KAP1 chrl9 44598400 44598496 8828 chrl9 5.17 ! ::S38 53716288 AP1 chrl9 5371 i-522 KS47 chr20 39677388 39677812 KAP1 chr20 39677561 39677643 9018 chrl7 4233071 .¾2.Π4'.<5 AP1 chrl7 ■ A ViC) 4233406 8163 chrl7 16525745 16526272 KAP1 chrl7 16526168 16527131 8179 c.hrl7 1652.6526 16527173 KAP1 chrl7 16526168 16527131 8179 chrl7 17327868 17328318 KAP1 chrl7 17328054 17328152 8197 chrl7 38084266 KAP1 chrl7 38083901 38083979 S2 ¾5 chrl6 19566428 19567151 KAP1 chrl6 19566661 19566971 7888 chrie 57334312 AP1 chrl6 5 ? VM2:">8 57334361 7985 chrl6 89571607 89572208 KAP1 chrl6 89571991 89572097 8110 chrlS 80167549 80167999 AP1 chrl5 80167431 80167.553 7770 chrl4 67426072 67426723 KAP1 chrl4 67425970 67426097 7463 chrlS 66808284 66808734 AP1 chrl3 66808224 66808308 7117 chrl3 67500326 67500776 KAP1 chrl3 67500381 67500454 7121
Chrl2 22765717 22766167 AP1 chrl2 Λ77!,¾&ϊ« ?.1 Μ' ΥΠι i >6!, chrl2 46528029 46528479 KAP1 chrl2 46527982 46528053 6643 c.hrl2 92147404 92147854 KAP1 chrl2 92147505 9214762.7 6785 chrl2 107657715 107658165 KAP1 chrl2 107658015 107658113 6829 chrll 10066106 10066650 KAP1 chrll 10066059 10066157 6112 chrll 58672521 58672971 KAP1 chrll 58672559 58672657 6243 chrlO 43977570 ■J W 'M'2 AP1 chrlO 43978411 5 ?.V5 chr8 29940575 29940959 AP-2alpha chr8 29940717 29940806 4813 chr7 143077215 143077599 AP-2alpha C.h: 7 143077464 143077619 4599 chr7 150760310 150760694 AP-2alpha chr7 150760678 150760783 4628 chr6 3849429 3849813 AP-2alpha chr6 3849487 3849596 3520 chr6 46604807 46605191 AP-2alpha chr6 46604921 46605015 3655 chr4 84205319 84205703 AP-2alpha Chr4 84205458 84205558 2509 chrl 1623733 1624381 AP-2alpha chrl 1624211 1624313 17 chrl H2'.«)022 8299406 AP-2a!pha chrl 8299471 66 chr21 46549259 46549643 AP-2alpha chr21 46549585 46549671 9283 chrlS 883713 884097 AP-2a! ha chrl9 Si-7-ϊ chrl4 62000200 62000381 AP-2alpha chrl4 62000319 62000391 7452 chrl 2 680288 ¾)i>72 AP-2alpha chrl2 680540 680670 6480 chrl2 132863469 132863853 AP-2alpha chrl2 132863686 132863803 6937 chrll 66261251 66261635 AP-2alpha chrll 66261290 66261356 6265 chrll 68024947 68025331 AP-2alpha chrll 68025191 68025327 6275 chrS 145040723 145041093 AP~2gamma chrS 145040791 145040899 5201 chr7 102003865 102004235 AP-2gamma chr7 102004049 102004154 4460 chr7 143077340 143077506 AP- 2g3tTi!ria chr7 143077464 143077619 4599 chr7 150760356 150760726 AP-2gamma chr7 150760678 150760783 4628 chr6 3849430 3849800 AP-2g3rr!ina c r6 3849596 3520 chr6 46604813 46605183 AP-2gamma chr6 46604921 46605015 3655 chr4 84205713 AP-2gamma chr4 84205458 2509 chr2 20841844 20842214 AP-2gamma chr2 20841783 20841872 918 chrl 1623801 K.2 B7.1 AP-2gamma ch l 1624211 1624313 17 chrl 8299079 8299449 AP-2garnma chrl 8299330 8299471 66 chrl 15532910 15533280 AP-2gamrt)a chrl 15532803 15532924 89 chr21 46549286 46549859 AP-2gamma chr21 46549585 46549671 9283
Chrl9 8S3772 884142 AP-2gi>mma chrl9 883889 883967 8674 chrl9 50937886 50938256 AP-2gamma chrl9 50938230 50938327 8855 chrlS 1237/242 12377612. AP- 2g3tTi!ria chrlS 12377506 ! 2 V.7 ,7.' 8450 chrl7 26698325 26698695 AP-2gamma chrl7 26698597 26698706 8216 chrl6 19566487 19566857 AP-2gamiT)a chrlS 19566661 19566971 7PSK chrl4 62000161 62000401 AP-2gamma chrl4 62000319 62000391 7452 chrl2 680298 680668 AP-2gamma Chrl2 680540 680670 6480 chrl2 132863456 132863826 AP-2gamma chrl2 132863686 132863803 6937 chrll 309310 309680 AP-2gamrt)a chrll 309226 WH 17 6070 chrll 66261263 66261633 AP-2garnma chrll 66261290 66261356 6265 chrll 68024952 68025.122 AP~2gamma chrll 68025191 68025327 6275 chrlO 99478468 99478838 AP-2gamma chrlO 99478551 99478665 5928 chr9 138863666 138864116 8AF155 chr9 138863933 138864042 5551 chr5 33049895 33050345 BAF155 chr5 33049885 33050059 3061 c r5 \ ?(,2<-i»n 176265071 BAF155 chr5 176264742 176264828 3470 chr3 106147449 106147899 BAF155 chr3 106147511 106147661 1884 chrl 221785594 221786044 BAF155 chrl 221785629 221785736 690 chrl9 883638 884088 BAF155 chrl9 883889 883967 8674 chrl9 55582878 8AF155 chrl9 55582867 55582926 8876 chrl6 24267212 24267662 BAF155 chrl6 24267330 24267430 7943 chrl 6 89571949 8AF155 chrl6 89571991 S95 097 8110 chrl2 132863427 132863877 BAF155 chrl2 132863686 132863803 6937 chrlO Ή')2 Γ,¾2 < ?'-)2 liW2 BAF155 chrlO 92923953 92924065 5910 chr5 443365 443815 BAF170 chr5 443593 444175 2903 chr3 106147396 106147846 BAF170 l iir i 106147511 106147661 1884 chrll 66115395 66115845 BAF170 chrll 66115701 66115785 6263 chr2 55367677 5536S021 Brgl chr?. 55368003 55368125 1025 chrl 22231418 22231961 Brgl chrl 22231610 22231744 109 chrl7 42237144 42237488 Brgl chrl? 42237391 42 ?.Γ.'-! 7 sr.3 chrl2 680349 680799 Brgl chrl2 680540 680670 6480 chrX 71933520 71933764 CEBPB chrX 71933490 ? 1« > V.<>,: 9622 chr9 33619649 33619893 CEBPB chr9 33619736 33619812 5312 chr9 8877047S 88770694 CEBPB chr9 88770684 88770795 " 7 chr9 126830621 126830877 CEBPB chr9 126830546 126830648 5504 chrS 29:>.;;n>¾3 29940727 CEBPB chrS 29940717 29940806 4813 chr7 64119850 64120066 CEBPB chr7 64119907 64120077 4263 chr7 73173032 73173288 CEBPB Chr7 73173265 73173375 4319 chr7 103755153 103755409 CEBPB chr7 103755284 103755374 4471 chr7 137919411 137919627 CEBPB chr7 137919417 137919513 4» j ^ 9 chr7 148793534 148793790 CEBPB chr7 148793654 148793760 4618 chr6 4113975 4114219 CEBPB chr6 4114175 4114280 -, ? chr6 26702145 26702389 CEBPB chr6 26702208 26702296 3584 chr6 31671743 31671987 CEBPB chr6 31671813 31671911 3608 chr6 33479764 33480020 CEBPB chr6 33479790 33479889 3614 chr6 58167925 58168141 CEBPB chr6 58167997 58168085 3585 chr6 137561427 137561690 CEBPB chr6 137561589 137561678 3963 chr6 154859186 154859404 CEBPB chr6 154859393 154859514 4006 chr5 18171862 18172118 CEBPB chr5 18171845 18171932 3001 chr5 !.^»7.'7 > q 52573010 CEBPB chr5 52572842 52572915 > U? chr5 86678099 86678355 CEBPB chr5 86678240 86678345 3215 chrS 122141254 122141498 CEBPB chrS 122141311 122141386 chr5 138884436 138884653 CEBPB chr5 138884471 138884576 3362 chr5 150594838 150595094 CEBPB chr5 150594761 150594868 chr5 175893453 175893752 CEBPB chr5 175893727 175893826 3467 chr4 36332641 CEBPB chr4 5 3 ^ 60 .;.., β.?όν·. 2.;.. 7 chr4 55649614 55649830 CEBPB chr4 55649675 55649759 2413 chr4 174783954 174784210 CEBPB chr4 174784027 174784134 2813 chr4 186631381 186631597 CEBPB chr4 186631274 186631385 2865 chr3 28092437 28092592 CEBPB l iir i 28092430 28092524 1652 chr3 69510607 69510863 CEBPB chr3 69510538 69510623 1776 chr3 106147417 106147773 CEBPB chr3 106147511 106147661 1884 chr3 114003576 114003828 CEBPB chr3 114003665 114003758 1905 chr3 132587726 Vi?.W 7')K2 CEBPB chr3 132587661 132587744 1954 chr3 170584342 170584598 CEBPB chr3 170584471 170584546 2087 chr3 192614915 192615131 CEBPB chr3 192614968 192615068 2162 chr3 195577798 195578147 CEBPB chr3 195577893 195577977 2184 chr2 44513318 ^ΐ^ί ~ _L3 74 CEBPB chr2 ^ΐ^ί ¾ -L33 4 44513464 998 chr2 55367770 55368054 CEBPB chr2 55368003 55368125 1025 chr2 61317573 61317739 CEBPB chr2 61317637 61317728 1040 chr2 133911681 133911926 CEBPB chr2 133911777 133911868 1219 chr2 2!0&3 3 .5 210633599 CEBPB chr2 210633437 210633539 1443 chrl 22231549 22231805 CEBPB chrl 22231610 22231744 109 chrl 40638285 40638541 CEBPB chrl 40638461 40638585 170 and chrl 113142145 113142401 CEBPB chrl 113142382 113142485 413 chrl 150521374 150521630 CEBPB chrl 150521576 150521685 4'.2 chrl 227640359 227640615 CEBPB chrl 227640543 227640631 716 chrl 228160558 228160814 CEBPB chrl 228160651 228161912 719 chrl 230263075 230263281 CEBPB chrl 230262996 230263096 725 chrl ..'ioBuHb'O 246868946 CEBPB chrl 2.·!ί,Κ ¾95 246868804 809 chr21 18873830 18874087 CEBPB chr21 18873881 18873961 9161 chr21 38938149 38938405 CEBPB chr21 38938279 5S" v. m < ?Vfi
Figure imgf000252_0001
chrlS 58723766 ¾Ρ7?-10Τ. CEBPB chrl9 5f-;'?.r.' H 8/2½ Si^8 chrlS 2309281 2309537 CEBPB chrl8 2309331 2309440 8425 chrl8 20823843 20824099 CEBPB chrlS .■ 3V ΠΠ8 20824016 S4i>« chrl7 4233230 4233474 CEBPB chrl7 4233309 4233406 8163 ch l7 55962594 r.5%.'? .n CEBPB chrl7 :·.5Γ)6.'5.·5 55962611 K.;:.'5 chrl7 75092627 75092871 CEBPB chrl7 75092816 75092964 8373 chrl7 77719666 77719910 CEBPB chrl7 77719715 77719791 ;; >¾.-; chrl6 89571933 89572177 CEBPB chrl6 89571991 89572097 8110
ChrlS 90124380 90124636 CEBPB chrl6 90124299 90124411 8124 chrl5 29149724 29149980 CEBPB chrl5 29149824 29149903 7629 chrlS H7V/4i)i 43757617 CEBPB chrl5 43757326 -UTY.i)2 7671 chrlS 45709793 45710049 CEBPB chrl5 45709938 45710050 7679 chrlS 69744291 69744535 CEBPB chrlS 69744385 697-54482 y, ? chrl4 55023368 55023605 CEBPB chrl4 55023585 55023655 7418 chrl4 62000218 t>2 00J67 CEBPB chrl4 62000391 7152 chrl4 79787585 79787829 CEBPB chrl4 79787571 79787718 7488 chrlS 76181659 76181903 CEBPB chrl3 76181845 76181957 7147 chrl3 113864551 113864795 CEBPB chrl3 113864788 113864905 7299 chrl2 115841622 115841838 CEBPB chrl2 115841622 115841712 68 -i?. chrl2 132863474 132863743 CEBPB chrl2 132863686 132863803 6937 chrll 952.477 "->;»')3 CEBPB chrll 952644 952729 6083 chrll 66115511 66115727 CEBPB chrll 66115701 66115785 6263 chrlO 74848167 74848423 CEBPB chrlO 74848135 74848222 chrlO 89500063 89500380 CEBPB chrlO 89500173 89500294 5893 chrlO 78527 99478801 CEBPB chrlO 99478551 v) S chrlO 103986858 103987152 CEBPB chrlO 103986947 103987039 5942 chrlQ 121644600 121644816 CEBPB chrlO 121644613 121644724 5991 chr9 38620470 38620746 E2F1 chr9 38620511 38620596 5325 chr6 7 5 75 2765751 E2F1 chr6 27G5t.5? 3512 chrl6 19566636 19566912 E2F1 chrl6 19566661 19566971 7888 chrX 153607077 153607337 E2F4 ChrX 153607264 153607413 chr6 2765592 2765679 E2F4 chr6 2765487 2765632 3512 chr4 84205456 84205796 E2F4 chr4 84205458 84205558 .'509 chr3 195577853 195578113 E2F4 chr3 195577893 195577977 2184 chrl7 38083758 38084018 E2F4 chrl? 38083901 38083979 S2.i5 chrl7 76250542 76250802 E2F4 chrl7 76250645 76250741 8375 chr9 J ¾8 ?™<VM> 138800012 E2F6 chr9 138799480 138799699 5521 chr7 25772409 25772713 E2F6 chr7 25772668 25772756 4181 chr7 39649148 39649452 E2F6 chr7 39649054 39649163 4219 chr6 604519 604823 E2F6 chr6 604752 604853 3498 chr6 2765598 2766041 E2F6 chr6 2765487 2/65632 3512 chrl 12612195 12612448 E2F6 chrl 12612417 12612513 SO chrl 2225J 537 227 1 M l E2F6 chrl 22231610 22231744 109 chrl 26333225 26333529 E2F6 chrl 26333300 26333385 124 chrl 150521358 150521662 F.2f 6 chrl 150521576 15052.1685 -i52 chrl 247542105 247542181 E2F6 chrl 247542130 247542214 818 chr20 60875966 60877270 E2F6 chf-20 60877210 60877541 9062 chrl7 17109534 17110015 E2F6 chrl7 17109779 17109885 8194 chrll 68025219 E2F6 chrll 68025191 68025327 6275 chr9 137518541 137518837 GTF2F1JRAP-74) chr9 137518528 137518639 5538 chr5 1641693 1641989 GTF2F1JRAP-74) eh; 5 1641811 1641910 2') 37 chr3 106147560 106147856 GTF2F1JRAP-74) chr3 106147511 106147661 1884 chr3 195577770 195578066 GTF2F1JRAP-74) chr3 195577977 2184 chrl6 89571941 89572237 GTF2F1JRAP-74) chrl6 89571991 89572097 8110
Chrll 66115465 66115761 GTF2Fl..{RAP-74) chrll 66115701 66115785 « 3 chrll 68024999 68025295 GTF2F1JRAP-74) chrll 68025191 68025327 6275 chrX 48659614 48660226 HA-E2F1 chrX 48660039 48660137 chrX 153607058 153607572 HA-E2F1 chrX 153607264 153607413 9864 chr9 38620455 HA-E2F1 chi-9 38620511 38620596 5325 chr9 99983756 99984435 HA-E2F1 chr9 99983766 99983852 5428 chr9 J ¾>5 ?™ 6 138800086 HA-E2F1 chr9 138799480 138799699 5521 chr8 29940351 29941008 HA-E2F1 chr8 29940717 29940806 4813 chrS 143851046 143851695 HA-E2F1 chr8 143851543 143851627 5195 chr7 102003958 102004274 HA-E2F1 chr7 102004049 102004154 4460 chr6 2765461 2766330 HA-E2F1 chr6 2765487 2 /6563? 3512 chr4 84205497 84206076 HA-E2F1 chr4 84205458 84205558 2509 chr2 26256342 HA-E2F1 Chr2 26255885 .762550^. 1-3 ί chr2 110873235 110873685 HA-E2F1 chr2 110873085 110873242 1154 chr2 232570871 232572040 HA-E2F1 chr2 32S7»?20 232570905 1515 chrl 1623857 1624342 HA-E2F1 chrl 1624211 1624313 17 chrl 150521143 150521634 HA-E2F1 chrl 150521576 150521685 452 chrl 152083537 152084138 HA-E2F1 chrl 152083626 152084811 439 chr22 w ww. -«17 < .' /.! 5 HA-E2F1 chr22 "..17 42703 9448 chr21 15646144 15646594 HA-E2F1 chr21 15646177 15646266 9151 chr20 60876946 60877309 HA-E2F1 chr20 60877210 60877541 <χι . chrl9 44598323 44598881 HA-E2F1 chrl9 44598400 44598496 8828 chrl7 17109515 17110103 HA-E2F1 chrl7 17109779 17109885 8194 chrl7 20058956 20059508 HA-E2F1 chrl7 20059180 20059290 10042 chrl6 2.';.2-> ;j 2262981 HA-E2F1 chrl6 22.62738 226282 i 78.58 chrl6 19566437 19567058 HA-E2F1 chrl6 19566661 19566971 7888 chrl6 78132915 78133536 HA-E2F1 chrl6 73 L 32S3') 78132916 8046 chrl6 82044889 82045339 HA-E2F1 chrl6 82045232 82045319 8061 chrie 83847833 f53.V.82i ¾ HA-E2F1 chrl6 S.i. J.' S 83848139 S(V>« chrl6 87739464 87739914 HA-E2F1 chrl6 87739575 87739930 8053 chrl 2 680291 680741 HA-E2F1 chrl2 680540 680670 6480 chrl2 129585667 129586117 HA-E2F1 chrl2 129585544 129585684 6904 chrlO 683167 683617 HA-E2F1 chrlO 683127 OK 13 Ϊ 5595
Figure imgf000253_0001
chr9 138863813 138864133 Inil chr9 138863933 138864042 5551 chr6 3849197 3849517 Inil chr& ■JS WIK; 3.V.;ivJ6 3520 chr5 176264646 176265010 !nil chr5 176264742 176264828 3470 chrl .>.-?:> ,ί,-, ι 22231728 Inil chrl 22231610 22231744 109 chrl 150521313 150521633 inil chrl 150521576 150521685 452 chr22 22936500 22936864 Inil chr22 22936417 22936532 •1 536 chr21 46549358 46549678 Inil chr21 46549585 46549671 9283 chrl7 17109544 17109864 Inil chrl7 17109779 17109885 8194 chrl7 20058998 20059318 Inil chrl7 20059180 20059290 10042 chrl6 2262614 226293 1 Inil chrl6 226273S _v.f>2;;23 ;s chrl6 89571918 89572238 Inil chrl6 89571991 89572097 8110 c.hrl2 680358 680678 Inil chrl2 680540 680670 6480 chrl2 132863582 132863902 Inil chrl2 132863686 132863803 6937 chrlO '•2r>2 5ί·'57 92924017 Inil chrlO 2'52-i^ 92924065 5910 chrX 48660030 48660280 MxilJbHLH) chrX 48660039 48660137 9583 chr9 138863872 138864129 MxilJbHLH) chr9 138864042 5551 chr5 176264720 176264893 MxilJbHLH) chr5 176264742 176264828 3470 chr2 5 i 7<<r.V 55368158 MxilJbHLH) chr2 55368003 55368125 1025 chrl 22231480 22231736 MxilJbHLH) chrl 22231610 22231744 109 chrl 154580138 154580388 MxilJbHLH) chrl 154580161 154580286 464 chr21 46549504 46549754 MxilJbHLH) chr21 46549585 46549671 9283 chrlS 12377359 12377609 Mxil JbHLH) chrlS 12377506 12377572 8450 chrl7 17109672 17109948 MxilJbHLH) chrl7 17109779 17109885 8194 chrl? 38083731 38083981 MxilJbHLH) chrl7 38083901 38083979 $2 i-> chrl6 2262597 2262895 MxilJbHLH) chrl6 2262738 2262823 7858 chrl6 19566586 19566842 MxilJbHLH) chrl6 19566661 19566971 7PSK chrl6 89571933 89572183 MxilJbHLH) chrl6 89571991 89572097 8110 chrll 68025021 68025271 MxilJbHLH) chrll 68025191 68025327 6275 chrlO 99478567 99478817 MxilJbHLH) chrlO 99478551 99478665 5928 chr9 138799611 138799779 Poi2{phasphoS2) chr9 138799480 138799699 5521 chr9 139260734 139261018 Pol2{phosphoS2) chr9 139260901 139260987 5556 chr9 139612098 1.5 173S2 Pol2{phosphoS2) chr9 139612303 L 396 ! 2387 ::5'i8 chr8 37942246 37942530 Pol2(phosphoS2) chr8 37942253 37942347 4836 chr6 2765583 2765867 Po!2(phosphoS2) chr6 2765487 2 HAW 3512 chrl 150521410 150521694 Pol2(phosphoS2) chrl 150521576 150521685 452 chr21 44515211 44515495 Po!2(phosphoS2) chr21 44515439 5259 chrl9 54974771 54975055 Pol2(phosphoS2) chrl9 54975046 54975738 8869 chr20 61578308 61578592 Pol2fphosphoS2) chr20 61578471 61578585 9109 chrl? 17109653 17109937 Pol2{phosphoS2) chrl7 17109779 17109885 8194 chrl 6 89571894 89572178 Poi2{phasphoS2) chrl6 89571991 895 .W7 8110 chrl5 69744288 69744572 Pol2{phasphoS2) chrl5 69744385 69744482 7732 chrll 66115583 66115804 Poi2{phasphoS2) chrll 66115701 66115785 6263 chrll 68025000 68025284 Pol2(phosphoS2) chrll 68025191 68025327 6275 chrlO 99478543 Pol2{phosphoS2) chrlO 99478551 99478665 5928 chrlO 105881285 105881569 Pol2(phosphoS2) chrlO 105881235 105881318 5948 chr3 106147367 106147611 P DMlJVa!90) chr3 106147511 106147661 1884 chrl4 79787478 79787722 PRDMlJVal90) chrl4 79787571 79787718 7488 chr22 31457547 31457791 RPC155 chr22 31457566 5351 chrl6 57333703 57334657 PC155 chrl6 57334258 57334361 7985 chrll 66115412 66115943 RPC155 chrll 66115701 66115785 6263 chr5 56378342 56378612 TFIIIC-110 chr5 56378414 56378504 3133 chrl 6 57 i 34 76 57334508 TFIIIC-110 chrl6 57334258 57334361 7!j :; chrll 66115534 66115754 TFIIIC-110 chrll 66115701 66115785 6263 chrlO 35624490 35624770 TFIIIC-110 chrlO Τ>62 5ί·02 35624731 rn? chr5 443881 444331 ZNF274 chr5 443593 444175 2903 chrS 33049767 33050217 ZNF274 Chr5 33049885 3061 chr3 32032196 32032580 ZNF274 chr3 32032546 32032636 1667 chrl 40960963 40961636 ZNF274 chrl 40961020 40961463 17 · chrl9 9491901 9492535 ZNF274 chrl9 9491833 9492531 8664 chrlS r.2- t si- ¾ 52568989 ZNF274 chrl9 52568484 52570122 SM¾ chrl9 52569595 52570193 ZNF274 chrl9 52568484 52570122 8845 chrl9 53452574 ZNF274 chrl9 53452936 chrl9 53715823 53716758 ZNF274 chrl9 53715821 53716522 8847 chrl9 ¾(·,¾.¾■: 776 56889160 ZNF274 chrl9 56889039 56889160 8890 chrl9 58723514 58723854 ZNF274 chrl9 58723778 58723872 8898 chrl7 16525675 16526364 ZNF274 chrl7 15526168 16527131 8179 chrl7 16526622 16527040 ZNF274 chrl7 16526168 16527131 8179 chrl 202971220 202971470 E A chrl 2029 -.'l.iV- 202971440 f»3K chrl7 38083767 38084011 GRp20 chrl7 38083901 38083979 8235 c.hrl6 19566763 19567007 ( ι¾·20 chrl6 19566661 19566971 7888 chrX 122914362 122914618 HNF4A chrX 122914371 122914480 9779 chr6 154859176 154859432 HNF4A c r6 154859393 154855514 4006 chr5 178691884 178692140 HNF4A chr5 178691893 178691989 3475 chr2 61317593 61317849 HNF4A chr2 61317637 61317728 1040 chr2 114743645 114743901 HNF4A cht-2 114743848 114743923 1165 chr22 19947174 19947430 HNF4A chr22 19947316 19947412 9328 chr22 36038467 36038723 H F4A chr22 36038553 36038634 9370 chrl7 1617889 1618145 HNF4A chrl7 1617853 1617940 8151
Figure imgf000255_0001
chr22 33827374 33827644 MafF_(M8194) chr22 33827465 33827549 9359 chr20 7486530 7486800 MafF_{M8194) chr20 7486365 7486547 8921 chr20 33933850 33934120 MafFJM8194) chr20 33933835 33933928 9001 c.hrl9 48672000 48672270 MafF_{M8194) chrl9 48672061 48672154 8840 chrl8 9912414 9912684 MafF_(M8194) chrl8 9912497 9912588 8441 chrl8 22725140 22726410 MafFJM8194) chflS 22 721.248 22 2. -.3·: 5 8476 chrl7 17536053 17536323 MafF_(M8194) chrl7 17536277 17536443 8200 chrl7 64978635 MafF...(MS194) chrl7 ιΛη78*72 GW .s%8 fi .H I chrl7 69025457 69025727 MafFjM8194) chrl7 69025415 69025513 8350 chrl6 21179569 2 J W MafF_(M8194) chrl6 2 J WOi 21179765 7931 chrl6 55367570 55367840 MafFJM8194) chrl6 55367774 55367873 7980 chrl6 89571884 89572154 Maf'FJM8194) chrl6 89571991 89572097 8110 chrl4 24105201 24105687 MafFJM8194) chrl4 24105224 24105380 7333
Chrl4 MafF..{M8194) chrl4 53085311 7412 chrl3 22986662 22986932 MafF_(M8194) chrl3 22986685 22986767 6969 c.hrl2 2Β37'.»7 52 28380002. MafF_{M8194) chrl2 ? 57')7¾ 8 ¾7'!W (,W7 chrl2 108258536 108258806 MafFJM8194) chrl2 108258469 108258623 6833 chrl2 121812716 121812986 MafF_(M8194) chrl2 121812718 121812830 6870 chr9 33619634 33619898 MafKJab50322) chr9 33619736 33619812 5312 chr9 98426937 98427177 MafK...(ab50322) chr9 98427108 98427195 5.1. ; chr9 102140605 102140845 af _(ab50322) chr9 102140697 102140777 5434 chr9 105123785 105124025 MafK_(ab50322) chr9 105123786 105123877 5 147 chr8 4530013 4530253 MafKJab50322) chr8 4530229 4530311 4730 chrS o.i Vi-.i;? ; 9336167 Maf _(ab50322) chr8 9335887 9335961 T.'-j.-j chr8 17335257 17335497 MafK_(ab50322) chr8 17335257 17335352 4778 chr8 30439213 30439453 af .(3b50322) chr8 30439425 30439511 4815 chr8 69763073 69763313 MafK_(ab50322) chr8 69762996 69763167 4944 chr8 133462426 133462666 afKJab.50322) chr8 133462525 133462628 5137 chr7 2016309 2016549 af Jab50322) chr7 2016387 2016572 4099 chiv 3¾7Si<\S3 39879123 MafKJab50322) chiv 39879001 39879071 122 1 chr7 40258268 40258508 MafK_.(ab50322) chr7 40258137 40258374 4189 chr7 48857492 4BW7 i MafK_(ab50322) chr7 48857605 48857704 4245 chr7 158550328 158550592 af _(ab50322) chr7 158550234 158550344 4678 chr7 158655755 158656019 MafKJab50322) chr7 158655912 158656014 4680 chr6 10720013 10720277 MafK_(ab50322) chr6 10719971 10720126 3543 chr6 10741833 10742073 MafK_iab50322) chr6 10741877 10742066 3493 chr6 28853341 28853581 MafK_(ab50322) chr6 28853240 28853347 3593 chr6 28975437 28975677 Maf _{ab50322) chr6 io?:.fjr» . 3596 chr6 80516408 80516648 af Jab50322) chr6 80516346 80516438 3764 chr6 87712200 87712314 MafKJab50322) chr6 87712299 3794 chr6 98475855 98476095 MafKJab50322) chr6 98475909 98476047 3815 chr& 112869397 112869637 MafK...(ab50322) chr6 112869592 112869737 3881 chr6 114607448 114607688 MafK_.(ab50322) chr6 114607342 114607465 3887 chr6 141337508 141337748 MafK_(ab50322) chr6 14 1 5.575.'" 141337629 S!i 72 chr6 164720605 164720845 MafK _(ab50322) chr6 164720820 164720909 4026 chr5 44959154 44959394 MafKJab50322) chr5 44959209 44959302 3110 chr5 68477861 68478101 MafK_(ab50322) chr5 68477934 68478113 3144 chr5 124050654 124050918 af ..(3b50322) chrS 124050751 124050841 iW' chr5 130823117 130823357 MafK_(ab50322) chr5 130823173 130823269 3346 chr5 141851267 141851507 Maf _{ab50322) chr5 141851319 141851410 ¾7 chr5 171624899 171625139 Maf Jab50322) chr5 171625038 171625105 3454 chr4 4350505 -! ¾()7"Γ. MafKJab50322) chr4 .'.350652 4350794 22 1 ? chr4 180155350 180155590 MafK_(ab50322) chr4 180155561 180155683 2838 chr4 180300112 180300352 Maf ...(ab50322) chr4 180300134 180300272 ,:<S40 chr3 665648 665918 Maf Jab50322) chr3 665695 665818 1572 chr3 4209013 420 '?·: 5 MafKJab50322) chr3 4209071 4209298 1570 chr3 32156641 32156881 MafKJab50322) chr3 32156701 32156841 1669 chr3 ■1258Si-.5b Maf _(ab50322) chr3 42588316 42588444 1706 chr3 44585267 44585507 MafK_(ab50322) chr3 44585354 44585447 1709 chr3 81231725 81231965 MafK_iab50322) chr3 81231812 81231924 1819 chr3 104498251 104498491 MafKJab50322) chr3 104498230 104498381 1879 c r3 117328258 117328498 Maf _{ab50322) chr3 117328328 11732.8420 1909 chr3 125062260 125062500 MafKJab50322) chr3 125062245 125062388 1929 chr3 134394985 MafKJab50322) chrS 134394867 134394941 1961 chr3 176981547 176981817 MafKJab50322) chr3 176981636 176981724 2109 chr2 26864200 26864440 Maf ..(ab50322) chr2 ,:(".8o-l.>J2 26864366 937 chr2 43042929 43043193 MafK jab50322) chr2 43043067 43043151 991 chr2 61152932 61153172 MafKJab50322) chr2 61152976 61153081 1039 chr2 61317450 61317690 MafKJab50322) chr2 61317637 61317728 1040 chr2 76553825 76554065 MafKJab50322) chr2 76553815 76553891 1075 chr2 84101352 84101438 MafK_(ab50322) chr2 84101340 84101491 1104 chr2 118462564 118462637 Maf .(ab50322j Chr2 118462565 118462768 1178 chr2 128202387 128202627 MafKJab50322) chr2 128202478 128202564 1203 chr2 12.8944638 128944878 Maf _{ab50322) chr2 128944529 128944661 1204 chr2 135561667 135561907 Maf Jab50322) chr2 135561881 135561982 1225 chr2 196962640 196962904 MafKJab50322) chr2 196962847 196962963 1403 chr2 202289159 202289360 MafKJab50322) chr2 202289153 202289258 1417 chrl 113142195 113142459 Maf ..(ab50322) chrl 113142382 113142485 413 chrl 180695200 180695464 MafKJab50322) chrl 180695227 180695321 543 chrl 182314550 182314790 MafKJab50322) chrl 182314788 182314886 ".So chrl 223897380 223897620 MafKJab50322) chrl 223897581 223897665 702 chrl ? '?. i-.?.S0h 230263070 Maf Jab50322) chrl 230262996 230263096 725 chr22 33827447 33827541 MafKJab50322) chr22 33827465 33827549 9359
Chr22 42051225 42051465 Maf .(ab50322j chr22 42051261 42051386 9391 chr20 33933828 33934068 MafKJab50322) chr20 33933835 33933928 9001 chrl9 8444157 8444397 MafKJab50322) chrlS 8444097 8444291 8711 chrl9 48672020 48672260 af Jab50322) chrl9 48672061 48672154 8840 chrlS 5019068 5019308 MafKJab50322) chrlS 5019011 5019122 8431 chrl8 9912399 9912639 MafKjab50322) chrl8 9912497 9912588 8441 chrl 8 λ? 72ι>Μ7 M ■ .72W/ MafKJab50322) chrlS 2272!,.?.·! * 227.'(; i J 8476 chrl8 55499280 55499520 MafKJab50322) chrlS 55499317 55499422 8567 chrl7 17536068 17536308 MafKJab50322) chrl7 17536277 17536443 8200 chrl7 62256491 62256731 MafK_(ab50322) chrl7 62256504 62256626 8323 chrl7 64978375 64978615 Maf Jab50322) chrl7 64978472 64978568 i'. Vi i chrl7 69025455 69025695 MafKJab50322) chrl7 69025415 69025513 8350 c.hrl6 21179657 21179746 Maf _{ab50322) chrl6 21179629 21179765 7931 chrl6 55367589 55367829 af Jab50322) chrl6 55367774 55367873 7980 chrl6 78132896 78133136 MafKJab50322) chrl6 73 l i2S3<! 78132916 8046 chrl5 29323788 29324028 MafKJab50322) chrlS 29323899 29324002 7630 chrlS 45709765 45710029 Maf ..(ab50322) chrl5 45709938 45710050 7679 chri s 95790916 95791156 MafK jab50322) chrl5 95790852 95791055 7811 chrl4 24105220 24105460 afK_(ab50322) chrl4 24105224 24105380 7 3 ΐ chrl3 22986728 22986865 MafKJab50322) chrl3 22986685 22986767 6969 chrlS S723 8W i 7 j¾ MafKJab50322) chrl3 ? VA-'H 57232961 7071 chrl3 63918909 63919149 MafK_(ab50322) chrl3 63918990 63919069 7100
Chrl2 28379744 28379984 af ..(3b50322) chrl2 28379786 2« }7-).W 6587 chrl2 108258554 108258794 MafK_(ab50322) chrl2 108258469 108258623 6833 c.hrl2 121812729 121812969 Maf _{ab50322) chrl2 121812718 121812830 6870 chrlO 59404954 59405194 af Jab50322) chrlO 59404936 59405088 5782 chrlO 86162043 86162283 Maf Jab50322) chrlO 86162116 86162190 chr9 33619702 33619853 Maf JSC-477) chr9 33619736 33619812 5312 chr9 38620679 Maf ..(SC-477) chr9 38620511 38620596 5.*25 chr9 102140594 102140838 MafKJSC-477) chr9 102140697 102140777 5434 chrS 4530018 4530262 Maf'KJSC-477) chrS 4530229 4530311 mo chr8 9335929 9336173 MafKJSC-477) chr8 9335887 9335961 4754 chrS S.iKOSMi 52831112 MafKJSC-477) chrS 52830847 52830924 4882 chr8 69763059 69763303 MafKJSC-477) chr8 69762996 69763167 4944 chr7 158550577 MafKJSC-477) chr7 158550234 lb¾r.b 34-i 4678 chr7 158655827 158656071 MafKJSC-477) chr7 158655912 158656014 4680 c r6 10720113 10720241 M3fKJSC-477) chr6 10719971 10720126 chr6 28853331 28853575 MafKJSC-477) chr6 28853240 28853347 3593 chr6 ;S3 ¾ J204 78334508 MafKJSC-477) chr6 73 Π 1472 78334565 3755 chr6 87712184 87712428 MafKJSC-477) chr6 87712299 87712397 3794 chr& 98475848 98476092 MafKJSC-477) chr6 98476047 3815 chr6 112869421 112869665 MafKJSC-477) chr6 112869592 112869737 3881 chr6 114607443 114607687 MafKJSC-477) chr6 114607342 114607465 5SS7 chr5 1564209 1564453 MafKJSC-477) chr5 1564323 1564422 2934 chr5 124050689 124050933 MafKJSC-477) chr5 124050751 124050841 5?': chr3 665683 665927 MafKJSC-477) chr3 665695 665818 1572 chr3 42588365 42588609 MafKJSC-477) l iir i 42588316 42588444 1706 chr3 67705779 67706023 MafKJSC-477) chr3 67705692 67705939 1750 c r3 117328253 117328497 MafKJSC-477) chr3 117328328 11732.8420 1909 chr3 134394769 134395013 MafKJSC-477) chr3 134394867 134394941 1961 chr3 176981563 176981807 MafKJSC-477) chr3 176981636 176981724 2109 chr2 26864223 26864467 MafKJSC-477) chr2 26864292 26864366 937 chr2 43042941 43043185 MafKJSC-477) chr2 43043067 43043151 991 chr2 61317446 61317690 MafKJSC-477) chr2 61317637 61317728 1040 chr2 84101235 84101479 MafKJSC-477) chr2 84101340 84101491 1104 chr2 128944625 128944869 MafKJSC-477) chr2 128944529 128944661 1204 chr2 196962665 196962909 MafKJSC-477) chr2 196962847 196962963 1403 chr2 202289188 202289276 MafKJSC-477) chr2 202289153 202289258 1417 chrl 4016599 4016843 MafKJSC-477) Chrl 4016840 4016929 44 chrl 113142211 113142455 MafKJSC-477) chrl 113142382 113142485 413 chrl 180695252 180695496 MafKJSC-477) chrl 180695227 180695321 543 chrl 223897377 223897621 MafKJSC-477) chrl 223897581 223897665 702 chr22 A Wi. ) MafKJSC-477) chr22 33827465 9359 chr20 33933802 33934046 MafKJSC-477) chr20 33933835 33933928 9001 chrl9 48672014 MafKJSC-477) chrl9 48672061 48672154 8840 chrl8 22726146 22726390 MafKJSC-477) chrlS 22726248 22726353 8476 chrl7 17536068 17536312 MafKJSC-477) chrl7 17536277 17536443 8200 chrl7 69025491 69025735 MafKJSC-477) chrl7 69025415 69025513 8350 chrl6 21179591 21179835 MafKJSC-477) chrl6 21179629 21179765 7931 chrl6 55367580 55367824 MafKJSC-477) chrl6 55367774 55367873 7980 chrl6 78132882 78133126 MafKJSC-477) chrl6 78132839 78132916 8046 chrl6 89571938 89572182 MafKJSC-477) chrl6 89571991 89572097 8110 chrl4 24105216 24105460 MafKJSC-477) chrl4 24105224 24105380 73 Π chrl3 22986676 22986920 MafKJSC-477) chrl3 22986685 22986767 6969 chrl3 63918913 63919157 MafKJSC-477) chrl3 63918990 63919069 7100 chrl2 28379741 28379985 MafKJSC-477) chrl2 28379786 28379892 6587 chrl 2 108258574 108258818 MafKJSC-477) chrl2 108258469 108258623 6833 chr6 2765408 2765712 SREBP1 chr6 2765487 2765632 3512 chr6 17744807 17745111 SREBP1 chr6 17745086 17745402 3494 chr2 220065476 220065823 SREBP1 chr2 220065792 220065897 1474 chrlS 12377500 12377804 SREBP1 chrlS 12377506 12377572 8450 chrl7 17109595 17109899 SREBP1 chrl7 17109779 17109885 8194 chrll 118559177 118559481 SREBP1 chrll 118559393 118559550 (vl .i chrl6 57334357 57334633 SREBP2 chrl6 57334258 57334361 7985 chrX 42806087 42806467 GAT.A-2 chrX 42806148 42806234 9568 chr9 84227998 84228342 GATA-2 chr9 84227929 84228048 5378 chr9 108061730 108062093 GATA 2 chr9 108062023 108062146 5452 chr9 137607883 137608227 GATA-2 chr9 137607871 137607955 5540 chrS 1487447 1487791 (JA1 -\ 2 chrS 1487776 1487871 4711 chr7 39648639 39649317 GATA-2 chr7 39649054 39649163 4219 chr7 .i b 7 157361211 GATA-2 chr7 157360912 157361008 4659 chr6 604530 604800 GATA-2 chr6 604752 604853 3498 chr6 3978551 .5 7S871 GATA-2 chr6 397.¾-.' 3 3521 chr6 154351799 154352020 GATA-2 chr6 154351785 154351889 4002 c r6 164109921 164110265 (ΊΛ ί Λ-2 chr6 164109836 164109964 4023 chr5 33049976 33050356 GATA-2 chr5 33049885 33050059 3061 chrS ;-: 53 i ίί '.ν 83314037 GATA-2 c rS 83313547 83313706 5202 chr5 134717871 134718141 GATA-2 chr5 134717838 134717942 3356 chr5 176264448 1 i:,:i".-V l GATA 2 chr5 \ 7i:,:G-V/A?. 176264828 3470 chr4 3307323 3307772 GATA-2 chr4 3307377 3307483 2230 chr4 120400236 120400329 GATA-2 chr4 120400257 120400341 2626 chr3 58737875 58738219 GATA-2 chr3 58737912 58738011 1747 chr3 52235847 62236191 UA1 -\ 2 chr3 62235777 622 YW- 1757 chr3 64866589 64866969 GATA-2 chr3 64866726 64866820 1762 chr3 74801527 74801871 jAi A 2 l iir i 74801414 74801563 1787 chr3 183276216 183276596 GATA-2 chr3 183276383 183276533 2128 c r3 188719424 188719644 (ΊΛ ί Λ-2 chr3 188719492 188719585 2 142 chr3 190956143 190956523 GATA-2 chr3 190956192 190956285 2156 chr2 99010866 99011246 GATA-2 chr2 99011046 99011142 1127 chr2 207083858 207084202 GATA-2 chr2 207083857 207083944 1430 chrl 22231495 22231844 GATA 2 chrl 22231610 22231744 109 chrl 51186794 51187064 GATA-2 chrl 51186859 51186947 207 chrl 5 630 1,7 :·.2.., 40 7 GATA-2 chrl 52630187 52630271 212 chrl 56844392 56844736 GATA-2 chrl 56844529 56844610 222 chrl 221785442 22 ! /S-MS? GATA-2 chrl 2 ! 221 ;';■;!-: -.'36 f.90 chrl 230262840 230263110 GATA-2 chrl 230262996 230263096 725 chrl 236150023 236150403 CjAi A 2 Chrl 236150197 5G 1502«2 751 chr20 36823912 36824292 GATA-2 chr20 36824062 36824143 9012 chr20 61420035 61420379 GATA-2 chf20 61420100 61420192 9106 chr20 61578283 61578627 GATA-2 chr20 61578471 61578585 9109 chrlS 68140786 68141130 GATA-2 chrlS 68141117 68141195 8595 chrl? 42237334 42237604 GATA-2 chrl7 42237391 42237467 8253 chrl 6 57 i 34 -16 57334630 GATA-2 chrl6 57334258 57334361 7<iS5 chrl6 67086641 67086985 GATA-2 chrl6 67086784 67086879 8009 chrl6 85286010 UA1 -\ 2 chrl6 85285821 85285917 8075 chrl5 29149692 29149962 GATA-2 chrl5 29149824 29149903 7629 chrl5 34934609 34934753 GATA-2 chrl5 34934736 34934839 7650 chrl5 42185980 42186280 GATA-2 chrl5 42186057 42186165 7668 chrl5 79658103 79658447 (ΊΛ ί Λ-2 chrlS 79658363 79658447 7766 chrl4 56048127 56048507 GATA-2 chrl4 56048179 56048283 7422 chrl3 99612556 59612936 GATA-2 chrl3 59612767 99612867 7225 chrl3 106936733 106937113 GATA-2 chrl3 106936719 106936831 7248 chrl3 114790943 114791287 GATA 2 chrl3 114790914 114791001 7310 chrl2 71055456 71055836 GATA-2 chrl2 71055506 71055592 6720 chrl l "■■.2»3S 953002 GATA-2 chrll 952644 952729 .^ f chrll 65975082 65975426 GATA-2 chrll 65975187 65975296 6262 chrll 66115381 66115861 UA1 A, 2 chrll 66115701 66115785 6263 chrlO 85408472 85408852 GATA-2 chrlO 85408377 85408490 5882 chrlO 101913023 101913411 CjAi A 2 chrlO 101913010 101913151 5934 chrlO 120015876 120015971 GATA-2 chrlO 120015967 120016051 5986 chrX 48660026 48660342. CCNT2 chrX 48660039 48660137 9W 3 chr8 29940472 29940939 CCNT2 chr8 29940717 29940806 4813 chiv 143077460 143077776 CCNT2 chiv 143077464 143077619 4599 chr6 604554 604870 CCNT2 chr6 604752 604853 3498 chr& 2765600 2765716 CCNT2 chr6 2765487 2765632 3512 chr6 31782175 31782491 CCNT2 chr6 31782084 31782199 3609 chrl 3418449 3418765 CCNT2 chrl 34 § ¾ ! 5 3418652 55 chrl 22231487 22231962 CCNT2 chrl 22231610 22231744 109 chrl 150521339 150521655 CCNT2 chrl 150521576 150521685 ■152 chrl 230262714 230263030 CCNT2 chrl 230262996 230263096 725 chrl9 6372838 6373154 CCNT2 chrl9 6373061 6373448 8661 chrl7 17109711 17109915 CCNT2 chrl7 17109779 17109885 8194 chrl? 20059043 .>oovi.;v> CCNT2 chrl7 20059180 10042 chrl7 38083698 38084014 CCNT2 chrl7 38083901 38083979 8235 chrl7 76250533 76250849 CCNT2 chrl7 76250645 76250741 S37!i chrl6 19566609 19566925 CCNT2 chrl6 19566661 19566971 7888 chrlS 45709904 45710027 CCNf 2 chrl5 45709938 45710050 7679 chrS 29940483 29940767 GTF2B chrS 29940717 29940806 4813 chr6 28917269 6TF2B chr6 28917254 2 ) L7 i2» 3594 chrl 22231427 22231711 GTF2B chrl 22231610 22231744 109 chrl2 131713324 131713608 GTF2B chrl2 131713564 131713705 6918 chrX 153607082 153607386 HMGN3 chrX 153607264 153607413 9864 chr8 29940468 29940989 HMGN3 chr8 29940717 9<M 30i> 4813 chr6 604577 604881 HMGN3 chr6 604752 604853 3498 c r6 2.7655S4 2765888 HMGN3 chr6 7654 * 7
chrl 22231447 22231751 HMGN3 chrl 22231610 22231744 109 chrl 150521329 150521633 H GN3 chrl 150521576 150521685 452 chrl 230262797 230263101 HMGN3 chrl 230262996 230263096 725 chr22 19947292 19947596 H GN3 chr22 19947316 19947412 '■I?.?. chrl9 6372814 6373118 HMGN3 chrl9 6373061 6373448 8661 ch l 7 1617896 1618200 H GN3 chrl7 1617853 1617940 8151 chrl7 17109710 17110014 HMGN3 chrl7 17109779 17109885 8194 chrl7 38084016 HMGN3 chrl7 38083901 38083979 K2V, chrl6 19566656 19566960 HMGN3 chrl6 19566661 19566971 7888
Chrl6 8·) ϊο8 ½ ί V)7l> (,-:>b HMGN3 chrl6 8Τ/!,84 ,0 89768554 8115 chrl5 45709840 45710144 HMGN3 chrl5 45709938 45710050 7679 chrX 1 5i-0V! 57 153607468 IRF1 chrX 153607264 153607413 .¾4 chr9 138799481 138799765 IRF1 chr9 138799480 138799699 5521 chrS 29940624 29940908 I F1 chrS 29940806 4813 chr6 2765439 2765723 IRF1 chr6 2765487 2765632 3512 chr5 M J. »> 6445013 IRF1 eh; 5 6444783 6444903 >2 chr2 55367753 55368037 IRF1 chr2 55368003 55368125 1025 chrl 22231584 22231868 IRF1 chrl 22231610 109 chrl 230262859 230263143 IRF1 chrl 230262996 230263096 725 chrl9 ϋ.Γ.'3-i .l f»3 7 IRF1 chrl9 6373061 6373448 8661 chrig 6373353 6373637 IRF1 chrl9 6373587 6373798 8662 c.hrl9 54975098 54975195 IRF1 chrl9 54975046 54975738 chr20 45501291 45501575 IRF1 chr20 45501398 45501505 9037 chrl8 12377371 12377655 IRF1 chrlS 12377506 12377572 8450 chrl7 17109700 17109911 IRF1 chrl7 17109779 17109885 8194 chrl7 20059092 IRF1 chrl7 20059180 20059290 10042 chrl7 26698426 26698710 IRF1 chrl7 26698597 26698706 8216 chrl 7 38084073 IRF1 chrl7 38083901 8235 chrl6 87328945 87329229 IRF1 chrl6 87329060 87329148 8085 chrlo 89768449 89768608 IRF1 chrl6 89768460 89768554 8115 chr9 33619747 33619859 NF-E2 chr9 33619736 33619812 5312 chr3 176981572 176981776 N ;" - !." ; l iir i 176981636 176981724 2109 chr2 128944634 128944838 NF-E2 chr2 128944529 128944661 1204 chrl 12156130 12156334 Nf- 2 chrl 12156124 12156284 / -. chrl7 17109726 17109930 NF-E.2 chrl7 17109779 17109885 8194 chrX 3088212 3088516 NF-YA chrX 3088505 9453 chrX 53506303 53506607 NF-YA chrX 53506408 53506501 9598 chrX 71388936 71389240 NF-YA chrX 71389028 71389120 9621 chrX 77043600 77043904 F-YA chrX 77043627 77043724 9643 chrX 105586391 105586695 NF-YA chrX 105586506 105586668 9705 chrX 111352656 111352800 NF-YA chrX 111352775 111352851 9730 chrX 115381882 115382186 NF-YA chrX 115381873 115382183 9706 chrX 116381971 116382275 NF-YA chrX 116381897 116382151 9750 chrX 118164108 118164412 NF-V'A chrX 118164115 118164309 chrX 118468203 118468507 NF-YA chrX 118468292 118468366 9764 chrX 119025199 119025503 NF-YA chrX 119025181 11902.5255 y767 chrX 150723143 150723648 NF-YA chrX 150723421 150723528 9856 chrX 153155791 153155925 NF-YA chrX 153155773 153155862 5861 chrX 153606996 153607499 NF-YA chrX 153607264 153607413 9864 chr9 10911499 10911803 NF-YA chr9 10911279 10911564 5214 chr9 27093384 27093688 NF-YA chr9 27093284 27093391 5290 chr9 81046010 81046314 NF-YA chr9 81046068 81046159 :" !,H chr9 90723786 90723963 NF-YA chr9 90723745 90723834 5393 chr9 93190192 93190496 NF-YA rhf •■ 51 "02<i7 93190515 5400 chr9 96625146 96625450 NF-YA chr9 96625253 96625436 5372 chr9 W?. 96644196 NF-YA Chr9 96643971 96644073 5414 chr9 97439159 97439293 NF-YA chr9 97439215 97439308 5419 c r8 33490921 33491097 NF-YA chr8 33491051 33491160 4825 chr8 40903249 40903553 NF-YA chr8 40903473 40903568 4849 chr8 50339491 50339795 NF-YA chrS 50339570 50339640 4876 chr8 54349590 54349894 NF-YA chr8 54349720 54349886 4891 chr8 54371950 54 V/ .' ?. - NF-YA chr8 54371958 4893 chr8 76090330 76090634 NF-YA chr8 76090555 76090662 4956 chr8 S379 5 2 4 NF-YA chr8 83793651 83793752 4977 chr8 116049477 116049781 NF-YA chr8 116049400 116049501 5083 chrS .IS.i 16239.5 133462697 NF-YA chrS 133462525 133462628 5 137 chr7 2016247 2016676 NF-YA chr7 2016387 2016572 4099 chr7 16983526 NF-YA Chr7 16983120 16983355 4134 chr7 17005370 17005628 NF-YA chr7 17005284 17005423 4160 chr7 20628781 20G2° S': NF-YA chr? 20628941 20629147 4135 chr7 23232965 23233269 NF-YA chr7 23233027 23233099 4172 chiv 23894466 23894770 NF-YA chiv 23894664 23894753 4176 chr7 32245083 32245233 NF-YA chr7 32245023 32245135 4196 chr7 -. 7t>2..,H i 27i, 7 > NF-YA .h: 7 5627!,.? 75 36276378 4208 chr7 38215313 38215465 NF-YA chr7 38215359 38215533 4217 chr7 40937419 40937723 NF-YA chr7 40937380 40937490 4225 chr7 70287522 70287826 NF-YA chr7 70287566 70287653 4312 chr7 74100305 74100609 NF-YA chr7 74100404 74100498 4321 chr7 91085934 91086162 NF-YA chr7 91086041 91086133 4406 c r7 <U 3 453 i 94335640 NF-YA chr7 94335419 94335493 4421 chr7 102003953 102004257 NF-YA chr7 102004049 102004154 4460 chr7 105682382 106682686 NF-YA chr7 106682502 106682576 4483 chr7 120700474 120700778 NF-YA chr7 120700519 120700671 4528 chr7 124939126 124939430 NF-YA chr7 124939364 124939469 4542 chr7 132582892 132583196 NF-YA chr7 132583149 132583221 4565 chr7 134063483 134063787 NF-YA .h: 7 134063535 134063629 4571 chr7 146484738 146485042 NF-YA chr7 146484858 146484964 4610 chr7 158655809 158656163 NF-YA chr7 158655912 158656014 4680 chr6 2765489 2765596 NF-YA chr6 2765487 2765632 3512 chr6 3254317 3254691 NF-YA Chr6 3254383 3254545 3489 chr6 6953178 6953521 NF-YA chr6 6953080 6953405 3491 c r6 9041495 9041799 NF-YA chr6 9041433 9041744 .U- chr6 10172512 10172816 NF-YA chr6 10172506 10172613 3542 chr& 10719831 10720135 NF-YA chr6 10719971 10720126 3543 chr6 10741899 10742219 NF-YA chr6 10741877 10742066 3493 chr& 17201304 17201517 NF-YA chr& 17201221 17201336 3560 chr6 17744905 17745209 NF-YA chr6 17745086 17745402 3494 chr6 28917023 28917297 NF-YA chr6 28917254 28917326 3594 chr6 31164058 31164229 NF-YA chr6 31163989 31164063 3607 chr6 55816026 55816330 NF-YA chr6 55815944 55816152 3640 chr6 67364815 67365119 F-YA chr6 67365069 67365217 3724 chr6 7.Ϊ.5 6 72396738 NF-V'A chr6 72396442 -.'?.i r» i r: .r.' j-.i chr6 104894957 104895095 NF-YA chr6 104894945 104895043 3844 c r6 112698176 112.698480 NF-YA chr6 112698368 112698469 3879 chr6 117956325 117956695 NF-YA chr6 117956427 117956519 3904 chr6 115337217 119337521 NF-YA c r6 119337127 YV? chr6 140018502 140018806 NF-YA chr6 140018755 140018827 3970 chr& 167093736 167093976 NF-YA chr6 167093511 167093744 4038 chr5 10066391 10066600 NF-YA chr5 10066404 10066479 2973 chr5 14455232 1 1-1555 if, NF-YA .h: 5 1 1-1555.' 3 14455707 2!i¾ chr5 16990523 16990827 NF-YA chr5 16990766 16990840 2998 chr5 17063081 17063288 NF-YA chr5 17062978 17063085 2999 chr5 20613154 20613458 NF-YA chr5 20613356 20613449 3016 chrS 39785593 39785856 NF-YA chrS Π7Κ5 ?IK VJ78'¾S«1 ifi'JC chr5 44007104 44007408 NF-YA chr5 44007325 44007422 3108 c r5 44959279 44959410 NF-YA chr5 44959209 44959302 3110 chr5 55544926 55545325 NF-YA chr5 55545074 55545234 3112 chr5 66076488 66076792 NF-YA chr5 66076527 66076705 3143 chr5 68477799 68478103 NF-YA chr5 68477934 68478113 3144 chr5 96743572 96743876 NF-YA chr5 96743409 96743603 ■j.'-r. chr5 100842418 100842722 NF-YA chr5 100842370 100842621 3254 chr5 101826566 101826870 NF-YA .h: 5 101826766 101826840 5256 chr5 102088393 102088697 NF-YA chr5 102088234 102088545 3257 chr5 .l ! 2 9.i52 112793824 NF-YA chr5 112793517 112793674 .'293 chr5 114404451 114404755 NF-YA chr5 114404634 114404729 3301 chrS 123284419 123284723 NF-YA chrS 123284521 123284709 chr5 124311214 124311518 NF-YA chr5 124311514 124311620 3327 chrS 126518285 126518589 NF-YA c rS 126518347 126518485 chr5 130823170 130823369 NF-YA chr5 130823173 130823269 3346 chr5 132383495 NF-YA chr5 132383519 132383716 chr5 158546977 158547198 NF-YA chr5 158546651 158547055 3492 chr5 171624769 171625053 NF-YA c.h; 5 171625038 171625105 3454 chrS 178120535 178120839 NF-YA chr5 178120698 178120810 3474 chr4 4350629 4350708 NF-YA chr4 4350652 4350794 242 chr4 17767665 17767983 NF-YA chr4 17767807 17767882 2303 chr4 17767665 17767983 NF-YA chr4 17767958 17768264 2278 chr4 45521996 45522300 NF-YA chr4 45522130 45522242 2399 c r4 58834132 58834436 NF-YA chr4 58834110 ; 13KS ? U? chr4 83255109 83255413 NF-YA chr4 83255325 83255415 2506 chr4 97443125 9744 M 32 NF-YA c r4 97442910 97443209 2551 chr4 97664158 97664462 NF-YA chr4 97664188 97664373 2552 chr4 98358580 98358884 NF-YA chr4 98358832 98358939 2556 chr4 100277027 100277331 NF-YA chr4 100277011 100277102 2560 chr4 102552. 26 102552630 NF-YA chr4 102:".525.'(i 102552610 25ι»Η chr4 128418296 128418600 NF-YA chr4 128418472 128418607 2651 chr4 137317294 137317415 NF-YA chr4 137317105 137317365 2684 chr4 156158158 156158462 NF-YA chr4 156158358 156158454 2727 chr4 158743370 158743674 NF-YA Chr4 158743383 158743578 Π73 chr4 171013094 171013398 NF-YA chr4 171013015 171013204 2788 c r4 172220087 NF-YA chr4 172220044 17222.0116 chr4 178113872 178114176 NF-YA chr4 178114045 178114117 2827 chr4 184403271 184403575 NF-YA chr4 184403129 184403272 .5 chr4 185836233 185836537 NF-YA chr4 185836458 185836554 2862 chr4 189100717 189101021 NF-YA chr4 189100633 189100865 ,:<S V: chr3 4208959 4209263 NF-YA chr3 4209071 4209298 1570 chr3 17823246 17823491 NF-YA chr3 17823250 17H2--U4-} 1626 chr3 20317223 20317527 NF-YA chr3 20317298 20317458 1635 chr3 245 ^ 22459554 NF-YA chr3 22459187 22 59 122 1633 chr3 28241295 28241464 NF-YA chr3 28241463 28241537 1653 chr3 32156524 32156990 NF-V'A chr3 32156701 32156841 1669 chr3 39755541 39755845 F-YA chr3 39755443 39755550 1700 c r3 41885191 41885495 NF-YA chr3 41885404 41885476 1704 chr3 44585288 44585401 NF-YA chr3 44585354 44585447 1709 chr3 49219527 49219831 NF-YA c r3 49219792 49219867 1724 chr3 67705759 67706125 NF-YA chr3 67705692 67705939 1750 chr3 113070924 113071228 NF-YA chr3 113070992 113071102 1902 chr3 120796382 120796686 NF-YA chr3 120796577 120796650 1919 chr3 i ?.■■-■■:■,?. Κ·55235.'ί: NF-YA ch3 Κ·55232ί!¾ \ r> v.i:-,uo 1930 chr3 128372941 128373133 NF-YA chr3 128372873 128372947 1938 chr3 152873024 NF-YA chr3 Γ>2ίί73222 152873296 2021
Figure imgf000263_0001
chr2 83404969 NF-YA chr2 83404760 83404872 1100 chr2 107201612 107201807 NF-YA chr2 107201600 107201708 1140 chr2 108370319 108370497 NF-YA chr2 108370412 108370573 1131 chr2 129455241 129455545 NF-YA chr2 129455376 129455465 1207 chr2 135561603 135561921 NF-YA chr2 135561881 135561982 1225 chr2 139011453 139011757 NF-YA chr2 139011482 139011580 1235 chr2 192312713 192313017 NF-YA chr2 192312824 LW..i l ?.-Vi-> 1383 chr2 196358290 196358419 NF-YA chr2 196358259 196358359 1401 chr2 ?. O(>i*v -:> 220065900 NF-YA Chr2 220065792 1474 chr2 224896316 224896433 NF-YA chr2 224896209 224896412 1486 chrl 10486048 10486352 NF-YA chrl 10486175 10486282 69 chrl 12156073 12156366 NF-YA chrl 12156124 12156284 75 chrl 22231537 223J..VU NF-YA chrl 22231610 22231744 109 chrl 24816905 24817256 NF-YA chrl 24816942 24817046 120 chrl ■13^ 5 4.Ϊ3Η.'Ϊ.'7 NF-YA chrl 43382271 n«.?i74 182 chrl 52312324 52312705 NF-YA chrl 52312458 52312533 209 chrl 52 ί 1 574 1 3J27(« NF-YA chrl 52312877 205 chrl 57808670 57808974 NF-YA chrl 57808825 57809020 223 chrl 58159066 58159370 NF-YA chrl 58159008 58159146 227 chrl 63136299 63136603 NF-YA chrl 63136197 63136304 241 chrl 80088494 80088798 NF-YA chrl 80088532 80088624 301 chrl 87267625 87267929 NF-YA chrl 87267855 87267968 326 chrl 89767800 89768104 NF-YA chrl 89767927 89768053 3iO chrl 90449778 90450082 NF-YA chrl 90449922 90450078 339 chrl 96613281 96613585 NF-YA chrl 96613348 96613446 358 chrl 113972080 113972384 NF-YA chrl 113972179 113972279 417 chrl 151879270 151879482 NF-YA chrl 151879130 151879287 .155 chrl 162403567 162403871 NF-YA chrl 162403509 162403616 488 chrl 174250325 174250629 NF-YA chrl 174250499 174250594 '.22 chrl 178944739 178945043 NF-YA chrl 178944748 178944939 534 chrl 179744378 179744522 NF-YA chrl 179744343 179744438 537 chrl 180695201 180695505 NF-YA chrl 180695227 180695321 543 chrl 185617602 185617906 NF-YA chrl 185617699 185617811 566 chrl 188783095 188783399 NF-YA chrl 188782658 188783172 580 chrl 191312798 191312894 NF-YA chrl 191312843 191312937 ■:'S chrl 194586406 194586710 NF-YA chrl 194586446 194586538 609 chrl 'l,:0-V/V/i- 212047474 NF-YA chrl 212047367 212047474 659 chrl 214845921 214846225 NF-YA chrl 214846198 214846355 664 chrl 220r>4KS¾G 220648890 NF-YA chrl 220648768 22 C fii " 684 chrl 225410185 225410387 NF-YA chrl 225410314 225410401 710 chrl 233531690 2.55:":31'.'3!": NF-YA chrl 2.55:":31 fj-: 233531883 737 chrl 239418514 239418630 NF-YA chrl 239418516 239418807 547 chrl 240087517 240087821 NF-V'A chrl 240087747 240087941 769 chrl 242937101 242937405 NF-YA chrl 242937271 242937376 783 chrl 246057482 2460577S6 NF-YA chrl 246057448 246057545 803 chr22 18623920 18624157 NF-YA chr22 18623780 18623949 9324 chr22 30907914 30908288 NF-YA chr22 30908003 30908098 93 9 chr22 47666275 47666579 NF-YA chr22 47666233 47666375 9411
Figure imgf000264_0001
chr21 32460306 32460507 NF-YA chr21 32460466 32460620 9218 chrl9 1783380 1783684 NF-YA chrl9 1783501 1783603 8679 chrl9 3070516 3070820 NF-YA chrl9 3070667 3070760 8689 chrl9 8444210 M W NF-YA chrl9 8444097 8444291 8711 chrl9 8451433 8451559 NF-YA chrl9 8451335 8451489 8713
Chrl9 36181454 361816S1 NF-YA chrl9 36181675 36181749 8798 chrl9 39558960 39559264 NF-YA chrl9 39559137 39559229 8807 chrl9 i 40349436 NF-YA chrl9 40349294 40349391 8809 chr20 18207905 18208209 NF-YA chr20 18208040 18208112 8950 chr20 33933766 33934133 NF-YA chr20 92S 9001 chr20 3953S431 39538945 NF-YA chr20 39538748 39538933 9017 chr20 616785S1 61678885 NF-YA Chr20 61678730 61678927 9113 chrl8 5018905 5019209 NF-YA chrlS 5019011 5019122 8431 chrl8 5047565 ">04?¾9 NF-YA chrlS 5047617 5047708 8432 chrl8 9912283 9912652 NF-YA chrl8 9912497 9912588 8441 chrlS 27754446 27754750 NF-YA chrl8 27754696 75.1s;-;; 8494 chrl8 29720353 29720657 NF-YA chrl8 29720302 29720407 8504 chrlS 37825710 378258S4 NF-YA chrlS 37825621 37825715 8518 chrl8 55499184 55499488 NF-YA chrl8 55499317 55499422 8567 chrl7 19920236 19920540 NF-YA chrl7 19920307 19920402 8206 chrl7 30098465 30098715 NF-YA chrl7 30098429 30098543 8222 chrl7 38083716 38084020 NF-YA chrl? 38083901 38083979 S.i.iS chrl7 50939268 50939572 NF-YA chrl7 50939257 50939369 8282 chrl7 52790107 52790411 NF-YA chrl7 52790251 52790 if.-') 8289 chrl7 62256451 62256755 NF-YA chrl7 62256504 62256626 8323 chrl7 64978252 64978666 NF-YA chrl7 64978472 64978568 K53j chrl7 79325366 79325670 NF-YA chrl7 79325544 79325699 10063 chrl6 391732 392036 NF-YA chrl6 391761 391917 7S3H chrl6 5235964 5236268 NF-YA chrl6 5236046 5236120 7870 chrl6 17195525 17195829 NF-YA chrl6 17195660 17195747 7915 chrl6 21648652 21648800 NF-YA chrl6 21648684 21648792 7937 chrl6 61983134 61983438 NF-YA chrl6 61983193 ί·ΐ9;·:5 ;η V.«)7 chrl6 78034294 78034598 NF-YA chrl6 78034328 78034424 8045 chrie 89768644 NF-YA chrl6 89768460 89768554 8115 chrlS 27854087 27854163 NF-YA chrl5 27854060 27854239 7622 chrlS r.u?:-,?.\ 2832/4 ? NF-YA chrl5 2832/266 ^.>7i77 7623 chrl5 31518301 31518605 NF-YA chrl5 31518461 31518554 7637 chrlS NF-YA chrlS 33815300 33815411 7644
Figure imgf000264_0002
chrl5 95691665 95691883 NF-YA chrl5 95691758 95691875 7810 chrl5 fj-7 0S67 95791105 NF-YA chrl5 95790852 95791055 7811 chrl5 97716389 97716693 NF-YA chrl5 97716315 97716498 7814 chrl5 100034250 100034709 NF-V'A chrl5 100034419 100034689 ;-.'7.i chrl4 31995S79 31996183 F-YA chrl4 31995930 31996115 7358 c.hrl4 32174614 32174918 NF-YA chrl4 32174634 32174918 10013 chrl4 41677562 41677866 NF-YA chrl4 41677755 41677842 7380 chrl4 45550379 45550683 NF-YA chrl4 45550275 45550435 73')2 chrl4 82080841 82080992 NF-YA chrl4 82080920 82081009 7499 chrl4 92045138 92045272 NF-YA chrl4 92044954 92045205 7529 chrl 93216603 93216737 NF-YA chrl4 93216507 93216641 7534 chrl4 102764727 102765031 NF-YA chrl4 102764653 102764970 7558 chrl3 21450959 21451288 NF-YA chrl3 21451140 21451229 6965 c rl3 23404650 254;n£r>4 NF-YA chrl3 23404779 23404939 6970 chrl3 27794272 27794576 NF-YA chrl3 27794147 27794338 6986
Chrl3 43754249 43754456 NF-YA chrl3 43754220 43754410 ) <2h chrl3 57232603 57232907 NF-YA chrl3 57232694 57232961 7071 c.hrl3 62546776 NF-YA chrl3 62546693 62546783 7096 chrl3 85779629 85779933 NF-YA chrl3 85779577 85779806 7161 chrl3 95151156 95151338 NF-YA chrl3 95151066 95151171 7210 chrl3 100149001 100149239 NF-YA chrl3 100148988 100149109 7228 chrl3 109970964 109971268 NF-YA chrl3 109971015 109971269 7230 chrl3 110384417 110384721 NF-YA chrl3 110384570 110384721 7272 chrl2 10377453 10377757 NF-YA chrl2 10377736 10377921 6517 chrl2 19860344 19860648 NF-YA chrl2 19860569 19860633 6553 chrl2 28348044 NF-YA chrl2 2S-MS1-W 6586 chrl2 29335247 29335511 NF-YA chrl2 29335317 29335475 6593
Chrl2 30041221 30041525 NF-YA chrl2 30041369 30041571 6554 chrl2 32679333 32679637 NF-YA chrl2 32679242 32679349 6611 chrl2 V.. <)5 14 56393894 NF-YA chrl2 56ϊ(·? ·:5 6671 chrl2 57188967 57189271 NF-YA chrl2 57189262 57189447 6677 chrl2 61753467 61753771 NF-YA chrl2 61753449 61753540 6694 chrl2 71559363 71559489 NF-YA chrl2 71559440 71559865 6726 chrl2 82768090 NF-YA chrl2 82768208 827(1?: »» 6753 chrl2 83052883 83053187 NF-YA chrl2 83052921 83053072 6754 chrl2 100582740 100582890 NF-YA chrl2 100582880 100582970 6808 chrl2 106627276 106627580 NF-YA chrl2 106627299 106627453 6824 chrl2 112957507 NF-YA chrl2 112957437 112957592 6845 chrl2 119034456 119034760 NF-YA chrl2 119034637 119034805 6863 c.hrl2 127256885 127257189 NF-YA chrl2 j 72 7076 127257168 6895 chrll 11879263 11879567 NF-YA chrll 11879359 11879542 6119 chrll 56613472 56613607 NF-YA chrll 56613293 56613478 62 Π chrll 66207731 66207879 NF-YA chrll 66207878 66207992 6264 chrll 76555088 76555177 NF-YA chrll 76555125 ?.->5V>:>21 6303 chrll 84807003 84807307 NF-YA chrll 84807012 84807100 6327 chrll 110287421 110287574 NF-YA chrll 110287413 110287506 (>K.V chrll 114522214 114522518 NF-YA chrll 114522421 114522512 6422 chrlO 4886687 4886991 NF-YA chrlO 4886817 Ά2 ί chrlO 4979122 4979426 NF-YA chrlO 4979377 4979484 5624 chrlO 14854215 14854519 NF-YA chrlO 14854385 14854508 5660 chrlO 18239289 18239549 NF-YA chrlO 18239519 18239619 5668 chrlO ;j^7 2^-> 31876547 NF-YA chrlO 31876432. 31876668 5714 chrlO 33302958 33303262 NF-YA chrlO 33302856 33302963 5727 chrlO Μΐ?ΜΛ<) *l.i?r.w.; NF-YA chrlO 34325070 34325177 5728 chrlO 50989961 50990088 NF-YA chrlO 50989933 50990044 5783 chrlO 60207391 60207695 NF-YA chrlO 60207498 60207849 5806 chrlO 70582416 70582681 NF-YA chrlO 70582613 70582765 5841 chrlO 85222481 H'>722 !*!i NF-YA chrlO K'>i:.2-n:< K5222'»70 5880 chrlO 95605559 95605863 NF-YA chrlO 95605423 95605584 5917 chrlO 123678392 123678824 NF-YA chrlO 123678364 123678550 5992 chrX 38188916 38188991 NF-YB chrX 38188935 38189028 9555 chrX 53506311 53506460 NF-YB chrX 53506408 53506501 9598 chrX 77043613 77043897 NF-YB chrX 77043627 77043724 9643 chrX 105586394 105586678 NF-YB chrX 105586506 105586668 ;.)70-> chrX 150723158 150723442 NF-YB chrX 150723421 150723528 9856 chrX 153607141 153607265 NF-YB chrX 153607264 153607413 V G-i chrX 153607284 153607450 NF-YB chrX 153607264 153607413 9864 chr9 10911543 10911827 NF-YB chr9 10911279 10911564 5214 chr9 96625319 96625425 NF-YB chr9 96625253 96625436 5372 chr9 9i.63 6 96644156 NF-YB chr9 96643971 96644073 5414 chr8 8470310 8470594 NF-YB chr8 8470292 8470405 4751 chrS 23031160 NF-YB chrS 23031068 23031175 4794 chr8 33490911 33491093 NF-YB chr8 33491051 33491160 4825 chr8 40903219 40903503 NF-YB chr8 40903473 40903568 4849 chr8 133462542 133462639 NF-YB chr8 133462525 133462628 5137 c r7 16983344 16983453 NF-YB chr7 16983120 16983355 4134 chr7 23232927 23233211 NF-YB chr7 23233027 23233099 4172 chiv 23894419 23894703 NF-YB chiv 23894664 23894753 4176 chr7 32245127 32245311 NF-YB chr7 32245023 32245135 4196 chr7 36276295 ■iG.V oy/ii NF-YB chr7 .*.")": ii -.7f5 4208 chr7 38215208 38215492 NF-YB chr7 38215359 38215533 4217 chr7 74100384 74100568 NF-YB .h: 7 74100404 74100498 4321 chr7 91085833 91086117 NF-YB chr7 91086041 91086133 4406 chr7 102004022 102004165 NF-YB chr7 102004049 102004154 4460 chr7 134063503 134063607 NF-YB chr7 134063535 134063629 4571 chr7 146484625 146484909 NF-YB Chr7 146484858 146484964 4610 chr7 158655845 158656164 NF-YB chr7 158655912 158656014 4680 chr6 ΪΗ-'ΛΧ', 2765669 NF-YB chr6 2765487 276':G 55 12 chr6 3254337 3254621 NF-YB chr6 3254383 3254545 3489 chr6 NF-YB chr& ■J7J«r,l K 3720703 3519 chr6 6953347 6953736 NF-YB chr6 6953080 6953405 3491 chr6 10719833 10720106 NF-YB chr6 10719971 J , 7.'(i] 2t> 55-H chr6 10741928 10742225 NF-YB chr6 10741877 10742066 3493 chr6 17744924 17745208 NF-YB chr6 17745086 17745402 3494 chr6 28917028 28917282 NF-YB chr6 28917254 28917326 3594 chr6 104894972 104895091 NF-YB chr6 104894945 104895043 .iS4-i chr6 112698176 112698460 NF-YB chr6 112698368 112698469 3879 c r6 117956181 117956465 NF-YB chr6 117956427 117956519 3904 chr5 10066278 10066634 NF-YB chr5 10066125 10066312 2972 chrS 10066278 10066634 NF-YB chrS 10066404 10066479 f; n chr5 14455300 14455584 NF-YB chr5 14455524 14455707 2988 chr5 20613154 20613438 NF-YB chr5 ,:0.-> ] 20613449 3016 chr5 39785709 39785852 NF-YB chr5 39785798 39785891 3090 chr5 44959230 44959514 NF-YB c.h; 5 4 Y)VM>? hW" i02 3110 chr5 55544929 55545159 NF-YB chr5 55545074 55545234 3112 chr5 55545171 NF-YB chr5 55545074 55545234 3112 chr5 57364607 57364891 NF-YB chr5 57364723 57364830 3138 chr5 68477796 i>SJ 7.¾V>0 NF-YB chr5 68477934 68478113 3144 chr5 102088395 102088679 NF-YB chr5 102088234 102088545 3257 c r5 103114327 103114611 NF-YB chr5 103114412 103114602 . r> chr5 126518433 126518717 NF-YB chr5 126518347 126518485 3336 chr5 130823221 130823364 NF-YB chr5 I jCS.i.il ,7 130823269 3346 chr5 158546994 158547216 NF-YB chr5 158546651 158547055 3492 chr5 171624756 171625045 NF-YB chr5 171625038 171625105 3454 chrS 178120578 178120711 NF-YB chr5 178120698 178120810 3474 chr4 17767675 17767930 NF-YB chr4 j V7tiV.¾07 17767882 2303 chr4 17767997 17768070 NF-YB chr4 17767958 17768264 2278 chr4 83255112 ;;3?-.5.¾:>o NF-YB chr4 ;;3?-.s.i2b 2506 chr4 97442995 97443279 NF-YB chr4 97442910 97443209 2551 chr4 128418375 128418485 NF-YB chr4 128418472 128418607 2651 chr4 178113919 178114203 NF-YB chr4 178114045 178114117 2827 c r4 185836206 NF-YB chr4 185836458 185836554 7H 7 chr4 189100786 189101070 NF-YB chr4 189100633 189100865 2842 chr3 I 7S25344 17823511 NF-YB c r3 17823250 1 7?2 53.1b 1626 chr3 20317190 20317474 NF-YB chr3 20317298 20317458 1635 chr3 32156484 32156929 NF-YB chr3 32156701 32156841 1669 chr3 44585176 44585460 NF-YB chr3 44585354 44585447 1709 chr3 !,770:Vi22 67706145 NF-YB chr3 67705692 67705939 1750 chr3 119056478 119056762 -YB chr3 119056546 119056652 1915 chr3 152999473 152999757 NF-YB chr3 152999459 152999615 20? ί chr3 171624347 171624631 NF-YB chr3 171624561 171624667 2088 chr3 19632546S 196325752 NF-YB l iir i 196325666 196325773 2194 chr2 107201601 107201721 NF-YB chr2 107201600 107201708 1140 chr2 108370314 108370472 NF-YB chr?. 108370412 108370573 1131 chr2 129455383 129455486 NF-YB chr2 129455376 129455465 1207 chr2 224896307 27<1S'J¾"63 NF-YB chr2 24S 67 -1 224896412 I486 chrl 10486084 10486223 NF-YB chrl 10486175 10486282 69 chrl 12156042 12156386 NF-YB chrl 12156124 12156284 chrl 24816901 24817249 NF-YB chrl 24816942 24817046 120 chrl 43382051 4.53873 ib NF-YB ch l 43382271 13 «7 i 74 182 chrl 52312311 52312558 NF-YB chrl 52312458 52312533 209 chrl 57808598 NF-YB chrl . /iiCSWb 57809020 2 -i chrl 80088499 80088783 NF-YB chrl 80088532 80088624 301 chrl 8·) ϊο/ 77 } 8T7',8 V7 NF-YB Chrl 89767927 89768053 336 chrl 116840114 116840398 NF-YB chrl 116840333 116840506 428 chrl 180695250 180695534 NF-YB chrl 180695227 180695321 543 chrl 225410202 225410368 NF-YB chrl 225410314 225410401 710 chrl 233531682 233531831 NF-YB chrl 233531795 ?.<V .Vi i<X3 73 / chrl 239418508 239418590 NF-YB chrl 239418516 239418807 547 chrl .7<12<i.¾7 <?" NF-YB ch l .?■!.?') .572 / 1 4 'i 37.576 783 chrl 246057514 246057798 NF-YB chrl 246057448 246057545 803 chr22 18623810 18624094 NF-YB chr22 18623780 18623949 « 57 chr22 30907996 30908286 NF-YB chr22 30908003 30908098 9349 chrl9 1 7S-M V. 1783653 NF-YB chrl9 1783501 1783603 8679 chrig 3070620 3070769 NF-YB chrl9 3070667 3070760 8689 c.hrl9 8444235 8444523 NF-YB chrl9 8444097 8444291 8711 chrl9 8451346 8451742 NF-YB chrl9 8451335 8451489 8713 chrl9 40349221 JO M« 4H NF-YB chrlS 40349294 40349391 8809 chr20 61678545 61678829 NF-YB chr20 61678730 61678927 9113 chrl8 5018961 5019032 NF-YB chrlS 5019011 5019122 8431 chrl8 9912280 9912571 NF-YB chrl8 9912497 9912588 8441 chrl 8 .'77Sd5„H 27754852 NF-YB chrlS 27754696 27754887 8494 chrl8 29720330 29720614 NF-YB chrl8 29720302 29720407 8504 chrl7 30098479 30098717 NF-YB chrl7 30098429 30098543 K272 chrl7 38083712 38083996 NF-YB chrl7 38083901 38083979 8235
Chrl7 b„> i«O.W 52790493 NF-YB chrl7 52790251 ¾27f.' ¾oO 87«<) chrl7 64978239 64978656 NF-YB chrl7 64978472 64978568 8331 c.hrl7 71848174 71848458 NF-YB chrl7 71848088 71848194 S 3 ',(> chrl7 79325377 79325661 NF-YB chrl7 79325544 79325699 10063 chrl6 5235970 ■ 2 ΐί-2 1 NF-YB chrlS ■ 2 ΐί- ι6 523 120 7870 chrl6 21648610 21648739 NF-YB chrl6 21648684 21648792 7937 chrie 78034314 78034598 NF-YB chrl6 78034328 ■'SO W 2.} SCUb chrl6 86631540 86631824 NF-YB chrl6 86631607 86631671 8081 chrlS ?.y. v. / \V: 8327.120 NF-YB chrlS 8327200 2S i2 i77 7623 chrl5 33815257 33815541 NF-YB chrl5 33815300 33815411 7644 chrl5 40874052 40874316 NF-YB chrl5 40874190 40874286 7664 chrl5 43799030 43799124 NF-YB chrl5 43799027 43799104 7672 chrl5 69220829 69221015 NF-YB chrl5 69220977 69221168 7713 chrl5 80219069 80219353 NF-YB chrl5 80219048 80219122 7771 chrl5 S1706775 81706892. NF-YB chrlS 81706648 81706799 7778 chrl5 91054423 91054707 NF-YB chrl5 91054385 91054459 7797 chrlS 92757790 92758074 NF-YB chrl5 '}Π'-:/$.Λ Ί V.¾) l chrl5 95691616 95691821 NF-YB chrlS 95691758 95691875 7810 chrlS 95790915 95791078 NF-YB chrl5 95790852 95791055 7811 chrl 31995665 31995949 NF-YB chrl4 31995930 31996115 7358 dirl4 20 . J 2 :"> 92045409 NF-YB chrl4 92044954 92045205 7'.i2>! chrl4 93216589 93216779 NF-YB chrl4 93216507 93216641 7534 chrl4 102764748 102765032 NF-YB chrl4 102764653 102764970 7VJ8
Figure imgf000268_0001
chrl2 71559334 71559446 NF-YB chrl2 71559440 71559865 6726 chrl2 S-l.12.i 33i· 83123620 NF-YB chrl2 K ¾ 12 i S3 L .1.5o.i 67-r, chrl2 100582890 100582981 NF-YB chrl2 100582880 100582970 6808
Chrl2 123898171 123898455 NF-YB chrl2 123898356 123898512 i>S7!, chrll 11879376 11879552 NF-YB chrll 11879359 11879542 6119 chrll 56613472 56613608 NF-YB chrll 56613293 56613478 02 Π chrll 76555070 76555213 NF-YB chrll 76555125 76555221 6303 chrll 110287390 110287574 NF-YB chrll 110287413 110287506 6407 chrlO 2802951 2803235 NF-YB chrlO 2803078 2803180 5610 chrlQ 14854264 14854409 NF-YB chrlO 14854385 14854508 5660 chrlO 50989967 50990144 NF-YB chrlO 50989933 50990044 5783 chrlO 91544966 91545250 NF-YB chrlO 91545004 91545092 5904 chrlO 120518987 120519136 NF-YB chrlO 120519097 120519171 5989 chrlO 123678360 123678644 NF-YB chrlO 123678364 123678550 5992 chrl 22231534 22231704 p300JF-4) chrl 22231610 22231744 109 chrl 230262831 230263107 p300JF-4) chrl 230262996 ? ; i> :;--<6 72.5 chr6 31804112 31804368 SIRT6 chr6 31804365 31804470 3610 chrl? 17109697 17109953 SIRT6 chrl? 17109779 17109885 8194 chrl5 45709839 45710095 SIRT6 chrlS 45709938 45710050 7679 chrl .>.-?:> ¾ M,Vi 22231778 STAT2 chrl 22231610 22231744 109 chrl 230262801 230263117 STAT2 chrl 230262996 230263096 725 chr9 774i,2 JSH 27.H>.'70* TALlJSC-12984) chr9 27462477 :·.2Γ>2 chr9 138863845 138864095 TALlJSC-12984) chr9 138863933 138864042 5551 chrS 59569481 59569731 TALlJSC-12984) chrS 59569411 59569507 4914 chr7 158659908 158660158 TALlJSC-12984) chr7 158659912 158660035 4681 chr5 134717927 134718099 TALl JSC-12984) ChrS 134717838 134717942 i V. chr4 3307448 3307698 TALlJSC-12984) chr4 3307377 3307483 2230 chr4 190880905 190881155 TALlJSC-12984) chr4 190881012 190881119 »W chr2 55367659 55368047 TALlJSC-12984) chr2 55368003 55368125 1025 chr2 144666522 144666772 TALlJSC-12984) chr2 144666700 144666812 1247 chr2 176885186 176885436 TALlJSC-12984) chr2 176885294 176885398 1335 chrl 22231461 22231892 TALlJSC-12984) chrl 22231610 22231744 109 chrl 230262836 230263154 TALlJSC-12984) chrl 230262996 230263096 725 chr22 18453055 18453305 TALlJSC-12984) chr22 18453056 18453157 chr20 51342808 51343058 TALlJSC-12984) chr20 51342870 51342961 9055 chr20 60849740 60849888 TALlJSC-12984) chr20 60849658 60849757 9096 chrl7 29055689 29055939 TALlJSC-12984) chrl7 29055786 29055917 8219 chrl7 42237406 2737ί-02 TALlJSC-12984) chrl7 .127 7 » 1 42237467 K2-i.i chrl5 29149713 29149960 TALlJSC-12984) chrl5 29149824 29149903 7629 chrl5 45709832 45710058 TALlJSC-12984) chrlS 45709938 45710050 7679 chrl4 75953259 75953450 TALlJSC-12984) chrl4 75952914 75953265 7472 chrl3 31228672 31228922 TALlJSC-12984) chfl3 31228908 31229026 6989 chrl3 113358680 113358930 TALlJSC-12984) chrl3 113358873 113358968 7291 chrl3 114203346 114203596 TALlJSC-12984) chrl3 114203518 114203659 7305 chrl2 12595180 12595310 TALlJSC-12984) chrl2 12595125 12595282 6526 chrl2 123449445 123449556 TALlJSC-12984) chrl2 123449512 123449601 t>875 chrll 71449477 71449727 TALlJSC-12984) chrll 71449410 71449506 6294 chrX 4969917 4970575 GATA-1 chrX 4970197 4970291 9481 chr9 27462461 27462950 GATA-1 chr9 27462477 27462590 5292 chr9 33619713 33619847 GATA-1 Chr9 i½ if.' ? ¾o 33619812 5312 chr9 108061786 108062100 GATA-1 chr9 108062023 108062146 5452 c r8 223 J 924 22. 74 GATA-1 chr8 22.31969 22320H 4718 chr5 134717904 134718145 GATA-1 chr5 134717838 134717942 3356 chr5 176264653 176264929 GATA-1 chr5 176264742 176264828 3470 chr4 3307324 3307774 GATA-1 chr4 3307377 3307483 2230 chr4 70057501 70057951 GATA-1 chr4 70057691 70057764 ,:4.>0 chr4 174307442 174307892 GATA-1 chr4 174307674 174307761 2812 chr3 128372848 1..· 573 9?: GATA-1 chr3 128372873 ] .> 72'ί.ι7 1938 chr3 150934435 150934966 GATA-1 chr3 150934928 150935030 2015 chr3 .l0.r:S-i.iS'".K 195854774 GATA-1 chr3 195853969 195854074 2189 chr2 224353 224803 GATA-1 chr2 224540 224646 832 chr2 55367603 55368134 GATA-1 Chr2 55368003 55368125 1025 chrl 22231302 22231987 GATA-1 chrl 22231610 22231744 109 chrl 203650739 203651375 GATA-1 chrl 203651242 203651350 642 chrl 230262656 230263334 GATA-1 chrl 230262996 230263096 725 chrlS 791808 ;n? .v. GATA-1 chrl9 791702 791821 Si- 73 chr20 42848038 42848488 GATA-1 chr20 42848008 42848137 9024 chr2Q 60849714 GATA-1 chr20 60849658 60849757 9096 chr20 61578260 61578710 GATA-1 chr20 61578471 61578585 9109 chrl7 38083669 38084119 GATA-1 chrl7 38083901 5SO. 'S7<- ί-:.?3·: chrl7 42237003 42237641 GATA-1 chrl7 42237391 42237467 8253 chrl7 62183641 62184091 GATA-1 chrl7 62184050 62184186 ΚΪ72 chrl6 88575510 88576061 GATA-1 chrl6 88576041 88576120 8094 c.hrl6 9012.3988 90124438 GATA-1 chrl6 90124299 90124411 8124 chrlS 29149686 29149962 GATA-1 chrl5 29149824 29149903 7629 chrlS 45709857 45710069 GATA-1 chrl5 45709938 45710050 7679 chrl5 85168305 85168755 GATA-1 chrlS 85168273 85168395 7788 chrlS 101677758 101678208 GATA-1 chrl5 101677648 101677779 7ri27
Chrl 4 56048153 56048603 GATA-1 chrl4 56048179 56048283 7422 chrl4 62000312 t>2 00767 GATA-1 chrl4 t>2 00:! ] 9 62000391 7 152 chrl3 31228570 31229020 GATA-1 chrl3 31228908 31229026 6989 chrlS 100148972 100149422 GATA-1 chrl3 100148988 100149109 7228 chrl3 113358565 113359015 GATA-1 chrl3 113358873 113358968 7291
Chrl2 12595065 12595462 GATA-1 chrl2 12595125 12595282 Wi, chrl2 68845048 68845498 GATA-1 chrl2 68845349 68845449 6711 c.hrl2 12.3449435 123449551 GATA-1 chrl2 123449512 123449601 6875 chrll 62528335 62528558 GATA-1 chrll 62528289 62528400 6250 chrll 71449474 71449611 GATA-1 chrll 71449410 71449506 6294 chrX 1540760 1541325 SETDB1 chrX 1540834 1540943 9464 chrX 122998285 U>2fi-)37 i¾ SETDBl chrX 122998475 122998706 9780 chr9 18694966 18695416 SETDB1 chr9 18695211 18695312 5265 chr9 94126998 «1.1 127.143 SETDBl ( r<' 94127157 94127266 5403 chr9 101864090 101864540 SETDB1 chr9 101864054 101864170 5431 chrS 3972-iO -i 39724504 SETDBl chrS 39724123 39724211 4846 chr8 87262178 87262628 SETDB1 chr8 87262289 87262406 4989 chrS 91789494 91789944 SET OBI chrS 91789474 91789594 5004 chr8 124766777 124767227 SETDB1 chr8 124767044 124767142 5108 chr7 3992.1710 39922360 SETDB1 chr7 39921722. 39921846 -1222 chr7 77455446 77455896 SETDB1 chr7 77455454 77455552 4333 chr? 1 ¾ if- ¾9"½ 133640276 SETDBl chr? 133640066 133640163 4569 chr7 158191377 158191827 SETDB1 chr7 158191681 158191796 4673 chr& 3039394 3039844 SETDBl chr6 3039668 3039816 3516 chr6 28916853 28917303 SETDBl chr6 28917254 28917326 3594 chr6 84817279 84817729 SETDB1 chr6 84817355 B4fU7«li,7 S7¾ chr6 111062734 111063427 SETDBl chr6 111063358 111063485 3869 chr6 133493682 133494132 SETDBl chr6 133493929 133494090 3948 chr6 143525180 143525630 SETDBl chr6 143525536 143525639 3977 chr5 91848493 91848943 SE DBl chrS 91848879 91848982 Ό.Ά-. chr5 98687870 98688320 SETDBl chr5 98688041 98688203 3248 c r5 104393077 104393397 SETDBl chr5 104393268 104393363 -2 6 chr5 163282686 163283136 SETDBl chr5 163282758 163283245 3414 chr4 20XiS; 0.i39 SETDBl chr4 20339005 20339116 2318 chr4 88618364 88618814 SETDBl chr4 88618696 88618793 2527 chr4 110656702 110657152 SETDBl chr4 110656732 110656818 25"0 chr4 137316903 137317557 SETDBl chr4 137317105 137317365 2684 chr3 .'402 5.557 SETDBl chr3 2 102.i 323 2-102 ¾.·! >.') 1646 chr3 133205486 133205936 SETDBl chr3 133205749 133205848 1956 chr2 40017522 40018171 SETDBl chr2 40018155 40018276 :>X.i chr2 45768576 45769026 SETDBl chr2 45768726 45768821 1003 chr2 61671901 61672351 SET DBl Chr2 i>!67,V "/''-> 61672360 1041 chr2 109486501 109486951 SETDBl chr2 109486485 109486596 1148 chr2 112802966 112803416 SETDBl chr2 112803264 112803415 1160 chr2 119792542 119792992 SETDBl chr2 119792880 119792970 1186 chr2 176884959 176885355 SETDBl chr2 176885294 176885398 1335 chr2 189271073 189271523 SETDBl chr2 189271497 189271590 1368 chr2 2 1 572 i 221057653 SETDBl chr2 221057326 221057474 1478 chrl 2029020 2029431 SETDBl chrl 2029019 2029117 22 chrl 12763777 12764431 SETDBl chrl 12764229 12764297 82 chrl 21362265 21362917 SETDBl chrl 21362636 21362729 108 chrl 227 J &37 22792087 SETDBl chrl 22791670 22791832 113 chrl 31152706 31153156 SETDBl chrl 31152933 31153040 136 chrl ;.;6.¾7'¾ -> 33690373 SETDBl chrl 33690165 3 iiVS02>!0 151 chrl 40960753 40961799 SETDBl chrl 40961020 40961463 173 chrl 60024244 60024896 SETDBl chrl 60024880 60025029 230 chrl 100224218 100224668 SETDBl chrl 100224633 100224721 373 chrl 152083846 152083989 SETDBl chrl 152083626 152084811 439 chrl 194388834 194389284 SETDBl chrl 194389130 194389293 607 chr22 34730773 H 7 U.7. SETDBl chr22 5 17 W0 .vi7.i lO t> chr21 46456622 46457072 SETDBl chr21 46456582 46456673 9281 chrl9 2Kr>?r:'H 2853871 SETDBl chrl9 2i?1 i liJS 2853228 8687 chrl9 7082817 7084031 SETDBl chrl9 7083049 7083177 8708
Chrl9 9491901 9492661 SET DBl chrl9 9491833 9492531 8664 chrl9 44611012 44611462 SETDBl chrl9 44611076 44611605 8813 c.hrl9 44611845 44612497 SETDBl chrl9 44611748 44612024 8812 chrl9 52569601 52570051 SETDBl chrl9 52568484 52570122 8845 chrlS 56604108 56604646 SETDBl chrl9 56604179 56604313 Sf'S,' chrl9 58290625 58290911 SETDBl chrl9 58290545 58291328 8849 chrl9 58290920 58291094 SETDBl chrl9 5<i.™0 l 58291328 .¾4« chr20 59815852 59816302 SETDBl chr20 59815781 59815854 9087 chrl7 1504838 1505489 SETDBl chrl7 1505130 1505211 8150 chrl7 16525767 16526597 SETDBl chrl7 16526168 16527131 8179 chrl7 16526649 15526853 SETDBl chrl7 15526168 16527131 8179 chrl7 17327833 17328283 SETDB1 chrl7 17328054 17328152 8197 chrl7 68479650 68480100 SET OBI chrl7 68479846 68479942 ;;347 chrl6 83609536 83609986 SETDB1 chrl6 83609526 83609624 8068 chrl6 85386673 85386993 SETDB1 chrl6 85386775 85386867 8076 chrl5 22462056 22462376 SETDB1 chrl5 22462316 22462420 7597 chrlS 95790562 95791012 SETDBl chrl5 95790852 95791055 7811 chrl4 106765125 106765575 SETDB1 chrl4 106765150 106765547 10014 chrl3 22986574 22¾ :' 5 SETDBl chrl3 22986685 22986767 6969 chrlS 66808287 66808737 SETDB1 chrl3 66808224 66808308 7117 chrl3 71865114 7J ¾55 3 SETDBl chrl3 71865441 71865535 7137 chrl3 78654730 78655180 SETDB1 chrl3 78654777 78654864 7155 chrl2 22765679 22766129 SETDBl chrl2 22765639 22765777 6566 chrl2 91323381 91323831 SETDBl chrl2 91323352 91323444 6781
Chrl2 92147418 92147868 SET DBl chrl2 92147505 ■J2 >»:■/ 6784 chrl2 107657695 107658145 SETDBl chrl2 107658015 107658113 6829 chrll 10066060 10066698 SETDBl chrll 10066059 10066157 6112 chrll 11879182 11879632 SETDBl chrll 11879359 11879542 6119 chrll 111829456 111829776 SETDBl chrll 111829591 111829758 6414 chrll 133103350 133103800 SETDBl chrll 133103371 133103453 6469 chrlO 42970819 ■ϊ2«7 12 > SETDBl chrlO 42971024 42971122 chrlO 43977672 43978486 SETDBl chrlO 43978304 43978411 5765 chrlQ 91787637 91788087 SETDBl chrlO 91787682 91787787 : i 5 chrlO 97466125 97466445 SETDBl chrlO 97466208 97466301 5921 chr9 96337510 96337960 ZNF263 chr9 96337914 5413 chr9 138863767 138864217 ZNF263 chr9 138863933 138864042 5551 chr9 139611997 139612447 2Μί\?0ϊ Chr9 139612303 139612387 5558 chr7 101080695 101080900 ZNF263 chr7 101080639 101080717 4454 chr7 102004050 102004500 Νί 20.1 chr7 102004049 102004154 4460 chr7 151411247 151411697 ZNF263 chr7 151411407 151411582 4625 chr6 113954215 113954665 ZNF263 chr6 113954396 113954498 chr6 166861867 166862317 ZNF263 chr6 166862086 166862190 4034 chr6 169087537 ZNF263 chr6 169087082 169087184 4056 chr5 1472943 1473483 ZNF263 chr5 1472894 1472998 2931 chr5 140953421 140953871 ZNF263 chr5 140953216 140953536 56 ¾ chr5 156891586 156892098 ZNF263 chr5 156892015 156892109 3408 chr5 170059951 170060662 ZNF263 chr5 170060476 170060580 3447 chr5 176264655 176264963 ZNF263 chr5 176264742 176264828 3470 chr3 2402 .3 J ZNF263 chr3 .' .io.? ;.;2-i 240 .;-i20 1646 chr3 52254406 52254856 ZNF263 chr3 52254310 52254418 1735 chr3 195577669 195578119 Νί 20.1 c r3 195577893 195577977 2184 chr2 1828294 1828744 ZNF263 chr2 1828463 1828552 851 chr2 109901233 109901683 ZNF263 chr2 109901231 109901306 1151 chrl 2954183 2954609 ZNF263 chrl 2954349 2954448 29 chrl YM.:W)2 u.;n v> ZNF263 chrl i.^ J H.I 3221180 .53 chrl 152080160 152081155 ZNF263 chrl 152080245 152080420 455 chrl 152080160 152081155 ZNF263 chrl 152080869 152080996 456 chrl 152081784 152084426 ZNF263 chrl 152083626 152084811 439 chrl 152084700 152085129 zwm chrl 152083626 152084811 VJ« chrl 228463585 228464221 ZNF263 chrl 228463761 228463942 678 chrl 242790032 242.790482 ZNF263 chrl 242.790415 Μ27>!0 > 7Η.' chr22 48682427 48682714 ZNF263 chr22 48682514 48682605 9418 chr21 45724630 45725283 ZNF263 chr21 45724586 45724667 269 chr21 46549318 46549768 ZNF263 chr21 46549585 46549671 9283 chrl9 1909476 1909870 ZNF263 chrl9 1909441 1909621 8C.60 chrl9 3696792 3697705 ZNF263 chrl9 3697633 3697727 8695 chrl9 28294506 28294956 ZNF263 chrl9 28294900 28294992 KV ti chr20 61446733 61447387 ZNF263 chr20 61447223 61447316 9107 chr20 62686649 62687099 ZNF263 chr20 62686774 62686855 9130 chrl8 12376989 12377657 ZNF263 chrl8 12377506 12377572 8450 chrlS 77557465 77557915 ZNF263 chrl8 77557576 77557665 ti ■ b-i?. chrl7 1329473 1329656 ZNF263 chrl7 1329538 1329634 8149 c.hrl7 79204226 79204637 ZNF263 chrl7 79204619 79204731 8393 chrl6 1396767 1397217 ZNF263 chrl6 1396753 1396894 7852 chrl6 73082909 73»?"! i'i Νί 2 3 chrl6 73083042 8029 chrl5 100275694 100276144 ZNF263 chrlS 100275711 100275794 7820
Chrl3 109038718 109039168 ZNf-.Hi.i chrl3 109038959 109039053 7261 chrl2 133306621 133307071 ZNF263 chrl2 133306929 133307026 6946 chrl l S 15865 816315 ZNF263 chrl l 815881 815967 77 chrll 10066146 10066596 ZNF263 chrll 10066059 10066157 6112 chrll 58672526 58672976 ZNF263 chrll 58672559 58672657 6243 chrlO 35624414 35624832 ZNF263 chrlO 35624602 35624731 5737 chrlO 135062824 135063409 zwm chrlO 135063265 135063360 6060 chr9 97060533 97060783 eGFP-FOS chr9 97060762 97060846 5416 chr5 176263^ 176264887 eGFP-FOS chr5 176264742 176264828 3470 chr4 3307436 3307686 eGFP-FOS chr4 3307377 3307483 2230 chr2 43934443 43934693 eGFP-FOS chr2 4393<i 08 43934523 995 chrl 151913850 151914100 eGFP-FOS chrl 151913718 151913859 441 chrie 19566610 19566860 eGFP-FOS chrl6 19566661 19566971 7riSK chrl6 83847822 83848072 eGFP-FOS chrl6 83848024 83848139 8069 chrl 2 116784658 116784908 eGFP-FOS chrl2 116784859 116784973 <>BSb chrlO 92923714 92923964 eGFP-FOS chrlO 92923953 92924065 5910 chr9 108061665 108062049 eGFP-GATA2 chr9 108062023 108062146 r. i-n chr6 3978439 3979023 eGFP-GATA2 chr6 3978588 3978673 3521 chr5 134717869 134718253 eGFP-GAl"A2 Chr5 134717838 134717942 i V. chr2 55367680 55368064 eGFP-GATA2 chr2 55368003 55368125 1025 chrl 22231471 22231885 eGFP-GATA2 chrl 22231610 22231744 109 chrl 179941007 179941591 eGFP-GATA2 chrl 179941551 179941631 539 chrl 221785515 221785899 eGFP-GATA2 chrl 221785629 221785736 690 ch'r20 37231892 37232276 eGFP-GATA2 chr20 37232184 37232293 9013 chrlS 45709781 45710165 eGFP-GATA2 chrl5 45709938 45710050 7679 chrl5 69744439 69744823 eGFP-GATA2 chrl5 69744385 69744482 7732 chrll 62528290 62528674 eGFP-GATA2 chrll 62528400 6250 chr5 176264670 176264990 eGFP-HDAC8 chr5 176264742 176264828 3470 chr22 19947291 19947611 eGFP-HDACS chr22 19947316 19947412 ¾?8 chr7 143077316 143077606 eGFP-JunB chr7 143077464 143077619 4599 chr5 1564188 1564478 eGFP-JunB chr5 ι:". -Μ2 ; 1564422 .'f 3 chr5 77893159 77893449 eGFP-JunB chr5 77893174 77893252 3188 chr2 43934429 43934719 eGFP-JunB c r2 43934408 995 chr2 55367755 55368045 eGFP-JunB chr2 55368003 55368125 1025 chr2 104051544 104051834 eGFP-JunB chr2 104051628 104051750 1135 chr2 176885256 176885546 eGFP-JunB chr2 176885294 176885398 1335 chrl 22231490 22231708 eGFP-JunB ch l 22231610 222.1 1 7 34 109 chrl 24743440 24743730 eGFP-JunB chrl 24743669 24743756 119 chrl9 2631400 2631690 eGFP-JunB chrl9 2631555 2631659 8683 chrl6 19566583 19566873 eGFP-JunB chrl6 19566661 19566971 7888
ChrlS H.W/ .-\?. 83848142 eGFP-JunB chrl6 83« 58 2 83848139 8069 chrl6 90124088 90124378 eGFP-JunB chrl6 90124299 90124411 8124 chrl5 45709774 45710064 eGFP-JunB chrlS 45709938 45710050 7679 chrl2 116784596 116784886 eGFP-JunB chrl2 116784859 116784973 6856 chrlO 92923732 92924022 eGFP-JunB chrlO 92924065 5910 chr9 27462477 27462773 eGFP-JunD chr9 27462477 27462590 5292 chr9 33619634 33619930 eGFP-JunD chr9 33619736 33619812 ¾.H V chr9 97060512 97060808 eGFP-JunD chr9 97060762 97060846 5416 chr7 143077310 143077606 eGFP-JunD chr7 143077464 143077619 4599 chr5 77893187 77893483 eGFP-JunD chr5 77893174 77893252 3188 chr5 176264675 176264971 eGFP-JunD chr5 176264742 176264828 3470 chr4 3307409 3307705 eGFP-JunD chr4 3307377 3307483 2230 chr3 195872672 195872968 e FP-JunD chr3 195872965 195873074 2190 chr2 43934505 43934648 eGFP-JunD chr2 43934408 43934523 995 chr2 55368018 eGFP-JunD chr?. 55368003 55368125 1025 chr2 101507851 101508147 eGFP-JunD chr2 101507790 101507891 1132 chr2 104051534 104051830 eGFP-JunD c r2 104051628 104051750 1135 chr2 176885362 176885462 eGFP-JunD chr2 176885294 176885398 1335 chrl 22231466 22231949 eGFP-JunD chrl 22231610 22231744 109 chrl 24743410 24743706 eGFP-JunD chrl 24743669 24743756 119 chrl ..· 30 1, ?57 7 50263053 eGFP-JunD chrl .7 i02 2>! i. 2 X >(, i b chr21 38346857 38347026 eGFP-JunD chr21 38346894 38346994 9226 chrl8 1006367 1006663 eGFP-JunD chrl8 1006297 1006436 fi.H K chrl6 17195495 17195791 eGFP-JunD chrl6 17195660 17195747 7915
Chrl6 19566580 19566876 eGFP-JunD chrl6 19566661 19566971 7888 chrl6 83847784 83848080 eGFP-JunD chrl6 83848024 83848139 8069 chrlfi 89571975 89572066 eGFP-JunD chrl6 89571991 89572097 8110 chrlS 45709758 45710054 eGFP-JunD chrl5 45709938 45710050 7679 chrl3 114459387 114459683 eGFP-JunD chrl3 114459421 114459558 7306 chrl2 68845238 68845534 eGFP-JunD chrl2 68845349 68845449 6711 chrl2 116784613 116784909 eGFP-JunD chrl2 116784859 116784973 6856 chrl2 127257106 127257189 eGFP-JunD chrl2 127257076 127257168 6895 chrlQ 92924000 eGFP-JunD chrlO fi2r}2.V'-. 3 92924065 5910 chromosome in which the transcription factor binding site resides
2 start position of the transcription factor binding site
3 end position of the transcription factor binding site
transcription factor that recognizes this position
5 chromosome in which the human CRISP resides
6 start position of the human CRISPR
7 end position of the human CRISPR
s unique patent ID given to the human CRISPR
Table 22 Human CRISPRs that reside in DNasel hypersensitive clusters in the Hgl9 genome
DNasel Hypersensitivity sites Human CR1SPR position
Chromosome1 start2 end3 Chromosome4 start5 end6 SEQ ID chrl 1624140 1624430 chrl 1624211 1624313 17 chrl 1624140 1624430 chrl 1624403 1624654 1 chrl 1624500 1624690 chrl 1624403 1624654 1 chrl 1677460 1677710 chrl 1677682 1677934 2 chrl 1677460 1677710 chrl 1677486 .io;-.'-iKS 18 chrl 1677780 1677970 chrl 1677682 1677934 2 chrl 3418500 3418970 chrl 3418555 i i l Bir..' 35 chrl 3712340 3712950 chrl 3712553 3712650 41 chrl 4016600 4016870 chrl 4016840 4016929 44 chrl 6042960 6043190 chrl 6043069 6043161 54 chrl 6093160 6093510 chrl 6093368 »0«V178 5» chrl 6156820 6156990 chrl 6156822 6156909 57 chrl 0V>.v,VD 6561170 chrl 6560641 59 chrl 6630240 6630470 chrl 6630379 6630476 62 chrl 7075720 7075990 chrl 7075851 7075955 63 chrl 7347680 7347930 chrl 7347581 7347732 64 chrl 8293420 8299710 chrl 8299471 66 chrl 8320940 8321130 chrl 8320950 8321039 67 chrl 9741920 9742130 chrl 9741915 9741994 68 chrl 10486120 10486370 chrl 10486175 10486282 69 chrl 12155860 12156330 chrl 12156124 12156284 75 chrl 12244060 12244670 chrl 12244495 12244576 76 chrl 17482680 17482950 chrl 17482788 17482910 96 chrl 18013720 18013930 chrl 18013856 18013926 97 chrl 20409600 20409790 chrl 20409708 20409805 103 chrl 22231420 22231710 chrl 22231610 22231744 109 chrl 22791600 22791750 Chrl 22791670 22791832 113 chrl 24743420 24743750 chrl 24743669 24743756 119 chrl 28052760 28053490 chrl 28053114 .'¾)■-> ; o i 129 chri 32237660 32238430 chrl 32238142 32238225 140 chrl 32479760 32480910 chrl .52-r.'9 S9 .iM 7W71 141 chrl 32913560 32913830 chrl 32913603 32913725 142 chrl 37031780 37032030 chrl -.7031 '-><"- 3 37032032 160 chrl 40961040 40961330 chrl 40961020 40961463 173 chrl 43084540 43084790 chrl 43084590 43084679 11111111111 chrl 50093480 50093810 chrl 50093557 50093641 201 chrl 51186800 51186970 chrl 51186859 51186947 207 chrl 52312400 52312590 chrl 52312458 52312533 209 chrl :".. H5?;oo 53436170 chrl ■-. w .¾„o? ¾ :"..vHi> 1 9 215 chrl 64039980 64040310 chrl 64040219 64040317 242 chrl 68154300 68155350 chrl 68155234 G.'U5": ?2K 254 chrl 72643460 72643730 chrl 72643385 72643496 273 chrl s s-mo 84235150 chrl 84234990 316 chrl 84493180 84493350 chrl 84493164 84493266 318 chrl 84977080 84977330 chrl 84977174 84977325 320 chrl 86862760 86862950 chrl 86862864 86862948 324 chri 89195960 89196210 chrl 89195980 89196073 331 chrl 95033640 95033930 chrl 95033687 95033783 352 chrl 95608500 l,¾tiG8 ? ΐϋ chrl 95608589 355 chrl 97665900 97666250 chrl 97666198 97666268 362 chrl 97910960 97911130 chrl 97910999 97911087 364 chrl 98799100 98799250 chrl 98799158 98799277 368 chri 100224680 100225010 chrl 100224633 100224721 373 chrl 104838220 104838370 chrl 104838298 104838389 391 chrl 105249300 105249750 chrl 105249637 105249736 394 chrl 108008700 108008870 chrl 108008702 108008784 400 chrl 108380780 108381010 chrl 108380783 108380882 402 chrl 108577560 108577790 chrl 108577655 108577769 403 chrl 109182940 109183150 Chrl 109183132 109183317 407 chrl 113972120 113972390 chrl 113972179 113972279 417 chrl 114581200 114581350 chrl 114581310 114581456 420 chri 119716500 119716670 chrl 119716500 119716622 436 chrl 147770060 147770310 chrl 147770073 147770172 450 chrl 150521380 150521750 chrl 150521576 150521685 452 chrl 151879200 151879350 chrl 151879130 151879287 ■i b.i chrl 151913660 151914130 chrl 151913718 151913859 441 chrl 152080180 152080990 chrl 152080245 152080420 455 chrl 152080180 152080990 chrl 152080869 152080996 456 chrl 152083360 152084410 chrl 152083626 152084811 4 W chrl 152084660 152085250 chrl 152083626 152084811 439 chrl 15419-1840 154195230 chrl 154194740 154194889 462 chrl 154579600 154580450 chrl 154580161 154580286 464 chrl 171490840 171491010 chrl 171490936 171491034 512 chrl 172769020 172769270 chrl 172769053 172769168 516 chrl 1 7 ¾ 538420 1 7 ¾ 5385<·0 chrl 1 7 53 iK4')2 173338601 520 chrl 177290240 177290490 chrl 177290329 177290432 531 chrl 180640920 180641110 chrl 180640913 180641015 542 chrl 183541900 183542130 chrl 183541861 183541943 560 chrl 188231060 188231290 chrl 188231274 188231385 576 chrl 189586100 189586370 chrl 189586194 189586297 585 chrl 197115160 197115610 chrl 197115082 197115186 617 chrl 200175540 200175970 chrl 200175619 200175695 628 chrl 201448980 201449250 chrl 201449122 201449240 iyU chrl 201566560 201567390 chrl 201566696 201566793 633 chrl 202756040 2 2 Γ>02¾0· chrl 202756011 202756100 637 chrl 204725040 204725190 chrl 204725051 204725126 644 chrl 206781500 206781830 chrl 206781797 206781892 649 chrl 207429540 207429750 chrl 207429628 207429704 650 chrl 211560240 211560570 chrl 211560375 211560567 658 chrl 212345820 212346070 chrl 212345795 212345913 660 chrl 215230000 215230230 chrl 215230229 215230322 666 chrl 219542140 219542390 chrl 219542052 219542209 675 chrl 221785400 221785730 chrl 221785629 221785736 690 chrl 223897380 223897610 chrl 223897581 223897665 702 chrl 223949140 223949390 chrl 2 .;9--:;) i-> 223949141 703 chri 224464900 224465190 chrl 224464803 224464931 705 chrl 228160500 228160750 chrl 228160651 228161912 719 chrl 228463660 228463930 chrl 228463761 228463942 678 chrl .7 -.G,:i". 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88790740 88790990 chr? 88790824 88790909 5388 chr9 90084780 90084970 c.hr9 90084791 90084885 5391 chr? 90225720 90225970 chr9 90225862 90225944 5392 chi-9 96337940 96338450 chr9 96337914 96338024 5413 chr? 96643920 96644110 chr9 96643971 96644073 5414 chr9 97694080 97694330 chr9 97694241 97694321 5420 chr9 99983780 99984050 chr9 99983766 99983852 5428 chr9 102140760 102141050 chr9 102140697 102140777 ).1W chr? 104637900 104638130 chr? 104638124 104638245 5444 chi-9 123672260 123672590 chr9 1 /: 36721 70 123672267 5490 chr? 124375760 124376050 chr9 124376013 124376103 5493 c r9 125066140 j 250;. 5 ch r9 125066248 125066343 5497 chr9 128463680 128463950 chr9 128463780 128463881 5510 chr9 129576360 129576590 chr9 129576542 129576648 5513 chr9 134422500 134422690 chr? 134422671 134422745 5529 chr9 136856620 136856850 Chr9 136856553 136856630 55 Vi chr9 137518400 137518810 chr9 137518528 137518639 5538 c r9 137607920 j 37 082:. ch r9 137607871 137607955 5540 chr? 138110500 138110690 chr9 138110626 138110747 5545 chr9 138404840 138405490 chr9 138404989 138405124 5547
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chrll 100605940 100606170 chrll 100606150 100606261 6371 chrll 115386940 115387190 chrll 115387075 115387167 6425 chrll 115795840 115796150 chrll 115795944 115796095 6427 chrll 117009420 117009690 chrll 117009658 117009785 6431 chrll 118559100 118559410 chrll 118559393 118559550 6435 chrl l 118890640 118890990 chrll 118890981 118891071 6436 chrll 119897100 119897390 chrll 119897079 119897183 10003 chrll 120083020 120083630 chrll 120082929 120083030 6439 chrll 122430560 122430870 chrll 122430785 122430935 6444 chrll 122695000 122695230 chrll 122695194 122695267 6446 chrll 127638960 127639110 chrll 127639071 127639145 6454 chrll 131848160 131848570 chrll 131848449 131848536 6465 chrll 680600 681290 chrl2 680540 680670 6480 chrl2 1683480 1683670 chrl2 1683516 1683664 6483 chrl2 6201440 6201750 chrl2 6201657 6201737 6498 chrl2 6616680 6617130 chrl2 6616829 6616944 6501 chrl2 7792780 7793170 chrl2 7792935 7793089 6504 chrl2 8781320 8781750 chrl2 8781560 *7H ,n 6509 chrl2 10531400 10531770 chrl2 10531650 10531735 6520 chrl2 12594740 12596010 chrl2 12595125 6526 chrl2 18273960 18274110 chrl2 18274000 18274079 6542 chrl2 18706900 18707090 chrl2. 18706966 18707072. 6546 chrl2 22471180 22471750 chrl2 22471424 22471554 6565 chrl2 26095700 26095970 chrl2 26095774 20>tV.<W) 6577 chrl2 28560420 28560590 chrl2 28560406 28560520 6588 chrl2 31546100 31546350 chrl2 31546057 31546162 6604 chrl2 31619780 31620010 chrl2 31620005 31620129 6605
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Chrl2 64597860 64598030 c rl2 64597795 64597912 6701 chrl2 67293540 67293710 chrl2 67293687 67293836 6709 chrl2 68844840 68846090 chrl2 68845349 68845449 6711 chrl2 71055580 71055910 chrl2 71055506 71055592 6720 chrl2 77287460 77287610 c rl2 7 :-.ί 77287545 6740 chrl2 88908880 88909170 c rl2 88908890 88908978 6771
Chrl2 89456880 89457090 c rl2 89456949 89457042 f.-ni chrl2 90545520 90545970 chrl2 90545536 90545641 6778 chrl2 MOO 9.}S2if-70 c fl2 94823551 9 S2 6789 chrl2 104972240 104972610 chrl2 104972523 104972607 6816 chrl2 105062800 105063090 c rl2 105062690 105062842 6818 chrl2 105096360 105096910 c rl2 105096249 105096361 6819 c.hrl2 108841280 108841550 c rl2 108841442 108841543 OS ϊ chrl2 115841700 115842010 chrl2 115841622 115841712 6852 chrl2 116784640 116784890 c fl2 116784859 116784973 6856 chrl2 116819340 116819690 chrl2 116819406 116819500 6857 chrl2 116872600 116872830 chrl2 116872828 116872899 6858 chrl2 121156800 121157190 chrl2 121156987 121157100 6868 c.hrl2 123319900 123320170 c rl2 123319859 123319962 6874 chrl2 123449380 123449570 chrl2 123449512 123449601 6875 chrl2 125622440 125622790 chrl2 125622683 125622766 6885 chrl2 126346280 126346470 chrl2 126346332 126346515 6888
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Chrl7 79024960 79025110 c rl7 7W.M972 }-)lV.W>0 JI chrl7 79241220 79241510 chrl7 79241172 79241255 8395 chrl7 79674300 79674690 chfl7 79674575 79674653 8401 ch'rl7 79816180 79816470 chrl7 79816199 79816327 8402 chrl7 80048680 SO ii!- ji; c rl7 80048928 80049020 8403 chrl7 80302440 80302690 c rl7 80302576 80302655 8405 c.hrl7 80309120 80309370 c rl7 80309288 80309376 8406 chrl7 80542940 80543150 chrl7 80542963 80543043 8408 chrl7 80778320 80778730 chfl7 80778467 80778693 8413 ch'rl7 80854780 80854990 chrl7 80854742 80854820 8415 chria 2960620 2960810 chrlS 2960595 2960669 B42« chrlS 6187240 6187450 chrl8 6187161 6187270 8434 hrlS 9912380 9912650 chrlS 9912497 9912588 8441 chrlS 11790200 11790410 chrlS 11790305 11790392 8448 chrlS 11995960 11996190 chrlS 11995947 11996057 8449 chrlS 12377200 12377850 chrlS 12377506 12377572 8450 chrlS 20420620 20420910 chrlS 20420544 20420705 8466 chrl8 21073680 21073870 chrlS 21073741 21073885 8471 chria ,:ί.Ου'^:>0 26065530 chrlS 26065344 26065419 8487 chrlS 28263160 28263370 chrl8 28263305 28263409 8498 chrl8 29661920 29662210 chrl8 29662080 29662190 8503 chrl8 45374080 45374330 chrlS 45374002 45374115 8537 chrlS 52847120 52847370 chrlS 52847211 52847300 ;;S'i8 chrl S 53201820 53202170 chrl8 53201992 53202096 8561 chrl 8 55093710 chrlS 55093504 55093689 8565 ch'rl8 58272900 58273150 chrl8 58273076 5827318g 8571 chrl8 71359100 chrl8 71359038 71359148 Sf-()7 chrl8 77228260 77228430 chrlS 77228353 77228453 8645 chrlS 77580160 77580350 chrlS 77580201 77580310 8653 chrl9 610100 610490 chrl9 610176 610270 8669 chrl9 626680 626890 chrig (,2(·ι, ν, 626729 8670 chrl? 707500 707810 chrl9 707409 707531 8672 chrlS 791620 792050 chrl9 791702 791821 Si- 73 chrl9 883740 883990 chrl? 883889 883967 8674 chrl9 903260 903490 c rl9 90 I 65 903545 8675 chrl9 1217440 1217630 chrl9 1217491 1217596 8677 chrl9 1909520 1909890 chrlS 1909441 1909621 8660 chrl9 2631220 2631790 chrl9 2631555 2631659 8683 chrlS 2765220 2765450 chrl9 J. -.'b-, -, V. 2765387 Si-X¾ chrig 2852640 2853210 chrl? 2853105 2853228 8687 c.hrl9 3070560 3070770 chrl9 3070667 3070760 8689 chrig 6373020 6373630 chrl9 6373061 6373448 8661 chrl9 6373020 6373630 chrlS 6373587 6373798 KM, ' ch'rl9 6373720 6374010 chrl9 6373587 6373798 8662 chrl9 7083000 7C8.to«0 chrig 7083049 7C8.H 7 / 8708 chrl9 9491880 9492430 chrl9 9491833 9492531 8664 c.hrl9 34166720 34166890 chrl9 34166800 34166887 S7'< S chrig 34595600 34595810 chrl? 34595802 34595882 8794 chrl9 40349240 40349450 chrl9 40349294 40349391 8809 chrl9 40651440 40651610 chrig 40651450 40651580 8816 chrl9 42049980 42050170 chrig 42050097 42050205 ίί< : chrl9 42807260 42807550 chrl9 42807266 42807377 8824 chrig 44502120 44502390 chrl9 44502185 44502263 a?.rr chrig 44598340 445g8570 chrl 9 44598400 445984g6 8828 chrl9 46512800 46513310 chrl9 46513048 46513130 KS-M chrl? 54974880 54975230' chrig 54975046 54975738' 8869 chrl9 5 Γ}75.?.·!0 54975790 chrig 54975046 5 19757 8869 ch'rl9 55407440 55407650 chrig 55407525 55407611 8873 chrig 55901180 55901410 chrl? 55501191 55901293 8879 chrig 56368640 56368830 chrl9 56368568 56368752 8884 chrig 56674600 56674750 c rl9 56674588 566746S6 8888 chrl? 56888940 56889190 chrl9 56889039 56889160 8890 chr2Q 1825860 1826130 chr20 1825836 1825917 8906 chr2G 6912200 6912350 chr20 6912266 6gi2368 8918 chr20 7486260 7'lSi-750 chr20 7486365 7 Si-Vi S921 chr20 11785680 11785930 chr20 11785896 11786021 8929
Chr20 13820420 13820630 c r20 13820451 138205S8 H ) ,h chr20 14685200 14685370 chr20 14685247 14685331 8 37 chr20 16896360 16896630 chf 20 16896479 16896569 8946 chr2G 18795980 18796190 chr20 18796067 18796158 8952 chr20 23142040 23142550 chr20 23142330 23142421 SO V) chr20 23735440 23735590 chr20 23735455 23735542 8962 chr20 24740520 24740770 chr20 2-i / -l0 2.; 24740799 8955 chr20 25265840 25266130 chr20 25266067 25266158 8968 chr20 36824000 36824190 chf 20 36824062 36824143 9012 chr20 37257640 37257930 chr20 37257887 37257g80 9014 chr20 ■}■!,> 520 39678150 chr20 39677561 39677643 9018 chr20 44393460 44393770 chr20 44393543 44393617 9028 chr20 44546980 44547310 chr20 44547106 44547200 '.·(! id chr20 45501060 45501530 chr20 45501398 45501505 9037 chr20 50481580 50481810 chr20 50481764 50481860 90-i2
Figure imgf000291_0001
chr21 47529120 47529450 chr21 47529124 47529211 9299 chr22 18008740 18009070 chr22 18008951 18009037 9321 chr22 18453000 18453430 chr22 18453056 18453157 9323
Chr22 21406160 21406390 chr22 21406112 21406221 9331 chr22 24253580 24253750 chr22 24253484 24253600 9337 chr22 28296800 28296950 chr22 2H2'.'G?0 ? 28296912 9342 chr22 30714940 30714950 chr22 30714854 30714960 9348 chr22 33216120 33216470 chr22 .55216312 33216421 38 chr22 33961600 33961970 chr22 33961551 33961650 9360 chr22 36038280 36038670 chr22 iiV).;s:,53 5 r. Si: i 3 9370 ch'r22 37736580 37736890 chr22 37736608 37736730 9374 chr22 39864980 39865170 chr22 39865078 39865191 9379 chr22 43074020 43074230 chr22 43074018 43074094 9394
Chr22 44849720 44849930 chr22 44849805 44849884 9400 chr22 45005080 45005290 chr22 45004991 45005113 9401 chr22 45056900 45057130 chr22 45057049 45057143 9402 chr22 45925900 45926310 chr22 45925879 45925984 9405 chr22 47145640 47145950 c r22 47145867 47146013 9407 chr22 47146000 47146270 chr22 47145867 47146013 9407
Chr22 47541720 47541930 chr22 47541717 47541825 9410 chr22 49014160 49014390 chr22 49014366 49014470 9423 chr22 49930920 49931190 chf22 49931059 49931161 «m« chr22 50209240 50209670 chr22 50209639 50209728 9444 chr22 50;' ,:S7i; c r22 50732704 9448 chrX 4969880 4970570 chrX 4970197 4970291 9481 chrX 12235540 12235710 chrX 12235505 12235601 9499 chrX 12963320 12963490 chrX 12963316 12963390 9502 chrX 26429240 26429450 chrX 26429329 6Λ2'·Μ2·¾ 9527 chrX 30127100 30127250 chrX 30127031 30127106 9538 chrX 31395980 31396210 ChrX 31395925 31396000 9542 chrX 39120320 39120570 chrX 39120253 39120341 9558 chrX 42806160 42806390 chrX 42.806148 42806234 9568 chrX 48660060 48660470 chrX 48660039 48660137 9583 chrX 49966760 49967010 chrX 49966843 49966939 9588 chrX 53506320 53506590 chrX 53506408 53506501 9598 chrX 71388940 71389170 chrX 71389028 71389120 9621 chrX 71933400 71933670 chrX 71933490 71933592 9622 chrX 77043600 77043850 ChrX 77043627 77043724 9643 chrX 87155340 87155630 chrX 87155486 87155585 9675 chrX 55986140 55986310 chrX 95986076 55986149 9698 chrX 100311600 100311790 chrX 100311657 100311793 9708 chrX 102685640 102685910 chrX 102685879 102685970 .'17 chrX 102695620 102695830 chrX 102695653 102695759 9718 chrX 110109760 110109910 chrX 110109659 110109781 fi.?27 chrX 113283980 113284150 chrX 113284101 113284193 9735 chrX 115376240 115376410 chrX 115376330 115376441 9744 chrX 115465980 115466130 chrX 115466008 115466101 9745 chrX 115860560 115860710 chrX 115860536 115860610 9747 chrX 130577840 130578070 chrX 130577953 130578043 10140 chrX 131391200 131391470 chrX 131391413 131391511 9802 chrX 131768580 131768830 chrX 131768695 131768789 9803 chrX 138173320 138173530 chrX 138173439 138173589 9816 chrX 152992640 152993070 chrX 152992934 152993010 9860 chrX 153219800 153220010 chrX 153219855 153219980 " b chrX 153607020 153607710 chrX 153607264 153607413 9864 chrY 7188660 7189110 chrY 7188662 7188780 9906 chrY 8898020 8898210 chrY 8898125 8898233 9917 chrY 16452700 16452930 chrY 16452759 9942 chrY 16456940 16457130 chrY 16456906 16457053 9943 chrY 19093780 19093930 chrY 190937S4 19093863 9953 chrY 21237660 21238110 chrY 21237567 21237701 9957 chromosome in which the DNasel hypersensitive site resides
start position of the DNasel hypersensitive site
end position of the DNasel hypersensitive site
chromosome in which the human CRISPR resides
start position of the human CRISPR
end position of the human CRISPR
unique patent ID given to the human CRISPR
Table 23 A subset of potential human CRISPR spacer targets in phages, plasmids and viruses
Protospacer ¾- ¾. Human CRISPR Spacer sequence6
SeqJD1 SEQ seqJd 3 ¾ ¾
ID 1
NO2 I 2 « 2
.E tt I 2 _ £tft tt £
R l ?f! 2 iiiiiii NC_002531.1 CTC NA GAGAAGGAGAAGGAGAAGGAGAAG Alee!aphine herpesvirus
CR 102.0 2 , 568 NCJ332555.1 CTT NA GAGAAGGAGAAGGAGAAGGAGAAG Beihai rhabdo-like
CR1020 2 ¾->8 NC_002687.1 AGG CT GAGAAGGAGAAGGA6AAGGAGAAG Ectocarpus silicuiosus
CR 020 7 ...568 ' ' Z~C '007239!i CTC NA GAGAAGGAGAAGGAGAAGGAGAAG Ensifer adhaerens
CR I M ^ 568 NC_0Q1596.1 , NA GAGAAGGAGAAGGAGAAGGAGAAG Human papillomavirus type 10
CR1020_2 568 NC_Q01S96.1 CTT NA GAGAAGGAGAAGGAGAAGGAGAAG Human papillomavirus type 9
Γ.Β1Γι9Π 9 !ii i JX042S78 ' i i NA GAGAAGGAGAAGGAGAAGGAGAAG vco bacterioDh aae
, R,IO,?J ,,?,,,,,. ,,,568,,,,, NC 019730.1 GGG CCC GAGAAGGAGAAGGAGAAGGAGAAG Oscillaroria nipro-viridis
NC 028091.1. CTT NA GAGAAGGAGAAGGAGAAGGAGAAG Ostreococcus lucimannus
.,,.568,,,,, NZ CP022667.1 CTT NA GAGAAGGAGAAGGAGAAGGAGAAG , Rhgobju m , I egu m, inpsa r p ,=,
NZ CP022667.1 r : : NA GAGAAGGAGAAGGAGAAGGAGAAG Rhizobium leeuminosarum
rR i rvjn ,,,,56ί!,,,,. NC 009430.1 CTT NA GAGAAGGAGAAGGAGAAGGAGAAG Rbpdpbacte
r;R-m n 9 1 ' NC 001350.1 , NA GAGAAGGAGAAGGAGAAGGAGAAG Saimiriine herpesvirus
,QR fl2p NC 010311.1 CTT NA GAGAAGGAGAAGGAGAAGGAGAAG .Streptomycfis.^
pirm 9 NC 00406S.1 GAA NA UUUCUUUCUUUCUUUCUU Cvcnnid herpesvirus
CRiO¾3,,9v, ,,,,,,,581,,,,, NC 0218S8.1 CC NA uuucuuucuuucuuucuu and rayj,^^
r.Bum 9 NC 021858.1 GAA NA u u ucmi ucu u ucuu ucu u Pandor3virus du!cis
ΓΡ Ι rm 9 !>!! 1 NC 002512.2 GAA NA uuucuuucuuucuuucuu .Rat cytp im.p ajpyi rus
CR 1033. 2 581 NC_023269.1 GAA NA u u ucuu ucu u ucuu ucu u Yellowstone lake virophage 5.
CR1038 586 NC_008043.1 GAA NA AUUCCCACAUCUUACCUGUCUUCUGAGCCCUC Ruegeria so.
CR 04 5687 NC_034383.1 C NA CUCUUUUUUUGGG.MAUCUCUGAGCUGAUUUCCACAGGGGCUGAACUAAUUUAUAA Pacmanvirus A23
.CR. ,044 59? KT429160 CAT NA UAUACACACACAUAUACAUAUACAUCUUCU Staphylococcus
CR 1067 b !b NC_031055.1 AGG CT U A U UU U U AUU G A6CAU MA A AUCAU C AU U C AA6 AG Bacillus
CR 1068 ...6.1.6 KY389064 OCT NA CCUUAUAAAAGGCUAUUUGAAGUUGUAGU Staphylococcus
CR107 5690 NC_032ill.l AGG CCT UCCAAAGUGCUAGGAUUACAGGCAAGA6CCACUGCGCCCA BeAn 58058 virus
CR1071 619 NC 015933.1 CAT NA UCUGGGAAUACAUUUAAUCUAAUGCUCCCUAA Escherichia
CR1071 NC_024790.1 CAT UCUGGGAAUACAUUUAAUCUAAUGCUCCCUAA Escherichia
CR 084 634 NC_014633.1 cc NA UGGGCGGGUGGAUCACGAGGUCAGGAGAUCGAGACCAUCCUAGCUAA llyobacter polytropus
CR1086 636 NC_021248.1 GAA NA ACCAAAAAGACCAUCCUUCAAAGAGUGAUGA Choristoneura biennis entomopoxvirus
CR1087 ...637 NC 032111 1 CTC NA ACCAGCCUGACCAACAUGGAGAAACCCCGUCUCUAC BeAn 58058
CR109S 'i-i!: NC_02546S.l CAT TTTTGATG AGCUGGAGAUAUGGGUGUAAGGCAGMUUCAUAU Carrot betafiexivirus
CR1 10 5693 NC 030947.1 GAA NA CUUUGAGCUUUCCAGUUGUUUUAUUUC Clostridium
CR1 10 <■·. NC_03O351.1 GAA NA CUUUGAGCUUUCCAGUUGUUUUAUUUC Clostridium
CR1 10 5693 NC_020871.1 CTT NA CUUUGAGCUUUCCAGUUGUUUUAUUUC Listeria
C 110 ·■: NC_009811.2 CTT NA CUUUGAGCUUUCCAGUUGUUUUAUUUC Listeria
CR 10 5693 NC_U25440.1 CTT NA aJUUGAGCUUUCCAGUUGUUUUAUUUC Listeria
C 110 5693 NC_Q243S3.1 r : : NA CUU UGAGCU UUCCAG U UG UUU UAUUU C L>-.Scr:,l
CRT 10 5693 NC_024787.1 CTT NA CUUUGAGCUUUCCAGUUGUUUUAUUIJC Listeria
CR110 5693 NC_021781.2 ' ; ; NA CUU UGAGCU UUCCAG UUGUUUUAUUUC Listeria
CR 1 10 ...5.693... NC..024360.1 CTT NA CUUUGAGCUUUCCAGUUGUUUUAUUUC Listeria
CR110 iiiliiii NC.024364.1 CTT NA CUU UGAGCU UUCCAG U UG UUU U AUUUC Listeria
CR.I.IQ 5693 NC_024359.1 CTT NA CUUUGAGCUUUCCAGUUGUUUUAUUUC Listeria
CR1112 r.w NC_Q32111.1 CTC NA UCUCACUCUGUCACCCAGGCCGGAGUGCAGUGGCACGAUCAUAGCUCAC BeAn 5S058
CR1114 665 C..018584.1 GAA NA UUCAAAUUUAUGAAAAAUUUCUUUUGUGUUUUCUUUUUUCAAAAUAUUUGUAAUUUUG Bacillus thuringiensis
CR1114 665 NC 008274.1 CTT NA UUCAAAUUUAUGAAAAAUUUCUUUUGUGUUUUCUUUUUUCAAAAUAUUUGUAAUUUUG Borreiia afzelii
CR1 114 665 NC .01 /229.1 CTT NA UUCAAAUUUAUGAAAAAUUUCUUUUGUGUUUUCUUUUUUCAAAAUAUUUGUAAUUUUG Borrelia afzelii
CR1 14 665 NZ_CP015797.1 ' i i NA UUCAAAUUUAUGAAAAAUUUCUUUUGUGUUUUCUUUUUUCAAAAUAUUUGUAAUUUUG Borreii3 rri3yonii
CR1114 665 NZj:P01578Ll CTT NA UUCAAAUUUAUGAAAAAUUUCUUUUGUGUUUUCUUUUUUCAAAAUAUUUGUAAUUUUG Borrelia mayonii
CR1114 665 NZ_CP018266.1 r : : NA UUCAAAUUUAUGAAA UUUCUUUUGUGUUUUCUUUUUUCAAAAUAUUUGUAAUUUUG Borreliella afzelii
CR1114 665 NC..012129.1 CTT NA UUCAAAUUUAUGAAAAAUUUCUUUUGUGUUUUCUUUUUUCAAAAUAUUUGUAAUUUUG Borreiiella valaisiana
CR1114 665 NZ_CP013615.1 CTC NA UUCAAAUUUAUGAAAAAUUUCUUUUGUGUUUUCUUUUUUCAAAAUAUUUGUAAUUUUG Clostridium perfeingens
CR1114 665 NC_Q06653.1 CTc NA UUCAAAUUUAUGAAAMUUUCU Cotesia congregata
CR1 17 CHS NC_028092.1 GAA NA AUGUGG AUU UGU UAAAU UAUU UAAAAC Ostreococcus mediterraneus
CR i 117 ...668 NC_010191.2 GAA NA AUGUGGCAUUUGUUAAAUUAUUUAAAAC Ostrepcpccus tauri
CR1 1 668 NC_013288.1 GAA NA AUGUGGCAUU UGU UAAAU UAUU UAAAAC Ostreococcus tauri
CR1.I23 ....674..... KX397371 GAA NA UAACUGUUACAUGGUUUGACAAUGUUAGAGGAAAAUUAAGAAAUCACACAAUUCUA Erwiriia
CR H?:i ■> i X397370 GAA NA UAACU6UUACAUGGUUU6ACAAUGUUAGAGGAAAAUUAAGAAAUCACACAAUUCUA Erwinia
CR1123 674 X397368 GAA NA UAACUGUUACAUGGUUUGACAAUGUUAGAGGAAAAUUAAGMAUCACACAAUUCUA Erwiriia
CR : '■ ' <> / i NC_03U27.1 GAA NA UAACUGUUACAUGGUUUGACAAUGUUAGAGGAAAAUUAAGAAAUCACACAAUUCUA Erwinia phage
CR.1.125...3.. ...678 NC_00615i.l cc NA GGAAGAGAGAGGAGGGAGGUGGGGCACUGA Suid herpesvirus
CR1133 6S7 ■.'.. ;.- ; ::! A ATTCTTT AU UUAAAGUAUAAUAAUAAUAAAAA Campylobacter
CR1133 687 GU296433 NA ATTCTTT AU UUAAAGUAUAAUAAUAAUAAAAA Campylobacter
CR1133 687 FR823450 NA ATTCTTT AUUUAAAGUAUAAUAAUAAUAAA.AA Campylobacter
CR1 133 687 KC821624 cc i NA AU UUAAAGU AUAAUAAUAAUAAAAA Cellulophaga
Figure imgf000295_0001
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CR 265 819 NC_021312.1 TGG CCA GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGUAGUCUCGAUGUAUGGUGGG Phaeocystis globosa virus ll!i!!Ii 819 NC 021312.1 NA TTTTACTT GUGUGUGUGUGUGUGUGCGUGUGUGUGIJGUGUGUAGUCUCGAUGUAUGGUGGG Phaeocystis g!obasa virus
CR 265 819 NC_003220 l CCT NA GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGUAGUCUCGAUGUAUGGUGGG Planaria asexual
llllSIIi 819 NC_003219.1 CCT NA GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGU AGUCUCGAUGUAUGGUGGG Planaria asexual
CR1265 819 NC .022233. ! CTC NA GUGUGUGUGUGUGUGIJGCGUGUGUGIJGUGUGIJGU AGUCUCGAUGUAUGGUGGG Porcine cytomegalovirus
819 NZ_CP017244.1 CC NA
lflll GUGUSUGUGUGUGUGUGCGUSUGUGUGUGUGUGUAGUCUCGAUGUAUSGUGGG Rhizofaium etli
CR 265 819 NZ_CP017244.1 CTC NA GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGU AGUCUCGAUGUAUGGUGGG Rhizobium etli
819 NC 014567.1 CTC NA GUGUGUGUGUG'UGUGUGCGUGUGUGUG'UGUGUGU AGUCUCGAUGUAUGGUGGG Saimiriine herpesvirus
CR 265 819 NC..026¾11. i NA TTTTATCC GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGUAGUCUCGAUGUAUGGUGGG Spodoptera frugiperda Betabacu
819 NC_003S36.1 TGG CCA GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGU AGUCUCGAUGUAUGGUGGG Tomato aspermy virus
CR1265 819 NC .002794. ! GAA NA GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGU AGUCUCGAUGUAUGGUGGG Tupaiid herpesvirus
CR 1265 819 NC_002?94.1 lllll CT GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGUAGUCUCGAUGUAUGGUGGG Tupaiid herpesvirus
CR 265 819 NC_031033.1 NA TTTCTAC GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGU AGUCUCGAUGUAUGGUGGG Volepox virus strain CA
819 NC 031033.1 CC NA GUGUGUGUGUG'UGUGUGCGUGUGUGUG'UGUGUGU AGUCUCGAUGUAUGGUGGG Valepox virus strain CA
CR 265 819 JQ965702 GGG CCC GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGUAGUCUCGAUGUAUGGUGGG Yersinia
819 EU73417G GGG CC GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGU AGUCUCGAUGUAUGGUGGG Yersinia
CR1265 819 NC..011038. ! GGG CCC GUGUGUGUGUGUGUGUGCGUGUGUGUGUGUGUGU AGUCUCGAUGUAUGGUGGG Yersinia
CR 127 5710 NC_01O391.1 TGG CCA UCUGCGGGCAUGGAAGGAAGCCCCAGGAAGCUGGGAAAUG Salmonella
CR 278 6069 NC_027925.1 NA TTTTGGTG AAAACAAAACAAAACAAAAAACCACU AAAAA Apis meliifera filamentous virus
NZ_CP022346.i NA TTTTAAAT AAAA.CAA.AACAAAACAAAAA.ACCACUAA.AAA Bacillus thuringiensis
..GB. .27.8.. . 60.69.. NC..0027 9.1 GAA NA AAAACAAAACAAAACAAAAAACCACUAAAAA Ba nana mild mosaic virus
6069 NC Ol 1966.1 NA TTTTATTT AAAACAAAACAAAACAAAAAACCACUAAAAA Borreiia burgdorferi
CR1278 6069 NC_G11966.1 NA TTTTGTTT AAAACAAAACAAAACAAAAAACCACUAAAAA Borrelia burgdorferi
lliill NC 031593.1 !ilii TTTTGTTT AAAACAAAACAAAACAAAAAACCACUAAAAA Burke-Gllman
CR1278 ,, 6069,, Y421186 GAA NA AAAACAAAACAAAACAAAAAACCACUAAAAA Flavobacterium
CR1278 iiiiii NC_029255.1 NA AAAACAAAACAAAACAAAAAACCACUAAAAA Myotis gammaherpes
CR1278 6069 NC_005029.1 NA TTTTGCTT AAAACAAAACAAAACAAAAAACCACUAAAAA Onion yellow dwarf
CP - siH 6069 NCJ333773.1 ' i i NA AAAACAAAACAAAACAAAAAACCACUAAAAA Pepper chlorotic spot
CR1278 6069 NC..003296.1 A TTTTGAAT AAAACAAAACAAAACAAAAAACCACUAAAAA Ralstonia soianacearum
Figure imgf000301_0001
CR i id i Λ 6094 NC_016596.1 cc NA UGGGGGUGGGGGCGGGGGCGCAGGCGGGGGCGGGGGCGCGGA Azospiriiiurn brasilense
CR1304_4 6094 NC_015727.1 cc NA UGGGGGUGGGGGCGGGGGCGCAGGCGGGGGCGGGGGCGCGGA Cupriavidus necator
CR1304.4 6 ί NC_007767.1 cc NA UGGGGGUGGGGGCGGGGGC6CAGGCGGGGGC6GGGGCGCGGA Hypharitria cunea nucleopolyhei
CR1304„4 6094 NC_U29691.1 TGG CCA UGGGGGUGGGGGCGGGGGCGCAGGCGGGGGCGGGGGCGCGGA Ixeridium yellow mottle
CR1304.4 6094 NZJ.N868939.1 CC NA UGGG6GU6GGGGCG6GGGCGCA6GCG6GGGCGG6GGCGC6GA Nocardia fara'nica
CR1304_4 6094 NC..007653.1 cc. NA UGGGGGUGGGGGCGGGGGCGCAGGCGGGGGCGGGGGCGCGGA Papiine herpes virus
CR 304..4 6094 NZ_CPQ21G28.i CCT NA UGGGGGUGGGGGCGGGGGCGCAGGCGGGGGCGGGGGCGCGGA RhiiOi u HS.
CR1304_4 6094 HG007973 TGG CCA UGGGGGUGGGGGCGGGGGCGCAGGCGGGGGCGGGGGCGC6GA Stenotrophomonas
Figure imgf000302_0001
Figure imgf000303_0001
C 138 HIM NC_01H89.1 NA ΤΤΤΤΛΤΑΤ CAAAAAAAAAAAAAAAAAAACCACUA ikania micrantha mosaiic virus
CR138 . 5720, , , NC .018702. ! cc NA CAAAAAAAAAAAAAAAAAAACCACUA Murine astrovirus
CR138 HIM NC 03O294.1 NA CAAAAAAAAAAAAAAAAAAACCACUA Negev virus
CR138 . 5720,,, NC_021858.1 ccT NA CAAAAAAAAAAAAAAAAAAACCACUA Pandoravirus dulcis
CR : w ΊΙ NC_0 1858.I GAA TTTCGTTG CAAAAAAAAAAAAAAAAAAACCACUA Pandoravirus dulcis
CP138 ...5.720... NC 021858.1 GGG CCC CAAAAAAAAAAAAAAAAAAACCACUA Pandoravirus dulcis
CR : Vi NC_026440.1 CTT NA CAAAAAAAAAAAAAAAAAAACCACUA Pandoravirus inopinatum
CR138 ...5720 ΝΟ_022098 CAT NA CAAAAAAAAAAAAAAAAAAACCACUA Pandoravirus salinus
CR138 5720 NC_Q25193.1 GAA NA CAAAAAAAAAAAAAAAAAAACCACUA
CR138 5720 NC..029->.02.1 A TTTTATTT CAAAAAAAAAAAAAAAAAAACCACUA Piscine myocarditis-like virus
CR 38 i./? NC_03415S.l CC NA CAAAAAAAAAAAAAAAAAAACCACUA Piura virus
CR1 8 ....5720, , NCJ319494.1 cc. NA CAAAAAAAAAAAAAAAAAAACCACUA Porcine astrovirus
CR138 6,70 NC G23S7S.1. TC NA CAAAAAAAAAAAAAAAAAAACCACUA Porcine astrovirus
CR. .38 ...572Q NC_022896.1 CTT NA CAAAAAAAAAAAAAAAAAAACCACUA Sclerotinia hypovirus
CR138 5720 NC_023861.1 CAT NA CAAAAAAAAAAAAAAAAAAACCACUA Sicinivirus
CR138 ...5720 .. NC_025890.1 CTT NA CAAAAAAAAAAAAAAAAAAACCACUA Tortoise picomavirus
CR138 /?0 NC_01O8Q0.1 CTC NA Turkey coranavirus
CR1.38 ...5.7.20,.. NC .023440. ! cc NA CAAAAAAAAAAAAAAAAAAACCACUA Wallerfie!d
CR138 hi n NC_033718.1 AGO CCT CAAAAAAAAAAAAAAAAAAACCACUA Wuhan spider virus
CR 138 .,, 5720, , NC_033712.1 cc NA CAAAAAAAAAAAAAAAAAAACCACUA Wuhan spider virus
CR 38 i./? NC_032128.I GGG CAAAAAAAAAAAAAAAAAAACCACUA Wuhan spider virus
CR139 5721 NC..004810.1 " "CAT NA AU AUGUAUAUGUAUAUAUMUAUACAUAUAUAUGU UACAUAU Cucurbit yellow stunting disorder virus RNA
CR : W NC_021246.I , NA AUAUGUAUAUGUAUAUAUAAU AUACAUAUAU AUGU UACAUAU Mythimna ento nopoxvirus
CR1392 6181 KX397369 CGG CCG UUGAAAUCAAUCGUAAAUACGAUAGAUUUCUAUU6AAAUC Erwinia
CR1 95 KU160494 CAT NA CAUCUUGGGADUUAUDUCAAAAAAUAAAUCCA Vibrio
CR1399 6188 NC_008724.1 CTT NA CAUUGAAGUUUUUUUUUUUCUUUUUUUUUUUUUUACA Acanthocystis turfacae chloreiia virus
CR1399 •v- NZ_HG969193.1 NA CAUUGMGUUUUUUUUUUUCUUUUUUUUUUUUUUACA Bartonella tribocorum
CR1399 6188 NCJ310160.1 CTT NA CAUUGAAGUUUUUUUUUUUCUUUUUUUUUUUUUUACA Bartonella tribocorum
CR 399 r. ¾w» NC_026440.I GAA NA CAUUGMGUUUUUUUUUUUCUUUUUUUUUUUUUUACA Pandoravirus inopinatum isolate KiaHel
CR1404 6193 NC 0030.38.1 CTT NA AUAUAUUUAAAAAAUCAAGGACAGUUUCACU Invertebrate iridecent virus
CR1413.3 NC.032111.1 TGG CCA UGUUAAUAUGAAAAUAUUUUAAUAUGAAACAAAUUACCAUUAA! iif.V)
CR 439 6226 NC_009233.1 CAT NA UAUUUUGUAAAAAUUGUUACUCUGGGAUACCUAUCACA Heliothis virescens ascovirus
CR1440 ■\'/ίι NC 016072.1 CC NA G UA AACAU UU UU AU UUUCCAAAUU UUCUCU AA.AAGGAAACCUU UUAU egavirus chtliensis
CR 444 6231 Νς_014756 cc NA CACUUUUUAAUGAGUUCCUCCUUAUUUAACGAUGACGAAAAG Sulfuricurvum kuijense
CR1451 ("■ \Λ NZ_CP0O3691.1 GAA NA UAAAAAAGCAAAUAUAAUACUAAAGUUUAUGUGUCUGUAAAAAUGUUAAAAAUUU Bacillus mycoides
CR1451 6238 NC_ 32993.1 CAT NA UAAAAAAGCAAAUAUAAUACUAAAGUUUAUGUGUCUGUAAAAAUGUUAAAAAUUU Hubei picona-like
CR 1454 62 i f NC_02O104.1 CAT NA AAUAAUAUUAAUUAAUUCUGUUAAGU Acanthamoeba polyphaga mourn ouvirus
CR 454 6241 NC_023426.1 CAT NA AAUAAUAUUAAUUAAUUCUGUUAAGU Anomala cuprea entomopoxvirus
CR1454 NC 016072.1 C NA AAUAAUAUUAAUUAAUUCUGUUAAGU egavirus chtliensis
CR 472 6259 NC_0201Q4.1 NA TTTCT AUAAUAAUAAUAAUAAUGUGAGAC Acanthamoeba polyphaga moumouvirus
Figure imgf000305_0001
C i \υ 6259 NC 026440.1 CGG CCG AUAAUAAUAAUAAUAAUGUGAGAC Pandoravirus incpinaturrs isa!3te laHel
CR1472 6259 NC_021312.1 CC NA AUAAUAAUAAUAAUAAUGUGAGAC Phaeocystis glabosa virus
CR 1476 6263 NC_034976.1 AGG CT GCA6CAAGCUGGAGGUGCGAGGGGUGAG Goattorovirus
CR1481 6268 NC_021858.1 CGG CCG (7v\(7v\L' UAACAAi!AACAAAACMGGUCCCACUGCAUUCAU Pandoravirus dulcis
CR I 49 5731 NC_022098.1 CC NA UAAAAAAACAGGGCAGAAGAGGUCAGGGGGAGGAUG Pandoravirus sali'nus
CR i 5 5598 NZ_CP022346.1 GAA NA GAAAGAAAGAAAGAAAGAAA Bacillus
CR15 5598 NC_006298.1 GAA NA GAAAGAAAGAAAGAAAGAAA Haemophilus
CR 5 5598 NC_004065.1 GAA NA GAAAGAAAGAAAGAAAGAAA Murid_herpesvirus
CR15 NC_026440.1 CCT NA GAAAGAAAGAAAG AGAAA Pandoravirus
CRi 5 5598 ,, NC_ 218S8.1 GAA NA GAAAGAAAGAAAGAAAGAAA Pandoravirus
C i ¾ 5598 NC_021858.1 TGG CCA GAAAGAAAGAAAGAAAGAAA Pandoravirus
CR 15 5598 NZ_CP012852 l GAA NA GAAAGAAAGAAAGAAAGAAA Persicobacter
CR 5 5598 NC_0Q2512.2 GAA NA GAAAGAAAGAAAGAAAGAAA Rat_cytomegalovirus
, CRI 5 559,8„ NC_028269.1 GM NA GAAAGAAAGAAAGMAGAAA virophage
CR 50 b <".'.? NC 032111.1 CGG i d - CCAGGCUGGUCUCGAACUCCUAACCUCAGUUGAIJCCUCCUGCCU BeAn 5S058 virus
CR 53 5735 NC _028461.1 NA ATTCTCT UCUUAAUCUUUUCAAAGUACAAAUAUUGUACUCAUACAAUAUUUGUCC Epizootic haematopoietic necrosis virus
CR153 5735 NC G17940.1. NA ATTCTCT UCU UAAUa!UUUCAAAGUACAAAUAUUGUACXICAUACAAUAUUUGUC European sheatfish
CR Ί7 5739 NC .028094.1 TGG CCA UAUAUAUAUAUAUUCCUAUGUAAAG Chrysochromulina ercina
CR157 5739 NC_019422.1 r : : NA UAUAUAUAUAUAUUCCUAUGUAAAG Clostridi m
CR157 573?, , NC .028951.1 CTT NA UAUAUAUAUAUAUUCCUAUGUAAAG Clostridium
CR157 bm V .029116.1 ! i i UAUAUAUAUAUAUUCCUAUGUAAAG Clostridium
CR1 57 5739 NC. .029001.1 CTT NA UAUAUAUAUAUAUUCCUAUGUAAAG Clostridium
CR 157 5739 NC .033778.1 c NA UAUAUAUAUAUAUUCCUAUGUAAAG Leptopilina bouiardi f il3rnemous virus
CR 6 5599 NZ_ CP012478.1 CTT and NA GAAGG AAGG AAGGAAGG AAG Arthrobacter
GAA
CR16 5599 lii CP012478 CTT NA GAAGGAAGGAAGGAA.GGAAG Arthrobacter
CR 70 5752 NC .004 ! 62.2 NA TTTTATAA UUUUUAGUGGUUUUUUGUUUUGUUUU Chikungunya
CR17 ..2 5758 NC_006151.1 TGG CCA ACCCCCUCUCACCUCCAUCUCCCCCAUCCCCCUCUCACCUCCAUCUCCCCCAUCCC Suid herpes virus
CR174_2 5758 NC .006151 TGG CCA ACCCCCUCUCACCUCCAUCUCCCCCAUCCCCCUCUCACCUCCAUCUCCCCCAUCCC Suid herpes virus
CR190 5777 N : .020292.1 CAT NA CUUAUUUUAUUUUUUUGUUUAUACUUAUGUCAUAAACAUAGU Clostridi u m saccharoperbutylacetonicutr,
CR190 bin NC. .020826.1 cfr NA CUUAUUUUAUUUUUUUGUUUAUACUUAUGUCAUAAACAUAGU Lactobacillus brevis
C 190 blii NZ CP021928.1 ' i i NA CUUAUUUUAUUUUUUUGUUUAUACUUAUGUCAUAAACAUAGU Pediococcus pentosaceus
CR 90 5777 NC. .031917.1 TGG CCA CUUAUUUUAUUUUUUUGUUUAUACUUAUGUCAUAAACAUAGU Pseudoalteromonas
CR21 1 5796 NC_035460.1 CCT NA UAUAGGUAUGAUAAUUACCUAUGAUAUAGGUA Eptesipox
CR217 5802 NC. .021247.1 cc A UUAUACAUUAUUAUAUAUAAUUAUAUACAUAUUAAGUGUAUUUA Adoxophyes enomopox virus
CR?■ • ?. NC_028G94.1 C NA UUAUACAUUAUUAUAUAUAAUUAUAUACAUAUUAAGUGUAUUUA Chrysochromulina ericina virus
CR217 5802 NC .006640.1 cc NA UUAUACAUUAUUAUAUAUAAUUAUAUACAUAUUAAGUGUAUUUA Cotesia congregata virus
CR2 ! /' HW.J NC ,006640.1 CCT NA UUAUACAUUAUUAUAUAUAAUUAUAUACAUAUUAAGUGUAUUUA Cotesia congregata virus
CR217 5802 hlC .006655.1 ccT NA UUAUACAUUAUUAUAUAUAAUUAUAUACAUAUUAAGUGUAUUUA Cotesia congregata virus
CR217 5802 N .006646.1 CCT NA U UAUACAU UAUUAUAUAUAAU U AU AUACAUAUUAAG UGU AU U UA Cotesi3 congregata virus
CR217 5802 NC, .006640.1 cc NA UUAUACAUUAUUAUAUAUAAUUAUAUACAUAUUAAGUGUAUUUA Cotesia congregata virus
CR21 5802 NC_00665S.l GAA NA UUAUACAUUAUUAUAUAUAAUUAUAUACAUAUUAAGUGUAUUUA Cotesia congregata virus
CR217 5802 NC _0O6655.1 CC NA UUAUACAUUAUUAUAUAUAAUUAUAUACAUAUUAAGUGUAUUUA Cotesia congregate virus
C 217 5802 NC G06S46.1. GAA NA UUAUACAUUAUUAUAUAUAAUUAUAUACAUAUUAAGUGUAUUUA Cotesia congregata virus
CR217 5802 NC .006546.1 cc NA UUAUACAUUAUUAUAUAUAAUUAUAUACAUAUUAAGUGUAUUUA Cotesia congregata virus
CfW NC _0±6072.1 GAA NA UUAUACAUUAUUAUAUAUAAUUAUAUACAUAUUAAGUGUAUUUA egavirus chiiiensis virus
CR218 5803 NC. _011875.1 AGG ccT CUCUCU CUCUCUAGAUG U AUAUAUAU ACACAU ACAUACAC Borrelia garinii
CR218 5803 NC .007029.1 CC NA CUCUCUCUCUCUAGAUGUAUAUAUAUACACAUACAUACAC Micropiitis bracovirus
CR231 5816 NC. _020104.1 CAT NA AUAAAAUUAUACAUUAUAUAUGUUACUUUUGACUAUACGCCCAGU Acanthamoeba polyphaga moumouvi
CR236 5821 Ill t ; TT NA UUGCCACUUUGCAAMGAGUUUCUAAUAAAGUUAAACGUAUAaJUUUCAUAUGACCCA Vibrio parah3etmo!ytiaj5
CR237 5822 NC. .008725 err NA AGCCUAAUUCAUAUUUUUAUAAUAAAAUUUUAAAUCUGUUA aruca vitrata
CR7- ',i>? > NC _0±94S5.1 NA TTTTGAAA AUUUUUUUGAAAOGUUUCUGAAAAAAAC Cypnnid herpesvirus
CR244 5829 NC. .009127. ! TGG CCA AU UUUUUUGAAAUGUUUCUGAAAAAAAC Cyprinid herpesvirus
CR/ VI W-l NC .029573.1 CC NA AU UUUUUUGAAAUGUUUCUGAAAAAAAC Raspberry leaf blotch
CR246 5831 NC .008724.1 CGG CCG AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Acanthocystis turfacea chlorella virus
CR W>.i ) NZ CP010358.1 TT NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Aci netaba cte r joh n so n i i
CR246 5831 NC. .032104.1 GGG ccc AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Arachis pintoi virus
CR246 5831 NC .032104.1 TGG ; i .·. AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Arachis pintoi virus
CR246 5831 NC .020102.1 TGG TTTTGCCA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Aspergillus foetidus mycovirus
CR246 5831 NC_Q2O100.1 TGG CCA AAAAAAAAA.AAGAAAAGAUAGAAAGA.AAAAAGAAAAUA Aspergillus foetidus mycovirus
CR246 5831 NC .02459/.1 GAA TTTTATTT AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Aureococcus anophageffen virus
CR W>3 ) NC ,006553.1 NA TTTTATAA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Avian sapeiovirus
CR246 5831 l2. .CP011836.1 e l NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Azotobacter chroococcum
CR246 5831 NC .012555.1 AGG CCT AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Bacillus anthracis
CR246 5831 NC. _007323.3 AGG CCT AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Bacillus anthracis
CR246 5831 NZ_CP0O9979.1 AGG CCT AAAAAAAAA.AAGAAAAGAUAGAAAGA.AAAAAGAAAAU A Bacillus anthracis
Figure imgf000308_0001
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CR246 5831 NC_024113.1 CCT NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Jingmen tick virus
ιιιιιιι 5831 N2_CPG20460.i AGG < ( i AAAA.AAAAA.AAGAAAAGAUAGAAAGAAA.AAAGAAAAUA Lactobacillus S3kei
CR246 5831 NZ_CP02046(U CCT NA AAAAAAAAAAAG AAAAGAUAGAAAGAAAAAAGAAAAU A Lactobacillus sakei
NC_0295S4.1 CTT NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Lake sarah associated circular virus 14
CR246 5831 NC_ 23627.1 TGG CCA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Laodelphax striatella honeydew ii!il 5831 NZ_CP01203 .1 !llll l!!!i AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Leptospira borgpetersenii
CR246 5831 NC_013424.1 GAA NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Leucas zeylanica
ιιιιιιι 5831 NC G04812.1. CT NA AAAA.AAAAA.AAGAAAAGAUAGAAAGAAA.AAAGAAAAUA acacine herpesvirus
CR246 5831 Ν€_004812 cc NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Macacine herpesvirus
'.ί' >, '■ NC_008737.1 TGG CCA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Mai de Rio Cuarto
CR246 5831 NC_ 08725.1 GAA NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Maruca vitrata MNPV
5831 NCJJ26771.1 CTT 11111 AAA AAAAAAGAAAAGAUAGAAAGAA AAGAAAAUA Mulberry mosaic dwarf associated
CR246 5831 NC_019559.1 cc NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Murid herpesvirus
Ιΐβΐι 5831 NC G19553.1. mil ( Ci. AAAA.AAAAA.AAGAAAAGAUAGAAAGAAA.AAAGAAAAUA urid herpesvirus
CR246 5831 NC..0 !¾¾9.1 CGG CCG AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Murid herpesvirus
Hell '.ί' >, '■ NC_01635S.l AGG ca AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Ndumu
CR246 5831 NC_ 306Sl.l CC NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Nylanderia fulva virus
5831 NCJJ21858.1 CAT 11111 AAA AAAAAAGAAAAGAUAGAAAGAA AAGAAAAUA Pandor3virus du!cis
CR246 5831 NC_021858.1 CC NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAU A Pandoravirus dulcis
lliisii 5831 NC G2185S.1. CCT NA AAAA.AAAAA.AAGAAAAGAUAGAAAGAAA.AAAGAAAAUA Pandoravirus dulcis
CR246 5831 NC..0218S8.1 CTC NA AAAAAAAAAAAGAAAAGAUAGAAAGAAMAAGAAAAU A Pandoravirus dulcis
'.ί' >, '■ NC_021858.1 .. NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Pandoravirus dulcis
CR246 5831 NC 021858 ! CT NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Pandoravirus dulcis
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CR246 5831 NC_008580.1 CCT NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Rabbit vesivirus
ιΐϋϋΐ 5831 NC G21097.1. CC NA AAAA.AAAAA.AAGAAAAGAUAGAAAGAAA.AAAGAAAAIJA
CR246 5831 ΝΟ_022617 CC NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAU A Red clover cryptic virus
NC_021G97.1 NA ΤΤΤΤΛΤΤΤ AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Red clover cryptic vf'rus
CR246 5831 NC .021097.1 NA TTTTGTTT AAAAAAAAA AAGAAAAGAUAGAAAGAAAAAAGAAAAUA Red clover cryptic virus
ii!il 5831 NC_02I097.1 NA TriTGGTT AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA §§1§S§§|| | ¾
CR246 5831 NC_021097.1 CC NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Red clover cryptic virus
ιΐϋϋΐ 5831 NC G23SSS.1. CC NA AAAA.AAAAA.AAGAAAAGAUAGAAAGAAA.AAAGAAAAIJA
CR246 5831 NC_028250.1 NA ΤΓΓΤΑΤΤΤ AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Rosellinia necatrix partitivirus
'.ί' >, '■ NC_028250.1 NA ΤΤΤΤΛΑΤΤ AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA
mmmmmmmmmmmmm
CR246 5831 NC_ 20235.1 NA TTTTAAAA AAAAAAAAA AAGAAAAGAUAGAAAGAAAAAAGAAAAUA Rosellinia necatrix partitivirus
5831 NC_001782.1 NA TTTCTTT AAA AAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA
CR246 5831 NC_001782.1 GAA NA MAAAA AM AAGAAAAGAUAGAAAGAAAAAAGAAAAUA Saccharomyces cerevisiae killer virus
Ιΐβΐι 5831 NC G0741S.1. CC NA AAAA.AAAAA.AAGAAAAGAUAGAAAGAAA.AAAGAAAAUA :ί |ίβ
CR246 5831 NC_024298.1 CC NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Sclerotinia sclerotiorum debilitation-associated RNA
Hell '.ί' >, '■ NC_0±134S.l CC NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA
CR246 5831 NC_ 06267.1 CC NA AAAAAAAAA AAGAAAAGAUAGAAAGAAAAAAGAAAAUA Sida yellow mosaic
5831 NCJJ28115.1 NA TTTTAGTA AAAAAAAAAAAGAAAAGAUAGAAAGAAMAAGAAAAUA
CR246 5831 NC_U16960.1 GAA NA AAAAAAAAA AAGAAAAGAUAGAAAGAAAAAAGAAAAUA Southern elephant seal
Ιΐβΐι 5831 NC G07391.1. GAA NA AAAA.AAAAA.AAGAAAAGAUAGAAAGAAA.AAAGAAAAUA i ¾ lj i¾
CR246 5831 NC_004122.1 CTT NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Spring beauty latent virus
'.ί' >, '■ NC_029119.I CAT NA AAAAAAAAAAAGAAAAGAUAGAAAGAAAAAAGAAAAUA Staphylococcus
CR246 5831 NC 001672.1 CC ATTCTGG AAAAAAAAA AAGAAAAGAUAGAAAGAAAAAAGAAAAUA Tick-borne encephalitis virus
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CR251 5836 NC_034620.1 NA TTTTAATT UCUUUCUAACGGAAAUCUACUAGUUA6AUUUUGAAUUUUAAA6AAAUUUCAA6ACAAAUG Sulfolobus islandicus illllli 5836 NC Q34S2S.1. NA TTTTAATT UCUUUCUAACGGAAAUQJACUAGUUAGAUUUUGAAUUUUAAAGMAUUUCAAGACAAAUG Su!fo!obus islandicus
CR254 5839 Νς_015466 CAT NA CUGGGAGGCCGAGGUGGGUGGAUCACAAGGUCAAAAGAUCAAGACCAG Roseobacter
a ts NC_032ill.l CCT NA UGAAGUCUUGCUAUGUUGCCUAGCCUGGUCUUGAACUCCUGG BeAn 58058
CR259 5845 NC_ 218S6.1 GAA NA AAAGCUAGUUCUCUGAAAUGGUCAAUAAAAIJUAAUAAACCU Bacillus
Ί8 ίΊ NC_03O903.1 GAA NA AAAGCUAGUUCUCUGAAAUGGUCAAUAAAAUUAAUAAACCU B-u iiius
CR259 5845 NC_022771.1 GAA NA AAAGCUAGUUCUCUGAAAUGGUCAAUAAAAUUAAUAAACCU Bacillus
ιΐϋϋΐ 5845 NC G28953.1. CTT NA AAAGCUAGUUCUCUGAAAUGGUCAAUAAAAUUAAUAAACCU Clostridium
CR259 5845 NCJD28883.1 CTT NA AAAGCUAGUUCUCUGAAAUGGUCAAUAAAAUUAAUAAACCU Clostridium ιιι¾ιιι '.ί' !', NC_001664.2 CAT NA AAAGCUAGUUCUCUGAAAUGGUCAAUAAAAUUAAUAAACCU Human herpes virus 6A
CR260 5847 NC .03211 i ! CC NA CUUCAUUAAAAACAAGCAU UAAUAUGUAUUAUAUAAAGAAGA BeAn 58058
Illllli ! « f NC_013025.1 CTT NA CUUCAUUAAAAACAAGCAU U UAUGUAUUAUAUAAAGAAGA Circovirus-!ike
CR260 5847 NC_016924.1 CC NA CUUCAUUAAAAACAAGCAU UAAUAUGUAUUAUAUAAAGAAGA Cotia
58 !/ NC G19526.1. CC NA CUUCAUUAAAAACAAGCAU UAAUAUGUAUUAUAUAAAGAAGA Enterobacteria
CR260 5847 NC..027399.1 CC NA CUUCAUUAAA/VACAAGCAU UAAUAUGUAUUAUAUAAAGAAGA Klebsiella mm '.f t/ NC_02O877.1 CCT NA CUUCAUUAAAAACAAGCAUUAAUAUGUAUUAUAUAAAGAAGA Staphylococcus
CR260 5847 NC J330933.1 CCT NA CUUCAUUAAAAACAAGCAU UAAUAUGUAUUAUAUAAAGAAGA Staphylococcus
Illllli NC_022090.1 CCT NA CUUCAUUAAAAACAAGCAU UMUAUGUAUUAUAUAAAGAAGA Staphylococcus
CR260 5847 NC_U19511.1 CCT NA CUUCAUUAAAAACAAGCAU UAAUAUGUAUUAUAUAAAGAAGA Staphylococcus
58 !/ NC G0987S.1. NA TTTCGGCG CUUCAUUAAAAACAAGCAU UAAUAUGUAUUAUAUAAAGAAGA Staphylococcus
CR260 5847 NC..023¾S0.1 NA TTTCGGCG CUUCAUUAAAAACAAGCAUUMUAUGUAUUAUAUAAAGAAGA Staphylococcus mmm 5850 NC_024447.I NA TTTTACGT AG AU AA AG AA AUC U CCAGCU A UAA ACA
CR263 585Q.. NC J316448.1 CAT NA AGAUAAAGAAAUCUCCAGCUAUAAACA Saimiriine herpes virus
NC_032481.1 CCT NA UUAAAUAUUAACUUUUCCUUUCAUUUAGCUAUG Beihai mollusks CR267 5854 NC 032539.1 CCT NA UU AAAUAUUAACUUU UCCUUU CAUU U AGCUAUG Beihai picorna-like
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CR272 5859 NC_019520.1 GGG CCC AUGGAUGGAUAGAUUAAAUGGAUGGAUGGAUAGAUAGAUAGAUAGAUAGAUAGAUAGAU Escherichia
A
CR272 5859 NC G24450.1. CC AUGGAUGGAIJAGAUUAAAUGGAIJGGAUGGAUAGAUAGAUAGAUAGAUAGAUAGAUAGAU Falconid herpesvirus
CR272 5859 ΝΟ_027867 CC NA AUGGAUGGAUAGAUUAAAUGGAUGGAUGGAUAGAUAGAUAGAUAGAUAGAUAGAUAGAU Mollivirus sibericum
A
CR/i'/. V-v-i NC_027867.1 CGG :£ AUGGAUGGAUAGAUUAAAUGGAUGGAUGGAUAGAUAGAUAGAUAGAUAGAUAGAUAGAU oiiivirus sibericum
CR272 5859 N ,οιοιιβ. l err NA AUGGAUGGAUAGAUUAAAUGGAUGGAUGGAUAGAUAGAUAGAUAGAUAGAUAGAUAGAU Pseudomonas
A
CP./// 'i»f;'J NC_0078U9.1 CTT II AUGGAUGGAUAGAUUAAAUGGAUGGAUGGAUAGAUAGAUAGAUAGAUAGAUAGAUA6AU Pseudomonas
CR272 5859 NC_018282.1 CTT NA AUGGAUGGAUAGAUUAAAUGGAUGGAUGGAUAGAUAGAUAGAUAGAUAGAUAGAUAGAU Pseudomonas
A
CR272 5859 NC G289S0.1. CTT AUGGAUGGAIJAGAUUAAAUGGAIJGGAUGGAUAGAUAGAUAGAUAGAUAGAUAGAUAGAU Pseudomonas
illiiilB
CR272 5859 ΝΟ_018282 TGG CCA AUGGAUGGAUAGAUUAAAUGGAUGGAUGGAUAGAUAGAUAGAUAGAUAGAUAGAUAGAU Pseudomonas
A
CR2 7 '»*»■»:* NC_01364S.l TGG CA AUGGAUGGAUAGAUUAAAUGGAUGGAUGGAUAGAUAGAUAGAUAGAUAGAUAGAUAGAU Streptococcus
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CR272 5859 NC .011217 ! IMA TTTCAGAC AUGGAUGGAUAGAUUAAAUGGAUGGAUGGAUAGAUAGAUAGAUAGAUAGAUAGAUAGAU Sulfolobus islandicus
A
CR280 5860 NC_003038.1 GGG CC AUAUGUAUAUAUAGAGUCACGUUUUUUUUUUUUUUUGUGUGUGUGUG Invertebrate iridescent virus
CR305 5892 NC_002520.1 CTT NA CUUAUUUUAUUUUUUUGUUUAUACUUAUGUCAUAGU Amsacta moorei entomopoxvirus
NC G06659.1 CAT NA CUUAUUUUAUUtjlJUtjlJGUlJUAUACUUAUGUCAUAGU Catesia congregate virus
CR305 5892 NC..02U8 6.1 CTT NA CUUAUUUUAUUUUUUUGUUUAUACUUAUGUCAUAGU Lactobacillus brevis
CR i!i!. '.i'- NZ_CP02iS28.1 CTT NA CUUAUUUUAUUUUUUUGUUUAUACUUAUGUCAUAGU Pediococcus pentosaceus
CR305 5892 NC_ 24447.1 CAT NA CUUAUUUUAUUUUUUUGUUUAUACUUAUGUCAUAGU Pigeonpox virus
CR305 5892 KX36574S TGG CCA CUUAUUUUAUUUUUUUGUUUAUACUUAUGUCAUAGU Pseudoalteromonas
CR307 1 7108 NC_029098.1 CC NA AGCCAGGGUGUCCUGAUGAGUGUUCAGCUCCU Streptomyces
CR308 5894 NC_008929.1 SAA NA UAAUUGUCAAAAUGUAAUUAUUGUCAAUA Glypta fumiferanae ichnovirus
CR309 5895 NC_032111.1 CC NA UUUGGGAGGGUGGGGCAGGGGAAUCACUUGAACCUGUGAGGCAGAGG BeAn 58058
CR332 5818 NC 024697.1 CC NA AUAUGUtjlJUtjCUlJUAACAUAUUAUAUGlJUCUUCUUUAACAUUAUlJAGUGlJAAUAAUA AureocQccus anophegefferens
CR332 5818 NC..021248.1 CC NA AUAUGUUUUUCUUUAACAUAUUAUAUGUUCUUCUUUAACAUUAUUAGUGUAAUAAUA Choristoneura biennis entomopoxvirus
CR i V 'si' S « NC_002i07.1 NA iiiiiiiii AUAUGUUUUUCUUUAACAUAUUAUAUGUUCUUCUUUAACAUUAUUAGUGUAAUAAUA Gracilaria hilensis
CR341. 2 5927 NC_032111.1 CGG CCG CUGAGGCAGGAGAAUCGCUUGAACC Be An 58058
CR346 3 3 NCJ327867.1 C NA UGU6U6U 3UGUGUGUAUGGGCUGCUUA o!iivjrus Sibeficum
CR346 3 3 NC_027867.1 AGG ccT UGUGUGUGUGUGUGUAUGGGCUGCUU A ollivirus sibericum
CR346..3 NCJ»J.?31.1 1111111 NA UGUGUGUGUGUGUGUAUGGGCUGCUUA Moiiuscum cant3giasurri
CR346 3 3 NC_0218S8.1 GGG ccc UGUGUGUGUGUGUGUAUGGGCUGCUUA Pandoravirus dulcis
C .i M- 3 3 Ht_02 m.t CTT NA UOUGUSUGUGUGUGUAUGGGOJGCUUA Porcine cytomegalovirus
CR347 4 NC_027925.1 NA TTTTGGTG AAAACAAAACAAAACAAAAAACCACUAAAAA Apis meillifera filamentous virus
CR347 NZJTP022346.1 NA TTTTAAAT AAAACAAAACAAAACAAAAAACCACUAAAAA Bacillus thuringiensis
CR347 4 NC . 0 29.1 GAA NA AAMCMAACAAAACAAAMACCACUAAAAA Banana mild mosaic
CR3 ': / 4 NC_01I966.1 NA ΤΤΓΤΑΤΤΪ AAAACAAAACAAAACAAAAAACCACUAAAAA Borreii3 burgdorferi
CR347 4 NC_011966.1 NA TTTTGTTT AAAACAAAACAAAACAAAAAACCACUAAAAA Borrelia burgdorferi
CR347 4 NCJ331693.1 NA TTTTGTTT AAMCMMCMAACAAAAAACCACUMAAA Burke-Giiman
CR347 4 KY421186 GAA NA AAAACAAAACAAAACAAAAAACCACUAMAA Flavobacterium
111111 Nf ..:i.>-V: . l iiiiiii ,ν· ί ΑΛΛί ΛΛΛΛΛΛί ; ι Ι ΛΛΛΛ Myot's ¾;w.m.i c:i pi'svir r. :ί:ί:ί:ί:ί:ί:ί:ί:
CR347 4 NC.0Q5029.1 NA TTTTGCTT AAAACAAAACAAAACAAAAMCCACUAMAA Onion yellow dwarf
CR3 M 4 NCJB3773.1 l!ll!!i NA AAMCMMCMAACMAAAACCACUAAAAA Pepper chiorotic spot
CR347 4 NCJ303296.1 NA TTTTGAAT AAAACAAAACAAAACAAAAMCCACUAMAA Ralstonia solanacearum
CR 4 NZ CP016915.I TGG t i n AAMCMMCMAACAAAAMCCACUAAAAA alstonia solanacearum
CR347 4 NZ_CP015613!l TGG CCA AAAACAAAACAAAACAAAAAACCACUAAAAA Ralstonia solanacearum
CR347 NZ_CPQ15116.1 TGG CCA AAAACAAAACAAAACAAAAAACCACUAAAAA Ralstonia solanacearum
CR347 4 NZ_CP01S5S5.1 TGG CCA AAAACAAAACAAAACAAAAMCCACUAMAA Ralstonia solanacearum
CR 4 NC_021745.1 TGG CCA AAAACAAMCMAACMAAAACCACUAAMA Ralstonia solanacearum
GR347 ■,,,Λ,,.,,.,. NZ_CP015851.1 TGG CCA AAAACAAAACAAAACAAAAAACCACUAAAAA Ralstonia solanacearum
CR347 4 NZ_CP009763.1 TGG ; i .·. AAAACAAAACAAAACAAAAMCCACUAMAA Ralstonia solanacearum
CR351 10 NC_027925.1 NA TTTTGGTG AAMCMMCMAACMAAAACCACUAAAAA Apis meillifera filamentous virus
CRK!> i 10 NZ.CP022346.1 NA TTTTAAAT AAAACAAAACAAAACAAAAMCCACUAMAA Bacillus thuringiensis
CR351 10 NC_002729.1 GAA NA MMCMAACAMACAMAMCCACUAMAA Banana mild mosaic
CR351 10 NC_D11S6&.1 NA TTTTATTT AAMCMMCMAACAAAAAACCACUAAAAA Borrelia burgdorferi
CR351 10 NC_011966.1 NA TTTTGTTT AAAACAAAACAMACAAAAMCCACUAMAA Borrelia burgdorferi
CR3 ) i 10 ut im.t NA TTTTGTTT AAAACAAAACAMACAAAAMCCACUAMAA Burke-Giiman
CR351 lo KY421136 GAA NA AAMCMMCMAACMAMACCACUMMA Flavobacterium
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llisi 55 NC_00¾959.1 CAT NA GUGUOUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCOUGUA Hyposoter fugitivus ichnovirus
CR397 55 NC_001493.2 AGG CCT G UGU GUG U GCG UGU GGG UGUG U G UG CAU AUG U G U G CG UG U A !ctalurid herpes
if$i! NC_020i3Q.l CTT NA GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCGUGUA Lawsonia intracelluiaris
CR397 55 NC_OO8OI4.I err A GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCGUGUA Lawsonia intracelluiaris
55 NC G2O130.1. GGG CCC GUGUGUGUGCGUGUGGGUGUGIJGUGCAUAUGUGUGCGUGUA Lawsonia intracelluiaris
CR397 55 C..0080 i 4.1 GGG CCC GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCGUGUA Lawsonia intracelluiaris
55 NC_0±8711.1 CC NA GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCGUGUA Lunk
CR397 55 NC 00173 i. 1 GGG CCC G UGU GUG U GCG UGU GGG UGUG U G UG CAU AUG U G U G CG UG U A Molluscum contagiosum
CR397 NC_001731.1 GAA NA GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCGUGUA Molluscum cant3giasum
CR397 55 NC_001875.2 CTT NA 6UGUGUGUGCGUGUGG6UGUGUGUGCAUAUGUGUGCGUGUA Orgyia pseudotsugata MNPV ll!!!li 55 NC G115SS.1. CTC NA GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGIJGCGUGUA Oryctes
CR397 55 NC..0218S8.1 AGG CCT G U G U G U G U GCG UG U GGG U GUG U G UGC AU AUG UG UGCG UGU A Pandoravirus dulcis
55 NC_021858.1 GAA NA GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCGUGUA Pandoravirus dulcis
CR397 55 NC .021858. ! TGG CCA G UGU GUG U GCG UGU GGG UGUG U G UG CAU AUG U G U G CG UG U A Pandoravirus dulcis
CR397 NCJJ21858.1 CAT NA GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCGUGUA Pandoravirus du!cis
CR397 55 NC_021858.1 CC NA 6UGUGUGUGCGUGUGG6UGUGUGUGCAUAUGUGUGCGUGUA Pandoravirus dulcis
CR397 55 NC G26440.1. NA TTTTGTGT GUGUGUGUGCGU6UGGGUGUGUGUGCAUAUGUGUGCGUGUA Pandoravirus inopinatum laHel virus
CR397 55 NC..026440.1 CAT NA G U GUG UG U GCG UG U GGG U GUG U G UGC AU AUG UG UGCG UGU A Pandoravirus inopinatum iaHel virus
55 NC_022098.I AGG CCT GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCGUGUA Pandoravirus saiinus
CR397 55 NC .022098. ! CCT NA G UGU GUG U GCG UGU GGG UGUG U G UG CAU AUG U G U G CG UG U A Pandoravirus saiinus
ΐϋϋΐι NCJJ220S8.1 CC NA GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCGUGUA Pandoravirus saiinus
CR397 55 NC_022098.1 CCT NA GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCGUGUA Pandoravirus saiinus
ill NC 02209S.1. CTT NA GUGUGUGUGCGUGUGGGUGUGUGUGCAUAUGUGUGCGUGUA Pandoravirus saiinus
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CR397 55 NC_ 31033.1 CC NA G UGU G UG U GCG UGU GGG UGUG U G UG CAU AUG U G UGCG UG U A Volepox
imii NC_003225.3 GGG CCC UUCCUUCUUCUUCUUCUUCUUCA'JCAUCAUCACCACUGAUAUUUUUACAU White spot syndrome
CR416. 593.6 NC_016141.1 CTT NA UUGUUU6UGUGUGUCUGUGUGUGCGUAUCCACA Hibiscus green spot
CR416! NC_007648.1 GGG CCC UUGUUUGUGUGUGUCUGUGUGUGCGUAUCCACA Vicia faba endornavirus
CR417 5937 NC_032111.1 CC NA CCUCCCAAGUAGCUGAGAUUACAGGCACAUGCCACCAUGACCGGCUAAUCUC BeAn 58058
CR426 5946 NC_0308S4.1 NA TTTCTAA CAUAUACAGUGUAUAAUAUAUAUACUAUAUAUAU Sulfolobus isiandicus rod-shape
CR426 5946 AJ 344259 CTT NA CAUAUACAGUGUAUAAUAUAUAUACUAUAUAUAU Sulfolobus isiandicus rudivirus
CR.IA; .'.'.·>· if. NCJ304086.1 CTT NA CAUAUACAGUGUAUAAUAUAUAUACUAUAUAUAU Su!fo!abus isiandicus rudivirus
CR426 5946 KX712143 NA TTTCTAA CAUAUACAGUGUAUAAUAUAUAUACUAUAUAUAU Sulfolobus isiandicus SIRV-2
ιιΐϋΐι 5948 NC 021312.1 AGG CCT GAACCACCACGCUGGAAUAGGCUGGAACCCAA Phaeocystis giobosa
CR439 5959 NZ_CP012101.1 TGG CCA AUUUUGAUUUAAUUUCAUUUUAUCUACAACUACGUUAAUUUUCUGU Bacillus thuringiensis
CR439 5959 NZ_CP0I4284.1 TGG CCA AUUUUGAUUUAAUUUCAUUUUAUCUACAACUACGU'JAAUUUUCUGU Bacillus thuringiensis
CR446 5966 NZ_CP020748 l CGG CCG UUUUUCACGCUUUUUUUUGUUUUUGUUUUGGUUUUG Bacillus mycoides
ΙΙϋϋΙ i.wr. AR23673 GAA NA UUUUUCACGCUUUUUUUUGUUUUUGUUUUGGUUUUG Bacteriophage
CR446 5966 C..012b39.1 NA TTTCTAT UUUUUCACGCUUUUUUUUGUUUUUGUUUUGGUUUUG Euproctis pseudoconspersa nucleopolyhedro line ,<;·><. NC 002671.1 GAA NA UUUUUCACGCUUUUUUUUGUUUUUGUUUUGGUUUUG Lactococcus
CR448 5968 NZ CP007648.1 CC NA UACAACCAGAGUUa\AGCAAUUCUCAUGCCUa\GCCUC Lactobacillus salivarius
CR459 §1111 NC_01757Q.l AGG CCT G AU U AG A ACUG UG AU U UC UG AG ACAAU AG CUGA Shewanelia baltica
CR460 5980 HE815464 CAT NA UAAAGUCAAAUGUUUAU UUUACUUAAU UUUAAAUACAUUCUAACA Campylobacter
5997 NC.027332.1 CCT NA AAAGUUUAUAAACCMACCCUGUAUAUACUGUUUUG Acinetobacter
CR488 6009 NC..0 5470.1 CAT NA UUUUUUUUU UUU UUUUUUUAAACAGGGUCUCACUCUGUCA Abisko virus
CR.lfrt 6009 Y2S8296 GAA TTTCTTC UUUUUUUUUUUUUUUUUUUAAACA,GGGUCUCACUCUGUCA Acinetobacter
CR488 6009 NC_004590.1 CTT NA UUUUUUUUUUUUUUUUUUUAAACAGGGUCUCACUCUGUCA Adoxophyes honmai
6009 NC 01O98Q.1 CC NA UUUUUUUUUUUUUUUUUUUAAAG^GGGUCUCACUCUGUCA Aiternarl3 alternate ds NA mycovirus
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i!ilil 6009 NC_025381.1 CC ΝΑ UUUUUUUUUUUUUUUUUUUA CAGGGUCUCACUCUGUCA Hibiscus latent fort pierce
CR488 6009 NCJ325381.1 CGG CCG UUUUUUUUUUUUUUUUUUUAAACAGGGUCUCACUCUGUCA Hibiscus latent fort pierce
NC_025381.1 AGG CCT UUUUUUUUUUUUUUUUUUUAAACAGGGUCUCACUCUGUCA Hibiscus latent fort pierce
CR488 6009 NC_021099.1 NA TTTTGTTT UUUUUUUUUUUUUUUUUUUAAACAGGGUCUCACUCUGUCA Hop trefoil cryptic
ΙΙϋΙΙΙ 6009 NC 033014.1 GAA NA UUUUUUUUUUUUUUUUUUUMACAiGGGUCUCACUCUGUCA Hubei mosquito
CR488 6009 ΝΟ_002645 CC NA UUUUUUUUUUUUUUUUUUUAAACAGGGUCUCACUCUGUCA Human coronavirus 229E
!i!!l 6009 NC_00Z64S.l GAA NA UUUUUUUUUUUUUUUUUUUA CAGGGUCUCACUCUGUCA Human coronavirus 229E
CR488 6009 NC_ 02645.1 NA TTTCGATA UUUUUUUUU UUU UUUUIJUUAAACAGGGUCUCACUCUGUCA Human coronavirus 229E
Ιίϋϋΐΐ NC_0065Q2.1 CC NA UUUUUUUUUUUUUUUUUUUA CAGGGUCUCACUCUGUCA Infectious sal on 3nemia virus
CR488 6009 NC_027919.1 GGG CCC UUUUUUUUUUUUUUUUUUUAAACAGGGUCUCACUCUGUCA Kobuvirus cattieKagoshima-l-22-KoV2014JPN
ΙΙϋΙΙΙ 6009 NC G27913.1. CGG CCG UUUUUUUUUUUUUUUUUUUMACAiGGGUCUCACUCUGUCA Kobuvirus cattle Kagosh ima- 1-22-KoV2014J P N
CR488 6009 NC..027918.1 CGG CCG UUUUUUUUUUUUUUUUUUUAAACAGGGUCUCACUCUGUCA Kobuvirus cattleKagoshima-l~22-KoV2014JPN
6009 NC_027918.1 GGG CCC UUUUUUUUUUUUUUUUUUUA CAGGGUCUCACUCUGUCA Kobuvirus cattleKagoshima-l-22-KoV2014JPN
CR488 6009 NC^027918.1 AGG CCT UUUUUUUUUUUUUUUUUUUAAACAGGGUCUCACUCUGUCA o'buvi rus cattle Kagosh ima- l-22-KoV2014J P N
Ιίϋϋΐΐ NCJJ27918.1 GAA NA UUUUUUUUUUUUUUUUUUUA CAGGGUCUCACUCUGUCA Kobuvirus cattleKagoshima-l-22-KoV2014JPN
CR488 6009 KM677185 GAA NA UUUUUUUUUUUUUUUUUUUAAACAGGGUCUCACUCUGUCA Lactococcus
ΙϋϋΙΙ 6009 NC G01S13.1. AGG CCT UUUUUUUUUUUUUUUUUUUMACAiGGGUCUCACUCUGUCA Lambdapapil!ornavirus 2
CR488 6009 NC_033778il CTT NA UUUUUUUUUUUUUUUUUUUAAACAGGGUCUCACUCUGUCA Leptopilina bouiardi filamentous
6009 NC_0Q3027.I GAA NA UUUUUUUUUUUUUUUUUUUAMCAGGGUCUCACUCUGUCA Lumpy skin disease
CR488 6009 NC J304812.1 CC NA UUUUUUUUU UUU UUUUIJUUAAACAGGGUCUCACUCUGUCA Macacine herpesvirus
6009 NC_004812.1 NA TTTTAAAA UUUUUUUUUUUUUUUUUUUA CAGGGUCUCACUCUGUCA
!!ϋ!ϋ! Macacine herpesvirus
CR488 6009 NC..004812.1 CTT NA UUUUUUUUUUUUUUUUUUUAAACAGGGUCUCACUCUGUCA Macacine herpesvirus
6009 NC Q04S12.1 CCT NA UUUUUUUUUUUUUUUUUUUAA.ACAGGGUCUCACUCUGUCA Macacine herpesvirus
Figure imgf000333_0001
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Figure imgf000336_0001
Figure imgf000337_0001
Figure imgf000338_0001
Figure imgf000339_0001
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Figure imgf000341_0001
Figure imgf000342_0001
Figure imgf000343_0001
Figure imgf000344_0001
in NC_03332$.l CAT UUUCAUUUUUUUtCUUCUCUUUUCU Hubei chuvirus
CR 76 .310 ,, |\iC_023423.1 Pithovirus sibericum
319 NCJ30944&.2 Saffold
CR79 5662 NC_028951.1 Clostridium phage
κι « 1 NZ_CP01210(U Bacillus thuringiensls
CR794J 328 NC_021249.1 Choristoneura rosaceana entomopox
CR794..1 '.■■2¾ NC_007346.1 Emiliania huxleyi
CR794J 328 iC .033778. ! Leptopilina bou!ardi filamentous
CR794..2 328 J60S1SS Leuconostoc
CR804 338 NC_004604.2 Bacillus megaterium
351 NC_ 10356.1. Glossina pallidipes
CR819 353 NCJJ02687.1 Ectocarpus siliculosus
CM,?/ M.ii NCJ314637.1 Cafeteria roenbergensis virus
CR833 367 NC .001993 ! elanoplus sanguinipes entomopox
il'A NC 015O49.1 Rodent herpesvirus
CR842 377 NC_006660.1 Cotesia congregata virus
381 N2_CP01S94£U Legionella pneumophila
CR846 NZ_CP015952 l Legionella pneumophila
111811 "> NZ_CP015943.1 Legionella pneumophila
CR874 409 NC_016072.1 Megavirus chiliensis
ι§8$ι 5670 NCj3S50.38.1 Adoxop yes granulovirus
CR88 5670 NC_014633.1 llyobacter
CR90 f>i3/2 NC_014649.1 CTT . NA UAUUAUUUUAUUAUUGUUAUUUGGAGAUUAAUAUGGUUUAUUAUUGUUGUUAUUUGGC Acanthamoeba poiypnaga wiimivir s
CR90 5672 NC..00^39.2 Agrotis granulovirus
nisi h\ . i '?. NCJ323639.I Mimivirus terra 2
Figure imgf000346_0001
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3 S 3 3 Si 3 S3SSS SS 3 SS 3 3 Si 3 .7. Si 3 iii 3 3 Si 3 ::. Si 3 iii 3 ss 3
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= £
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mm mm m mm III Hi AAGACUAAAUACUGUUAAGAUUCCAUUUAAAUGUAAUA: Lactococcus:
CR995 533 NC_015124.1 TG6 CCA AGUUAUAUAUGAAGCAUAUUAAUAAUGAGU Tomato leaf curl
hanoi virus specific sequence ID corresponding to the human CRISPR spacer in which CR(jiumber) corresponds to a specific spacer if multiple
spacers are present in the human CRISPR
2 unique patent ID given to the human CRISPR
J specific ID number that corresponds to a NCBI rerence sequence in which a protospacer is identified
PAM motif identified in the 3' strand of the protospacer
3 PAM motif identified in the 5' strand of the protospacer
6 human CRISPR spacer sequence that targets the protospacer
7 species in which the protospacer is detected

Claims

Claims
Method for diagnosing a disease or condition comprising the steps of:
a. taking a sample from a subject, preferably a human subject; b. determining in said sample the expression profile of at least one CRISPR nucleotide sequence selected form the sequences of SEQ ID NO: 1 - 11297; c. determining on basis of said expression profile whether the disease or condition is present.
Method according to claim 1, wherein the sample is chosen from blood, serum, saliva, hair, urine, lymph fluid, CSF, cells and tissue.
Method according to any of the previous claims, wherein the step of determining the expression profile is accomplished by probing the sample with an array of probes specific for the at least one human CRISPR nucleotide sequence, preferably wherein the sample comprises niRNA extracted from cells or tissue to be investigated.
Method according to claim 3, wherein said array of probes comprises at least one probe that is targeting a human CRISPR sequence that is not represented on the Affymetric U133 Plus 2GeneChip®.
Method according to any of claims 3 - 4, wherein multiple probes are available for different spacer sequences of the same CRISPR nucleotide sequence.
6. Method according to any of claims 3 - 5,, wherein the array comprises more then 50, preferably more than 100, more preferably more than 500 and more preferably more than 1000 probes.
7. Method according to any of the previous claims, wherein said CRISPR nucleotide
sequences are selected from SEQ ID NO: 1 - 10141, more preferably comprising at least one sequence defined herein as non-Affymetrix human CRISPR sequences.
8. Array spotted with probes targeting one or more of the nucleotide sequences of SEQ ID NO: 1 - 11297, more preferably the nucleotide sequences of SEQ ID NO: 1 - 10141, wherein said probes are short nucleotide sequences.
9. Array according to claim 8, wherein said probes are DNA sequences with a length of 15 - 100 nucleotides, preferably of 20 - 75 nucleotide, more preferably of 22 - 50 nucleotides, more preferably of 23 - 40 nucleotides, more preferably 24 - 35
nucleotides, most preferably of 25 - 30 nucleotides, optionally provided with a label.
10. Array according to claim 9, wherein said nucleotide probes are spotted on a carrier.
11. Array according to any of claims 8 - 10, wherein at least one of said sequences of SEQ ID NO: 1 - 11297 does not possess any sequences that occur on an Affymetrix U-133 Plus 2.0 GeneChip®.
12. Use of an array according to any of claims 8 - 11 in a method for diagnosing a disease or condition.
13. Method for the diagnosis of chronic B-lymphocytic leukemia by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 9342, and diagnosing that chronic B- lymphocytic leukemia is present when SEQ ID NO: 9342 is overexpressed ..
14. Method for the diagnosis of Francisella infection by assaying the under- or
overexpression of CRISPR sequence SEQ ID NO: 8709, and diagnosing that
Francisella infection is present when SEQ ID NO: 8709 is underexpressed.
Method for the diagnosis of hepatocellular carcinoma by assaying the under- ( overexpression of CRISPR sequence SEQ ID NO: 7930, and diagnosing that hepatocellular carcinoma is present when SEQ ID NO: 7930 is overexpressed
16. Method for the diagnosis of high-grade prostate cancer by assaying the under- or
overexpression of CRISPR sequence SEQ ID NO: 8566, and diagnosing that high- grade prostate cancer is present when SEQ ID NO: 8566 is underexpressed.
17. Method for the diagnosis of chronic pediatric immune thrombocytopenia by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8757, and diagnosing that chronic pediatric immune thrombocytopenia is present when SEQ ID NO: 8757 is overexpressed.
18. Method for the diagnosis of prostate cancer progression by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 9471, and diagnosing that prostate cancer progression is present when SEQ ID NO: 9471 is overexpressed.
19. Method for the diagnosis of fertility based on sperm health by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8713, and diagnosing that fertility based on sperm health is present when SEQ ID NO: 8713 is overexpressed.
20. Method to distinguish between acute and latent tuberculosis by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 8190, and diagnosing that acute tuberculosis is present when SEQ ID NO: 8190 is underexpressed.
21. Method for the diagnosis of tibial muscular dystrophy by assaying the under- or overexpression of CRISPR sequence SEQ ID NO: 6939, and diagnosing that tibial muscular dystrophy is present when SEQ ID NO: 6939 is underexpressed.
22. Method to distinguish between differentiated and undifferentiated embryonic stem cells by assaying the under- or overexpression of CRISPR sequences SEQ ID NO: 5465, 1423, 68,. 7865, 7648, 6872, 8273, 8190, 8678, and 3215, and diagnosing that the cells are undifferentiated if at least one of SEQ ID NO: 5465 and 68 is underexpressed and at least two of SEQ ID NO: 1423, 7865, 7648, 6872, 8273, 8190, 8678, and 3215 are overexpressed.
23. Method to distinguish between H1N1 infected and uninfected bronchial
epithelial cells by assaying the under- or overexpression of CRISPR sequences 5465, 7873,. 998, 1515, 9358, 8407, 8190, and 8861 and diagnosing that the cells are uninfected if at least two of SEQ ID NO: 5465, 8190 and 8861 are underexpressed and at least two of SEQ ID NO:, 7873, 998, 1515, 9358 and 8407 are overexpressed. 24. Method to diagnose cancer in a human subject by assaying the under- or
overexpression of one or more of the CRISPR sequences listed in Table 17.
25. Method to diagnose a cancer selected from the group of Bladder urothelial carcinoma, Breast carcinoma, Gastric carcinoma, Head neck squamous cell carcinoma, Kidney carcinoma, Kidney chromophobe, Liver hepatocellular carcinoma, Lung
adenocarcinoma, Lung squamous cell carcinoma, Lung squamous cell carcinoma and Thyroid carcinoma in a human subject by assaying the under- or overexpression of one or more of the groupings of CRISPR sequences listed in Table 18. 26. Method to diagnose a viral or bacterial infection in a human subject by assaying the under- or overexpression of one or more of the CRISPR sequences listed in Table 23.
27. Use of one or more of the CRISPR sequences listed in Table 21 or 22 for the diagnosis of a disease or condition.
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