Epigenetic marker for age and disease

Abstract

There is described herein methods for assessing survival risk of a human subject with haematological cancer or an age-related non-malignant disease. The method comprises analysis of at least 1000 of the 31744 differentially methylated regions (DMRs) set forth in Table 1 by determining an epigenetically stable loci (ESL) profile based on the methylation status of the at least 1000 DMRs; and categorizing the subject as having either low survival risk or high survival risk, each being associated with high DNA methylation instability (DMI) or low DMI respectively, wherein the subject has high DMI if the ESL profile has methylated DMRs exceeding a predetermined threshold and the subject has low DMI if the ESL profile has methylated DMRs below the predetermined threshold.

Description

[0001] EPIGENETIC MARKER FOR AGE AND DISEASE

[0002] FIELD OF THE INVENTION

[0003] The invention relates to the use of differentially methylated regions (DMRs) to assess human subject with haematological cancer or an age-related non-malignant disease.

[0004] BACKGROUND OF THE INVENTION

[0005] Clonal hematopoiesis (CH) of indeterminate potential is an age-related condition marked by the dominance of one or more genetically distinct clones of blood cells1-3. This phenomenon, often initiated by leukemia-associated gene mutations in hematopoietic stem and progenitor cells45, is associated with increased risks of blood cancer development6-9, adverse cardiovascular events1011, and overall mortality risk612. While the genetic basis of clonal hematopoiesis is well studied, the non-mutational mechanisms driving the emergence and expansion of blood cell clones remain unclear. Recent studies have shown that ‘driverless’ clonal hematopoiesis, clonal expansion without known genetic drivers, is common and carries health risks comparable to cases with mutations in driver genes613-15, underscoring the need to uncover additional mechanisms contributing to the reduced hematopoietic diversity observed in the elderly.

[0006] Somatic cell evolution is driven by genetic alterations that enable cells to circumvent normal regulatory mechanisms governing proliferation and tissue organizations1617. For these alterations to enhance clonal fitness, they must be both persistent and heritable, thereby increasing the population of affected cells and facilitating the accumulation of additional drivers of clonal expansion. In extreme cases, the accumulation of genetic alterations can result in more extensive genomic instability and cancer1618. Consistent with these established principles, genetic mutations follow a paradigm in which they persist throughout the lifespan of a cell and its lineage1920. Conversely, epigenetic modifications present a paradox: while they can be heritable across cell divisions, they are also influenced by environmental factors and intrinsic cellular cues, making them more reversible and malleable than genetic mutations21. These features complicate efforts to define a clear baseline of epigenetic normalcy. Inthe absence of a stable reference framework, it becomes challenging to distinguish early or subtle pathological epigenetic changes from normal variation, limiting our understanding of how epigenomic alterations contribute to disease onset and progression.

[0007] Individuals can show considerable differences between their chronological years and their physiological state, reflecting variability in the rate of functional decline and susceptibility to disease. Among the most widely used biomarkers of this process are epigenetic clocks, which leverage DNA methylation (DNAm) patterns at CpG loci to estimate biological age. These clocks can capture aging-related changes, including associations with morbidity and overall mortality risk22. Clonal hematopoiesis has also been linked to epigenetic age acceleration23, although correlations are generally weak, consistent with the notion that stochastic CpG epimutations are largely excluded from conventional clocks. Traditionally, epigenetic clocks are built using penalized multivariate regression, where a function of age is expressed as a weighted linear combination of CpG methylation values. An alternative approach emphasizes DNAm outliers rather than linear associations with chronological age2425. In this framework, CpGs exhibiting the greatest deviations from standard methylation states are considered informative, offering complementary insight into biological aging processes. This approach has been especially valuable for cancer-risk prediction, with DNAm outliers in preneoplastic tissues marking subclonal expansions with increased malignant potential, as demonstrated in cervical and breast cancers2627. Beyond oncology and certain neurodegenerative diseases28, the full spectrum of disorders influenced by DNAm outliers and the degree to which these changes are truly stochastic remains unclear.

[0008] SUMMARY OF THE INVENTION

[0009] DNA methylation instability (DMI) in blood was investigated, examining a broad set of normally stable CpG loci. We find that DNAm variability at those loci increases with age and can inform leukemic burden and cardiovascular risk. We also explore mechanisms by which methylation of these sites may alter cellular function and contribute to disease, offering insights into the biological consequences of epigenetic instabilityAccordingly, in an aspect, there is provided a method of assessing survival risk of a human subject with haematological cancer or an age-related non-malignant disease comprising:

[0010] a) providing a sample from the subject comprising DNA that includes at least 1000 of the 31744 differentially methylated regions (DMRs) set forth in Table 1.

[0011] b) determining an epigenetically stable loci (ESL) profile based on the methylation status of the at least 1000 DMRs; and

[0012] c) categorizing the subject as having either low survival risk or high survival risk, each being associated with high DNA methylation instability (DMI) or low DMI respectively, wherein the subject has high DMI if the ESL profile has methylated DMRs exceeding a predetermined threshold and the subject has low DMI if the ESL profile has methylated DMRs below the predetermined threshold.

[0013] In an aspect, there is provided a computer-implemented method for assessing survival risk of a human subject with haematological cancer or an age-related disease, the method comprising:

[0014] a) receiving, at at least one processor, data reflecting the subject’s methylation status of at least 1000 of the 31744 differentially methylated regions (DMRs) set forth in Table 1;

[0015] b) constructing, at the at least one processor, an epigenetically stable loci (ESL) profile based on the methylation status of the at least 1000 DMRs; c) categorizing, at the at least one processor, the subject as having high DNA methylation instability (DMI) or low DMI, wherein the subject has high DMI if the ESL profile has methylated DMRs exceeding a predetermined threshold and the subject has low DMI if the ESL profile has methylated DMRs below the predetermined threshold.

[0016] In an aspect, there is provided a computer program product for use in conjunction with a computer having a processor and a memory connected to the processor, the computer program product comprising a computer readable storage medium having acomputer mechanism encoded thereon, wherein the computer program mechanism may be loaded into the memory of the computer and cause the computer to carry out the method described herein.

[0017] In an aspect, there is provided a method of assessing risk of a human subject developing a haematological cancer or an age-related disease comprising:

[0018] a) providing a sample from the subject comprising DNA that includes at least 1000 of the 31744 differentially methylated regions (DMRs) set forth in Table 1.

[0019] b) determining an epigenetically stable loci (ESL) profile based on the methylation status of the at least 1000 DMRs; and

[0020] c) categorizing the subject as having either low risk or high risk, each being associated with high DNA methylation instability (DMI) or low DMI respectively, wherein the subject has high DMI if the ESL profile has methylated DMRs exceeding a predetermined threshold and the subject has low DMI if the ESL profile has methylated DMRs below the predetermined threshold.

[0021] BRIEF DESCRIPTION OF FIGURES

[0022] These and other features of the preferred embodiments of the invention will become more apparent in the following detailed description in which reference is made to the appended drawings wherein:

[0023] Figure 1. Identification of Epigenetically Stable Loci (ESLs) across the human genome, a, Schematic overview of the approach used to identify ESLs from blood DNA methylation data, b, Density plot of average p-values for all identified ESLs. Blue shading indicates ESLs characterized by stable hypomethylation, while red shading represents ESLs characterized by stable hypermethylation. Inset: Illustration of 6 diploid cells from 3 individuals. CpG 1 is stably unmethylated, CpG 2 is variable across individuals, and CpG 3 is stably methylated, c, Violin plots showing the distribution of P-values for ESLs identified in blood across 82 human cell types using whole-genome bisulfite sequencing data. Top panel: ESLs stably hypermethylated in blood; bottompanel: ESLs stably hypomethylated in blood. Source data are provided as a Source Data file.

[0024] Figure 2. Destabilization of unmethylated ESLs in hematological malignancies, a, Average p-values of 31,744 unmethylated ESLs across various cancer and control cohorts. Each point represents the average p-value for a single ESL in a given cohort. The red dashed line indicates the destabilization threshold derived from the control samples. Marker shapes denote tissue source: circles = bone marrow, squares = peripheral blood, triangles = lymphoid tissue, b, Boxplots and violin plots showing the number of destabilized ESLs per cohort. An ESL was considered destabilized if its |3-value exceeded the 99.9th percentile of values observed in the control cohorts (destabilization threshold: p-value = 0.05932). For boxplots: black line represents the median, bounds of box represent the first and third quartiles, whiskers extend to (median ± 1.5 * interquartile range), and points represent outliers. Abbreviations: CML - Chronic Myeloid Leukemia; MDS - Myelodysplastic Syndrome; AML - Acute Myeloid Leukemia; CLL - Chronic Lymphocytic Leukemia; pPCL - Primary Plasma Cell Leukemia; FL - Follicular Lymphoma; MPAL - Mixed Phenotype Acute Leukemia; BCP-ALL - B-cell Precursor Acute Lymphoblastic Leukemia; T-ALL - T-cell Acute Lymphoblastic Leukemia; MNKPL - Myeloid / Natural Killer Cell Precursor Acute Leukemia; Ped - Pediatric; Ad - Adult; M - Male; F - Female. Source data are provided as a Source Data file.

[0025] Figure 3. Chromatin accessibility patterns in normal hematopoietic cells at lineage-enriched perturbed ESLs. a-b, UMAP projections of single-cell ATAC-seq profiles from normal blood cells (n = 22,737). Cells are colored by their relative chromatin accessibility at genomic regions overlapping a, lymphoid-enriched or b, myeloid-enriched ESLs. Accessibility was quantified using deviation scores that reflect enrichment relative to a background model. Red indicates higher relative accessibility (less compacted chromatin), and blue indicates lower relative accessibility (more compacted chromatin), c-d, Relative chromatin accessibility at ESL-associated regions in hematopoietic stem and progenitor cells (HSCs, CMPs, GMPs; n = 8,321) compared with lymphoid cell types (CLP, Pre-B, B, CD4+T, CD8+T, NK; n = 14,416), for c, lymphoid-enriched ESLs and d, myeloid-enriched ESLs. For boxplots: black line represents the median, bounds of box represent the first and third quartiles, whiskers extend to (median ± 1.5 * interquartile range), and points represent outliers. **"P < 2.2 x 1016by two-sided Wilcoxon-rank sum test. Abbreviations: ATAC-seq - Assay forTransposase-Accessible Chromatin using sequencing; UMAP - Uniform Manifold Approximation and Projection; HSC - Hematopoietic Stem Cell; CMP - Common Myeloid Progenitor; GMP - Granulocyte-Monocyte Progenitor; CLP - Common Lymphoid Progenitor; NK - Natural Killer. Source data are provided as a Source Data file.

[0026] Figure 4. Aberrant DNA methylation at ESLs links leukemic epigenetic clones at diagnosis and relapse, a, Recurrence of ESL perturbation is shown on the x-axis as the proportion of patients (n = 3,019) in which a given locus exceeds the methylation destabilization threshold. The y-axis represents the mean p-value calculated only across patients in whom that locus is perturbed. Thus, the plot reflects the relationship between the frequency of ESL destabilization across individuals and the average methylation magnitude among those affected samples. Pearson's correlation coefficient (r) = 0.79; P < .001 by two-sided t-test. The bottom panel show the number of ESLs (log10scale) across different recurrence levels, b-d, Hierarchical clustering of paired diagnosis and relapse samples: b, 15 AML patients, c, 40 CLL patients, and d, 24 BCP-ALL patients. The 15 low recurrence sites (i.e., perturbed in <5% of the pan-hematological cancer cohort) with the highest methylation levels were selected from each patient's relapse sample for clustering. Correctly paired diagnosis-relapse samples are indicated in green. P = .002 by two-sided permutation test for AML; P < .001 for CLL and BCP-ALL. e, p-values of the top 15 low-recurrence ESLs in two BCP-ALL patients sampled at diagnosis, remission, and relapse. Each line connects the |3-values of a single ESL across disease stages, f, DMI levels in bone marrow samples from four AML patients, sampled at four distinct time points during disease progression, g, Analysis of peripheral blood samples from four additional AML patients at diagnosis and two subsequent time points during remission. The top panels display DMI levels and the bottom panels show VAFs of the patients’ leukemic mutations. Abbreviations: VAF - variant allele frequency. Source data are provided as a Source Data file.

[0027] Figure 5. Increasing DNA methylation instability correlates with advanced age.

[0028] DMI levels were measured across four independent cohorts: a, GSE40279, b, GSE87571, c, GSE115278, d, GSE197676. Participants were grouped into 5-year age intervals. Black dots represent the mean DMI for each age group, with error bars indicating the 95% confidence interval. Linear regression was performed on group means; the regression line is shown in red, with the 95% confidence interval shaded inblue. The number of samples, Pearson’s correlation coefficients (r), and two-sided P values are indicated. Source data are provided as a Source Data file.

[0029] Figure 6. Association of DNA methylation instability with cardiovascular risk and mortality, a-d, Univariate Kaplan-Meier analyses of 2,281 participants from the Framingham Heart Study (Exam 8) for a, mortality, b, cardiovascular disease, c, coronary heart disease, and d, congestive heart failure. Participants were classified into low or high DMI groups based on the cohort median split. Shaded areas represent the 95% confidence interval. Hazard ratios (HR) and Rvalues are indicated, e, Forest plot showing the effect of high DMI on each endpoint using multivariate Cox proportional hazards regression on the same 2,281 samples, adjusted for age and biological sex. Error bars represent the 95% confidence interval. Mortality: HR=1.09, P=0.400; CVD: HR=1.30, P^0.018; CHD: HR=1.57, P=0.011; CHF: HR=1.42, P=0.080. f, Survival analysis of cardiogenic shock patients (n=64), stratified into low DMI or high DMI groups based on the cohort median split, g, Survival curves of the same patients, further stratified into the following categories: i) high DMI with CH mutations, ii) high DMI without CH mutations, iii) low DMI with CH mutations, and iv) low DMI without CH mutations. P values were calculated using the multivariate logrank test. Abbreviations: CVD - Cardiovascular Disease; CHD - Coronary Heart Disease; CHF - Congestive Heart Failure; CH - Clonal Hematopoiesis. Source data are provided as a Source Data file.

[0030] Figure 7. DNA methylation instability at promoter regions and its impact on gene expression, a, Genomic distribution of ESLs (left) and non-ESLs targeted by the Infinium array (right), indicating enrichment of ESLs at CGI. P < .001 by two-sided Fisher’s exact test. Each site is classified by its proximity to CGIs: within a CGI, in a shore (0-2 kb from an island), in a shelf (2-4 kb), or in the open sea (>4 kb), b, Density plot showing the distance to the nearest TSS for ESLs (green) and non-ESLs (orange), c, Diagram depicting the total number of genes with recurrent ESLs in their promoter regions (i.e., recurrence greater than 5%; n=1,916), genes with a significant negative correlation between methylation and expression (n=3,227), genes with a significant negative correlation between age and expression (n=2,066), and the final intersected list of candidate genes (n=236). d, Volcano plot showing differential methylation analysis of promoter-associated CGIs for the 236 age-dependent genes. The y-axis represents the negative log-transformed P values (two-sided, Bonferroni-corrected), and the x-axis shows the log2fold change. Significant increases in overallpromoter methylation in AML compared to CD34+controls (P < .05 by two-sided Wilcoxon-rank sum test after Bonferroni correction) are highlighted in green, e, Heatmap showing the overlap between age-dependent genes and transcription factor motifs within their promoter-associated CGI. Red cells highlight regions where the ESLs intersect with key transcription factor binding motifs, f, Visualization of genomic features upstream of RGS2. The CGI, promoter, and first exon are shown. For the promoter element, the "thin" section represents the 49 bp region upstream of the TSS, while the "thick" section represents the TSS plus 10 bp downstream. Red lines on the CGI indicate ESLs. Transcription factor binding motifs containing the ESLs are shown. Asterisks denote reverse complement sequences. Abbreviations: CGI - CpG Island; TSS - Transcription Start Site; TPM - Transcripts Per Million. Source data are provided as a Source Data file.

[0031] DETAILED DESCRIPTION

[0032] In the following description, numerous specific details are set forth to provide a thorough understanding of the invention. However, it is understood that the invention may be practiced without these specific details.

[0033] The abundance, dynamics, and context-dependent heterogeneity of DNA methylation, where a pattern considered abnormal in one cell type may be normal in another, complicate the identification of early methylation changes that drive or signal disease development. This complexity can obscure early markers of increased disease risk, making it challenging to detect and intervene in disease processes at their inception. Here, we report 31,744 CpG loci exhibiting highly consistent methylation profiles in the blood of young, healthy individuals. We assess alterations at these epigenetically stable loci in 8,886 individuals across 29 diverse cohorts, including those with hematological cancers (n = 3,159), cardiovascular complications (n = 2,788), and healthy controls (n = 2,939). Our findings reveal methylation pattern disruption in myeloid and lymphoid malignancies, correlating with clonal burden dynamics and mutation frequency throughout leukemia treatment. In non-cancer cohorts, we observe that methylation levels at epigenetically stable loci become increasingly variable with age, a shift linked to higher cardiovascular disease risk and lower survival rates. This study highlights DNA methylation instability as a blood-based biomarker for both hematological cancer and cardiovascular disease and uncovers a mechanistic linkbetween methylation dynamics and the expansion of maladaptive hematopoietic clones.

[0034] In an aspect, there is provided a method of assessing survival risk of a human subject with haematological cancer or an age-related non-malignant disease comprising: a) providing a sample from the subject comprising DNA that includes at least 1000 of the 31744 differentially methylated regions (DMRs) set forth in Table 1.

[0035] b) determining an epigenetically stable loci (ESL) profile based on the methylation status of the at least 1000 DMRs; and

[0036] c) categorizing the subject as having either low survival risk or high survival risk, each being associated with high DNA methylation instability (DMI) or low DMI respectively, wherein the subject has high DMI if the ESL profile has methylated DMRs exceeding a predetermined threshold and the subject has low DMI if the ESL profile has methylated DMRs below the predetermined threshold.

[0037] As used herein, a "differentially methylated region" (DMR) refers to a segment of DNA that exhibits a difference in the methylation status, typically of cytosine residues at CpG dinucleotides, between two or more biological samples, cell types, tissues, developmental stages, or disease states. The methylation difference may be an increase or decrease in the proportion of methylated cytosines within the region, and such differences can be indicative of regulatory changes, such as gene silencing or activation, or may serve as biomarkers for specific physiological or pathological conditions.

[0038] A DMR may be identified by comparing the methylation patterns of corresponding genomic regions in different samples using techniques such as bisulfite sequencing, methylation-specific PCR, or array-based methods. The presence of a DMR can reflect epigenetic modifications associated with processes like imprinting, X-chromosome inactivation, cancer, or other diseases, and may be used for diagnostic, prognostic, or therapeutic purposes.

[0039] The term “sample” as used herein refers to any fluid, cell or tissue sample from a subject that can be assayed for biomarker expression products and / or a referenceexpression profile, e.g. differentially methylated regions in cfDNA. In preferable embodiments, the sample is a liquid biopsy.

[0040] Prognosis refers to a clinical outcome group such as a better survival group or a worse survival group associated with a disease subtype which is reflected by a reference profile such as a biomarker reference expression profile or reflected by the epigenetically stable loci (ESL) profile provided herein. The ESL profile may reflect high DNA methylation instability (DM I) or low DM I respectively.

[0041] The prognosis provides an indication of disease progression and can include an indication of likelihood of death due to the disease. A subject with high DMI, for example reflected in methylated DMRs exceeding a predetermined threshold may be categorized as having a risk of low survival, or “low survival risk”, from the disease as compared to a control or reference cohort. Conversely, a subject with low DMI, for example reflected in methylated DMRs below a predetermined threshold may be categorized as having a risk of high survival, or “high survival risk”, from the disease as compared to a control or reference cohort

[0042] As used herein, the term “control" or “reference” may refer to a specific value, cohort or dataset that can be used to prognose or classify the value e.g. DNA methylation instability obtained from the test sample associated with an outcome class.

[0043] In some embodiments, the predetermined threshold is the median DMI of a reference cohort.

[0044] In some embodiments, the DMI is determined as the standard deviation of ESL |3-values within the sample.

[0045] In some embodiments, the ESL profile comprises at least 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, or 10000 of 31744 DMRs in Table 1.

[0046] In some embodiments, the ESL profile comprises at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98% or 99% of the 31744 DMRs in Table 1.

[0047] In some embodiments, the ESL profile comprises the top DMRs ranked by recurrence in Table 1.In some embodiments, the ESL profile comprises all of the 31744 DMRs in Table 1. Preferably, the ESL profile consists of all of the 31744 DMRs in Table 1.

[0048] In some embodiments, the methylation status is determined using methylation bead array.

[0049] In some embodiments, the methylation status is determined using methylation sequence conduced following enzymatic or chemical conversion of methylated or unmethylated cytosines.

[0050] In some embodiments, the haematological cancer is leukemia, lymphoma, myeloma, myelodysplastic syndrome, or myeloproliferative neoplasm.

[0051] In some embodiments, the age-related disease is a cardio vascular disease. Preferably, the cardio vascular disease is coronary artery disease, cerebrovascular disease, myocardial infarction, heart failure, hypertension, arrhythmia, cardiomyopathy, peripheral artery disease, deep vein thrombosis, pulmonary embolism, or aortic aneurysms / dissection.

[0052] In some embodiments, the sample is blood, plasma, urine, saliva, cerebrospinal fluid, bone marrow aspirate, lymph node, or pleural fluid. Preferably, the sample is blood plasma.

[0053] In some embodiments, if the subject is categorized as high risk, the method further comprises treating the haematological cancer or age-related disease. Preferably, the treatment is aggressive therapy.

[0054] In an aspect, there is provided a computer-implemented method for assessing survival risk of a human subject with haematological cancer or an age-related disease, the method comprising:

[0055] a) receiving, at at least one processor, data reflecting the subject’s methylation status of at least 1000 of the 31744 differentially methylated regions (DMRs) set forth in Table 1;

[0056] b) constructing, at the at least one processor, an epigenetically stable loci (ESL) profile based on the methylation status of the at least 1000 DMRs;c) categorizing, at the at least one processor, the subject as having high DNA methylation instability (DMI) or low DMI, wherein the subject has high DMI if the ESL profile has methylated DMRs exceeding a predetermined threshold and the subject has low DMI if the ESL profile has methylated DMRs below the predetermined threshold.

[0057] In an aspect, there is provided a computer program product for use in conjunction with a computer having a processor and a memory connected to the processor, the computer program product comprising a computer readable storage medium having a computer mechanism encoded thereon, wherein the computer program mechanism may be loaded into the memory of the computer and cause the computer to carry out the method described herein.

[0058] In an aspect, there is provided a method of assessing risk of a human subject developing a haematological cancer or an age-related disease comprising:

[0059] a) providing a sample from the subject comprising DNA that includes at least 1000 of the 31744 differentially methylated regions (DMRs) set forth in Table 1.

[0060] b) determining an epigenetically stable loci (ESL) profile based on the methylation status of the at least 1000 DMRs; and

[0061] c) categorizing the subject as having either low risk or high risk, each being associated with high DNA methylation instability (DMI) or low DMI respectively, wherein the subject has high DMI if the ESL profile has methylated DMRs exceeding a predetermined threshold and the subject has low DMI if the ESL profile has methylated DMRs below the predetermined threshold.

[0062] The advantages of the present invention are further illustrated by the following examples. The examples and their particular details set forth herein are presented for illustration only and should not be construed as a limitation on the claims of the present invention.EXAMPLES

[0063] Methods and Materials

[0064] Ethics

[0065] Patients samples were collected in accordance with procedures approved by the Research Ethics Board of the University Health Network (REB #01-0573) and viably frozen in the Princess Margaret Leukemia Tissue Bank. Blood biospecimens from cardiogenic shock patients were collected under UHN REB approval (#18-6188) from the Peter Munk Cardiac Centre Cardiovascular Biobank. Written informed consent was obtained from all patients in accordance with the Declaration of Helsinki. University of Toronto REB approval was obtained for the use of datasets in secondary data analysis under Protocol #00041924.

[0066] DNA methylation profiling

[0067] Venous blood and bone marrow biopsies were collected from 14 AML patients, resulting in a total of 46 longitudinal samples. For patients experiencing cardiogenic shock (n=64), buffy coat samples were utilized for DNA methylation profiling. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit (Qiagen) according to the manufacturer's instructions. The concentration and purity of the DNA were assessed spectrophotometrically on a Qubit Fluorometer, with criteria set at an A260:A280 ratio greater than 1.7 and an A260:A230 ratio greater than 1.7. DNA integrity was evaluated through 1% agarose gel electrophoresis, loading 50-100 ng of DNA per sample. Samples exhibiting a clear single band above the 10 kb DNA ladder were deemed suitable for further processing. High-quality genomic DNA (500 ng) was bisulfite-converted using the EZ DNA Methylation Kit (Zymo Research) following the manufacturer's protocol. DNA methylation profiling was conducted using the Infinium MethylationEPIC microarray (Illumina).

[0068] Methylation array data preprocessing

[0069] Raw IDAT files were processed using the minfi R / Bioconductor package62. IDATs were loaded via read. metharray. exp into RGChannelSet objects. To ensure cross-platform consistency among different datasets, only probes shared between the 450K and EPIC arrays were retained. Background correction and dye-bias normalization were performed using the preprocessNoob method, which applies single-samplenormalization independently to each array63, p-values (0-1 methylation levels) were calculated using getBeta. We then applied additional probe filtering criteria. Probes with detection P > 0.001 in more than 5% of samples were removed using the detectionP function. We also excluded non-CpG (CpH) targeting probes, probes overlapping SNPs (identified with dropMethylationLoci and dropLociWithSnps, with no minimum minor allele frequency cutoff), probes with previously reported crossreactivity30, age-associated CpGs31-32, and probes on sex chromosomes. A final set of 397,346 probes were considered for further analysis.

[0070] Identification of Epigenetically Stable Loci (ESLs)

[0071] Whole blood DNA from 1,658 young individuals (age 18), sourced from Hannon et al., 201829, was used to identify CpG sites with low variability in DNAm levels. The CpGs retained after data preprocessing (n=397,346) were ranked by p-value variance and the 10% least variable sites across the cohort were classified as epigenetically stable loci (ESLs). The average p-values at these stable sites showed a pronounced bimodal distribution, with one peak near zero (maximum p-value = 0.043) and another near one (minimum p-value = 0.962). Sites with low p-values were classified as unmethylated ESLs (n=31,744), and those with high p-values as methylated ESLs (n=6,143). To account for potential residual cell type bias, p-values were assessed in purified blood cell types (B cells, CD4+ T cells, CD8+ T cells, granulocytes, and monocytes). ESLs showing outlier methylation levels in any of these cell types were excluded. In addition, we evaluated these ESLs in a separate dataset generated using whole-genome bisulfite sequencing from 82 purified human adult healthy tissue cell populations, sourced from Loyfer et al., 202364. In this dataset, p-values for each locus were calculated as the ratio of methylated reads to total reads.

[0072] Establishing a threshold for Epigenetically Stable loci (ESL) destabilization

[0073] To determine whether an ESL was destabilized in a given patient, we established a threshold based on the p-values of ESLs observed across three control cohorts from the Gene Expression Omnibus (datasets: GSE124413, GSE132203, and GSE141682). For each control cohort, the mean p-value for each ESL was calculated individually, and all values were pooled. The destabilization threshold was set at the 99.9th percentile of the pooled values. This resulted in a threshold of p-value = 0.05932 for normally unmethylated ESLs. ESLs with methylation levels exceeding thisthreshold were classified as perturbed, also referred to as destabilized. Following the same approach, a p-value of 0.8321 was calculated for normally methylated ESLs. Frequency and recurrence of ESL destabilization in a pan-cancer hematological dataset

[0074] To assess the frequency of ESL destabilization, we compiled a pan-cancer dataset comprising 3,019 samples from various hematological malignancies, including AML, T-ALL, BCP-ALL, CLL, FL, DLBCL, pPCL, MNKPL, and MPAL. CML and MDS were excluded from this analysis due to their characteristic low burden of blast cells and minimal ESL destabilization. A p-value matrix was generated, with CpGs as rows and patients as columns. This matrix was then binarized by assigning a value of 1 to |3-values exceeding the predetermined ESL destabilization threshold (P-value = 0.05932), and a value of 0 to p-values below the threshold. For each ESL, the proportion of patients exhibiting destabilization was calculated by dividing the sum of the binarized values for that row by the total number of samples (n = 3,019). Low-recurrence ESLs were defined as those perturbed in less than 5% of the samples, while recurrently perturbed ESLs were defined as those exhibiting perturbation in 5% or more of the samples. In the analysis examining the correlation between ESL perturbation recurrence and their average destabilized p-value (Fig. 4a,), the average P-value for each ESL was calculated only from patients exhibiting destabilization at that site.

[0075] Identification of lymphoid- and myeloid-enriched perturbed ESLs

[0076] A comparison was conducted between AML samples and T-ALL and BCP-ALL to identify ESLs whose destabilization shows a stronger association with myeloid or lymphoid leukemias. The matrix of binarized p-values was used to conduct a two-sided Fisher's test to assess the number of destabilized samples among myeloid cancer patients compared to lymphoid cancer patients. We only retained ESLs with a P value < 0.05 following Bonferroni correction. To identify lymphoid-enriched perturbed ESLs, we first selected sites that had an odds ratio greater than 1 and exhibited destabilization in at least 50% of the combined T-ALL and BCP-ALL samples, thereby emphasizing ESLs that are frequent in these lymphoid leukemias. This set of ESLs was ranked by their odds ratios and the top 50% of these sites were designated as lymphoid-enriched ESLs - those most strongly associated with lymphoid cancers. To identify myeloid-enriched perturbed ESLs, we adapted this approach to account for therelatively lower frequency of ESL perturbations observed in AML. Comparisons between AML and T-ALL, as well as AML and BCP-ALL, were conducted separately and the intersection of both the resulting lists was designated as myeloid-enriched. Additionally, we retained only ESLs that exhibited destabilization in at least 10% of the AML samples.

[0077] Chromatin accessibility and its association with lineage-enriched perturbed ESLs A cell-by-peak matrix was obtained from Granja et al. 201965, corresponding to peaks called from the aligned scATAC-seq fragments for each cell. In the original study, latent semantic indexing (LSI) followed by singular value decomposition (SVD) was used to perform dimensionality reduction, normalization, and selection of informative peaks. We leveraged this data to investigate the relationship between lineage-enriched perturbed ESLs and chromatin accessibility. Specifically, a subset of the LSI-SVD matrix was created including the following relevant cell types: HSC, CMP, GMP, CLP, Pre-B cells, B cells, CD4 T cells, CD8 T cells, and NK cells. UMAP was performed on this matrix using the implementation in the uwot R package, with the same parameters used in the original publication. To assess chromatin accessibility at the lymphoid-enriched and myeloid-enriched ESLs, we first mapped ESLs to peaks in the scATAC-seq dataset by constructing, for each ESL, a 200 bp window with the CpG bases at the center. Any scATAC-seq peaks overlapping with these windows were retained. This process was performed separately for lymphoid-enriched ESLs (n=1,075) and myeloid-enriched ESLs (n=80), yielding two peak sets corresponding to these loci. ChromVAR deviation scores66were generated for each peak set using the ‘AddChromatinModule’ function from the Signac R package67. Each cell type in the UMAP was colored according to its average chromVAR deviation scores for lymphoid-enriched ESLs and myeloid-enriched ESLs. The same approach was used for the analysis of a second single cell ATAC-seq dataset from Izzo et al.68In this dataset of hematopoietic cells derived from patients with JAK2V617F-mutated myelofibrosis, only cells that were wild type for this allele were analyzed (n = 6,088). UMAP coordinates provided in the original publications were used for visualization.

[0078] Power calculation for selection of cardiogenic shock patients

[0079] Prior to DNA methylation profiling and the analysis assessing the impact of DMI status on the survival time of cardiogenic shock patients, we conducted a power analysis to determine the required sample size of a sub-cohort that would provide sufficientstatistical power to detect a significant effect. This analysis was performed using the ‘ssizeEpiCont’ function from the powerSurvEpi R package. Over 10,000 iterations, we randomly assigned a fixed number of patients from the entire cardiogenic shock cohort from our original study39to high DMI status, while an equal number were assigned to low DMI status, mimicking the process of splitting patients based on median DMI values. The analysis was designed to achieve 85% power, assuming a hazard ratio of 1.5 and a type I error rate (alpha) of 0.05. This simulation indicated that a sub-cohort of 64 patients would be adequately powered to examine the relationship between DMI status and survival time in these high-risk patients.

[0080] Survival and time-to-event analyses

[0081] DNA methylation instability (DMI) was defined as the standard deviation of ESL |3-values within a sample. Participants in the Framingham Heart Study42(Exam 8; n = 2,724) were stratified into high DMI and low DMI groups based on the cohort-wide median. This categorical variable was used to perform Kaplan-Meier survival analysis using the lifelines Python package69. Cox proportional hazards (CoxPH) models incorporated DMI, age, and sex as covariates, with further adjustment for 12 distinct immune cell types43. Outcomes analyzed were overall mortality, cardiovascular disease, coronary heart disease, and congestive heart failure. Only individuals without prior occurrence of these endpoints at the time of sampling were included (n = 2,281). Confidence intervals (95%) were computed using the log-log method. The same methodology was applied in the cardiogenic shock sub-cohort to assess the association between DMI and survival among patients already diagnosed with disease. In multivariate CoxPH models, DMI, age, and clonal hematopoiesis status were included as covariates. Clonal hematopoiesis was treated as a categorical variable, distinguishing individuals harboring somatic mutations in DNMT3A or TET2 from those without mutations.

[0082] Genomic Distribution of ESLs

[0083] The association of ESLs with CpG islands, shores, shelves, and open sea regions was extracted directly from the Illumina 450K bead-array manifest. Enrichment analysis for ESLs within these regional categories was performed using Fisher's exact test. Additionally, genomic coordinates of TSS were obtained from the UCSC Genome Browser annotation track database (https: / / genome.ucsc.edu / cgi-bin / hgTables; specifically, “NCBI RefSeq” track from the “Genes and Gene Predictions” group).Promoter regions were defined as the area from 1500 bp upstream to 1500 bp downstream of a TSS. The enrichment of ESLs within these regions was assessed using a two-sided Fisher's exact test, with non-stable CpG loci (n = 359,459) serving as the reference set.

[0084] Identification of ESL-regulated, age-associated genes through integrated methylation, expression, and recurrence analysis

[0085] To identify genes for which ESL perturbation significantly influences their expression, we conducted a pan-cancer analysis using harmonized DNA methylation and RNA-seq transcript per million (TPM) data from 8,960 solid cancer samples (TOGA Pan-Cancer dataset downloaded from https: / / xenabrowser.net / datapages / ). We focused on recurrently perturbed ESLs located within 1,500 bp upstream of TSSs, resulting in 3,584 sites associated with 1,916 genes after intersecting with the TCGA data. For each ESL, Pearson’s correlation coefficient was calculated between the methylation level (P-value) and the expression (TPM) of the corresponding gene. For genes with multiple ESLs in their promoter regions, the mean correlation coefficient (r) was calculated. In a second analysis, the correlation between gene expression and age was calculated for each of the 1,916 genes using a dataset of healthy individuals from the Genotype-Tissue Expression (GTEx) project45who had their peripheral blood assayed with RNA-seq. In a third analysis, we calculated the mean recurrence across ESLs within each gene promoter. These steps yielded three variables for each gene: methylation versus expression (r), age versus expression (r), and recurrence. A total of 236 genes were selected for further interrogation based on the following criteria: 1) a significant negative correlation between age and expression, 2) a significant negative correlation between methylation at promoter-related ESLs and expression, and 3) a mean ESL recurrence greater than 5%. Statistical significance was determined using an alpha of 0.05, with Bonferroni correction applied for multiple hypothesis testing. Differential methylation analysis

[0086] CpG islands located in the promoter regions of the 236 age-dependent genes were analyzed using whole-genome bisulfite sequencing data from six genetically diverse AML samples (IDs: 412761, 868442, 400220, 545259, 548327, 573988) sourced from Wilson ER, et al. (2022)70, along with six CD34+ cells from healthy donors as controls. Differential methylation between the AML and control samples was assessed by comparing beta values for each CpG island and its associated ESLs using a two-sidedWilcoxon rank-sum test. A P value < 0.05, adjusted for multiple comparisons using the Bonferroni correction, was considered statistically significant.

[0087] Transcription factor motif mapping

[0088] To investigate the regulatory mechanisms underlying age-dependent gene expression changes, gene set enrichment analysis was performed using g:Profiler71on a curated list of 236 age-associated genes identified through the analysis described above. To evaluate whether TF binding sites overlapped with ESLs, we utilized JASPAR72motif coordinates through the “JASPAR Transcription Factors” track available via the UCSC Genome Browser. Only motifs with JASPAR position weight matrix scores corresponding to a Rvalue below 0.0001 (i.e., scores greater than 400) were retained. Intersection of these filtered motif sites with the genomic coordinates of ESLs resulted in TF binding motifs containing ESLs across age-related genes.

[0089] Permutation tests

[0090] For the analysis pairing diagnosis and relapse samples based on low-recurrence, highly destabilized ESLs, a permutation test was performed to evaluate the probability of obtaining a similar matching success rate by chance. For each cancer-type dataset, 1,000 simulations were performed in which 15 random low-recurrence ESLs were selected for each patient. In each iteration the total number of randomly selected sites (n = 15 times the number of patients) was then used to perform unsupervised clustering, with Ward’s linkage method and Pearson’s correlation as the distance metric. The P value was defined as the proportion of simulations in which the number of correctly paired patients equaled or exceeded the observed count, reflecting the likelihood of achieving such a result by chance.

[0091] Statistics and reproducibility

[0092] Statistical analysis was done with R / RStudio version 4.2.2 and Python version 3.1.1. Statistics for each analysis are described in the relevant section. For the cardiogenic shock cohort, sample size was determined by power analysis. For all other cohorts, sample sizes were based on the maximum number of available samples or data. In the Framingham Heart Study cohort, participants who had already experienced the endpoints of interest prior to sampling were excluded; no other samples were excluded. As this study retrospectively examines associations between abnormalmethylation at specific loci and disease states, no treatments were tested, and the experiments were not randomized. The Investigators were not blinded to allocation during experiments and outcome assessment, as blinding was not relevant for the reported analyses.

[0093] Consideration of sex and gender

[0094] CpG sites on sex chromosomes were excluded to ensure results are generalizable across sexes. Perturbation of autosomal ESLs was analyzed separately in males and females with chronic lymphocytic leukemia, demonstrating that this phenomenon occurs independently of sex. Biological sex was included as a covariate in Cox proportional hazards regression analyses of the Framingham Heart Study cohort. Gender-based analyses were not carried out due to limited reporting of gender information in the available datasets.

[0095] Results and Discussion

[0096] Low-variability CpG loci define a stable epigenetic landscape in human blood

[0097] To identify stable features of the human methylome, we analyzed whole blood DNAm profiles from a large cohort of young, healthy individuals29(n=1,658, age=18), in whom substantial clonal expansions are expected to be rare.1-3Genome-wide DNAm levels were assessed using Illumina 450K Infinium arrays. Methylation levels were calculated using the ratio of intensities between the methylated and the combined locus intensity (P-value). CpG sites were restricted to autosomes, excluding sites near common single nucleotide polymorphisms, sites with previously reported cross-reactivity30, and sites predictive of biological age31-32. We defined Epigenetically Stable Loci (ESLs) as the 10% least variable CpG sites based on methylation level variance across the cohort. Given the heterogeneous cellular composition of peripheral blood, we validated stable methylation levels across isolated blood cell populations and further refined our selection of ESLs by excluding CpG loci exhibiting outlier methylation levels (i.e. |3-values) in any of the purified cell types. This approach identified 31,744 unmethylated and 6,143 methylated sites, with no sites exhibiting intermediate methylation levels (Fig. 1a,b). Notably, although these ESLs were identified in blood, we were able to detect their characteristic methylation patterns across non-hematological tissues usingdifferent profiling technologies (Fig. 1c). While some variation exists, the overall patterns, largely extreme hyper- or hypomethylation across ESLs, are consistently preserved across diverse tissue types and developmental stages, suggesting the presence of stringent regulatory control established early in embryonic development and largely maintained throughout human life.

[0098] Epigenetic perturbations at ESLs occur frequently across blood malignancies We quantified DNAm at ESLs across a broad spectrum of myeloid and lymphoid malignancies to evaluate their disruption during carcinogenesis. To enable inter-cohort comparisons, we established a destabilization threshold based on ESL p-values from three independent control cohorts (total n = 878), representing baseline methylation levels at these sites (Fig. 2a; p-value = 0.05932). These cohorts encompassed diverse ethnic backgrounds, age ranges, and tissue sources, ensuring that the threshold reflects a broadly generalizable background level. Apart from chronic-phase CML, all investigated malignancies exhibited elevated methylation at normally unmethylated ESLs (Fig. 2a). This pattern was observed across both pediatric and adult cancers, independent of biopsy tissue origin or patient sex. Lymphoid cancers exhibited a greater degree of epigenetic destabilization than myeloid cancers, reflected in both the number of ESLs with p-values above the threshold established from healthy controls (termed perturbed ESLs) and in methylation levels at those typically hypomethylated loci (Fig. 2a, b). Reduced methylation of normally methylated ESLs was also observed, though this pattern was less consistent across cancers and more variable among controls. Accordingly, we focused on the unmethylated ESLs for all subsequent analyses; any mention of ESLs hereafter refers exclusively to this subset.

[0099] Chromatin status in precursor cells associates with ESL perturbation susceptibility

[0100] Given the mechanistic link between DNAm and chromatin architecture,21 3334and the differing levels of ESL destabilization in cancers of distinct lineages, we examined chromatin accessibility at lineage-enriched, perturbed ESLs in corresponding cell types. To identify lineage-enriched perturbed ESLs, we compared AML profiles (n=997) to T-ALL (n=353) and BCP-ALL (n=663). This analysis identified 1,075 ESLs, predominantly perturbed in T-ALL and BCP-ALL, compared to 80 myeloid-enriched ESLs. This disparity aligns with the lower degree of ESL hypermethylation observed in AML relative to lymphoid cancers (Fig. 2). Single-cell ATAC-seq profiles of healthy hematopoietic cells were used to explore the relationship between instability inlineage-enriched perturbed ESLs and chromatin accessibility at these sites. Chromatin regions corresponding to lymphoid-enriched instability exhibited low accessibility in common lymphoid progenitors, T-cell, and B-cell lineages, and relatively higher accessibility in hematopoietic stem cells (HSCs), common myeloid progenitors, and granulocyte-monocyte progenitors. Conversely, myeloid-enriched perturbed ESLs exhibited significantly reduced chromatin accessibility in HSCs and myeloid progenitors, but relatively increased accessibility in lymphoid-lineage-associated cells (Fig. 3). These contrasting patterns link lineage-associated ESLs, their frequent perturbation in leukemia, and differential chromatin accessibility in corresponding precursor cells, an observation confirmed in a second dataset. We further confirmed these associations using an orthogonal data modality.

[0101] Long-lasting methylation changes at ESLs indicate clonal epigenetic memory in leukemia

[0102] We curated and analyzed a pan-hematological cancer cohort of 3,019 samples to assess the recurrence of ESL destabilization events. ESLs that were destabilized in a higher proportion of patients exhibited greater average methylation levels among those affected samples, suggesting that recurrent destabilization is associated with a larger fraction of methylated cells within each patient. (Fig. 4a). To evaluate somatic methylation inheritance at ESLs versus in-situ methylation occurring independently across cells, we focused on ESLs perturbed in fewer than 5% of patients, as these are more likely to represent patient-specific, clone-related epigenetic alterations. Analyzing paired diagnosis and relapse leukemia samples, we identified the 15 low-recurrence ESLs with the highest methylation levels in relapse samples for each patient. Unsupervised clustering then paired diagnosis samples with their corresponding relapse specimens. In AML (n=15 diagnosis-relapse pairs), this approach resulted in 9 correct matches. For chronic lymphocytic leukemia (CLL), 31 out of 40 pairs were correctly paired. In BCP-ALL (n=24 pairs), all diagnosis samples were correctly assigned to their corresponding relapse sample (Fig. 4b-d). These results provide strong statistical evidence (P = .002 for AML; P < .001 for CLL and BCP-ALL by permutation test) for the clonal preservation of ESL methylation, suggesting long-term epigenetic memory in leukemia cells throughout disease progression. In patients with available remission samples, the observed reduction in DNAm supports a somatic, leukemia-specific signal (Fig. 4e). Importantly, the patient-specific backtracking of methylation at these ESLs from relapse to diagnosis indicates that the methylationobserved at ESLs in therapy-resistant epigenetic clones (epi-clones) was established in the majority of patients prior to treatment initiation. Similarly, significantly improved pairing compared to random expectation was observed when analyzing the 15 most destabilized low-recurrence ESLs from diagnostic samples. Overall, these results support somatic and persistent methylation at ESLs, characteristics that are relevant for driving potential functional impact.

[0103] DNA methylation instability is largely independent of genomic background

[0104] To quantify ESL perturbation on a per-sample basis, we introduced a metric called DNA methylation instability (DMI), defined as the standard deviation of p-values for ESLs within each sample. Since most ESLs remain unperturbed in individual samples, we focused on recurrently perturbed ESLs (n=9,164), defined as those perturbed in over 5% of samples in the pan-hematological cancer cohort. Longitudinal measurements of bone marrow samples from AML patients revealed that DMI levels correspond to expected patterns of leukemic burden across clinical stages of the disease (Fig. 4f), consistent with our observations of somatic DNAm modifications based on individual ESLs in BCP-ALL (Fig. 4e). Notably, in Patient 2, who was clinically defined as being in remission at the third sampling, we observed an increase in DMI, potentially indicating the impending relapse which was diagnosed 24 days later. DNAm profiling of a subset of leukemia patients with distinct genetic mutations, previously characterized by next-generation sequencing35, revealed that DMI levels closely reflected the allelic burden of these mutations (Fig. 4g). Notably, in Patient 8, where clonal tracking was hindered by the absence of identifiable mutations, the ability to monitor DMI highlights its potential as a complementary approach to traditional mutation-based methods for assessing complete remission and residual disease posttreatment.

[0105] Progressive epigenetic instability with age

[0106] Given that DMI measurements share similarities with genetic clonal markers in the hematopoietic system, particularly in their association with leukemic cell burden and the persistence of the alteration, and considering that hematopoietic clonality increases in frequency with age3638, we hypothesized that DMI may also reflect age-related changes in individuals without hematological malignancies. To test this relationship, we examined several cohorts of healthy blood donors and found a significant correlation between DMI and age (Fig. 5). These results demonstrate thatglobal deviation from the normally hypomethylated state of ESLs increases progressively, suggesting that DM I may be a general feature of aging hematopoietic cells rather than a phenomenon restricted to malignant transformation. Notably, DMI levels in these healthy cohorts were consistently lower than those measured in individuals with hematological malignancies (Fig. 4f-g), suggesting an accelerated rate of methylation instability following malignant transformation.

[0107] DNA methylation instability is associated with increased cardiovascular risk and mortality

[0108] Clonal hematopoiesis has consistently been linked to increased cardiovascular risk and related adverse outcomes1011 39-41. Given the similar associations between genetically defined clonality and DMI in cancer and aging, we hypothesized that elevated DMI could serve as an indicator of cardiovascular disease. To investigate this relationship, we analyzed DNAm data generated as part of the Framingham Heart Study42, with follow-up spanning up to 14 years. Kaplan-Meier analysis showed that individuals with elevated DMI had a significantly higher risk of all-cause mortality, as well as cardiovascular disease (CVD), coronary heart disease (CHD), and congestive heart failure (CHF) compared to those with low DMI (Fig. 6a-d). Hazard ratios for elevated CVD and CHD risk remained significant after adjusting for age and sex (Fig.

[0109] 6e). Previous analyses of health outcomes revealed that higher fractions of naive CD4+T-cells, naive B-cells, and NK cells were associated with a reduced risk of allcause mortality, independent of major epidemiological risk factors and baseline comorbidities43. Cox regression analyses adjusting for the relative abundance of immune cell types44confirmed that the associations between high DMI and CHD and CHF risk remained significant. To assess the impact of extreme epigenetic profiles, we repeated the analyses considering only individuals in the top and bottom quartiles of DMI values. This comparison of extreme quartiles accentuated the differences in clinical outcomes between individuals with high versus low DMI.

[0110] We previously performed next-generation sequencing on cardiogenic shock patients and identified significant survival differences between those with clonal hematopoiesis and those without detectable clonal hematopoiesis39. To investigate the prognostic value of DMI in these high-risk patients, we profiled a subset of the original cohort, including 29 patients with clonal hematopoiesis driven by common DNMT3A or TET2 mutations, and 35 without clonal hematopoiesis. As a result, we intentionally obtainedan underpowered cohort with respect to the significant association between clonal hematopoiesis and mortality rates seen in our original study39. Despite this, individuals with elevated DM I had significantly lower survival compared to those with low DM I (Fig. 6f). This association remained significant after adjustment for age and clonal hematopoiesis status (Cox proportional hazards models: HR = 3.76; Rvalue = 0.006), and after accounting for immune cell fractions. Stratification of patients based on DM I levels and clonal hematopoiesis status demonstrated that DMI is an independent risk factor (Fig. 6g). This finding further supports our earlier observation that elevated DMI is largely independent of the underlying genomic context (Fig. 4g).

[0111] ESLs overlap transcription factor motifs and are linked to gene silencing

[0112] The widespread associations between DMI and aging, cancer, and cardiovascular disease prompted us to investigate underlying mechanisms. Given DNA methylation’s role in gene regulation, we hypothesized that accumulating epigenetic instability may disrupt gene expression. Consistent with this, ESLs were significantly enriched within CpG islands relative to non-ESLs (OR = 15.1, P < 0.001) and were preferentially located in gene promoters, with the majority (92.6%) occurring within 1 ,500 bp of a transcription start site (TSS) (Fig. 7a, b).

[0113] To identify genes most likely influenced by ESL perturbation, we focused on three criteria (Fig. 7c): the presence of recurrently methylated promoter-associated ESLs, as infrequent perturbation and lower methylation (Fig. 4a) are less likely to drive meaningful regulatory changes; a negative correlation between ESL methylation levels and gene expression; and a negative correlation between gene expression and age. Age-related genes were identified using data from the Genotype-Tissue Expression project45, while The Cancer Genome Atlas data46, which provides paired methylation and expression profiles across large, heterogeneous cancer cohorts, was used to identify genes for which promoter ESL methylation was associated with lower gene expression (Methods). Genes meeting all three criteria were prioritized for further investigation (n = 236).

[0114] PRDM5 is a well-characterized tumor suppressor frequently silenced by promoter hypermethylation in multiple solid cancers, the loss of which is associated with increased tumor cell proliferation and poor prognosis47^19. Among all genes, the PRDM5 promoter harbors ESLs with the highest likelihood of perturbation in the pan-hematological cancer cohort, reinforcing independent evidence of widespread CpGisland hypermethylation at this locus observed in AML. A similar trend towards widespread promoter hypermethylation in AML was observed across the 236 prioritized genes (Fig. 7d).

[0115] Functional enrichment analysis revealed significant enrichment of transcription factor (TF) binding motifs within the 236 genes, including those for the SP and AP-2 families, linking ESL perturbation to key regulators of the cell cycle, differentiation, proliferation, and apoptosis5051. An independent analysis confirmed that the CpG loci corresponding to ESLs are integral components of many of the enriched motifs (Fig. 7e). A notable example is RGS2, whose promoter region contains recurrently perturbed ESLs that overlap with several TF motifs (Fig. 7f). Reduced expression of RGS2 in peripheral blood mononuclear cells has been associated with hypertension52. Given that these cells are known to exhibit functional abnormalities in hypertension53and contribute to the pathogenesis of atherosclerosis10, RGS2 dysregulation in blood through ESL perturbation may contribute to the observed association with cardiovascular disease, although a causal role remains to be established.

[0116] To shed more light on the potential role of ESL methylation in modulating TF binding, we cross-referenced promoter-proximal ESLs (Fig. 7e) with TF motifs whose methylation sensitivity has been characterized using methylation-sensitive SELEX54. This approach allowed us to identify TFs for which the presence of 5-methylcytosine (5mC) within the binding motif can either enhance or inhibit binding. KLF12 emerged as a compelling example: its binding is enhanced by 5mC, and it functions as a transcriptional repressor5556. Perturbation of ESLs within KLF12 target promoters (Fig.

[0117] 7f) could therefore influence gene expression by altering TF occupancy. We emphasize that the impact of ESL methylation on gene regulation is inherently complex. The functional consequence depends not only on whether 5mC enhances or inhibits TF binding, but also on the TF’s regulatory role as activator, repressor, or context-dependent modulator, and on combinatorial effects when multiple TFs and ESLs are involved.

[0118] Together, these examples illustrate a broader mechanism by which ESL perturbations may modulate the binding of common TFs at promoter regions, thereby altering the expression of age-related and disease-associated regulatory genes critical for maintaining hematopoietic homeostasis.

[0119] DiscussionIn this study, we identify epigenetic instability as a risk factor associated with several hallmarks of clonal hematopoiesis. Our analysis identified a set of CpG loci, termed epigenetically stable loci (ESLs), that exhibit a consistently hypomethylated state across healthy young adults and diverse blood cell types. This stability extends to other normal tissues, suggesting that ESL methylation patterns are established during early development and largely maintained throughout differentiation, consistent with current understanding of methylation reprogramming during embryogenesis57.

[0120] We found that disruptions in the hypomethylated state of ESLs, accompanied by increased methylation variability, termed DNA methylation instability (DM I), are linked to adverse health outcomes. Our findings underscore the critical role of maintaining ESL hypomethylation in preserving stable and healthy hematopoiesis. ESL destabilization was seen across a wide range of hematological malignancies, with elevated DMI at leukemia diagnosis and significant reduction post-induction therapy, mirroring leukemic mutations and supporting somatic acquisition of this signal. Notably, elevated DMI was also observed in the absence of known driver mutations, suggesting its potential as a complement to genetic testing for enhanced diagnostic and prognostic assessment. DMI patterns persisted from diagnosis to relapse, indicating an epigenetic memory that endures selective pressures of cancer treatment. This persistence underscores the heritability of ESL methylation during cell division and its potential to accumulate over time, priming healthy cells for malignant transformation.

[0121] DNA methylation can reflect both changes in clonal composition and functional epigenetic alterations occurring within individual clones. In the first scenario, clones harboring specific epigenetic variants may expand; in this case, stochastic ESL methylation marks would primarily serve as tracers of clonal dynamics and, on their own, are unlikely to directly alter cellular behavior5859. Similar patterns are observed for other molecular markers, such as mtDNA mutations, which reveal a rich polyclonal architecture of hematopoietic stem cell contributions to hematopoiesis, with clonal expansions arising from multiple independent origin60. Alternatively, instability may occur within individual clones, progressively altering the epigenome and programmatically influencing gene regulation and cellular fitness, potentially leading to disease-associated patterns such as focal hyper- or hypomethylation, disrupted TF networks, and altered clonal selection dynamics. Distinguishing these scenarios will help determine whether specific epi-mutations act as drivers of cellular behavior,representing actionable therapeutic targets, or as passengers reflecting clonal history, which can serve as robust biomarkers for diagnosis, prognosis, or monitoring treatment response.

[0122] We observed that elevated DM I levels correlate with age, reflecting the progressive nature of ESL methylation instability. Additionally, ESL perturbation was associated with differential chromatin accessibility, suggesting that ESL destabilization is not entirely stochastic, with chromatin context potentially predisposing specific loci to epigenetic disruption or influencing the stability of methylation once it occurs.

[0123] Similar to clonal hematopoiesis associations, elevated DMI was linked to increased cardiovascular risk and higher mortality in high-risk cardiac patients. We observed a hazard ratio for developing coronary heart disease similar to that reported for CH in other epidemiological cohorts1061. Importantly, the association between DMI and survival among cardiogenic shock patients not only remained independent of CH mutations in TET2 and DNMT3A, but also amplified their prognostic impact39, suggesting that DMI contributes to cardiovascular risk through mechanisms that are both distinct from and additive to those of established CH drivers. Future studies in larger cohorts are needed to assess the independence of DMI from other CH mutations and its clinical utility across diverse pathological contexts.

[0124] Our findings link DMI to genes exhibiting age-associated downregulation that are involved in cell fitness, cancer, and cardiovascular disease. Many of these genes may be affected by ESL perturbations through their embedding in TF binding motifs. ESL perturbations, often observed in leukemia, coincide with SP, KLF, FOS, JUN, EGR, and AP-2 motifs, suggesting that DMI may globally disrupt cellular processes involved in proliferation, apoptosis, and differentiation. As we age, this accumulated dysregulation could impair hematopoietic stem cell maintenance, lineage commitment, and increase disease susceptibility.

[0125] This study establishes a framework linking epigenetic stability to hematological normalcy, and instability to reduced cellular diversity and pathogenesis. A limitation is the use of Infinium array data which covers less than 2% of the human genome and is biased toward promoter regions. This underscores the need for more comprehensive profiling to explore intergenic, stable genomic regions that, when methylated, may act as disease drivers. Such profiling could uncover new regulatory regions with critical roles in disease progression. Future efforts to establish a comprehensive referenceepigenome of normalcy will be essential for advancing our understanding of epigenetic drivers and mitigating the impact of both clonal and epi-clonal hematopoiesis on human health.

[0126] Although preferred embodiments of the invention have been described herein, it will be understood by those skilled in the art that variations may be made thereto without departing from the spirit of the invention or the scope of the appended claims. All documents disclosed herein, including those in the following reference list, are incorporated by reference.Reference List

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[0200] 2020;48(D1):D87-D92.TABLE 1: Recurrent and Non-Recurrent Regions

[0201] 1 ■ Recurrent Regions (>= 0.05) _

[0202] chr1:

[0203] 905238|925233|925545|925585|940869|942109|960608|999029|999282|999527|999759|1020919|1040171 |1040792|1040847|1068880|1 137522|1201737|1246846|1273329|1307515|1406850|1427900|1471575|1540295|1575047|1599604|1599775|1919696|2045173|205037 7|2050386|2205406|2205628|2227199|2290814|2467419|2526770|2526817|2530381 |2530461 |3069802|3070002|3454540|3531176|3611 218|3611513|3650233|3652137|3652146|3652158|3652482|3747500|3747520|3772352|4656477|5991498|6179415|6205969|6242104|64 0478516419669|6419753|6447968|6485967|6486514|649011116490585|6497674|6603604|661294116613369|6785154|768021117680226| 7704582|7704677|7771113|7902790|8025735|8026248|9128866|9129052|9234512|9292904|9539332|9539342|9540056|9654339|99436 94|9997100|9997245|9997254|10211133|10694105|10794250|11099976|11100036|11478664|11478783|11479194|11650553|11691327| 11736115|11859319|11934842|12019380|12019392|12063497|12167360|12617083|12618200|12618202|13513913|13583714|13584074| 13584205|13700089|13700123|13749463|14924773|14925048|15152465|15152486|15152496|15152514|15153740|15247159|15409469| 15584940|15603628|15603709|15758653|15758876|16013001 |16073230|16155220|16162553|16167963|16440526|16701337|16980472| 17119434|17119532|17439677|18108280|18902959|18952240|18956052|19597709|19882533|20152485|20186451 |20291838|20508109| 20508119|20508293|20508309|20508347|20508350|20552536|20633941 |20717714|20718192|20731951120732621120733252|21176968| 21177145|21290332|21345417|21345760|21440239|21509192|21509199|21509210|21659489|21669706|21669822|21669883|21814366| 21814521122142697|22143221122710375|22710487|22710875|23168937|23217312|23568412|23619517|23777968|23867963|24150593| 24187182|24187449|24187728|24187730|24321838|24413397|24413749|25246371125543798|25543800|25617400|25859765|25922894| 26169689|26169712|26234069|26336624|26890442|26960109|26960453|26993612|26993709|26993723|26993893|26994000|26994162| 26994446|26994452|26994654|26997980|27012922|27012944|27013295|27322886|27366696|27726197|28088783|28235709|28260425| 28553153|28812407|29122113|29122524|29123590|29259787|29259902|29260068|30756722|30802015|30908006|31296776|31296944| 31297053|31297079|31413003|31413043|31413738|32179581132180266|32205492|32205889|32291801132464567|32539490|325401011 32712453|32886583|32886668|32924923|33036911133081324|33127269|33181301133255858|33431102|33431319|33472516|34163958| 34164630|34165243|34792993|34866048|34866536|34885739|34985186|35193188|35557424|35557553|35557827|35770075|35883028| 36306494|36307065|36450592|37554207|37554248|37692457|37752861 |37793714|37793813|37793829|37793893|38012707|38012768| 38045433|38046566|38046923|38047573|38559577|38578524|39026303|39409130|39409137|39409206|39409292|39409379|39491457| 39491534|39491626|39491863|39691414|39691453|39691530|39691557|39789023|39789040|39789187|39789338|39902155|39954931 | 39955003|40477698|40783829|40783841140783911 |40861600|40861969|40862461 |41366360|41382302|41383067|41496396|41496475| 42036066|42036265|42380447|42380806|42381229|42766995|43147894|43172128|43172448|43358796|43358810|43358938|43358985| 43367245|43367280|43531775|43707127|43969891 |43969943|43969955|43970265|43970284|44213332|44213539|44405304|44405427| 44405625|44406830|44407392|44739846|44986568|45206399|46131687|46132209|46133456|46167024|46203198|46303442|46485805| 46533539|46604386|46668516|47232276|47232293|47416650|47437713|47438499|47508122|47508142|47508481147593501147996924| 47997433|47997632|48471981150333297|50333644|50977442|51330709|51990747|51990757|52142795|52633576|52703398|529215311 52921758|52927362|53062265|53738828|53945344|54199760|54200264|54200271154542063|54542568|54716179|54801259|54887044| 54980714|55039507|55039670|56477658|56579546|57423932|58249881159147038|59814831159815044|61043181161043252|61057044| 61057340|61076965|61742516|63317309|63317317|63317399|63317496|63322257|63322753|63773939|63773947|63773960|63774517| 63774531163774983|64469923|64470174|64470915|65002976|65003132|65147611165147722|65148831165254697|65266006|67307492| 67307721167685246|67832246|69567909|70410915|75131142|75135591175616277|76074425|76074463|76867437|76867474|76868385| 77683711 |77888697|78046172|78046445|83998962|83999467|84077686|84077691 |84078414|84298595|84299021 |84893285|84997129| 84997270|84997681 |84998317|85048206|85048209|85048451 |85062196|85201287|85308380|85464623|85464793|85465182|85577049| 85580829|85580887|86156869|86395975|87151667|87331325|87331440|87331633|89198899|90707213|90710986|90711130|90717962| 90851268|90851691 |91885490|91886125|91886129|91886527|92030261 |92080331 |92298862|92299276|92484256|92484529|92785315| 93681905|94237523|94237611194237616|94237620|94247662|94541987|94542017|94820234|94926569|94927122|94927126|95073096| 95117269|97920879|97920896|97921127|98045475|98323979|99969754|100539378|103525496|103525499|107057390|107141437|107 141633|107965445|108661050|108661546|109113655|109113698|109114086|109114155|109249901 |109509578|109619624|109740213 |1100692011110070775|110083918|110084355|1100848511110150374|110150990|110211465|1106075111110674875|110674953|11078 1086|111204702|111989353|111989456|112619095|113390511 |113390791 |113391318|113871786|114153073|114153840|114154019|1 14670280|115089615|115089955|115099529|115828566|115976149|116667325|116667710|116910262|116910283|117121966|1176069 48|117754170|118987977|119001447|119008360|119647927|1196485011119712222|1197124811145961388|146052038|147084692|147 243864|147670351 |147670789|147670795|148318690|148844491 |148952178|148952509|149885602|149886791 |149887554|149887906 |149917778|1500104511150010453|150010883|150010895|150067032|150149826|150236317|150282028|150282427|150282458|15029 3774|150293893|150294184|150876684|151058810|151058845|151131527|151146734|151165850|151540231 |151763779|151791072|1 51791390|151909498|151909667|151909808|152515433|153634186|153679646|153679771 |153958698|154502663|154760517|1549552 33|155000926|155003555|155062899|155062912|155078680|155080261 |155082121 |155127298|155127602|155139996|155243923|155 277400|155859639|156066520|156081699|156114607|156114725|156114868|156114959|156161035|156245864|156421518|156435703 |156677444|156705622|156752414|156814080|156814152|156924000|157993658|158113685|158181573|159780652|159781041 |15985 4748|159855076|159855203|159945779|160031649|161068716|161153908|161154366|161258706|161314128|161726385|161727451 |1 62023752|162023955|162024180|162069712|162561383|162561913|162822579|163321703|165117629|165356436|165630933|1656312 33|165698807|165768596|165768762|165768850|165769096|166165109|166975593|167220609|167455384|167629887|168136154|169 485894|169485900|169485938|169486083|169486171 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[0204] 37

[0205] CAN DMS: \1015053120\1539180|201739708|201740007|201740208|201740262|201888819|201955894|202160127|202342080|202710376|202808167|203007949 |203026948|203128234|203487748|203629445|203629466|203629495|203629961 |204073142|204151819|204152372|204190704|20437 8022|204685282|205043221 |205043321 |205211674|205228717|205321253|205430817|205456509|205569299|205680733|205812971 |2 058131211206117326120611773912065073871206508045|206557838|206635184|2070532711207454256|207911070120791109112079634 52|209756201 |209756782|209784840|209806253|209938058|210234139|210234211 |210292827|210328592|211382567|211382626|211 382656|212035761 |212606901 |212608110|212608770|212699337|212700621 |212950623|212951554|213987908|214551968|215567354 |215567358|215567839|216601335|218285143|218347126|219928383|220527979|220528883|220690454|220879237|220879363|22087 9387|223143134|223712991 |224114883|224330577|224435153|224616524|224618051 |224929974|226223558|226224117|226548704|2 26549010|226549640|226550118|226871053|227318318|227318825|227728419|227948057|227948426|228082782|228109391 |2283788 59|228445759|22845776112284577811228457811 |228457987|228458523|228459245|228459269|228464007|228735064|228735120|228 735138|228735556|229626785|230425504|230425947|230426676|231039529|231040232|231240878|231337786|231626492|232629671 |232630508|232805507|233328287|233328448|233904649|234963342|235367537|235649540|235649972|236065298|236141595|23614 1710|236395165|236395396|236395574|236604310|239386326|240092186|241357298|241423934|242524779|243850425|243917567|2 44653920|244919018|245154648|245154669|245154907|245154943|245155033|245155515|245156714|247008020|247008128|2471121 87124785707512488378821248858473

[0206] chr2:

[0207] 46043|264164|264166|264178|264199|264204|1743074|3303746|3377713|3377807|3378170|3558550|6917534|6917814|8678196|86787 73|8681928|8685243|8837453|9003879|9004117|9143011 |9206088|9206463|9207163|10043144|10122695|10448928|10721578|107221 79|10832589|11345287|11688632|12716500|12716591 |12717526|15939799|15939861 |15939999|15940379|15940493|17518473|178308 83|17877933|17879223|19351989|19352099|19359047|19863543|19902305|19990067|19990319|19990321 |20012662|20012748|200127 56|20012763|20012836|20012839|20224565|20225223|20225485|20225563|20446759|20447612|20666085|20666471 |20666482|206665 01 |20666647|20666740|23351678|23385080|24009995|24010019|24010104|24049581 |24049674|24050058|24793469|24972273|250419 12|25273521 |26184874|26693024|26847882|26848047|26970720|27032814|27051515|27123660|27123723|27123725|27263099|272631 93|27380939|27489688|27489746|27489763|27489824|27495422|27629364|27771584|27890459|28390895|28810486|291152111291152 34|29115247|29115392|29115566|29921681 |29921700|32277954|32946935|36356878|37157238|37390458|37672212|37925149|380757 49|38076244|38076330|38076689|38076857|38076924|38077047|38077375|38377300|38536212|38536391 |38602034|38602814|386031 34|38778122|38875572|38960392|38960402|39666045|40452379|41841037|42102306|42169302|42494911 |42792873|43637107|438319 55|43996100|44952648|45004243|45009128|45168681 |46297220|46297224|46617390|47272382|47403648|47569994|47570824|477825 91 |47782670|48440392|54456185|54456997|55232497|55232599|55282643|55924004|56184073|56184399|56184925|56184942|561858 99|58428929|58428970|60570078|60735727|61538345|62505979|63047722|63050809|63054004|64750156|66425746|66435453|664399 69|66440417|68319447|68319920|68320009|68643680|68643760|69012979|69012982|69012992|69013063|69013065|69013974|693066 47|69306823|69648338|70553252|70554124|70554170|70768002|70768217|70768219|70901408|71130183|71227150|71276610|721450 38|72862646|72887831 |72887882|72916164|72916192|72916405|72917515|73112879|73176045|73203246|73293648|73293961 |740026 48|74198453|74498079|74503139|74516310|74529258|74654083|74654165|74834978|74919999|75199660|75199663|75199674|755610 86|75561105|80304472|84880627|85133478|85577609|86036101 |86106083|86195835|86337313|86337762|86337821 |86440643|867196 92|86791259|86808565|86808587|88055539|88451886|88452538|88452804|88692061 |95025755|95026010|95159533|95207525|953455 73|95346216|95346580|96116704|96209003|96508256|96538664|96637438|96870165|96870550|98086970|98086987|98346671 |986091 99|98936170|98936274|98936364|98937179|99559306|100142697|100321982|100322337|100322351 |100322441 |100820461 |10082046 5|101002104|101387316|101387623|101475145|102355598|102356298|102618952|102619261 |104856882|104872474|105399061 |1053 99070|105399360|105746260|106886221 |108719247|108786837|109129158|109129192|109129356|109129372|109614326|110115908| 111122429|1111224411111899052|112584493|112584524|112584664|112645103|112764630|118088307|118224172|118224207|118310 177|118774654|118843372|119223708|119223758|119432046|120012895|120013114|1200132311120343640|120345453|120345784|12 0346824|120347283|120695813|120736231 |120736238|120736467|120736719|126656532|126656879|126776900|126777223|12677760 9|126886395|126972184|127025667|127081963|127219037|127220273|127408431 |127526555|127526578|127674950|127675583|1283 17624|129923411 |130356157|130391535|130727913|130756132|130756151 |130797897|132670929|134718401 |134718727|134719131 | 134719323|134918074|135530329|135876525|135985890|136118618|136765390|138501583|138501593|142131464|143128757|143937 113|143937511 |143937690|147843827|148888229|149038455|149038848|151410068|152098136|152098692|152099136|152099235|15 2099251 |152099580|152176156|152335010|152335213|152336018|153478834|153478854|153478872|156332796|156332804|15633299 8|156333243|156435899|157628903|157629014|157629029|157629059|158456885|159287023|159904314|160062636|160407862|1604 93818|161238356|161418957|162074156|162318893|164841468|165794295|165794372|166376135|167293009|168456177|169361840| 169362180|169363732|169825021 |170714567|170715345|170716353|170770485|170770770|170771211 |170771280|170816389|170816 762|171922505|172085368|172085392|172085397|172090784|172235369|172736259|173075702|173075704|173075833|173076317|17 4335100|174336334|174395973|175005079|175005103|176080394|176086461 |176097492|176119087|176140670|176140675|17617806 11176189578|176269332|176269367|176269513|176269541 |176269579|176270009|176637656|177392831 |177392857|177392862|1773 92998|178072818|178072871 |178193971 |179861520|179861601 |181457541 |181457552|181457774|181656801 |181680806|181680828| 182522774|182522789|183038200|183038661 |184598856|184598861 |186485788|186589687|186589863|186589886|186590020|186694 068|186694070|186694154|189580348|189580751 |189661149|190180583|190180704|190180837|190180942|191150663|191151027|19 1151033|191245264|191245269|191245839|191245932|196172056|196592706|196593322|196593369|196593380|196639929|19692621 9|197453306|197500886|197515515|197705915|197804389|197804615|197805024|199456148|199456288|199457021 |199457311 |1994 59507|199459945|199851207|200585852|200585878|200963027|202238862|202871143|203014720|203014930|203535059|203535436| 203535471 |204545385|205681936|206274721 |206274747|206443520|206765210|207166008|207770999|208025737|209423816|209424 243|213284252|215435876|216013224|216081750|216082122|216372062|216372276|216372313|216372317|216633167|216692179|21 6692437|217756597|218010293|218216824|218292633|218292684|218368024|218671843|218672281 |218859681 |218871590|21888051 11218898337|218909164|218959602|218959607|218984413|218984467|218985401 |218993071 |218993205|218993525|218994089|2189 96290|218996308|219001790|219002930|219060526|219060538|219060589|219160990|219218780|219218974|219218979|219245663| 219253223|219253551 |219254517|219435018|219435387|219442190|219484486|219498906|219498910|219514274|219541748|219541

[0208] 38

[0209] CAN DMS: \1015053120\182112195440711219570784|219571116|219597496|2195979511219597959|219627464|219627835|221571779|2215723611221572369|22 1572410|222291122|222295119|222297175|222424841 |222656142|224038652|224038676|225041024|226423802|226791341 |22679887 7|226798953|226799005|227164025|227164058|227164060|227164717|227718081 |229271213|229713992|229714201 |230067077|2308 65494|231037701 |231053123|231530350|231530597|231530615|231781748|231927104|232503405|232633247|232633454|232633513| 232633915|232876374|232928378|233060003|233060079|233854667|233854801 |234497324|234951772|234951799|234951805|234951 891 |235669603|235669607|236178348|236236794|237475716|237475763|237691418|238158958|238239491 |238239978|238240056|24 0136595|240136865|240435302|240435306|240435965|240585975|240586236|240819484|240819997|240820747|240820773|24099874 2|240998749|240998762|241149470|241149472|241217805|241273055|241314755|241559234|241803799

[0210] chr3:

[0211] 2098006|3126641 |3179911 |3799446|8501658|9302757|9810163|9844117|9862873|9915775|10164729|10164839|10249213|10505542|1 1060921|11154759|11272443|11272477|11719986|11770563|12288246|12484309|12968009|12993851113479664|13650669|13650712|1 3878314|13880306|14124836|14124863|14178547|14178829|14402675|15427535|15601572|15860482|16264548|16338456|18445466|1 9147964|19148259|23203199|24494586|24495389|24495669|24522006|25428082|26622794|27369539|27369574|27484388|27484393|2 7712900|27721775|27722374|32106531 |32106548|32107090|32238230|32816788|32817915|32818095|32818512|33277344|33277532|3 3277727|33798511 |36992855|36993163|36993202|37452454|37452458|38029675|38030007|38039434|38347108|39107744|39153863|3 9809293|39810150|39810297|40387147|40477307|42013378|42263474|42502528|42502568|42502575|42654360|42773400|42979299|4 2979301 |43106079|43106220|43622170|43690833|43894540|43894601 |43995636|43995697|43998714|44022101 |44555192|44555278|4 4624998|44729610|44729621 |44761262|44762146|44861696|44861699|45167695|45167704|45689225|45689425|45796545|45796582|4 5796591 |45796602|45841889|45842037|45842201 |46464802|46488785|46566109|46693505|46693519|46693829|46882056|46883466|4 6892482|46979636|47476200|47802821 |48087698|48503946|48662904|48662942|48662958|48663065|48847893|48847899|48847905|4 8918263|48919502|48989792|49120478|49166076|49412109|49412115|49429152|49554209|49719303|49719873|49723818|49856670|5 0089001150259956|50275482|50299410|50341180|50341233|50351228|50502830|50503249|50503647|51942411151967979|52154709|5 2154752|53130591 |53156693|53160712|53346776|53495360|53846351153891271153891804|53892008|53892257|54123326|55481140|5 5481513|55482683|55487113|55487323|55488273|55488603|56468237|56468265|56468666|56468719|56801801 |57079217|57165394|5 7693278|57757131 |58008119|58008304|58009214|58177768|58238474|58306096|58434090|59050003|61564705|62875467|62875470|6 3913058|64688247|66038817|66038881 |66038886|66500494|66501117|66998093|66998153|69386188|69541485|69542652|71064965|7 1754407|71785489|71785555|72847969|72848611 |84958954|84959005|86990537|86991119|86991490|87227233|89107645|96813180|9 7764627|97764747|97822219|97822601 |97972252|97972548|98734096|98901726|98901728|98901791 |98902013|99817465|101561702| 101574042|101779354|101779372|105367299|107430000|107432062|107927895|111071760|111071920|111859600|112086230|112333 144|113211935|113212279|119034858|119034860|119579573|119579666|11970302111198103111121660930|123027572|123066907|12 3201660|123201863|123448923|123884459|123884461 |123884464|123884608|124887151 |124887337|124887654|125142027|12635740 0|126357523|126357632|126358014|126389568|126524282|126524442|126524453|126654979|126655124|126655137|126679318|1267 04710|126982364|127455638|127629135|127629312|127823099|128489173|128493426|128680712|128681311 |128879348|128994214| 129278509|129440347|129605856|129605874|129974646|130746795|131381869|132035014|132035168|132722010|133895593|133895 734|133895954|133895960|134029965|134651132|135965624|135966289|137764221 |137768344|138115740|138329560|138329828|13 8329886|138348508|138348560|138348562|138348567|138434515|138594208|138608677|138947142|138947198|138947206|13894720 8|138950089|138950295|139343861 |139677682|139934703|139935073|139935403|141051171 |141051464|141051681 |141051707|1410 51775|141051841 |141231392|141231756|141231986|141659935|141876813|142225476|142596365|142596378|142596724|142724073| 142724405|142724415|142724498|142889097|142889139|142889209|142963446|142963810|146160644|146250909|146250913|147359 340|147406576|149086763|149657506|149658253|149658255|149658530|149752123|149970118|149970725|149970796|150545566|15 1085508|151086271 |151086703|152835088|152835272|153163296|154121141 |154121211 |154121326|154324236|154428079|15508012 8|155080158|155080169|155744056|156675983|156826281 |156826286|156826289|156826292|157160815|157543317|158098019|1581 06420|158571083|158672547|158801777|158801838|158801844|159763387|159764802|159988751 |159988756|159988790|160039142| 160225533|160449958|160450001 |160755241 |161105123|161105443|161221122|161372242|168094965|168095663|168095679|168249 994|169146313|169146323|169146525|169147301 |169149624|169658682|169661766|169668719|169669351 |170908693|171459531 |17 1460597|171461174|172448727|172523279|173395586|173398304|173585403|174441090|180036745|180036815|180037298|18060205 2|180602102|180679514|180679538|180679548|180679554|180679706|181696233|181711866|181726724|181727201 |182793302|1831 62689|183179408|183253139|183253221 |183253875|183254260|183254538|183556019|183884874|183885143|184018015|184134968| 184230270|184230467|184230525|184261090|184492313|184525298|184525399|184525623|184561548|184561627|184561710|184561 740|184561805|185153105|185499082|185499095|185823488|185823662|185824047|186109152|186109504|186362456|186617305|18 6617336|186931812|187139530|187139687|187139805|187368399|187739528|187739732|187739926|187739944|187746056|19032246 1 |190513593|190514461 |190514469|190862846|191329269|192409171 |192409567|192918329|193241179|194058303|194633531 |1946 85745|194687787|194688116|195748096|196318467|196431733|196942757|197456482|197510283|198080484

[0212] chr4:

[0213] 336862|337330|337549|337821 |473685|577582|826139|826968|973644|973672|973679|973751 |986816|1010322|1010853|1011245|101 1278|1011596|1011613|1012206|1012216|1012228|1012332|1012482|1347095|1410658|1748647|1767832|1793513|1793524|1794415|2 009997|2041562|2041987|2042133|2042246|2042329|2058586|2059207|2059291 |2059598|2059780|2060203|2242215|2242611 |241853 3|2764195|2764408|2793618|3073757|3766370|3871691 |4248324|4248358|4290082|4290377|4386190|4387782|4387993|4852963|4853 621 |4856755|4859603|4865375|4865437|5887605|5888631 |6199703|6200654|6200657|6269758|6269785|6269830|6269905|6471330|65 74858|6640832|6716736|6716821 |6909228|6987608|7068058|7068116|7068905|7192792|7940037|8159366|8269687|10019010|104569 07|10457043|10457595|10461279|11428823|13522417|13539322|13544545|13544586|13544858|13547870|13547872|15003839|150050 10|15778683|15779472|16084191 |17577649|17781419|17781638|17781699|17781708|18022010|20251654|22515436|24584495|250308 50|25312792|25655208|25862696|26320706|26857306|37453719|38319140|38664741 |38867641 |38867650|38867815|39459052|394595 98|40200323|40749828|40857232|41214017|41214254|41214462|41360380|41881591 |41990328|41990345|41990543|41990604|421516 91 |42397686|42397775|42397781 |42397826|42397834|44448945|44449043|44449060|44677936|44726625|44726630|44726722|469936

[0214] 39

[0215] CAN DMS: \1015053120\120|48270065|48483552|51844883|52038213|52038404|52051373|52051375|52712386|52862343|52862487|54064545|54099696|541008 51 |54217676|54227445|54228170|54228332|54231963|54234101 |54657978|54658166|55636225|55854061 |56049163|56049485|565057 02|56505761 |56821673|57110590|57163796|61202581 |65670478|70688282|70839167|71187081171187157|71187207|71187323|725684 92|73620462|73836731 |74039073|74365227|74932927|74933059|75630593|75630672|75630858|75941114|75941272|76251490|763063 36|76306468|76306475|76306478|76689450|76898381 |76949685|76950217|78057411 |78057543|78058053|78551785|80202967|802033 30|80266456|80335657|80335696|81030799|81069948|81215669|81215685|81472024|82798755|83535858|83536305|83536316|835363 46|84498341 |84498377|84582876|84582898|84583238|84966616|85475284|86594547|86892432|87006823|88007389|88008506|881590 27|88159039|88457309|88523283|89110818|89837646|92303836|94451685|94452725|94757666|95548368|95548483|95549992|984678 42|98658970|99946942|100190715|105146409|105146607|105708808|105708895|105895613|105896535|106316845|107036205|10703 7334|107825119|107931365|107931399|107931411 |107931495|107932230|108762663|109302811 |109302813|109559927|110198583|1 10618196|110623115|112145592|112515076|112515469|112516753|113760724|113761457|113761729|113762020|113762126|1145983 60|114598916|118278576|118888816|118888820|1188889111118888937|119212227|119212412|119212506|119212508|119212536|119 212649|119212766|119213427|119300845|1193008511119627434|1196281011119628685|119629063|120922052|1209230211121072937 |121380585|121696852|121697222|121697346|121765164|121765301 |121823497|121870558|121951212|121951841 |121951863|12195 1992|122732763|122922626|123397368|123398251 |123398807|123505768|125314851 |127632757|127632992|127782025|127964980|1 29093832|133146835|133148081 |133148149|137532348|138242381 |139279569|139453667|140151472|140154214|140154250|1401543 61 |140373392|140427708|140427796|140568809|140568943|140569197|141133625|141133664|141636429|141636512|141636889|142 846492|143559391 |143559405|143559408|144645823|146522326|146522510|147684473|147732292|147732766|148442760|148444190 |148445761 |150078395|150078747|150078753|150078759|150078771 |150078797|150078932|151099788|151409185|151409187|15140 9197|151761290|152680197|152936971 |153466276|154491525|154550567|154627024|155208573|155376464|155376702|155376706|1 55376850|155666920|157076026|158672154|158769580|163165857|163167014|165327067|165378862|165378865|165378899|1653791 00|165873634|165873819|165874108|167233973|168480566|169010648|169612230|170026244|170026628|170090276|171813356|171 813692|173538261 |174522646|176001930|176002391 |176002393|176065636|176195582|176195675|176195684|176195790|182141307 |183099108|183099299|183407169|183722864|183905171 |184168559|185005466|185019815|185021592|185128533|185143494|18520 4286|185471592|186104732|186104743|186190786|186190887|186190991 |186191365|186191369|186191383|189202452 chr5:

[0216] 54013|1008713|1008743|1111616|1111748|1111995|1112136|1801028|1876223|1877021 |1883400|1883826|6378654|6378693|6448977| 7395889|9544670|10250050|10307632|11384955|11903998|11904330|14108672|14581420|14581833|14871801 |15500140|16465779|16 935586|16936282|16936710|17216570|17216813|31193737|31193901 |31638832|31638844|31639592|32709195|32709828|32710125|32 710350|32711249|33936127|33936187|33936202|34656455|34656458|34839105|34839247|34915007|36606693|36745009|37371453|37 839821137839987|38257439|38556333|38556983|40679063|40679747|40680448|40680568|40681791141925114|42424502|42952011142 992896|43121484|43192138|43192326|43397130|43557419|43557649|44389746|50964211 |52787759|52788113|52788221 |52988955|52 989079|52989730|53109661 |53109664|53109676|53109688|53110015|53479872|53480514|53480800|53482611 |53482915|55176429|55 176742|55220977|55233398|55233931 |55233959|55535291 |55712284|56814436|58460117|58460197|58460199|59039029|59039353|59 894107160843881160844111161332191161333064|64506445|65721554|66596199166596259166596262166596271166596281166596359|67 004047|68288386|68288390|69093903|69217523|69493114|72955499|72955908|72956053|73216364|73448143|73498254|73565886|73 625828|73625983|73626072|74640228|74641474|74641476|74641503|74866398|74866796|75053078|75237027|75237069|75511864|76 082277|76715313|76716097|76716421 |76716766|76818987|76818997|76849984|76953951 |77492462|77628163|77638868|77972507|77 972910|78648520|79236089|79513920|79514544|79991304|80407833|80487901 |80570176|80960347|83471631 |83473211 |83474621 |84 384901 |88675976|88676238|88676309|88680750|93602526|93620844|93620973|93621120|94618891 |95284430|95285326|95555106|95 731112|95731432|95731993|95962088|96662283|98768359|98773040|98773662|102295801 |102296467|102296623|102296668|102755 000|103120237|103259695|107671425|107673507|108748289|108748975|109410606|110738594|110739099|111070808|111073212|11 1073218|111073299|111224066|111224474|111224674|111512408|111512482|112418106|112419735|113293868|114055642|11436163 31115170069|115180239|115180618|1152964711115601838|115816788|115816795|115816797|1165747711116574896|116575036|1165 75772|116576251 |116576324|120464167|120464169|120465736|122077275|122774858|122845054|122845099|123036784|123036786| 123037027|123037033|123088364|123089730|123090007|123090705|123512050|123512057|123512559|124651730|126423130|126423 599|126594975|126595309|127030093|127030772|128537859|129094210|129460386|129460404|129460475|129461614|131797646|13 2011863|132227811 |132228089|132257568|132294443|132294482|132294519|132656422|132777474|132777499|132813271 |13281328 6|132813321 |132866675|133026394|133026886|133612526|133612560|133612565|134526104|134632946|134737889|134905414|1350 31409|135536117|136132945|136193266|138274438|138274537|138274566|138439269|138465654|138753967|139439096|139711427| 139748116|139756250|139764470|139848477|139848565|139848568|139904096|140043040|140043244|140114421 |140146072|140174 930|140174984|140175424|140547525|140547579|140547582|140547594|140547886|140564530|140647796|140664397|140664653|14 1094550|141407940|141475915|141475980|141638108|141651555|141651558|141651575|141651580|141651642|141849426|14185042 2|142325144|142325791 |145835416|145835418|145835430|145835492|145936538|145936647|146878299|146878626|146878632|1468 78674|146878791 |146878864|146878900|147234830|147234841 |147454102|148826661 |149141512|149271796|149271800|149345290| 149357976|149581268|149581303|149581441 |149581444|149581448|150412686|150412767|150412900|150412952|150449954|150485 866|150624833|150624946|150672452|150701331 |150778496|151158004|151447388|154038365|154038766|154038838|154038852|15 4039058|154039061 |154039233|154405292|154475793|154478264|154479262|154480180|154482623|154482834|154610554|15494097 9|157460121 |157671415|157671537|157743432|159100455|159100565|159106934|159263238|159773669|160008966|160008979|1603 11794|160312824|160312844|160370611 |161547831 |167573707|168291977|168292257|168486314|168486341 |168486529|168529301 | 169301266|170333265|170862634|171309017|172454753|172454767|172958875|173228922|173229163|173234967|173245956|173888 148|174045714|174045729|174312138|174419554|175478417|175478849|175658242|175796979|175797560|175872584|176365451 |17 6365475|176365490|176365495|176365507|176388571 |176537268|176537615|176630426|176630464|176743373|176743477|17681038 0|176810980|176817739|177351671 |177352050|177352088|177425890|177517155|177591949|178280100|178730771 |178859880|1790 23762|179023881 |179060381 |179060383|179060409|179344775|179344780|179345202|179345371 |179795638|180591564|181053234| 181184441 |181191016|181204909|181243110

[0217] 40

[0218] CAN DMS: \1015053120\1chr6:

[0219] 391764|393239|475074|1312240|1312276|1607825|1609962|1610434|1611477|1624743|2903024|3023364|3156890|3227517|3227715|3 229145|3232012|3456206|3457885|3750965|3751384|3751505|3752187|3752199|5851411 |5997010|6002533|6004095|6008778|738966 2|7541323|7541614|7541893|7590045|7726116|7726412|7726734|7728655|8435693|10404130|10413000|10414844|10419694|1042640 4|10886766|11043873|11044308|11044325|12290340|13486786|13924811 |15663237|16128702|16760943|16761437|17281571 |1798700 1117987426|17987476|17988173|18122714|20212442|20212747|20400959|20400987|20401377|20401565|21596565|21596728|2412610 2|24360163|24402915|26020444|26032053|26156999|26189006|26189182|26199946|26204482|26240554|26250119|26250122|2625045 7|26313046|26537724|26550555|26614307|27096990|27132814|27133854|27157721 |27238724|27312644|27388911 |27472703|2747320 5|27479592|27687895|27694035|27810029|27810298|27838456|27838476|27838615|27865343|27867585|27893157|27893229|2789330 0|28124642|28219019|28219046|28225201 |28225302|28267065|28399794|28542905|28587302|28589709|28634849|28635077|2863515 0|28635181 |28635193|28648863|28709495|28810347|28825677|28837631 |28838859|28839079|28863760|28863958|28863962|2886408 1128864109|28864276|28866730|28922905|28940846|28988733|29011578|29016806|29016894|29017126|29553791 |29553825|2972335 8|29723468|29723949|29723958|29723978|29723983|29748759|29748777|29748791 |29748820|29748824|29748860|29752908|2975291 0|29753224|29792992|29793046|29976728|29976994|29977071 |30006938|30006946|30075203|30075208|30075272|30075318|3007532 0|30075329|30075516|30100810|30100890|30102020|30102024|30102282|30103283|30103290|30171761 |30213936|30214070|3021439 5|30259549|30259583|30259952|30259955|30260006|30260023|30450804|30451131 |30481395|30490381 |30516105|30516109|3054180 8|30555663|30571286|30683067|30684622|30686970|30686974|30717162|30744086|30884796|30884922|30914317|30914581 |3140377 3|31403776|31403787|31498099|31498181 |31729944|31740255|31815184|31815220|31862629|31862839|31898370|31901524|3208762 5|32087740|32087748|32130392|32130470|32130476|32154060|32413754|32838848|32845767|32853844|33009803|33161896|3319337 1133248687|33249383|33249406|33249494|33249509133277351133277386|3327773913328879713330001113330002113331274113339186 5|33410071 |34465936|34465977|34465998|35214147|35687987|35689071 |36027902|36593606|37171766|37696675|38640330|3864033 2|39229457|39229641 |39229650|39313645|39313674|39313918|40587992|41470170|41503935|41546361 |41638701 |42771229|4289090 9|42890961 |42984176|43077033|43171942|43243573|43247112|43269592|43285120|43477495|43576309|43635686|43687927|4377026 9|43770703|44219315|44561344|46015850|46129655|46129704|46130047|46170793|46491251 |46491487|46652910|46652924|4665292 9|46653041 |46653198|46735246|46735485|46735488|46735495|47309154|47309587|50724539|50840986|50844011 |53349005|5354458 8|53545055|53545058|53545080|53548005|53548174|53651909|54846631 |56542740|56542927|56844233|56954825|56955114|5695528 9|57172157|57172294|68635174|69866631 |69867306|70412978|70413209|70413301 |70413493|70413587|70566758|70955692|7095623 3|70957100|71288682|71420844|71886432|71886588|71886769|72621386|72621924|72623157|73309930|73310295|73389089|7345137 6|75749360|75935073|77463510|78867352|79630933|79631566|79869820|79947171 |79947256|79947698|80106500|80106506|8010671 7|81752743|81752748|81752860|81753029|81753306|81753588|81754059|82248034|83066011 |83853173|83853211 |84763520|8544996 4|86937652|88166121 |88167582|89117925|89819849|90295213|90295443|93419516|93419918|96837529|96837786|96837867|9883486 0|98835325|98835428|98848192|99349966|99588920|99602894|99602936|105137304|105180142|105180147|105981441 |105981568|10 5992087|107824216|107824335|107824454|108115315|108118307|108133974|108163839|108168773|108175512|108261434|10855840 71108560916|1085609811109381526|1096913711110982279|111087560|113854809|1138570411113857316|113857322|113857328|1138 58997|116254176|116616314|116877022|116877059|117907330|117907706|118650518|118650644|119078155|119078760|119078763| 121334646|122610270|122789453|122789596|125154182|125748026|125748077|125749239|125749316|125749572|126340128|126340 482|128519992|128520810|128520824|128520868|130019711 |130365552|131062747|131063467|131063524|131135640|131136006|13 1807873|131807897|131807904|132401176|133240728|133241058|133241198|133889976|133891795|133891831 |134175203|13549845 8|136250581 |136289776|13654995111365505711136792926|136793105|1369220811136922248|136990150|137044593|137044624|1374 98130|138107494|138107603|138161566|138161570|138404419|138773313|138988546|142088924|142301671 |142926635|143450484| 143511439|143511718|144150061 |144151218|146857633|147203705|147506807|147508663|147508907|148559990|148747728|148747 838|149482308|149546471 |149567237|149718400|149923256|149938794|149941627|149941635|149941899|149941934|149964498|14 9990169|150005596|150068878|150069054|150069172|150142829|150142854|150142884|150142988|150866945|151494106|15168183 4|151807402|152636860|152637029|154510636|154510640|154995246|154996108|156776985|157323897|157823236|157823654|1579 81492|158643986|159969797|160767542|161274271 |162727469|162727745|165885032|165988212|166168718|166168822|166253534| 166307667|166383770|166383779|166383805|166626952|166627187|166862346|166862355|166862511 |166862787|169253923|169702 793|169790027|169790033|170290745|170290773|170291474

[0220] chr7:

[0221] 149290|193580|519339|519363|815938|876194|1044274|1459230|1459421 |1667600|1743119|2354724|2403275|2403287|2521395|2688 131 |2688710|3301228|3301347|4775321 |5297082|5420865|5421681 |5421849|5425176|5425244|5495090|5555625|5592620|5592631 |55 92638|5592641 |5781674|6448118|6503483|6526693|6526797|6536898|6664077|8261486|8262030|8262063|8433755|12210891 |122111 34|12211574|12570570|12570758|12686804|12686806|12687167|12687188|12687316|12687319|13990502|13991182|13991385|167544 53|17298754|17299404|19118943|20778239|20798159|21543127|21543140|22356677|22356791 |22357018|22357025|23680232|236808 35|24757483|24757744|25180429|25857104|25951186|26291826|26291868|26292082|26376281126398791126864821126864836|268648 51 |27096127|27096572|27156534|27165581 |27165598|27166039|27174365|27184504|27184692|27185909|27242689|27246456|281808 95|28410228|28854306|28926843|28957869|28958462|29146537|29195371 |29563595|29563711 |29564405|29685529|29685534|299896 15|29989622|29989774|29989826|30026956|30028468|30134615|30134969|30682704|30682711 |30682743|30682745|30771612|310521 03|31052198|31052210|31336247|32299338|32728244|32942968|33905023|35037994|35038094|35038113|35038143|35038155|351869 12|35254142|36153226|36153735|36291724|36367579|37921300|38631357|39609760|42228120|42228148|42237217|42237220|422372 49|42237382|42237748|42237776|42237811 |43869916|43926019|44325430|44325717|44582359|44582448|44582824|44797434|449790 59|44979406|45089176|45157747|45574691 |45922173|45922453|50303765|50468136|50793352|51315964|51316822|51316882|545423 29|64888777|64889179|64947753|65269796|66044395|66205254|66205487|66493680|66493996|66628362|66654864|70596078|705961 49|71752335|73433719|73624558|73647952|73648088|73667620|73667647|73667726|73682928|73719340|73719652|73719763|737197 81 |73770287|73770292|73770326|73770341 |73770704|73770706|73842549|74002867|74209989|74453597|74453773|74453784|744538 21 |74454540|75074056|75486390|75639108|76047400|76166613|76178193|76201876|76201887|76201892|76201914|76202219|762818

[0222] 41

[0223] CAN DMS: \1015053120\108|76549227|77415924|77695891 |77798742|78019250|78019283|78019307|78019860|78020223|79453331 |80134975|83162968|874756 16|87475900|87600236|87601028|87628040|87628222|87628357|87628470|87876415|87934147|87934180|87934258|87934334|879346 16|87935030|88306910|90211900|90212121 |90403221 |90597136|91265712|91880779|91880870|91880884|92134119|92134597|921346 93|92134759|92134872|92246101 |92247060|92590510|92833537|92833947|92836548|93890712|93890762|93921963|94655553|946555 88|94655605|94908035|95434913|96322249|97117616|97117733|97872176|97872424|98869948|99465801 |99616609|100081755|10008 2655|100088668|100088736|100569941 |100612011 |100612017|100633158|100895744|100895879|100895901 |100896228|101085450|1 01165529|101165612|101173459|101252284|101362808|101363682|103446027|103989108|103989566|103990102|104328347|1043287 18|105522288|105522412|107661919|108001999|1080035011108003503|1080035111108569197|108569855|112790559|113086494|114 085413|116210322|116210387|116210396|116499574|116499795|116524713|116524823|116526160|116526367|116672211 |116672219 |116672237|116953312|116953602|116954015|120857944|121330186|121873890|122144048|122144332|122886780|122886782|12288 6789|123533141 |123534545|124032136|124764768|124765706|127391570|127588168|128032182|128032511 |128032605|128104158|1 28104337|128167779|128455520|128830545|128830560|128862597|128937860|128937862|128937867|128937872|129780384|1297815 13|130734282|130734297|131107846|131558203|131945559|132576659|132577594|133082282|134127187|134127278|134459284|135 662337|135980934|136869031 |139035829|139036057|139133503|139231287|139483705|139483735|140398660|141014947|141014981 |141015119|141073778|141074105|141074361 |141551639|142796911 |142797022|142797060|142797230|142855395|143345542|14340 9037|143902176|144835366|144836378|146115916|148698089|149239481 |149423175|149461007|149715199|150716592|150898583|1 50978428|151051197|1510579511151080784|151167900|151167907|151245872|151277187|151341574|151440076|15151831111516318 38|151876507|151876828|151876859|151877677|152025376|152025729|155190762|155205651 |155345227|155374816|155375149|155 375543|155453779|155456953|155510204|155805148|155812398|156640606|156640623|156640656|156640673|156999951 |157000156 |157005887|157009629|157010884|157018823|157691867|158704862|158977244|159143940|159144415

[0224] chr8:

[0225] 738132|6800886|6835603|9903367|9903370|9903661 |9905753|10054126|10054159|10054250|10054255|10054478|10054795|10055122 |10730259|10730503|10734123|10928640|11016705|11059514|11200886|11201520|11201529|11201768|11201794|11347738|11693063 |11704111 |11808508|11986462|12951911113133401113566675|17027040|17027046|17027067|17576951117801050|17801052|17801338 |17922659|19013483|19313680|19756896|19757435|22024593|22130634|22156926|22157042|22367882|22551549|22565501 |22565542 |22692291 |23069041 |23069347|23069396|23069398|23103086|23103106|23164040|23403799|23682426|23682875|24959093|25184281 |25184825|25184833|25184959|26045464|26046336|26046754|26047962|26448815|26449156|26449900|26514048|26577775|26866067 |27274850|27311739|27592350|27592530|27614722|27614804|27614868|27633740|27772362|28386527|28490411 |28701756|28890322 |29348835|29349000|29349940|29350107|29350609|29350636|29351291129351355|29351466|29352087|30083405|30096085|30912354 |33514478|37695743|37695769|37695778|37697387|37736361 |37798322|37965774|38467095|38468816|41646559|41653656|41653795 |41767672|42152624|42152915|42271350|43056198|47738183|47738560|48556240|48556268|48556428|52565514|52939883|53251521 |53880435|53880981 |54466474|55879986|56113103|56157454|57343498|57994481 |57994683|60281156|60281431 |60281518|60281552 |60651960|60679380|60680481 |61714765|61714786|63038913|63039238|63039253|63086172|63086219|63168536|63169283|64577382 |64580289|64581544|64798859|65644777|66177153|66428727|66429125|66432353|66774617|66961943|66961971167028541167028588 |67028678|67065202|69833231 |69833501 |69834077|69834133|70669080|70669210|70669220|70669366|71843823|71843920|72075509 |72075681 |72537284|72537289|73295283|73972502|73976833|74320918|74321378|74350347|75407603|75407729|75407909|76682360 |77000090|77000097|77000112|77000354|77000437|78516334|78665889|79784176|79784207|80030084|80873958|80874627|81111694 |81112245|81281225|81780705|85463690|85464048|86342585|89757342|89757918|89757991190645957|90646539|92102819|92965460 |93700383|93700401 |93700582|93754773|93754905|93754926|93755144|93991692|94262338|94640349|94823035|94823085|96145628 |96145787|96157692|96160252|96161107|96495367|96645325|97277920|97869029|97869031197869395|98064506|98944646|10031041 8|100649690|1010807311101080737|102654005|1032988511103501455|1035016811104589413|106270255|106657555|108787374|1096 44945|109644953|109644955|109644968|109974142|115669019|1156690211115669395|118110815|118111812|118111864|118621916| 118622044|118951885|119638950|119874605|120811222|120811242|120811978|120812165|120812179|120812193|120812227|120812 248|121641783|121641805|122781086|123541947|124371938|1244745111124727876|124728395|124973226|124998536|124998763|12 5432009|126558260|126558478|127735508|130358083|132480229|132480924|132481177|132481187|133074976|135457237|13545734 2|135457537|139704430|139705799|1414154811141415536|14245147111424515611142453275|142475388|1426144611142614466|1426 14772|142727022|143160612|143291099|143291107|143368763|143407688|143421637|143429872|143430830|143609578|143684327| 143733479|143733737|143733893|143734040|143734152|143815390|143815406|143815969|143840716|143878459|1439390811143939 742|143973545|143977323|144051398|144082336|144327326|144337826|144428624|144529175|144529177|144529205|144685857|14 475576011447876661144852898

[0226] chr9:

[0227] 841436|841559|841636|1052046|3181659|4297626|4298749|4299549|4490315|4666477|4666499|6645468|7799961 |14693084|1469350 6|16871108|23820981127573891133001305|34379716|34637481 |34701534|35096061 |35102906|35162154|35829208|36036738|3640011 4|37036497|37037529|66900691 |69672905|69673182|70412946|70414472|70419869|71769387|75890746|76394517|77909455|7829692 5|78297142|83063336|86946260|87497615|87974615|88387985|89178450|89234795|89604272|91362080|91424675|91950190|9229394 9|92325052|92765693|93058631 |93951361 |95507035|95508690|95511067|95516884|96566529|97985277|98707429|98807708|9982338 7|100352050|100598927|101738676|105656528|107465988|107489545|111037999|113151501 |113151503|113340512|114612028|1166 87311 |121599521 |122347179|122371035|122371039|124013901 |125408255|126614625|127877460|127927348|129080659|129175304| 129178713|129258670|129496133|129569385|130053423|130172396|130433501 |130578981 |130681300|130681454|130834874|130939 372|131096638|131125893|131274839|131276467|131282874|132161802|132241001 |132586904|133030594|133238944|133418318|13 4025826|134325544|135479646|135500205|135701969|136267262|136327864|136411213|136484077|136533554|136800415|13704618 8|137054132|137139159|137169165|137169562|137205270|137241753|137295350|137301546|137407041 |137441775|137459023|1375 51788|137579154

[0228] 42

[0229] CAN DMS: \1015053120\1chr10:

[0230] 134421 |134564|134659|1056521 |1737736|3067607|5412469|6202721 |6204127|6580003|6580332|6580335|6580593|7666906|8035006|8 045332|8053537|8053688|8053868|8054033|8054125|8054342|8054348|8054356|8054405|8054409|8054634|8054637|8054670|833243 7|11017762|11017764|11823526|12448845|13302445|13440679|13707625|15168265|15370707|16817457|17229945|18141215|2117431 4|21494772|21495503|21496745|21496779|21496804|21496806|21497068|21516473|21525864|21526786|21527338|22229098|2225243 7|22252513|22253095|22325765|22335445|22336536|22336804|22345503|22345510|23192460|23344397|23344461 |23344589|2369460 9|24723244|24724542|24724950|24952498|24952533|25016146|25016167|25016246|25016288|25016489|25016945|25176421 |2710067 1 |27258625|27259036|27742162|27743441 |27743789|27745162|28302807|28303032|28677546|29735813|29735874|30027503|3005948 6|31318996|31320962|31603226|32378791 |32958505|33335695|34814947|34816170|35640992|35641597|35642307|35643291 |3564346 3|38094143|42782766|42933696|43076911 |43077173|43105258|43138764|43304779|43304934|43574399|43574595|43649077|4438509 714438511114438537114486503814537426714541900214730014614738429214738430914852427014911566114953852214953854314953903 8|49614345|49762392|50418465|50739802|50991581152308870|58269209|58512994|59362605|59708970|59710062|59710087|6094431 2|62268786|62268905|62374401162805576|62818709|63466239|63630766|67764269|68231440|68231765|68560280|68900772|6895710 6|69087643|69318385|69451512|69572988|69573430|69573722|69630203|69801746|69801749|69801818|70132606|70132837|7014682 9|70169800|70672421170815758|70888572|70888622|71212319|71212375|71212380|71212447|71213144|72297589|72297719|7229794 7|73252634|73414524|73496168|73496172|73496178|73647827|73730522|73772213|73772216|75401430|75401892|75401895|7540194 4|77638172|77926924|79981798|80356609|80408323|80408539|81874224|81876569|84194575|84194580|84540849|86363696|8636654 2|86366549|86756663|86971189|87505566|87660257|89206944|89207408|89208137|89251426|89645249|90871863|91887460|9307335 1193073763|93073839|93073858|93893813|93893896|93893932|93893948|93893954|93894185|94402421194402432|94403052|9529539 3|95561349|95561431195561578|96043209|97185374|97185907|97333704|97446023|97633460|97640675|97640684|9764071119764109 3|97687409|97771888|97772008|97849724|97850079|97850169|97850225|98467662|99233830|99234181 |99520499|99532826|9953287 8|99532894|99533332|99536862|99659236|99659490|99731841 |99731867|100346601 |100346839|100347054|100374063|100529936|10 0713852|100735597|100737763|100741998|100744265|100744282|100744479|100744540|100745726|100748850|100748876|10098724 11101050344|101213675|101213766|101839943|101839963|101844112|102226367|1022263711102241717|102245128|102394445|1023 94450|102419714|1024197211102917843|103193463|103276944|103276970|103276990|103277106|103396428|103396506|103494193| 103855236|103908479|104232367|104232449|104353853|109923724|110497854|110497859|110497863|110497888|110498185|110644 680|110672563|110672660|1110761011111076923|111076930|111077027|112950852|114044046|114101040|114174652|114174922|11 4404591 |114821585|115093052|115093106|115094269|116273393|116741996|116742732|116788380|117216673|117216793|11724155 5|117534456|117538064|117542542|118241414|1190814011119651348|119872088|120456866|120979614|121598696|121928199|1221 63535|1221635511122374827|122461213|122461540|122954473|122954556|123135925|123148024|123148037|123148084|124093386| 124093522|124418388|124418902|1244190411124419096|124419098|124419167|124447866|124448038|124450052|1244502311124450 310|125160174|125161040|125161055|125161193|12516121111279071511128268229|128286935|129964334|129969765|129969834|13 1982054|131982119|131982292|132023325|132036937|132185783|132186857|132307915|132308208|1323300311132537850|13278633 2|132787147|132787344|132787354|133088185|1331601011133160544|133236570|133236638|1332374011133308318|133330059|1333 36993|133337013|133357999

[0231] chr11 :

[0232] 208423|416605|417189|441986|507555|537287|5374961575426|637175|696374|706098|720859|827328|830320|1336179|1383313|1383 324|1389790|1391040|1547319|1571445|1572325|1572567|1573082|1573096|1763896|1852863|2269385|2270030|2270117|2271406|24 44865|2444908|244491112445368|2445425|2884266|2885449|2885778|2885827|2885829|2885837|288584112886102|2886107|2929402| 2929408|2930348|2930360|2930383|2930546|2930627|29927711305769113203428|3642302|379780116235569|6259874|6320637|64188 35|6419049|6419226|6419233|6419474|6419501 |6419551 |6419578|6474026|6474029|7020424|7020454|8081470|8169112|8268427|859 3959|8594128|8594190|8594295|8594324|8689263|9004183|9314989|9384466|10303192|10305023|10540748|10541366|10858045|116 21867|11622269|12110331112673952|12674031 |13008927|13009129|13668610|13669155|13963449|14643789|14645127|14891751 |148 92435|14974809|16604562|17014790|17351633|17351755|17351987|17352565|17389496|17389723|17476967|17544470|17722214|177 35439|18526861 |18588527|18588893|18698610|18721675|18721829|19346674|19712944|19713155|19713522|19713730|19777196|203 63624|20363626|20363630|20363734|20363755|20363764|20363843|20364082|20364084|20364093|20669174|20669261 |20669883|206 70546|27507045|27700519|27701643|27701690|27722943|30585521 |30586436|30586446|31369669|31369707|31369746|31803678|318 10426|31811162|31811459|31813986|31818004|32433418|32435840|32829694|32829800|32829810|32829815|32829825|32829832|328 29985|33015851 |33016078|33016246|33700953|34357250|34357506|35138915|35419465|35419651135420011 |35420230|35618138|359 44158|43575491 |43575723|43578753|43579575|43579892|43581295|43581307|43581329|43581370|43942270|43942357|44066055|440 66066|44066258|44066518|44311114|44950282|44950742|45286360|45340335|45371430|45665713|45922540|46238010|46295603|463 33012|46333017|46333024|46333085|46333253|46392266|46392902|46617264|46617287|46826891 |46846376|47187408|57458411 |574 58541157515739|57530834|57667470|57712206|57712569|58575845|58900872|58905694|60841920|60924411 |60924439|60924606|611 60974|61295438|61295492|61392675|61430287|61508615|61680362|61752419|61752786|61792620|61793551 |61815225|61815291 |618 15297|61815313|61815418|61828013|61917120|61917714|62337482|62337680|62546005|62573977|62574047|62653429|62709072|627 09802|62771063|62882005|62923779|62925984|63491240|63614593|63986126|64000568|64007599|64028726|64036549|64060874|640 61290|64165740|64206659|64206757|64207483|64226820|64240881 |64247069|64270056|64291582|64291585|64291981 |64292007|642 92122|64300291 |64713546|64803037|64917231 |65083954|65421313|65524836|65615058|65663551 |65780415|65833731 |65833794|658 33830|65833861 |65833914|65833946|65833956|65858737|65900618|66126992|66257176|66257217|66267931 |66268269|66312910|663 71525|66371725|66371750|66371760|66371871 |66510566|66510570|66510646|66546229|66579268|66958389|66958434|66958762|670 23685|67373664|67391647|67443837|68038965|68842050|68843860|68844011 |68844128|68904229|69443466|69443596|69640670|696 40725|69641072|69641933|69775514|69775541 |69775560|69775564|69817452|69817567|69818115|70203329|70269939|70398308|703 98328|70398347|70398364|71787669|72239880|72241087|72244069|72589847|72642390|72642536|72642538|72676989|73218125|732 18267|73218337|73307267|74311513|75241742|75241745|75525569|75525863|75525873|75667455|75668579|75768418|76152385|762 06360|76209234|76210389|76670643|76670893|76783123|76783898|77046231 |77474082|77474353|77637688|78079314|82901724|831 94157|85810962|85811051 |85811392|85854920|86672213|86672515|86800503|86954958|86955510|86955516|86955809|86956133|883

[0233] 43

[0234] CAN DMS: \1015053120\137493|88338027|93197824|93198224|93330526|93661458|94401573|94401590|94494014|94740502|94740505|94768552|94769492|951 50957|96389983|99021081 |100687265|101914940|101914953|101914967|101915075|102047414|102047440|102110076|102110399|10 2111058|103109313|104163891 |105035162|105610590|106021831 |107017666|107018592|107018638|107591059|107591168|10759170 4|107591719|107858753|107859279|107859796|107928365|107928471 |108222659|108593056|108593091 |108593623|108593690|1100 93497|110296028|110712313|111299236|1115147711111977440|112226146|112961758|113314432|113314444|113314839|113475479| 113773934|114036259|114059708|114060278|115504623|115659872|115760203|1167732411117328550|117797320|117797325|117876 702|117986422|118145543|118145977|118152730|1181532811118608224|119031025|119031038|119057255|119149389|119149405|11 9149428|119316311 |119340730|119356618|119364026|119364134|119584519|119584789|119585097|119728199|119728466|11972871 5|119728912|120169209|120240103|120325644|120335841 |120336223|120336726|120511218|121023926|121451913|121452849|1228 82721 |122882735|122883242|122883269|122977536|123430159|123431040|123577133|123654352|123654954|124622602|124673506| 124762494|124763285|124839349|124839681 |124839900|124843229|124865319|124868975|124876858|124954229|125063010|125063 018|125496369|126269056|126356101 |128687097|128693132|128695624|128717065|128725818|128891259|128905618|129364290|12 9364308|129374546|129375794|130159720|130428787|130428798|130448808|130448811 |130862068|130916641 |130916738|13191135 2|133956434|133957361 |134036798|134037219|134068915|134069046|134069169|134276181 |134276238|134276430|134360437|1344 12313|134412510

[0235] chr12:

[0236] 189212|401499|402196|643480|991211 |1531226|1691322|2004635|2035290|2052495|2053172|2691280|2691297|2890595|2958860|295 9212|2959975|3077338|3200329|3200650|3491151 |3492927|3493380|4272611 |4272622|4272637|4273015|4273018|4273022|4273206|4 273814|4274115|4274856|4604943|4909632|4909639|4909649|4910316|5430786|5432054|5432087|6075189|6200298|6200447|631085 7|6342150|6363525|6470772|6493477|6700721 |6700723|6700754|6914351 |7130079|8033335|8242897|8698343|9448279|10212863|102 12965|10674154|10674307|10674372|10723310|10723454|10723564|10723578|12350260|12350290|12350373|12891555|13001495|130 44893|14567453|15221369|15789588|16605781 |21437610|21527574|21527735|21657816|21775004|21775037|21941545|24562550|245 63142|24563270|24903149|25958415|25959132|26195398|26195400|26195410|26195504|26833186|27332783|27780200|27969438|308 22429|31659646|38906942|39443560|40106009|40106214|40224773|40692998|41932580|42483083|42483738|42589127|42590291 |438 36255|44876209|44876424|45215444|46268638|47773312|47813280|48004537|48004591 |48004752|48183937|48682379|48716863|487 17007|48865931 |48971541 |48979963|49094804|49337406|49343031 |49742194|49828288|50283241 |51026321 |51270608|51424649|514 24852|51424873|51425235|51590719|51591350|51951403|52037536|52051291 |52069879|52308280|52308534|52874352|52903763|529 48811 |52948851 |52948964|53201072|53295295|53938673|53938679|53945040|53953075|53989855|53989894|53995693|53999658|539 99661 |53999676|54009125|54014880|54016703|54016709|54016848|54018244|54033389|54053459|54127135|54324954|54419165|544 19262|55681681 |55707661 |55817759|56079975|56126181 |56158235|56221913|56221922|56221943|56258476|56688416|56688522|572 16295|57216564|57216672|57216922|57220317|57225507|57242959|57488102|57591294|57611560|57619692|57619734|57619756|576 19853|57619862|57621074|57621343|57621618|57627786|57628134|57633247|57633318|57633330|57744990|57752390|59595871 |621 92096|62603629|62631991 |62632168|62934378|62934925|62934937|62935116|63779837|63844263|63844545|63844758|64390472|643 90718|64780880|64824480|64824633|64825089|65169123|65278679|65278751 |65741747|65823100|65826244|66189025|66189249|661 89423|68933117|69470572|69739283|70242879|70610042|70610056|70610184|71439290|71439754|71440457|71840533|72272484|753 30332|75334678|75334689|75334691 |76348084|76879052|77065705|77325628|79691192|79691197|79691200|82358409|82686902|826 87051 |82687269|85278845|89353697|94873531 |95073836|95790637|95790780|95790802|98894917|99984480|100142658|100573744|1 01408238|101831133|102957402|102957410|102958222|102958489|103841185|104216202|105084607|105084609|105107584|1052364 27|106581893|106774143|106955375|106955413|106987152|107093319|107093605|107093930|107093936|107318286|107318343|107 318363|107320896|107903810|108129279|108129632|108339484|108515697|108562542|109154543|109154857|109155182|109900121 1110502111 |110846964|110847175|111033388|111034379|111035404|111369196|111369215|111843083|112109101 |113057232|11313 5417|113135616|113135806|113154514|113154639|113358831 |113462554|113465427|113467670|113476082|113638176|114396145|1 144054911114662828|114668407|114683502|1146982911114698453|114698482|116533289|116879710|116881388|117968928|1179694 24|118136463|118981524|118981526|118981830|1189819811119668487|119988746|120317525|120368375|120369077|120470088|120 640855|120725694|120726048|121467946|121579342|121687236|121839454|121889008|122203445|122775242|122896259|123383721 |123389909|123633626|124466238|124940212|124988885|125049497|1251834111125186558|127381158|128267513|128824164|13182 8157|131828196|131828312|131828330|131828935|131895455|132066533|132329853|132490094|132710297|132711184|132887299|1 32887488|132887737|132887765|1328877711132887910|132888015|132888099|132888103|132904934|132909105|133181715 chr13:

[0237] 19633272|19781961119957479|20128783|20161198|20161231120161393|20161680|20193829|20232338|20232524|20232593|20566637| 21061281121061288|21061596|21075583|21075889|21669316|21670090|21671038|21671194|21675384|23375800|23578835|23579339| 23579359|23579365|23979801124160736|24160912|24270723|24680344|24680604|24680729|25046816|25372519|26051996|26557539| 26557587|26557993|26761014|27251480|27424301127533301127622233|27792463|27821253|27823222|27917453|27919865|279214611 27929236|27953118|28100314|28495366|28532285|28532366|28820387|28820638|30306959|31846351 |31846553|31847119|32031765| 32316215|33016135|33016205|33016263|33016357|34942352|36346507|36346523|36346676|36346828|36346970|36919342|369203111 37000454|37059259|38349439|40664364|40664988|40666366|41457145|41457448|41960838|41961092|41961154|42040043|43786942| 43879728|44373787|45120905|45311756|45341172|45417440|45418434|45418445|45615764|46168632|48303821 |48975353|49220499| 49248025|49444395|49691681 |49791438|49792978|49936015|51454165|51804344|51804394|52011496|52128709|52129232|52406127| 52449844|52652688|52848673|61415279|61415568|67230153|67230522|70107995|72727940|73058624|73058747|73059150|74133723| 74575837|74575935|75219928|75482200|76885343|76885542|76886472|76886582|76886584|76886588|76886921 |76886923|76980173| 77698237|77698243|77698258|77919094|77919516|78602137|78602437|78603060|78603385|78603565|78603742|79481036|79481045| 80339879|80340160|80340987|80341325|80342923|80343297|87671352|91398466|91398537|94549833|94596097|94707464|94707720| 95002918|95003070|95300975|95301228|95301251 |95301687|95552616|95552619|95552930|95644454|95644590|95644729|96053593| 96053599|96090159|96091641197110035|97222384|97433121197975806|981433011100088787|100088907|100088909|100089033|1000 89156|100674918|101917465|102394386|102394580|102394593|102400118|102773974|102798574|102799016|102799030|102799034|

[0238] 44

[0239] CAN DMS: \1015053120\1102800185|102800439|106533244|106535908|106536068|106917861 |106918094|107867904|108270013|109786559|109786659|110138 057|110306630|110616094|110616367|110712569|1120581611112943178|112968919|112969325|112969530|114132743|114314889 chr14:

[0240] 20663462|20684604|20971142|20971281 |20971748|21024816|21477241 |21511259|21511430|22767256|22823001 |22919628|22919637| 22956700|22982756|23183707|23352361 |23352693|23555828|24188487|24189043|24189086|24334667|24334719|24340236|24366942| 24399264|28760249|30874493|33950340|33950614|33951207|34462592|34462616|35122366|35533645|35533654|35533868|35533975| 35534002|35534005|35534161 |35534322|35534620|35534891 |35535477|36505595|36514337|36520249|36520717|36520731 |36661803| 37595327|37595947|37596230|37599796|37599874|37600434|38256505|39114309|39114343|45134638|45253414|49635256|49688052| 49868525|50312114|50396523|50943971 |50944452|50944549|50944678|50944681 |51651392|51651397|51652379|52068460|52069040| 52069348|52267679|52267807|52314201 |52730200|52950609|52950718|52951546|54396832|55129050|55129240|55129522|55129929| 58152451 |58152501 |58298227|58396247|59189998|59465395|59465410|59630529|59870295|59870930|60091755|60647245|60649788| 60657255|60721527|60722833|60981098|60981100|60981109|60981205|61321596|61321610|61321627|61322092|61568867|62117244| 62117287|62117306|63728327|63728330|63728367|64539563|64540059|64540343|64540348|64704010|64704311164704380|64704586| 64971989|66508578|66508654|67533134|67533584|67600163|67600373|67600381 |67619625|67619836|67619859|67675006|67675013| 67695263|68795548|68979420|69191329|69191423|69259537|69260221 |69548156|69548257|69727022|69879504|69880081 |70187880| 70189128|70189145|70189351 |70808914|71320498|72892293|72892602|72894056|72894785|73613063|73851735|73851741 |73886573| 73949854|73950273|74241610|74257596|74426041 |74426394|74612788|74955644|75003321 |75069174|75127227|75127266|75279373| 75427580|75577885|75578248|75986116|76352825|76761517|76761779|76761816|76812316|76812784|77038218|77125179|77125318| 77498780|77498941 |77498970|79279236|81436002|81436392|81436619|85530151 |87992872|88385402|88555133|88792731 |88824160| 88824577|88824614|88824756|89027217|89681159|90061043|90061262|90061634|90061855|90061869|90235425|90816253|91264668| 91510556|91510962|91574428|91947807|92323156|92324236|92923127|92923531 |94026251 |94026330|94026413|94174153|94174158| 94768489|94769786|94770202|94773044|94773233|95876679|96741777|97218821 |99270050|99270222|99270641 |99272115|99273362| 99604558|99604849|99605100|99683649|99684327|99792992|99793464|99793523|99971855|99972103|100159752|100159766|100159 857|100159868|100375588|100376012|100567993|100587017|101459368|101559749|101560218|101628593|101781736|102509814|10 2509824|102510166|102510519|103056968|103057582|103058093|103075830|103084115|103091554|103189231 |103220911 |10333341 9|103521473|103522439|103522871 |103522978|103563330|103715538|103846941 |103848097|103848101 |104138556|104650248|1046 50344|104796011 |104967822|104978047|104978387|104978560|104978567|105021311 |105045734|105093862|105168050|105168899| 105181397|105196450|105197065|105411316|105474840|105474913|105486907|105491165

[0241] chr15:

[0242] 22980530|22980768|22980884|25863252|25863254|25863265|25863465|28095313|28096416|28096834|28099342|28107412|29269938| 30191830|30903696|31391940|31441242|31870620|32029434|32030626|32030817|32030824|33194857|33194919|333111111342102811 34583624|34583690|34583729|34583736|34755193|34795436|35546490|36579364|37101373|37101788|37102914|38251389|38252225| 38252840|38565057|39580571 |39580718|39581005|39581059|39581087|39919975|39921079|39921113|39921138|39933885|40160835| 40239151140252849|40252942|40252944|40252974|40253095|40307898|40308078|40308292|40406191 |40422037|40440911 |40764054| 40764096|40807706|40844264|40844301 |40953329|41230700|41230724|41230727|41230853|41230895|41231041 |41585608|41621545| 41660447|41660863|41894981 |41972647|42057138|42057180|42920817|42920824|43133393|43133500|43330055|43792120|43792128| 43826862|44195094|44195347|44427467|45129885|45187557|45198903|45378328|45378667|45378674|45378677|45430391 |48178319| 48645016148646042148646150148646173148811107148878446149620949150182191150182400151093719151681464|517513751519716421 52019434|52529657|52790938|52803838|52804657|52804863|53197546|55251066|55408703|55498311155498373|55588696|55588799| 55742603|55743173|55993286|56365417|56365425|56365434|56365437|56465301157376349|57376354|57376614|57591840|58066186| 58750043|59371788|59438388|59438456|59997218|60003960|60003970|60591894|60592431160592520|60592822|61228225|61229475| 63042307|63042817|63189216|64151556|64151674|64151771164356453|64775182|64911835|65377966|65422055|65423016|65423018| 65530748|65791257|66703301 |67833727|67836295|67968236|68054003|68431351 |68432031 |68559747|68578640|68579235|68674309| 69160445|69299016|70099035|70099330|70100523|70892542|71115418|71115741172197700|72320288|72320379|72637073|72784294| 72796893|72796977|73051639|73369428|73684338|73684627|73927328|73927914|74129194|74129941 |74130592|74136230|74136233| 74245622|74366212|74366232|74373786|74614931 |74725881 |74725918|74725925|74726154|74726197|74726392|74826677|74957103| 74957549|75178693|75202771175347807|75368749|75368843|75640418|75738659|75758511175758654|76335253|76336769|77632355| 77633139|77633618|77634963|77944518|78149954|78264598|78507242|78507366|78810683|79089525|79090206|79090653|79091043| 79091548|79091582|79091605|79310935|79311240|79432175|79432452|80403941180404103|80999830|81001951181296907|81323969| 81324000|81324435|81410611182046233|82046245|82046892|82047682|82263049|82647889|82709569|82709885|82709887|82710007| 82710084|82952765|82952942|83107517|83107519|83207802|83284938|83447059|83447266|83447363|83447399|83653842|84654040| 84982153|85794980|85795192|88256292|88256295|88257279|88705213|88894977|88895380|88895500|88913552|89017715|89088928| 89359072|89359339|89411614|89411760|89496587|89690616|89690626|89690795|89690836|89690847|89751376|89894369|90201397| 90265484|90352705|91022383|91854049|92393588|92393800|92394055|92395065|92655265|92655819|92655911192714683|93072448| 93073195|93073359|93089382|93089390|93089501196330725|96352112|96357043|96363503|97960538|98428262|98647328|98647826| 98852404|99059137|99100689|99104882|99104890|99105997|100341960|100342026|100342129|10035025111008790911100879313|10 1252633|101277709|101489745

[0243] chr16:

[0244] 54183|786311181390|234385|276049|276064|280732|324988|381255|560895|642366|668123|675543|6755811679763|715416|715434|78 8206|981205|1103182|1103273|1152468|1152819|1152923|1153586|1153593|1153595|1352334|1379728|1493285|1493689|1493910|16 11096|1774040|1782981 |1783552|1783615|1872154|1930031 |1971790|1971876|1990414|1990980|1991511 |1992465|2020747|2268613| 2720900|2752228|277830112785330|2868179|2963405|2964232|3018314|3046483|3046487|3046710|3058783|3124415|3159179|31834 52|3263947|3305295|3457582|3717868|3939230|4116766|4116863|4253412|4253588|4425544|4476226|4538413|4538825|4538843|453

[0245] 45

[0246] CAN DMS: \1015053120\18859|4538916|4624676|4693298|4768783|4846606|4847241 |4936246|4937315|4937318|5033352|5071972|5490757|7304040|8674568|9 090628|10182723|10182942|10580469|10580471 |10580600|10580605|10580806|10942794|11233284|11255166|11257279|11257301 |11 257308|12803827|12803829|12803953|12803964|12902377|12902481 |14301774|14634124|15055418|15434901 |15856983|18790223|18 801511 |18801956|18983928|18984069|19113815|19113884|19114450|19167929|19555237|19886486|20073892|20806693|20900675|21 278218|21278234|21278446|21278491 |22162394|22162444|23149639|23182527|23302238|23509903|23510284|23596514|23641853|23 678571124610607|25067118|25691832125692509128063063128063067|28063141128880280|28985037|28985041129862598|30011227|30 011277|30011404|30011707|30021232|30184702|30355639|30430019|30472897|30534869|30571904|30650546|30748120|30775650|30 776034|30805603|30897169|31094956|31105803|31108319|31179848|31442627|31443258|31508631 |31529558|31569568|31700531 |31 700551 |31713193|46689508|46883971 |46883976|46884248|46884521 |47142025|47143264|47143692|47144156|47144159|47144167|47 144448|48366243|49855033|49855332|49856809|50066606|50245896|50468225|50468307|50547812|51156154|53703966|54282137|54 929489|54930825|55329146|55478958|55479503|55480558|56190870|56190881 |56191147|56589303|56589400|56589478|56608849|56 625640|56625740|56643423|56657937|56682455|56729960|56964710|56989324|57284704|57284785|57284797|57284808|57284832|57 284968|57284978|57284990|57802330|57984976|58025201 |58249802|58463491 |58463863|58464286|58464681 |58487819|58501189|58 515394|66844523|66844672|66844806|66925332|67000979|67029416|67151015|67163277|67164126|67248934|67279126|67279128|67 279140|67326831 |67326902|67393703|67430926|67431139|67659669|67660865|67816802|67968935|67969082|68022875|68448688|68 520834|68529983|68530207|68644938|68737279|69106989|69386231 |70250990|70346655|70439544|70686230|70801382|71358725|71 484329|71626560|71895609|72664953|73058492|73063067|73063158|74774857|75251605|75495458|75516778|75566116|77213071 |77 236160|77434561 |77722526|77788536|79589854|79600513|79600778|79601528|79770664|80540860|80541029|80804841 |81007367|81 077613|81095713|82170562|83807906|83953150|84504578|84617488|84648388|85169026|85750697|86508160|86509486|86509913|86 509932|86509937|86509961 |86510702|86568477|87391848|87602192|87602933|87602988|87926466|88454822|88634508|88662741 |88 663883|88804068|88968370|89093648|89561447|89574888|89576005|89701089|89828900|89922707|89948554|90019893|90019902 chr17:

[0247] 385444|410495|732720|781911 |951998|996542|117941111179900|1180197|1253963|1649908|1684700|168515111710278|1710287|2041 860120542351205431112054404|2054728|2054912|23369291239410212724954|275601112756032|27767701279621112796412|2796424|36 36460|3893488|4264114|4433799|4433816|4433907|4710397|4806737|4833934|4899518|4899552|489961114968409|4987208|4997370| 4998283|5078303|5078308|5078528|5191900|6070746|6443833|6444317|6556048|6641583|6652123|6713564|6713711 |6831797|72198 19|7234759|7242473|7242735|7262530|7281696|7281704|7281715|7294188|7294559|7294748|7404078|7404100|7404105|7439575|765 0822|7651195|7651612|7686062|7717329|7845003|7916153|8002724|8016363|8079352|8079488|8110139|8123095|8124142|8124175|8 125543|8186586|8210586|8210589|8327032|8630869|8631583|8745852|8745910|8867686|8965517|8965782|8965819|8965896|900306 5|9003069|9003896|9022435|9023477|9576612|9645449|9645503|9645585|9646029|12665444|12665772|12665896|13601155|1429959 9|14301045|14301168|14301276|15257370|15260789|15260803|15260816|15260953|15260975|15262605|15262745|15262836|1534177 2|15341774|15699566|15944753|15944796|15944907|15944950|15999346|15999380|16352425|16353353|16353660|16353676|1635369 6|16439820|16440085|16492135|16535756|16569440|16584507|16589432|17784108|17972840|19004922|19237359|19362606|1953447 8|19744948|19745101 |19867597|20008864|20073507|21214948|21376307|21376562|21376976|21377279|28318497|28318987|2833508 7|28335449|28371689|28372148|28372466|28406284|28406340|28645194|28720409|28729037|28744551 |28855119|29006090|2900609 9|29006167|29566389|30236090|30905894|32127722|32265638|32266696|32266786|32487607|32487682|32876459|32928250|3329139 1 |34579375|34579435|34579437|34579603|34580712|34637577|34961893|34981343|35090040|35119947|35242728|35242971 |3524300 1135243003|35243011135373161135373728|35373738|35373740135741405136535424|36657981136722348|36808594|3693509013693717 5|36937184|36937194|36937298|36948717|37406956|37742584|37744227|38572612|38578658|38703572|38729881 |38748526|3874974 5|38824941 |39225920|39627235|39668273|39700151 |39952777|40191458|40219161 |40287840|40318126|40318180|40560550|4164862 7|41648799|41734242|41786729|41786791 |41836092|41836100|41930801 |42050599|42098361142180991142181342|42181362|4227650 6|42288898|42389252|42458737|42458747|42458827|42562388|42608937|42609120|42609354|42609673|42609685|42659420|4267396 2|42674194|42676376|42676887|42761037|42823961 |42824249|42980463|42980611 |43211880|43399011143545934|43713670|4371384 1 |43755385|43755607|43779121 |43779127|43832998|43833427|43900583|43900656|43907102|43907776|43938189|44005938|4400662 1 |44015063|44315068|44315191 |44315329|44326829|44557046|44708457|44758952|44759228|44759377|44829301 |44830569|4496801 8|44970488|45135474|45149790|45247949|45262130|45785251 |45894545|45894940|45895440|45895603|45895612|45895780|4681865 1 |46818781 |46818846|46818857|46819058|46841937|46979268|46979280|46979429|47189233|47323782|47789964|47790320|4803744 5|48048260|48101256|48101565|48101569|48107267|48430343|48430415|48577927|48578199|48578218|48578428|48593769|4859387 2|48594135|48597710|48610820|48610959|48610967|48611043|48611051148611057|48611071148611231148611367|48614458|4861480 6|48625196|48646776|48647413|48719546|48723722|48725526|48816829|48817101 |48817103|48817124|48817128|48817294|4881731 2|48996074|48997308|48997311148997521149193026|49193071149224379|49230381149230592|49496502|49575656|49575854|4957594 7|49708000|49851923|49880534|49880623|49902149|49968609|49968693|49971726|49972910|50055746|50056526|50117575|5013015 5|50130298|50345734|50508613|50559539|50560590|50560742|50634833|54900571 |54900833|55238422|55238587|55238750|5526373 7|55265241 |55265922|55266200|56593785|56593982|56594079|56597776|56597793|56780188|56833904|56834782|57086113|5725582 7|57443398|57954913|58249953|58328757|58517864|58517871 |58518002|58518044|58659219|58659502|58755715|58755738|5875583 4|58755836|58755840|58756064|59107216|59707098|59892800|59892926|60135748|60139996|60421616|60677181 |60677780|6139897 3|61399658|61400196|61411082|61411627|61412423|61416901 |62808158|62808310|62808495|62966657|63446485|63446712|6344693 1 |63476745|63523028|63601305|63826787|63843047|63843061 |64262783|64780412|64781659|65100517|65137132|65560197|6556049 0|66191990|66192048|66192285|66965024|67246297|68101972|68601359|69326692|72120293|72122874|72592479|73165183|7316578 7|73192373|73232493|73311375|73312059|73312065|73312072|73312165|73312200|73644201 |73644230|73902202|73952710|7421305 9|74326004|74326249|74430969|74431802|74432153|74454093|74592273|74748510|74776373|74859931 |74873806|74893619|7492322 3|74924267|74924283|74972873|74982431 |74987533|74987539|75012492|75033798|75034637|75087792|75261710|75289439|7552597 3|75587989|75779793|75784490|75784582|75844772|75877824|75878362|75878709|75978780|76240170|76385199|76537995|7653800 8|76736209|77088541 |77088596|77246868|77373575|77528922|77958612|78129071 |78132595|78132602|78214095|78924949|7892542 2|78925747|79024084|79024138|79024161179183627179798223179802917179803850|79810311179811151179843665|7993018618003653 1 |80036677|80220408|80475847|80476072|80545282|80833070|81034887|81285736|81295688|81393815|81395446|81395456|8139545

[0248] 46

[0249] CAN DMS: \1015053120\18|81400381 |81487898|81488175|81519474|81703660|81902559|81928226|81937194|81937217|81937224|81937481 |81937648|8196122 6|81977337|82038037|82228397|82228399|82297581 |82321554|82519134|82698736|82698855|83079867

[0250] chr18:

[0251] 501109|596943|657649|712731 |712795|812602|904877|908395|2846986|2847073|2847303|2847532|2906285|3450162|3499255|519687 5|5197328|5238220|5238311 |5544090|5544100|5544232|5544238|5629181 |5629372|5630017|5895540|6415088|6415119|7567550|8367 377|8367570|8705769|8706262|8706722|9913481 |10454684|10454687|11689207|11689219|11752593|12271804|12407733|12407798|2 2169207|22169434|22169579|23453859|23586754|23586758|23619551 |23689116|23689808|24397910|24398009|24398054|24398056|2 4426550|24426657|25349844|25352122|25352445|25352486|26226467|26547911126548491126548542|26548910|26549302|2654935112 6549713|26656334|28175644|28178195|31042946|31042952|31685524|32091809|32470435|32470855|32470909|32471049|32471051 |3 2471213|32471220|33578141 |33578867|34159243|34223494|35498047|35498052|35498098|35950597|36187430|36297058|36297843|3 6298267|37566087|37566134|37566136|37566264|37567116|37567283|44680156|45967369|46071869|46072206|46072266|46072289|4 6333602|46333736|46917641 |46946904|47260515|48008366|48161623|48409676|48409686|48540035|48540129|49813864|50560035|5 4828402|57434773|57441620|57586880|57803169|57803172|58043763|58195345|58195446|58768461 |58863557|59220047|59697630|5 9697636|61892858|62325152|62716909|63319678|63421921 |63970703|67516329|69401494|70205889|70288625|74291935|74292078|7 4292172|74495714|74495963|76491082|76492179|76494766|76495482|77132053|77132055|77132811 |77249495|77249768|77249771 |7 7650964|77900100|79394869|79395094|79399786|79798211 |79798846|79964428|79964453|80108959|80247354|80247604|80247766 chr19:

[0252] 344165|572359|590538|639566|639726|639746|663515|708709|708918|822195|917654|920423|982979|1069321 |1194863|1207125|123 8235|1260515|1286261 |1315733|1315877|1315963|1401768|1401782|1438439|1446350|1450019|1479219|1479574|1491230|1503538|1 508043|1513261 |1513400|1605630|1672532|1672540|1676012|1725759|1752207|1753445|1753484|1757700|1864252|2096904|246204 4|2462067|2475639|2477196|2611239|2614088|2702926|2702931 |2740055|2820491 |2841290|2841334|2841396|2945145|2977350|3061 759|3094188|3136099|3178957|3506441 |3557540|3585408|3585937|3606837|3761511 |3785857|3822128|3822191 |3881143|4064915|42 46853|4304576|4304580|4328748|4369396|4535303|4535313|4558529|4759807|5339660|5340799|5340821 |5790795|5827800|5828161 | 5828288|6110302|6110683|6110696|6110779|6110806|6459525|6460049|6464264|6502142|6739986|67680111719838117198489172940 76|7294576|7294972|7394933|7394959|7395103|7395175|7488937|7489100|7501067|7595618|7595771 |7636937|7636955|7670353|768 1527|7888544|7916345|7916483|7917828|8050476|8209181 |8209185|8209399|8308253|8308402|8308410|8343164|8343244|8343318|8 343436|8343439|8363903|8364276|8367532|8390143|8413259|8513883|8578791 |8831990|9435595|9538565|9827971 |9827976|993635 8|9937050|10231554|10231564|10251779|10286966|10289169|10295688|10404058|10416812|10420758|10505842|10653782|10701255 |10718489|11090673|11197909|11262166|11262419|11293778|11355333|11355344|11383088|11418720|11420676|11481949|11578911 |11639806|11639912|11739119|11766928|12035694|12035760|12035800|12053110|12064646|12064675|12064690|12139963|12140430 |12294753|12495369|12640228|12696831 |12757951 |12801764|12828773|12835486|12841315|12881256|12881601 |12891721 |12957362 |13013401 |13098671 |13795349|13833757|13865926|14057403|14249090|14574404|14979934|15125142|15231938|15464874|15508544 |16185252|16198520|16542850|16572455|17215623|17281620|17281847|17448658|17680388|17688421 |17950447|17952232|18007270 |18008255|18193083|18193211 |18226548|18340458|18340516|18429031 |18429033|18429520|18437773|18438035|18571899|18606831 |18610901 |18611810|18611944|18612747|18612759|18790091 |18790857|18940348|19138672|19203483|19406093|19532363|19532443 |19538232|19538245|19618749|19618759|19643666|19732898|19733125|19733267|20051861 |20052096|21397109|21836292|23395458 |29526922|29528622|29665489|29665554|29811886|29812588|29812590|30719653|31348758|31349831 |32224734|32224762|32345604 |32345753|32405972|32406349|32972036|33301775|33301808|33302235|33302240|33302255|33521420|33796313|33796438|33906005 |34134911 |34254314|34255298|34359433|34365234|34404366|34404565|34428506|34772796|34773062|34773164|34773284|34773323 |35142765|35142890|35143068|35248043|35248699|35545979|35612545|35628755|35641725|35702505|35742546|35856789|35868614 |35868654|35869494|35936308|35959219|35959313|36054692|36140172|36214811 |36331770|36418424|36418511 |36418516|36666959 |36666977|36666997|36797803|36838372|36916355|36916472|37172933|37467542|37468962|37469038|37469047|37506889|37692154 |37692309|38256561 |38264290|38361775|38389059|38433542|38433679|38433707|38618032|38736228|38900083|38930615|39445666 |39498945|39498952|39515027|39540381 |39834326|39970771 |40218401 |40226409|40285405|40285414|40465902|40465923|40465962 |40465997|40466321 |40530433|40549302|40549391 |40570636|40597201 |40600249|40601176|40609853|40717018|41193160|41310146 |41310393|41940907|42177360|42199611 |42281073|42302113|42313563|42324469|42387194|42397173|42423863|42528435|43464343 |43475312|43475462|43532892|43533857|44002712|44052105|44094294|44113016|44113031 |44141386|44304745|44448490|44747381 |45076120|45076587|45178229|45340636|45429010|45602208|45768150|45769196|45769348|45769385|45953067|45973307|45973367 |45974030|46077183|46297210|46413484|46426858|46428910|46471629|46488005|46493456|46493611 |46601226|46634187|46661173 |47021226|47021661 |47239572|47241260|47243221 |47273471 |47713356|47779093|48110574|48271144|48271383|48291163|48330278 |48391669|48393748|48393886|48394795|48414859|48511517|48624249|48624253|48713998|48795461 |48811204|48933461 |48933529 |48933539|48933609|48933710|49018256|49056326|49056331 |49056535|49057963|49128040|49150188|49451910|49495965|49534623 |49867940|49867958|49877974|50026253|50050810|50312462|50432291 |50476304|50476317|50694206|50695631 |50718346|50836232 |50912957|51017277|51019385|51065003|51108918|51366550|51422218|51531716|51571095|51594023|51594549|51704067|52008318 |52336192|52897292|53132824|53132855|53866317|53869371 |53869554|53869696|53882158|53890140|54102920|54115736|54137368 |54137809|54162482|54173254|54190323|54415263|54415631 |55063057|55063309|55069529|55166351 |55166968|55167051 |55173924 |55180384|55353920|55353988|55354961 |55385474|55408447|55442629|55477283|55640833|55642115|56368185|56368276|56393628 |56393663|56477409|56567411 |57191404|57191422|57191435|57191933|57191996|57240646|57363507|57411142|57487668|57527253 |57584100|57584227|57584291 |57614310|57632986|57709126|57747278|57814858|57819710|57916738|57947401 |57947768|57947771 |57947774|57947880|57947990|58003129|58150595|58150821 |58155089|58183403|58183661 |58228620|58228887|58228889|58229089 |58278759|58327076|58408581 |58475632|58520096

[0253] chr20:

[0254] 653200|728550|844597|844625|1002487|1226038|1226056|1226114|2207106|2379750|2509189|2524470|2800616|2800753|3159906|32

[0255] 47

[0256] CAN DMS: \1015053120\104630|3407622|3407760|3407780|3470975|3820191 |3846678|4015800|4172387|5001550|6052559|9515978|9839072|10034798|100350 12|10218786|10218813|10218821 |10218825|10219541 |10674816|10674996|11890663|13220567|13220578|13220681 |13221003|132210 08|13221197|13221790|13221829|14337752|16573267|16573276|17531181 |17531343|17569220|17969072|18056896|18057930|181377 14|18567591 |18567831 |18587897|18587924|18588552|19212416|20017227|20017802|20051955|20368259|20368276|20368524|203685 97|21101631 |21126046|21512463|21705615|23049805|23049809|23637418|23637953|25407733|25585243|25623340|25624007|256241 01 |25624123|25624405|31475446|31514776|31604210|31606089|31822800|31870258|32018989|32052234|32052318|34312000|345584 59|34558463|34558567|34558739|35147446|35278149|35541968|35699392|36092219|36154472|36646224|36646236|36951656|369518 32|36951855|37179673|37345889|38165324|38165342|38165345|38446600|38446640|38447061 |38674453|38731115|38805122|389261 97|40683429|40689497|41366899|41366902|41366906|43190130|43457756|43507790|43590747|43666873|43666898|43666903|439148 02|43914806|43915006|43915138|43916076|44210922|44326832|44475834|44522276|44745765|44810759|45348069|45348293|453484 06|45348438|45348440|45348559|45373882|45406430|45406775|45791786|45857558|45890757|45912138|45912155|45972188|460139 31 |46031890|46032222|46117753|46312721 |46364596|46406772|46709690|47786122|47786255|48828461 |49188402|49219267|492195 01 |49482711 |49484425|49568155|49936169|49982755|49982994|50794345|51023036|51562653|52104369|52105258|52972246|541741 94|54207813|54475501 |54475694|56358875|56629210|57264232|57351061157391361157709500|57710180|58150831 |58179925|589810 11 |59007066|59403834|59577226|59604189|60055899|62123385|62220100|62220306|62238400|62238721 |62366856|62367462|623864 97|62476376|62476382|62550971 |62551557|62708755|62708757|62708764|62816471 |62816630|62816640|62816727|62816851 |630070 81 |63178205|63178580|63178996|63179272|63253897|63253910|63253918|63253939|63254574|63254730|63273348|63472140|634722 74|63499157|63499159|63519778|63652350|63653135|63658449|63659042|63786460|63829941 |63830537|63894694|63979946 chr21:

[0257] 14216051 |14216287|15064392|17512743|17513326|17612452|17612996|17613065|17613069|17819518|17819526|17819821 |25639168| 25639170|26170431 |26170806|26170911 |26171092|26846327|28885322|29024477|31344269|31559158|31659422|31659647|31659679| 31873158|32278828|32412250|32412461 |33019895|33025823|33025914|33070205|33072033|33072076|33266230|35026929|36060287| 36060770|36134901 |36135300|36320477|36698683|36705173|36747619|37006736|37073643|37675465|38805241 |38805963|38806507| 41168034|41168941 |41316691 |41316748|41361820|41426204|41508071 |41953760|42879457|42879490|43075485|43108183|43864481 | 43866017|44107076|44932169|44939660|44940529|45075474|45405275|45478696|45974101 |45981492

[0258] chr22:

[0259] 17117911 |17158822|17159388|17370490|18906298|18970324|18970326|18970335|19447714|19714304|19714348|19714553|19714568| 19723500|19723513|19730957|19755506|19760855|19760875|19766728|19855129|20016833|20016854|20079790|20320457|20436698| 20436927|20437856|20437930|20437935|20437937|21014418|21032596|21045878|21568515|21630131 |21630194|21642057|22508566| 23070046|23070880|23839004|23849615|24592762|24593098|24593104|24806070|25421299|25773077|26657231 |26657257|26657438| 26657970|27800846|27802230|29073047|29268182|29268190|29306855|29306864|30267005|30267327|30289767|30396927|30396935| 30397203|30635683|30694236|30694760|31107660|31107884|31160581131630887|31970720|32801632|35300550|36816862|37334517| 37519319|37519335|37560422|37567400|37607200|37658583|37804972|37805130|37805135|37807670|37807748|37818972|37825088| 37906853|38057097|38057289|38412810|38794377|38871638|39242087|39242356|39244954|39245073|39400165|39664703|40044618| 41022969|41205066|41301697|41621413|41832720|41915035|41919638|41926735|41976512|41976524|41976996|42070847|42070863| 42070891 |42283798|42368540|42368754|42369132|42553721 |42553804|42720411 |42720632|42720940|42857515|43015592|43110366| 43110414|43151428|43151673|43812366|43812396|43812504|43812655|43923699|44024025|44024031 |44498382|44498386|44498506| 44668331 |44668591 |44702060|44702081 |44702455|44703027|44752492|45007927|45008962|45009740|45009743|45009946|45009999| 45010018|45010023|45268936|45413715|45413738|45413765|45867327|45970979|45971737|46044872|46537193|46537753|48490231 | 49848844|49929530|49961776|50169789|50170092|50170714|50270792|50342765|50481394|50481584|50526697|50530087|50530423| 50563222|50600294|50628084|50628496

[0260] 2. Non-Recurrent Regions (< 0.05) _

[0261] chr1:

[0262] 904894|9592211960925|1019703|1019783|1020340|1020377|1020728|1069395|1116515|1116527|1116714|1122303|1206410|1273816|1 274340|1307623|1308182|1308193|1308976|1324318|1324529|1348936|1349872|1375335|1375598|1399418|1399423|1399434|140004 4|1400189|1407178|1407340|1407697|1407750|1471465|1471800|1511667|1511855|1511985|1512187|1574984|1615268|1615280|1615 390|1615393|1658982|1658998|1659171 |1659256|1724399|1778158|1778769|1778798|1778826|1780582|1890542|1908762|1909043|20 44955|2194712|2194867|2194986|2195337|2227912|2227930|2227934|2391388|2391539|2391988|2412287|2412694|2412975|2413147| 2525975|2526582|2526659|2546366|2546650|2586508|2587064|2587066|3619308|3624518|3624522|3624822|3624874|3625092|36251 99|3649921 |3650015|3650137|3650151 |3650199|3796424|3796530|3856748|3856752|3857258|3900045|3900452|5991546|5992427|599 2533|5992582|6199085|6199628|6199644|6236035|6393367|6393392|6394142|6490620|6497719|6554284|6554447|6554527|6579875|6 579899|6580089|6602936|6613241 |6613267|6625089|6625102|6701597|6701874|7771545|7961493|7961551 |7961902|8423944|842409 7|8424109|8703313|8817080|8817715|8878040|8878642|8878662|8878692|8878695|8879047|9234854|9293551 |9428838|9539360|9588 5611958924119651903|9652518|9652629|9823831198239111982397119823974|9910578|991073119942887199433721100329521100336451 10210381 |10210596|10210600|10210677|10398542|10398848|10398885|10398946|10430439|10430580|10430610|10430886|10430928| 10472561 |10472636|10472639|10474903|10474977|11012685|11059787|11059804|11060088|11060517|11099712|11099790|11099851 | 11262324|11262474|11262842|11654816|11664083|11664188|11664335|11664485|11680952|11681382|11681626|11736019|11736022| 11736111 |11806002|11806098|11806179|11908922|11934640|11980085|11980151 |11980165|11980390|12019619|12019832|12019845| 12230310|12230371 |12617655|12617930|12617989|13700322|13748867|15524006|15524203|15526686|15526693|15526757|15526768| 15526783|15836158|15847264|15847855|15847871 |15848115|15848176|15848285|15848565|15849377|15976089|15976095|16206939| 16237232|16237287|16352089|16352659|16367184|16367188|16440515|16440690|16441025|16441152|16613200|16613615|16613686|

[0263] 48

[0264] CAN DMS: \1015053120\116905298|16913894|16914257|17011914|17012094|17012117|17054090|17054093|17054151117054207|17437679|17438199|17438547| 17438558|17438572|17438574|17438898|17439731 |17439742|18902555|18902559|18902567|18902597|18956608|19209794|19210047| 19210466|19210532|19251447|19251487|19251673|19251683|19251949|19312403|19485937|19485985|19596876|19596911 |19596935| 19596996|19597003|19644678|19799687|19799735|19800167|19882474|20633399|20633427|20633433|20633709|20661580|20661629| 20661742|20697010|20732132|20786457|20786706|20787150|20787265|21176939|21177099|21177131 |21290126|21290491 |21782682| 21783064|21783102|21783215|21783367|21783659|21937363|22025242|22052897|22053457|22053470|22451935|22451949|23019232| 23168882|23168900|23344284|23344286|23344420|23344725|23368417|23368442|23368456|23368854|23369037|23483940|23530829| 23531040|23559514|23691980|23743115|23743547|23778308|23778752|23791040|23800687|23800734|23800752|23825387|23868083| 24199499|24415709|24415759|24502478|24502607|24503277|24556189|24643003|24643037|24643127|24643622|24745151 |24745265| 24745398|24745425|24745725|24848254|24848572|24929878|24930448|25232462|25240262|25246689|25247439|25247464|25247524| 25247826|25247883|25267786|25338672|25429964|25430364|25430379|25430791 |25430913|25431113|25431621 |25616625|25617350| 25819700|25819732|25820080|25820761 |25859501 |25859622|25875375|25875646|25906215|25906235|25906240|25906544|25997907| 25998418|26035166|26110833|26110923|26111003|26111031126111039|26111305|26111629|26112354|26169804|26169807|261699111 26169916|26233959|26234051 |26234076|26234183|26234289|26234437|26306457|26306774|26306776|26306797|26432052|26432146| 26432175|26432180|26432299|26432317|26432355|26472232|26472456|26472461 |26472874|26473350|26500186|26530157|26620829| 26620952|26621238|26692596|26787745|26788340|26789136|26789162|26865082|26865419|26889876|26890241 |26890246|26890268| 26890305|26890436|26921630|26921647|26921662|26921842|26921941 |27155200|27234309|27234338|27234344|27234354|27234565| 27322019|27322141 |27322183|27322373|27322509|27341954|27392508|27392539|27392541 |27489789|27490121 |27490279|27604332| 27604354|27663476|27672435|27725783|27725887|27726167|27726273|27773059|27773452|27830536|27830840|27831161 |27872457| 27872598|27914515|27914527|27914816|27914875|27914887|27959898|27959900|28088493|28088651 |28232828|28235862|28236159| 28259230|28259326|28259352|28259406|28328920|28328992|28329006|28369562|28369577|28369594|28369598|28369951 |28505869| 28506029|28507076|28518357|28518701 |28553051 |28580966|28581997|28582020|28582039|28643275|28643290|28668580|28668669| 28736919|28736955|28887123|28887163|28887555|29181583|29181647|29181747|29230718|30718801 |30718899|30801919|31065249| 31065585|31065670|31065732|31065756|31065865|31066032|31154874|31296773|31296788|31296985|31297358|31394839|31644876| 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[0265] 49

[0266] CAN DMS: \1015053120\192484822|92484870|92485018|92485141 |92485154|92486632|92486635|92784698|92831995|92832265|92961365|92961911 |92962134| 93079013|93079108|93079173|93079451 |93179921 |93180274|93180298|93180611 |93180772|93180820|93180839|93180841 |93180847| 93345579|93345717|93345774|93346074|93346320|93846405|93846650|93846677|93846804|93848044|93848189|93878956|93879226| 93879228|93879235|93879253|93879255|93909471 |93909508|93909603|93909690|94417990|94418198|94418534|94418633|95072738| 95072889|95072990|95073230|95234000|96721749|96721855|96722612|99849929|99850105|99850173|99850371 |99850415|99850474| 99850558|99969956|100037967|100038210|100132822|100266036|100266230|100351387|100351405|100352283|100895219|10089581 9|100895831 |100895870|100896154|100896286|101025696|101025852|101025919|101026005|101026046|101026096|101236407|1012 36506|101236963|101309586|101309814|101309896|107056624|107056907|107057125|107057469|107964190|107965144|107965926| 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4755363|184755497|184973923|184974059|184974429|184974498|185045934|185156956|185156993|185157029|185157153|18531671 4|185317864|186375481 |186375487|186375648|186375830|192808913|193059008|193059439|193059462|193059797|193104672|1931

[0267] 50

[0268] CAN DMS: \1015053120\105424|193105534|193105582|193121673|193121915|197146764|197146797|197774830|197902470|197902496|197903062|198156862| 198159231 |200409835|200409837|200410038|200670074|200670374|200738899|201023476|201023528|201023646|201023660|201506 823|201507162|201829056|201829327|201955351 |201982974|201983133|202144134|202348958|202808331 |202808462|202808490|20 2889020|202889025|202889108|202889207|202889259|202889265|202926875|202927077|202927329|202927352|202957994|20295813 8|202958305|202958317|203007218|203007323|203007335|203007338|203305293|203305560|203327342|203487892|203627062|2036 27812|203861747|204162669|204411674|204411832|204411890|205122270|205122273|205122377|205211399|2052114111205211499| 205227808|205227839|205591874|205592210|205631118|205631439|205631956|205632068|205632444|205679963|205680296|205750 213|20577528912058131111205813119|205813394|206470822|206507555120650763312065573021206635254|2066355911206635601120 6685192|207321127|207454236|207454837|207868776|207868778|207963607|208245426|209784307|209784620|209784685|20978469 0|209827847|209828054|210328812|211258797|211259035|211259194|211259403|211259412|211260703|211326692|211326954|2113 27006|211515436|211577785|211578451 |211579278|211579553|211675748|211830160|211830827|211830933|212035588|212035977| 212284626|212285384|212285396|212285948|212414334|212558742|212609436|212665423|212791633|212791648|212791709|212791 771 |212791929|212792239|212792359|213051276|213051423|214280946|214603132|218285201 |218285305|218285527|218345890|21 9173768|219173998|220046481 |220046718|220094040|221742176|221742397|221743320|222465433|222465511 |222465595|22258991 6|222590069|222617828|222618296|222618544|222712492|222712729|222713148|222713221 |222815086|222815097|222815524|2230 81634|223845358|223845405|223846129|223846269|223846518|224114171 |224114407|224182914|224330133|224357018|224357402| 224433750|224434159|224434896|225427970|225652674|225653129|225777739|225777809|225809947|225882219|225883108|225924 104|225924465|225999241 |225999355|226062108|226062151 |226062742|226110372|226121751 |226122021 |226122407|226186582|22 6186645|226186650|226187025|226224014|226309652|226407793|226408075|226737480|226739263|226828215|226828221 |22682827 0|226870894|226939935|226940337|226940359|227728364|227735162|227735526|227787985|228082180|228082323|228082328|2280 82489|228082506|228082524|228082780|228083667|228103167|228109459|228140028|228140235|228213577|228406132|228406555| 228406763|228487179|228487208|229271330|229271465|229342391 |229342412|229508070|229508237|229508396|229508402|229508 530|229558051 |229559037|229626373|230067337|230067361 |230067864|230068247|230642334|230868433|230868439|230868580|23 0868761 |230868903|230978126|230979031 |230979057|231240975|231241106|231241149|231241271 |231241291 |231241300|23124135 7|231241441 |231337792|231337900|231337967|231422171 |231528390|231528514|231528556|231626713|232950540|232950581 |2329 50591 |232950600|232950628|233295789|234373447|234373566|234373593|234373595|234373711 |234373754|234478262|234478868| 234478994|234478999|234479088|234600346|234600373|234608562|234609032|234610058|234610751 |234610800|234610822|234612 872|235128816|235128979|235129050|235161096|235161122|235327430|235327662|235327713|235328048|235367365|235367680|23 5504380|235504603|235867190|235867203|236142700|236281764|236282086|236282089|236282147|236523971 |236604312|23660450 8|236604589|236604635|236795044|236795230|236795625|236795682|236795881 |241640380|241848080|241848094|241848211 |2418 48596|243255459|243850908|244048480|244451945|244451974|244452247|244652911 |244652919|244652972|244653363|244834862| 244834881 |244834903|244834983|244835242|244835354|244835379|244835543|244835839|244863833|244864102|244864467|244864 470|244864757|244864773|244864823|244918877|244971046|246507157|246507424|246507426|246507452|246566157|246566276|24 6566283|246724078|246724464|246931924|246932305|247078106|247078741 |247078828|247104023|247104406|247331624|24733246 7|247332516|24882625212488263721248826443124882647012488382071248858244124885880612488589231248858933124887329012488 73488

[0269] chr2:

[0270] 264731 |264756|264767|264910|677101 |677162|677534|677816|1550882|3379642|3380204|3519444|3519762|3558117|3558393|355844 7|3558459|3575137|6866149|7097449|8683553|8685777|8837360|8837553|9206564|9423441 |9423514|9423751 |9424119|9555791 |9555 824|9556173|9556476|9631061 |9813992|9843298|9843301 |9951559|9951571 |9951768|10120294|10120744|10122196|10122307|10122 693|10122916|10302742|10302815|10303692|10448342|10448345|10690106|10812608|10812885|10812929|11130066|11155591 |11155 793|11466351 |11746994|12717685|15561242|15591948|16609070|16609102|17753220|17753608|17753612|17753954|17753960|17754 452|18560604|18560738|19901745|19901875|19902018|19902123|19902200|20052064|20052082|20350011 |20350444|20650956|20651 042|20651049|20651127|20651289|20651392|20823117|23926546|23927007|23927253|23940513|24047577|24049677|24076381 |24084 201 |24123345|24123350|24123367|24123890|24359784|24360252|24360589|24360709|24491007|24491618|24793209|24793403|24793 565|24793574|24793610|24971987|24972258|24972687|25042028|25042268|25341533|25341602|25342346|25342398|25342419|25342 640|25361952|25362085|25377190|25673309|25673451 |25673852|25878479|25878497|25878499|25982648|25982737|25982746|26033 225|26033494|26034585|26244445|26244725|26244976|26244980|26345992|26346250|26346850|26764314|26764329|26785985|26786 242|26846499|26970463|26970471 |26970628|27032824|27033166|27033252|27050140|27050334|27050347|27051889|27071396|27071 837|27071845|27071851 |27071853|27086449|27134054|27211749|27211842|27212347|27212851 |27217308|27357117|27369786|27369 979|27370072|27370187|27370249|27370425|27370595|27370598|27371168|27380744|27380874|27380893|27380899|27409655|27409 660|27428531 |27428704|27582950|27582957|27582962|27629000|27629105|27663340|27663888|27771654|27771817|27890438|27890 546|27890734|28391700|28391771 |28393058|28393326|28566949|28870029|28870296|28870312|28870572|28870644|28894518|28894 550|28894942|30231409|30231497|30232723|31233881 |31233895|31234177|31234192|31234195|32010856|32010931 |32010954|32063 301 |32063375|32063457|32063842|32064346|32165722|32165855|32278150|32356643|32356966|32358115|32627864|32627941 |32627 956|32627972|32628162|33599103|33599183|33599295|33599304|33599328|33599360|33599617|36967012|36967213|37084234|37084 384|37084437|37084440|37084508|37084515|37157086|37157088|37157105|37231214|37231585|37231587|37231621 |37231638|37231 678|37231737|37231925|37324748|37671495|37671880|37672214|37672301 |37672321 |38377543|38377711 |38751415|38778180|38778 187|38875813|38875927|39119742|39120136|39120436|39120590|39124249|39436990|39437205|39437207|39779194|42169316|42169 318|42169573|42361198|42361284|42361357|42495207|42810261 |42827844|43220000|43223826|43224729|43225422|43226112|43226 310|43226401 |43226733|43226999|43227046|43227397|43227470|43227489|43227622|43227713|43227811 |43596000|43596137|43596 142|43596199|43774010|43774113|43995910|44361653|44361672|44361882|44361895|44362015|44362028|45611299|45651720|46297 009|46297226|46297418|46500217|46543142|46543218|46616835|46616997|46698614|46698930|46699051 |46699078|46915728|46915 996|46916193|46940893|46941301 |46941766|47176776|47176789|47176870|47272541 |47272577|47402810|47403008|47403155|47403 294|47782958|47782966|47783197|47783223|47905616|47906478|47906609|48314125|48314393|48440515|48440735|48440881 |48441 006|48530338|53786794|53786807|53786866|53787324|53970649|53971022|53971199|53971229|54115514|54115669|54330837|54558

[0271] 51

[0272] CAN DMS: \1015053120\1238|54558413|54723325|54723602|54724941 |54724944|54725078|55050436|55050485|55231937|55232707|55269008|55269359|55269 416|55282122|55519573|55617386|55617960|55693797|58241058|58241296|58241440|58241446|60549578|60549916|60552482|60554 411 |60554505|60581859|60735886|61017500|61017559|61017650|61017709|61065650|61065944|61066137|61066167|61066195|61177 012|61177443|61177629|61470393|61536234|61538375|61538643|61538799|61694617|61764381 |61854147|61854150|61854320|61888 441 |61888545|61888802|61888804|61888854|61905643|62195849|62197361 |62705295|62705618|63050164|63050549|63050695|63050 715|63051045|63051076|63588913|63588940|63840650|63840785|63840804|63840806|63840842|63840862|63840987|63841948|64018 545|64018678|64144041 |64144509|64228417|64454599|64454601 |64524176|64524369|64524462|64652777|64653767|64750514|64988 327|64988338|64988504|64989161 |65056009|65056188|65056273|65056287|65056303|65056439|65056494|65129491 |65130395|65130 458|65130629|65130647|65130724|65227558|65227641 |65431390|65432744|65436346|65436699|67397255|68062840|68063042|68157 899|68252488|68253090|68467216|68467381 |68467839|69387142|69387324|69387330|69387332|69387341 |69437185|69437592|69437 640|69437669|69437683|69643760|69644399|69644553|69741721 |69741947|69742095|69829333|69829500|69829528|69829565|69829 920|69914973|70086640|70124392|70125125|70142659|70142684|70190992|70191008|70191054|70191062|70248669|70248677|70248 770|70248866|70258171 |70293434|70293726|70293892|70293919|70301708|70302065|70553707|70553772|70553776|70553969|70554 155|70554193|70994967|70995162|70995166|70995168|71068097|71068230|71068264|71130160|71130270|71332180|71332210|73071 845|73071860|73112966|73113129|73113200|73113361 |73177517|73214284|73214370|73214574|73233212|73233288|73233527|73234 100|73234135|73284555|73385528|73385660|73385761 |73779937|73780146|73780239|73828850|73829067|73926757|73926769|73926 852|73926889|73926916|73927094|73985604|74147782|74148086|74178819|74178839|74178913|74178918|74178937|74198622|74199 315174391508174391812174421573174421581174421627174422022174454974|74457593174464865174465352174465481174465486174472 085174472709174472776174482539174483386174483404|74507482174507780174529245174530017174530023174554969174715401174835 315|75609265|75646664|75646940|75647087|84459446|84881249|84882294|84905268|84905272|84905539|84905783|84927012|84927 074|84971430|85328117|85354588|85354789|85437648|85437703|85538521 |85539128|85539271 |85561549|85561687|85561874|85595 282|85595284|85602656|85602710|85602881 |85602894|85603073|85611712|85612020|85615990|85616109|85616257|85616659|85888 577|85888926|86105814|86106133|86106187|86106360|86106385|86195074|86195456|86441415|86441613|86563497|86563504|86563 550|86622920|86623743|86623761 |86623765|86623912|86623948|86807677|87075520|87077074|88055483|88055667|88055785|88055 793|88055848|88055960|88627381 |88627432|88628096|88691476|88691500|88691631 |88692026|95076944|95077006|95121367|95121 509|95122138|95122188|95159897|95160008|95165675|95402663|95402703|96144951 |96145319|96208256|96208769|96208911 |96208 914|96208993|96209078|96209235|96265829|96266115|96266286|96305451 |96305697|96321966|96322183|96335563|96336080|96527 552|96638450|96760633|96760741 |96760748|96760890|96761184|96816106|96816226|96816322|96816996|96857620|96858113|97113 175|97646083|97646105|97664060|97664161 |97664181 |97664347|97995131 |97995232|97995868|97995896|97995907|98444812|98608 295|98608372|98608379|98608431 |98608855|99141295|99141641199141711199154696|99154960|99155062|99155164|99180976|99181 026|99181069|99181075|99181269|99336087|99336327|99336337|99336502|99337211 |99337236|99337282|99337286|99337300|99489 685|99489823|100263049|100562768|100562867|100562897|100563435|101002131 |101151159|101151420|101252562|101252887|101 308450|101474329|101697426|101698295|102241000|102736633|102736772|105037908|105037950|105037964|105337502|105337873 |105745193|105745219|105745568|106194530|106194540|106194626|106194718|108534598|108534822|108719291 |108786653|10878 6683|108786912|110205049|110678366|111120717|111120870|111120876|111120904|111884053|1118841611111884302|111884315|1 11884322|111898685|112254710|112255054|112275297|112275456|112275507|112275593|112482336|112542024|112542616|1126458 77|112764800|112764966|113157105|113157267|113627336|113889775|113889839|113890529|117814620|117814654|117814749|117 814816|118014093|118014245|118014286|1180142911118088339|118088363|118186330|118186421111936643111193668711119366927 |119366946|1193671011119367610|1196790811119679125|119679323|119759523|119760250|120223262|120223429|120223681112022 3787|120252643|121530475|121530606|121530704|121530712|121530803|121530902|121649587|121649633|1216496711121736657|1 21737298|121755334|121755800|121756068|126656255|127107350|127293858|127294132|127294277|127294349|12738724111273878 59|127388095|1274082811127416174|127423253|127526239|127526444|127526447|127526533|127526889|127526922|127675036|127 7012711127810622|1278112911127811344|127858052|127858067|127858204|127858388|127886832|128027340|128027399|128028096 |128028104|128028248|128090974|128091115|12809124111280914011128091635|128091906|128233472|128233478|128317910|12831 9077|128322227|130181789|130182107|130342221 |130342412|130342455|130342740|130342834|130342861 |131093336|131105369|1 34120074|134918652|135052370|135052455|135531548|135532144|135532182|135741842|135741947|135875860|135876037|1358766 32|135876638|135985476|135985852|136116728|136117146|136117745|144516874|144517408|144520285|148644103|148645053|149 587856|149587915|15128961111512897811151409850|1514099811151828026|151828558|151828675|152175855|152717369|152717653 |152717668|152717683|152717910|152718600|152718619|156436252|156436292|156436349|159615907|159712178|159712254|15971 23011159712307|160407542|161161078|161308189|161308256|161308258|161308372|161308469|161308482|162318534|165794789|1 65953579|165953767|168247228|1682474611168890494|169364593|169573693|1695739311169584287|169584295|169584443|1695845 44|169694375|169694436|169694576|169694753|169694842|169733788|169733928|169798753|1697988111169827409|169827687|170 929019|170973804|171160095|171160922|171161257|171434063|171687392|171687936|171894273|171894484|171894578|171922240 |17192245111719226011171922772|172000069|172102937|172102942|172102948|172427479|172427488|172427534|172427540|17242 7543|172556035|172556050|1730759111173354620|173355472|173964568|173965725|173965775|174248879|1743953811174395607|1 74395668|174395700|174486743|17448692111746826711175005476|175167799|1751678111175167825|175167872|175168177|1751683 97|175181242|175181740|176002428|1771488511177149079|177212460|177212596|177263922|177263959|177264038|177264044|177 264270|177265556|177392837|177552787|178112488|178112614|1781130911178413605|178450685|178450920|178451221 |178451434 |178478770|178478772|178480295|1784804411178480446|178480476|179264180|179264885|180007084|181457059|182716179|18271 6223|183124240|183124339|183124379|186486016|186486089|186486182|189440798|189440977|189441093|189441162|189441765|1 89661195|189661447|189674786|189763204|189783737|189783908|189784413|189784552|1903196111190319842|190344296|1904078 78|190408005|1905346111190648329|190880522|190880690|190880776|190880923|190881010|190881826|191013960|191013979|191 0144011191020294|191020627|191677822|191677874|191677877|1916781511195656949|195656966|195657010|195657048|195657068 |195657217|195657653|196068542|196068822|196068932|196170866|196171573|196171676|196171916|196639514|196799645|19692 6672|196926695|197199057|197309818|197310313|197434565|197434707|197434862|197435022|197435210|197435216|197435237|1 97453278|197453289|197453548|1974993911197499805|1974998611197499872|197499906|19750006111975003411197515660|1975157 4111975160011197516030|197516040|1975166111197705188|197705314|197705349|199911562|199955276|199955502|200510019|200

[0273] 52

[0274] CAN DMS: \1015053120\1526166|200811668|200812242|200812313|200864556|200864616|200864640|200864679|200864691 |200864853|200889417|200963554 |200963557|201071885|201071948|201071986|201116423|201118510|201118580|201257649|201451383|201451492|201451596|20145 1647|201452017|201642876|201643506|202238222|202238709|202265680|202265715|202265870|202375968|202376304|202376384|2 02634946|202635008|202871633|202871707|202871800|202871802|202912137|202912256|202912258|202912272|202912274|2030147 57|203239448|203328068|203328083|203328128|203328131 |203535443|205682439|205682507|206086030|206159464|206159473|206 159624|206159838|206765230|206765251 |206765435|207167010|207529242|207529726|207529790|207530247|207530265|207625367 |207625378|207711408|207711413|207711473|207711475|207769397|207769480|207770209|208025498|208025515|208254306|20825 5513|208266165|208266254|210476591 |213151506|214809381 |215311803|215311827|215311850|215312114|216013261 |216013617|2 16013628|216013743|216081822|216081894|216081903|216081957|216109220|216109265|216109337|216412359|216412552|2164126 31 |216498897|216499100|218034890|218216987|218217033|218217191 |218217292|218217304|218217308|218269976|218270124|218 270255|218270508|218323306|218323474|218368152|218396506|218398426|218399290|218399559|218400073|218568390|218568392 |218568880|218659352|218659702|218671726|218671956|218671965|218710759|218710765|218710779|218711273|218893002|21916 0496|219160878|219177204|219177483|219178210|219178219|219178799|219206915|219229446|219229449|219229570|219229677|2 19229792|219230361 |219245360|219252982|219253146|219253876|219253950|219254048|219279118|219279258|219295052|2194988 62|219498864|219542034|219597800|219597912|219598108|222656092|222656126|222656133|222861028|222861304|223837982|223 945275|223957218|223957512|224038610|224038770|224039260|224585895|224585919|224586142|225041368|226791532|226799637 |226836122|226836145|227325699|227325944|227326056|227472093|227472212|227472538|227472762|230219808|230327201 |23041 1648|230411953|230416163|230416192|230712931 |230713589|230713933|231056700|231056801 |231056881 |231057238|231198475|2 31198537|231198673|231198685|231464385|231464553|231514415|231514511 |231514617|231612799|231613741 |231677821 |2317064 47|231707109|231707524|231708356|231708370|231709302|231710258|231781196|231781386|231786399|231786424|231786427|231 786480|231926391 |231961476|231961565|232550481 |232550739|232550742|232550755|232605992|232697313|232697766|233060291 12330604711233251484|2332514911233251503|233251659|233251776|2332519511233354318|233854655|237086232|237966891123806 0612|238060812|238060850|238203786|238203929|238288306|238288498|238320354|238320541 |238320560|238320724|238426806|2 38426825|238427181 |239400707|239401023|239401139|239401669|239401911 |240025598|240136103|240136484|240136641 |2405690 62|240586264|240586394|240587103|240587417|241102420|241102426|241149433|241149527|241149584|241150317|241150324|241 150473|241150530|241272502|241272504|241315350|241315743|241315750|241315855|241315870|241315921 |241316006|241356193 |241356363|241508740|241508743|241610222|241636435|241636996|241637443|241637744|241638120|241686801 |241686844|24168 6855|241687121 |241701434|241701843|241701969|241702061

[0275] chr3:

[0276] 3126886|3179755|3179881 |4303364|4303490|4303562|4303564|4303575|4467008|4467191 |4492776|4493107|4493221 |4493255|49790 57|4979174|4979569|4980457|4986989|5122202|5122205|5187274|5187693|5188124|5195793|8963543|8963546|9249590|9397537|939 7554|9397587|9649311 |9649358|9650129|9731567|9732381 |9749831 |9750300|9792993|9810142|9810178|9843912|9843918|9844038|9 84413119890498|9933372|9933652|9933683|9933736|9933780|9933824|9933849|9952250|9952377|9952421 |9986696|9986846|100111 09|10011216|10026264|10026458|10026580|10115471110115636|10115642|10142037|10248403|11272250|11272329|11642877|116438 33|11719135|11719627|11720779|11846866|11846960|11846981112484251112484264|12557325|12663792|12664205|12796637|128420 04|12967626|12967734|13419586|13420160|13479753|13479870|13480024|13480134|13480142|14124388|14124844|14124933|141250 10|14125063|14178350|14178355|14178357|14178614|14178671114651561114947322|14947328|14948165|15064981115099100|150992 85|15099292|15099382|15205965|15427338|15427678|15601780|15601814|15859732|16178536|16264943|16265002|16265088|162651 29|16265177|16265191 |16265302|16513403|16513872|16884842|16884845|16884847|16885181 |17741999|17742906|18424989|184447 49|18444813|19946968|19947636|20040024|20040090|20186024|20186178|20186297|20186309|20186448|23806641 |23916473|239169 99|23945444|23945715|23945939|23945968|23945976|25664039|25664939|25664946|25783433|28241426|28241577|28241682|283491 46|28349339|28349442|28349507|30606316|30607525|30658564|31532570|31532806|31532817|31533003|31981271132238988|323919 01132401787|32402004|32502584|32502772|32570384|32570870|32570949|32570969|32570987|32685042|32685044|32685277|326852 94|33097021 |33113752|33114150|33439791133440361133440477|33440909|33441122|33717396|33717930|33718399|33798323|337983 74|33798535|33798977|36944505|36945022|36945064|36992663|36993004|36993170|36993239|36993599|36993677|36993714|369937 29|36993791137176502|37243092|37243099|37243103|37243108|38025294|38039213|38136644|38136765|38138394|38138445|381384 94|38138612|38165239|38165339|38165348|38346681138496228|38496258|39052004|39107523|39107529|39107547|391075811391076 90|39153619|39180928|39406493|39406595|39406726|40309667|40309673|40309719|40310259|40453180140453242|40457327|404573 51140505944|40524794|40524906|41199214|41199496|41962061141962232|42014228|42014436|42581723|42582019|42582065|425823 37|42590766|42590783|42591130|42600492|42600506|42600561142600654|42773260|42773301142773362|42804595|42804616|428046 90|42881243|43286509|43622374|43690811143690837|43691079|43691742|44439832|44477571144510824|44761662|44761675|447617 99|44761801144861838|44861971144862024|44975408|44976363|45388384|45388537|45388556|45388560|45388597|45593959|455941 98|45594201 |45689196|45689255|45689307|45689728|45689748|46883278|46976491 |46976804|46979429|46979483|46979658|469797 21146979906|46980067|47163437|47163944|47164137|47164166|47164174|47164811147282523|47282661147282980|47283043|473809 68|47381082|47381650|47475773|47476010|47476014|47476131 |47512838|47512929|47513459|47513825|47513872|47781577|477820 34|47782041147782148|47782330|47802697|47802772|47802801147802825|47802831147802873|47803163|47825065|48188353|481887 30148240984|48241100148241151148241326148301344|48301390148301509148301541148301674|48429390148429824|484400051484400 58|48440115|48440223|48440286|48440346|48440733|48446571 |48446815|48447019|48556786|48557205|48609821 |48635544|486355 52|48635568|48685874|48717319|48717343|48847756|48847881148898957|48899023|48918530|48918582|48918780|48919504|489898 50|48989914|48990395|49007030|49007040|49018653|49018707|49018735|49020328|49020502|49020900|49021142|49021153|490220 54|49022238|49029392|49093471149094105|49094234|49104612|49104857|49105126|49120766|49120864|49120870|49120944|491209 55|49166336|49166338|49171468|49171572|49340109|49340269|49340518|49358490|49411916|49412056|49412070|49412074|494124 15149429428|49429854|494697531494701121495543151495543191496745401497234821497241671497242901497862311497864611497867 18|49786727|49786751149786815|49802714|49803279|49856531149929728|49929831149929925|49939937|49939955|49939957|499399 85|49939995|49940158|49940163|50088820|50088843|50089578|50155016|50226254|50226278|50236100|50236278|50238014|502730 53|50273408|50291990|50292419|50292452|50292595|50292600|50298987|50299359|50299396|50299399|50299425|50299555|503215

[0277] 53

[0278] CAN DMS: \1015053120\150150321588|50328121150328296|50328367|50328411150328444|50337239|50337430|50337432150337501150337518|50337523|503377 33|50337763|50341000|50341096|50350684|50350701150350891150359543|50503595|50503597|50503764|50568915|50611730|506118 38|50611867|50612195|50612252|50615966|50617068|50617355|50617357|50617527|51385014|51385066|51385075|51385226|513852 45|51385401 |51391090|51391217|51391220|51499466|51499984|51500282|51538728|51671069|51671072|51671081 |51671134|516718 96|51941952|51941954|51974986|51983481 |51996041 |52056126|52056716|52057266|52057468|52057588|52154562|52239275|522392 79|52239289|52239291 |52246021 |52278941 |52287916|52410601 |52410749|52411210|52455405|52455429|52533588|52533617|525365 70152536575152685559152686015152686019152686040|52686045|527056711527059111527059591527061371527062301527063111527705 44|52771062|52771184|52897290|52897516|52897588|52897641 |53045780|53130409|53130560|53130603|53160929|53161132|531960 94|53255274|53255712|53256102|53347558|53881774|53882108|53882264|53891560|56556912|56556914|56682730|57170256|572274 91 |57227523|57556099|57556300|57556742|57597550|57597553|57597676|57597682|57692787|57692876|57692946|58008177|580082 66|58008287|58008372|58177887|58237646|58306169|58306474|58333033|58333233|58433648|58433861 |58433982|58491846|584918 87|58492217|63864416|63864602|63864788|63912104|63912447|63912922|64023420|64023466|64023472|64023478|64023541 |640235 50|69013623|69013906|69051563|69052071 |69052312|69052503|69080310|69084775|69084797|69085351 |71064417|71582593|715830 37|71583526|71584675|72446714|72446750|72446815|72447302|72848109|72848389|72848395|72848480|72848527|72848641 |729971 89|81761204|81761470|87227076|87227227|88058986|88059035|88059059|88059353|88059559|88149367|88149720|88149735|881499 73|88150006|88150124|93973920|93979924|93980120|93980122|94063181 |94063263|98522714|98523083|98593179|98593671 |985936 90|98593700|98593703|99817917|99876189|100260703|100260738|100261008|100334644|100334752|100335082|100400874|1007092 96|1007093011100709303|100709328|100709554|101513265|101513388|101513439|101574047|101574112|101574165|101574176|101 677128|101677164|101677200|101677240|101686367|101686553|101686817|101686828|101686843|101724564|101724575|101724635 |101779013|101779136|101779138|101779435|101849329|101849396|101850007|101850201 |105366753|105366770|105367147|10586 8875|105868877|105868970|105869176|107240702|107240745|107522789|107523777|108090848|108091109|108091126|108091149|1 08222395|108589410|108589676|108589756|111674489|111674606|111674693|111674741 |111860311 |111978907|111978969|1119790 45|11197924111125618311112562039|112990922|112990924|112990940|112990946|112991273|112991344|113019530|113515210|113 515218|113515246|113532342|113532869|113533132|113696415|113696799|113746273|113746736|113947578|113947737|114056618 |114056625|114056629|114056734|114056931 |115147395|115148276|115658745|115658897|115784673|119240621 |119240699|11924 0716|119240993|119241003|119293902|119294208|119294737|119463435|119463676|119463698|119463823|119468839|119498395|1 19676995|119677180|119677378|119677466|119677514|120094463|120094469|120094717|120094842|120349378|120596178|1205962 80|120742502|121660944|121749705|121750098|121835093|121835165|121835168|121835172|122383288|122384076|122384189|122 384306|122416067|122416159|122416186|122416202|122416212|122416217|122515005|122515033|122515056|122564164|122564405 |122564418|122564466|122681159|122794114|122795102|123067085|123202094|123202247|123584617|123585265|123585286|12358 5561 |123961372|124730465|125055663|125056011 |125056033|125375472|125520186|125520219|125520223|125520273|125520354|1 25520465|125520483|125595246|125595493|125595680|125595722|126083772|126084169|126475616|126476065|126704102|1267042 13|126704220|126704222|126704226|126704244|126704277|126983462|127590181 |127590669|127590876|127591010|127591067|127 598294|128052218|128052246|128052474|128052482|128052918|128123873|128123890|128124048|128153304|128153435|128153445 |128650087|128650519|128650841 |128680934|128681377|128879252|128879351 |128879475|128879626|128879645|128879846|12916 1211 |129161217|129183877|129249508|129249554|129316199|129316297|129316368|129439959|129440041 |129440171 |129605658|1 29893125|129893726|130893835|130893940|130894447|130894563|131502986|131503001 |131503006|132417258|132417506|1324175 08|132659761 |132659909|132660139|132722338|133573696|133574583|133661876|133661902|133661944|133661946|133661963|133 805728|133805814|134250434|134485587|134485912|134485936|134486015|134486180|134486410|136194491 |136194648|136195537 |136195703|136195903|136195915|136195952|136197121 |136250294|136752534|136752720|136752961 |136862125|136862193|13686 2878|138174590|138174951 |138187224|138187371 |138187559|138329904|138594324|138594478|138594551 |138834049|139329496|1 39344083|139344174|139389556|139389631 |139389693|139389698|139389740|139389839|140941615|140941661 |140941906|1413117 67|141487260|141487852|141738005|141738473|141876261 |141877481 |142149152|142225235|142447689|142448215|142578793|143 001292|143001450|143001452|143001735|143119153|143848008|143970968|143972149|143972567|148991791 |149129811 |149752584 |149752588|149971059|149971139|150221454|150408748|150409769|150546159|150546491 |150546589|150546810|150703912|15070 4231 |150761973|150762043|150762493|152268551 |152268821 |152269535|153160574|153160827|153161062|153161524|153162309|1 53162312|153163193|153163392|154324489|155744513|155806402|155870593|156554896|156555117|156555236|156555282|1566746 28|1568170711157088963|157160112|157174823|158110178|158110376|158644520|158801942|159988760|160399225|160399522|160 399714|160399782|160400396|160400402|160400822|160401055|160565097|160565583|160565588|160565594|161221370|161221404 |161221444|167734775|167734935|167734957|167734969|167734982|169765111 |169772965|169773177|169812480|169966895|16996 7154|169967300|169967530|170037960|170181277|170357455|170357664|170357985|170358152|170358240|170870266|172039716|1 72040383|172711050|172711084|172711323|172750955|177196476|179071438|179071919|179071996|179148432|179148907|1791493 63|179322582|179323112|179323586|179323700|179347629|179347644|179347650|179451464|179451783|179604458|179604646|179 604666|179604856|179652991 |179653036|179653326|180989663|182793113|182793524|182793544|182794345|182980221 |183428158 |183428223|183428624|183428633|183447642|183447648|183447806|183555769|183635605|183636105|183697908|183825126|18388 4895|183884958|184017872|184018038|184155138|184155189|184174805|184174812|184174818|184185925|184185994|184186009|1 84186186|184229568|184249609|184249748|184249755|184314495|184314498|184314923|184315094|184363022|184363374|1843634 20|184363434|184513925|184514014|184711995|184812655|185499079|185499089|185586040|1855861711185938007|185938127|186 566958|186567247|186567449|186570654|186783296|186783342|186783505|186783934|186784250|186806325|186806509|186806511 |186806517|186806522|186806785|186806961 |186930490|186930496|187737946|187738659|187738676|187738791 |187738993|18773 9687|187744008|187744298|187744833|187745506|187745719|188153731 |188153742|188153750|188154013|190513878|190514026|1 90514028|190514144|193593062|193593097|193593335|194003258|194003375|194058451 |194071281 |194071476|194135100|1941351 46|194135149|194135326|194136130|194487119|194487358|194487530|194633186|194633511 |194633627|194672110|194672201 |194 672249|194672502|194672600|194672610|194672648|194685843|195260037|195260426|195270956|195271531 |195443097|195443208 |195443343|195542885|195543496|195543522|195543529|195908094|196081384|196081731 |196082008|196082050|196082327|19608 2484|196287801 |196287822|196287925|196287931 |196287951 |196318351 |196318353|196503437|196503578|196568544|196569395|1 96632777|196632987|196639550|196639566|196640123|196712402|196867708|196942585|196942729|196969640|197029750|1970298

[0279] 54

[0280] CAN DMS: \1015053120\144|197297838|197298102|197298527|197299148|197456610|197736939|197736974|197737005|197737074|197737220|197737272|197 749444|197749720|197750360|197750555|197791287|197791473|197959984|197960309|197960338|197960371

[0281] chr4:

[0282] 499067|499272|499312|674263|674355|674487|674504|674520|781828|932066|932350|932506|932519|932527|932550|986820|986888| 987253|1012449|1012452|1248488|1248969|1249299|1289608|1289684|1289772|1289879|1346124|1346296|1346418|1346563|134681 4|1347098|1347124|1347128|1347193|1347276|1347583|1347787|1712323|1712328|1712672|1713045|1721331 |1721401 |1721691 |1748 715|1748749|1856090|1862407|1870889|2008974|2009199|2009279|2009357|2009652|2242274|2261911 |2261945|2262095|2262105|22 62123|2262470|2262597|2418970|2468576|2469298|2537207|2756195|2756557|2843508|2843604|2843717|2843726|2843849|2934271 | 2934856|293492112934979|2935005|2962937129631111296342112963464|2963468|2963476|296366112963665|3074532|3074618|30748 30|3075180|3292673|3532549|3532559|3532581 |4248256|4290096|4290148|4290267|4290281 |4290286|4290507|4290560|4541972|454 2180|6640525|6640592|6640706|6641371 |6673953|6674029|6709423|6709865|6709985|6716098|6716105|6716254|6782443|6783353|6 909282|6909285|6909763|6909767|6987026|7043010|7043132|7043136|7043146|7043241 |7043251 |7043254|7043263|7068184|815883 9|8158842|8158853|8158857|8428422|8440776|8440914|8440939|8441239|10116636|10116641 |10116835|10116892|10117053|134842 73|13484908|13628135|15002177|15002467|15003002|15003842|15003863|15003866|15003893|15654880|16226439|17512211 |175772 35|17577379|17614159|17614380|17614616|17614642|17810641 |17810788|17810839|17810850|17810950|17810958|18021642|180221 02|18022332|20700266|20700327|20700367|20700422|20700706|20700754|24584624|24584626|25160398|25160417|25160590|251606 53|25160731 |25160859|25233837|25233992|25312596|25312778|26319514|26319521 |26319608|26319614|26319616|26319637|263197 34|26320722|26583723|26584065|26857864|26860361 |26860435|26860560|26860567|26860575|26860834|26860861 |26861230|362442 36|36244720|37686794|37826471 |37826762|37826959|37977545|37977682|38319016|38663978|38664827|39044572|39044983|391822 62|39182399|39182509|39182521 |39182852|39366323|39366368|39366381 |39366406|39458468|39458620|39458770|39458893|394589 02|39458979|39459290|39459535|39527649|39527734|39527745|39527766|39527790|39527792|39638103|39638537|39638951 |396389 54|39638972|39639162|39697770|39697935|39697983|39698339|39976508|39977690|39977752|39978163|39978168|40055621 |400559 25|40056724|40056986|40057297|40057390|40057864|40057995|41935165|41990468|42656427|42656935|42657269|44678845|474636 591474853391479140331479140391479146191479146231479147421482699011482699251482700601482701031482702491483413161483416 06|48779894|48830935|48831071148831263|48831275|48831288|51842543|51842990|51843034|51843192|52712311153377518|533775 66|53377662|55346059|55346204|55395938|55396278|55396535|55546092|55546576|55547044|55547062|55948907|56387354|563874 07|56387502|56387649|56434954|56435806|56435832|56435917|56467693|56907717|56907789|56976962|56977374|56977668|675454 59|67701243|68349957|68350035|68350068|68350147|68350178|68350183|68350194|68350202|70688165|70688168|70688178|706883 47|70705497|70839091170902257|70902260|70993755|70993996|73069660|73069755|73069761173069807|73069885|73258747|741581 32|75514385|75514485|75514488|75514616|75673290|75673293|75673340|75673499|75673583|75673609|75673633|75673709|756737 15|75724538|75940652|75941123|75990989|76148415|76148420|76148545|76213852|76214033|76214052|76214194|76949620|769507 41177075360|77075687|77076035|77076048|77076774|77156759|77862951177863109|78775493|78776175|78776429|78939225|789395 32|80072665|80073082|82285263|82285381 |82372767|82372948|82374129|82374178|82374208|82429381 |82430300|82430361 |824305 23|82430529|82430705|82798886|82798949|82891118|82891212|82891356|82891363|82891466|82891552|82900547|83012903|830131 21183035098|83109989|83110255|83284229|83284559|83334825|83455832|83455845|83455906|83455923|83455956|83456210|834851 75|86934722|86934785|86934790|86934820|86934830|86935276|87006503|87006826|87006891 |87006958|87007209|87219842|872206 74|87391303|87391369|88007918|88008459|88158657|88284185|88284739|88284897|88523770|88592389|88592407|88592410|885927 71188593026|89307664|94207543|94207775|94207859|94451696|98261265|98261271198261404|98261647|98658464|98658820|989285 02|98929100|98929107|98995225|98995851 |98996229|98996393|99088749|99088842|99088909|99088931 |99089060|99563748|995638 49|99564034|99894655|99894661199950377|101346032|101347697|101348217|102344790|102345070|102345264|102345266|1023457 50|1025022111102760784|102760939|102826715|102827210|102827968|1028280511102828569|102868805|102868899|103076730|103 198039|103198369|103198482|105146715|105473664|105473872|105474164|105708638|105708689|105708858|106316026|106316834 |107720192|107720446|107720450|107720596|1079896311107989712|107989714|107989918|108168345|1086208811108650568|10943 3664|109433740|109434524|109560136|109560140|109560146|1095608011109703195|109730035|109815337|109815447|109815475|1 098154911110196434|110197076|110197335|110198064|110198202|110198733|112145915|112231603|112231694|11223172111122857 19|112285907|112286079|112516074|112636788|112637125|112637394|112637400|1126374311113762666|118685429|118835714|118 836086|118836580|118836600|119300610|11930062111193008311120066557|120066863|120066976|120067000|120067260|121801458 |121801564|121823677|121823840|121823945|121823949|1218239511121824078|121824105|121870607|122152620|122732823|12292 2120|122922428|1229225811122922616|1229232611123398104|127880848|127880850|127880855|127880858|1278810711127965127|1 27965153|127965255|127965266|12796527111279652911127965677|127966040|128060763|128061299|128062286|128287940|1282884 47|128288453|128809515|128809564|128809574|128809577|1288100011128810180|129093214|129093544|129093549|129093556|129 093623|129093663|139015663|139015669|1390156711139082915|139084604|139178150|139178247|139295616|139295844|139295909 |139301369|139301466|139301490|139301548|139301909|1393024711139453289|139556338|139556566|139556573|139556909|13965 1790|139734942|140253103|140373875|140524039|140524093|140524152|140524239|141220884|141220891 |141221120|141221284|1 43184439|143184586|143185013|143336539|143337295|143513266|143513288|143513290|143513418|143513484|14351397111450981 80|145098216|1450985811145179444|145179806|145180407|1451809311145619393|1456194011145619424|145938865|146175757|146 521992|146522063|146522085|146522105|1465225511146522569|146522844|147617340|147617343|147617370|147617376|147617490 |147684178|147684190|147684246|1476842611147684315|147684412|151014730|151015887|151099464|1510995711151760942|15176 10811152535173|1526799711152779519|152779734|152779736|1527798911153249258|153344263|153344464|153344907|153345042|1 53345061 |153466269|153466451 |154550415|154550441|155953614|158672019|158672079|158672088|158672245|158723389|1587234 06|158723409|158723462|158723489|159103936|163166709|163166943|163167034|163494396|163494434|165113000|165207851 |165 327303|165327315|165327473|165327561 |165327563|165327655|168480331 |168832059|169010313|169270812|169612274|169612467 |169612488|169612605|169620101 |169620395|169758077|173168251 |173168934|173170271 |173334408|173335252|173370844|17428 3654|174283874|174284008|176320069|176320468|177309780|177309789|177309818|177310289|182916937|182916944|182917583|1 82917600|183398551 |183398881 |183444460|183444721|183444735|183444894|183445083|183505230|183658786|183659213|1836592 26|183659248|183659309|183659355|184474698|184474733|184474744|184474760|184474828|184475144|184649722|184734081 |184

[0283] 55

[0284] CAN DMS: \1015053120\1734198|184734295|184734305|184825907|184826221 |184826225|185204180|185396606|185396734|185425656|185425894|185425944 |185426145|185426249|185426280|189793221

[0285] chr5:

[0286] 219012|271438|271454|271462|271494|271566|443339|472892|473265|473996|612140|612162|612182|612418|892592|892595|892598| 892609|892616|892900|892907|892934|892957|89296111344727|138589011386035|1523759|1524112|1645153|1799372|1799603117999 58|1801368|5422083|5422686|6378130|6378525|6378534|6378621 |6378769|6632998|6633184|6713118|6713313|6713321 |6714079|671 4424|6714542|7868897|7869144|7869180|10353220|10353323|10441553|10441733|10441791 |10441991 |10442129|10564257|10564259 |10564336|10564402|14664553|14665369|14872098|14872275|16616725|31532182|31532203|31532414|32174464|32313329|32585498 |32585633|32585635|32585789|33440613|33440736|33440738|33440957|33440964|34007778|34007840|34008022|34008358|34915516 |34915531 |34915661 |34915700|34915944|34916313|34929853|34929855|36151256|36151896|36152023|36152033|36152075|36152104 |36152106|36152124|36242118|36242233|36606499|36690335|36875435|36876435|36876565|36876578|36877524|37249303|37370778 |37370865|37370945137370954|37371090137371111139074021139074383|39074566|39074575139074685139074960140679631140679643 |40679730|40679931 |40756139|40798352|40798581 |40835408|41904354|41904448|41925284|41925670|42992672|43008717|43018180 |43018341143018527143040896143042075143042186143042624|43066204|43066373143066436143067031143120840143121473143121477 |43121797|43122070|43313308|43313542|43313623|43483662|43483982|43514886|43515116|43557033|43557380|43602503|43602564 |43602817|44808736|44808952|44808996|50441402|50441515|50666675|52799661 |53109836|53109845|54517701 |54517711 |55173229 |55233624|55233796|55233798|55307601 |55307613|55307616|55307704|55307716|55307726|55307773|55307796|55307891 |55307897 |55307961 |55308330|55534678|55534701 |55535143|55712340|55712382|55712388|55712411 |55712503|55712525|55712649|55994811 |55995176|55995560|56481290|56481643|56815009|56815595|56952416|57173355|57173495|57173900|57173934|60699888|60700198 |60700201 |60700239|60700278|60700288|60700293|61332189|61332266|61332549|61333048|62403865|62403924|62404007|62404041 |62412606|62412813|64768431 |64768675|65035807|65035967|65481851 |65481950|65563106|65563145|65563170|65563303|65624055 |65624179|65624362|65624371 |65624433|65624612|65624625|65624855|65722239|65722328|65722350|65926520|65926537|66144271 |66144283|66144646|66144935|69093877|69094169|69094530|69189593|69189595|69234939|69368946|69369415|69369566|69369721 |69369735|69369773|69370113|69560250|71455608|71587238|71587245|71587260|72320299|72320635|72816504|72816536|72816632 |72816902|72848937172955931173498261173565212173565334|73565341173565357|73565362173565424|73565611173565924|74640612 174685141 |74685143174685288174685481174766999|74767021174767131174767185|74767235|75337097|75337101175337115|75337141 |75337197|75511710|75511717|75512082|75717517|76402907|76403459|77087060|77210667|77776041177776185|78294670|78295596 |78295674|78360271178360359|78360379|78360655|78510346|78984659|78985059|79514350|79612174|79612307|79612397|80256051 |80256246|80256314|80256358|80407918|80407931180488187|80654256|80654301181301565|81301574|81301576|81301663|81301690 |81301732|81301899|81750939|81751667|81971885|81971903|82278026|82278337|82278506|83077048|83077335|83077341183077457 |83077527|86617853|86617889|86618338|90409529|90409818|90410198|90474043|90474760|90474783|90474934|90529718|91280611 |91280640|91380789|91383317|91383392|91383403|94618593|94618598|94618726|94618823|95554983|95555079|95555113|95646723 |95646729|95731141195731607|96662019|96807889|96807895|96808373|96935257|96935493|96936118|96936514|98770874|98927713 |98928579|98929560|100900635|100900662|100902951 |100903273|100903279|100903318|100903346|103119805|103258422|1032586 46|103258792|103259204|108380767|108381929|1083822711108382274|108382342|108728199|108728340|109409693|109409728|109 409874|109410252|109689196|109691176|110738683|110738962|110739477|111092335|111512990|111757320|111758058|112707578 |1127376511112861153|112861247|112861500|112921915|113513588|113513913|115262877|115544109|115544633|115544684|11554 4811 |115544970|115545048|115625862|115626138|115626482|115626539|115841797|115842080|116084847|116085455|118988165|1 19070867|119071275|119071540|119269112|119452596|119452657|1219617911121961810|121961880|121961989|122774944|1227750 30|122775470|122845322|122845328|122845330|122845410|123422965|126776747|126777055|126777058|1267771911127030505|127 030780|127030796|127517686|128082855|128083092|128083258|128083900|129094476|129094548|129094562|129094566|129094970 |129095368|1311644711131170785|1312638111131263959|131635036|131635140|131635328|131635333|131635342|131635418|13163 5429|131797108|131797143|131797312|132294217|132294288|132410724|132410978|132490173|132490766|132490919|132496620|1 32496860|132557314|132737094|132737565|132737578|132737584|132777449|132777509|132830207|132866552|132866589|1328666 59|1329635511133026543|133051609|133968824|134004845|134004879|134004990|134114547|134114590|134114624|134115546|134 115549|134177179|134177181 |134226259|134226292|134226338|134226399|134226468|134226716|134226736|134366985|134367149 |134371025|134371047|134371128|134411902|134412012|134412145|1344659911134526030|134526043|134526053|134526056|13463 2606|134632876|134632978|134648699|134738494|134738496|134738714|134738747|1347585111134758673|134758692|134758736|1 34758838|134845804|134845837|134845839|134845910|134845917|134874334|134874543|1349050811134905087|13490549111350342 10|135034343|135399214|135399244|135399378|135399414|135399570|137753930|137754334|137754395|137754399|137754513|137 754960|138178696|138179320|138331746|138331866|138332118|138337978|138338213|138338505|138352566|138352734|138353005 |138438955|138439195|138465352|1384654211138465476|138542823|1385754311138575476|138575507|1385758111139198182|13919 8448|139274272|139293493|139293502|139294766|139342252|139342509|139392996|139393015|139403845|139404184|139404189|1 394042711139439229|139439417|139439448|1394395111139561109|13956111111395617811139648483|139648564|139648569|1396494 38|139649917|139649957|1397113511140108106|140175684|140303135|140357840|140401086|140401292|140401733|140547606|140 547686|1405573611140557429|140564495|140639326|140639339|140639344|140639357|140639359|140639702|140639885|140647148 |140647340|140647646|140647648|140664730|140664867|140691397|140691416|141619042|141619062|141619065|141636905|14163 6910|141637702|141692094|141914352|141923695|141923728|141968949|141968967|141968985|141969190|141969538|142012972|1 42013087|142013091 |142108879|142109046|142109300|142770371 |142770450|142770756|142771240|143402850|143403814|1434038 20|143404074|143404278|143404897|143405417|144170556|144170724|146182871 |146182967|146447179|146447206|148383830|148 383978|149345392|149345478|149345513|149357789|149357836|149357916|149357963|149357996|149550811 |149551508|149551515 |149551520|149551524|149551640|149960489|149960562|149960591 |149960721 |149960736|149960757|149961205|150000447|15000 0462|150000581 |150000670|150000684|150001093|150357497|150357515|150357740|150358091 |150449617|150449687|150449807|1 50449813|150449827|150449830|150450105|150656837|150701140|150758326|150759023|151080602|1510809511151081428|1512237 41 |151223992|151224078|151447492|151447597|151758519|151758807|151758812|151758847|151771020|151771528|151771864|151 771886|151771961 |151772043|151772498|154038866|154038901 |154038966|154038979|154039108|154405296|154445962|154446226

[0287] 56

[0288] CAN DMS: \1015053120\1|154446736|154755492|154755610|154857375|154857810|154857940|154858609|154858782|154938246|154938324|157142380|15726 5962|157266045|157266284|157575705|157575797|157575809|157731630|157743438|157743566|157743593|157858948|159099324|1 60009027|160009452|160119211 |160399815|160400209|160419112|160419216|160419239|163459879|163459946|163460187|1634602 13|163460356|163460446|163504465|163504719|163505466|163506099|168269393|168486486|169583521 |169583596|169583740|169 583833|170297827|171387512|171387652|171387874|171419931 |172006888|172006892|172007016|172107013|172188052|172188458 |172283969|172454422|172697805|172771028|172771138|172771159|172771323|172771873|172772098|172772154|172772315|17277 2415|172772457|172959296|172959354|172959402|172959408|172959410|172983830|172984102|173056358|173144435|173144533|1 73144536|173144563|173144652|173144831 |173145034|173573254|173616650|173616711 |173616738|173616847|175478397|1754784 03|175534243|175968013|175968050|176361533|176361946|176361965|176388444|176388478|176388714|176388748|176389260|176 416711 |176448030|176448208|176536617|176537452|176537863|176538157|176609805|176609955|177006244|177006270|177006639 |177022622|177022646|177022686|177022850|177303197|177312308|177312311 |177312370|177351887|177351923|177357964|17742 6284|177426445|177426835|177427008|177446418|177446652|177446655|177446807|177473000|177473009|177473446|177497577|1 77497673|177497681 |177497826|177517131 |177517495|177554625|177591985|177592064|177599953|177599992|177875788|1781134 51 |178113565|178130699|178130818|178130917|178131099|178153567|178164348|178204445|178204498|178204513|178204523|178 232382|178232584|178627016|178627038|178627171 |178627297|178730517|178730824|178859874|178860111 |179550376|179551233 |179623665|179623687|179623721 |179623751 |179678621 |179698477|179698658|179698824|179698829|179698836|179698922|17973 3250|179820990|179858780|179858854|179858867|179858952|179858978|179859124|179907739|180291685|180292171 |180292190|1 80292199|180292416|180802753|180803022|180803113|1808104911180831154|180831265|180860825|180861429|180861554|1811893 43|181189850|181205251 |181205321 |181206772|181223158|181223194|181223259|181223368|181223516|181243537|181243701 |181 244165|181244389|181246203|181261062|181261229|181261280|181261628

[0289] chr6:

[0290] 475038|692947|693257|710835|711212|1604462|2245515|2764742|2764797|2765265|2765323|2765353|2765711 |2765958|2841641 |284 1912|2842005|284202112971716|2999738|2999858|3118689|3118691 |3118704|3157487|3157693|3157736|3259005|3259012|3259679|3 457032|4018714|4018722|4135375|4135519|4135523|4135610|4776256|4776761 |5003775|5260813|5260858|7107703|7107707|710771 9|7312939|7313382|7389588|7389646|7389815|7389946|7390107|7590172|7590642|7910086|7910608|7911007|8064389|8102548|8102 649|10694399|10694640|10723025|10723173|10723176|10747599|10747663|10747665|10838600|11093591 |11093842|11093861 |11094 058|11172687|11232537|11537781 |11538413|11538534|12011697|12012347|12012769|13328217|13328592|13328737|13328852|13486 701113487436|13487631 |13487647|13487651 |13574610|13574631 |13614670|13615245|13615322|13615351 |13711491113814333|13814 643|13814741 |13924905|14117390|14117672|14118184|15246165|15248380|15248919|15662533|15662793|15662939|15663125|15663 129|16128893|16128987|16128991 |16129079|16129176|16129673|16238436|16760306|16760508|16761675|17600152|17600307|17600 529|17706446|18154870|18155348|18155362|18264056|18264488|18264868|18387329|20401492|20401711 |20401795|20401868|20404 111 |20534401 |24402834|24402908|24403418|24494844|24495036|24645985|24646136|24646245|24646317|24646323|24666757|24666 871 |24667016|24667048|24667112|24719760|24720590|24721575|24775419|25138188|25138677|25278937|25279490|25963214|25992 173|26021540|26021551 |26021571 |26026523|26027285|26027347|26027353|26056331 |26056514|26056537|26087548|26103957|26123 230|26123240|26124373|26126192|26156254|26156259|26156271 |26156329|26233833|26234232|26235059|26284710|26383445|26457 893|26521157|26595860|26595923|26659903|26659961 |27132336|27132892|27133052|27133081 |27133500|27133883|27473187|27473 282|27478886|27502787|27519184|27867625|27894022|28080978|28081096|28081180|28081183|28104781 |28142160|28142196|28251 944|28251966|28252345|28281651 |28839041 |28864070|28864072|28896247|28896275|28896417|28896926|28896937|28896994|28922 841128923110|28923134|28923202|28923204|28923287128923311128923334|28923450128923512128923521128923563128923671128923 957|28924066|28924213|28924302|29017292|29633203|29650071 |29650091 |29752648|29752708|29753117|29753238|29942496|30060 787|30060961 |30061225|30061262|30061362|30061366|30061402|30061593|30066401 |30213185|30213396|30213398|30213406|30213 412|30213417|30213827|30214311 |30325841 |30326236|30326238|30326426|30326664|30327062|30327075|30327077|30327203|30327 259|30345265|30345268|30345344|30345382|30345387|30345397|30345411 |30345539|30345617|30451095|30451125|30453878|30463 807|30463813|30463819|30489475|30489947|30490214|30516146|30555910|30556011 |30556023|30556179|30556335|30556341 |30557 197|30557234|30557335|30557495|30571207|30571212|30571228|30571267|30571282|30571289|30571295|30571315|30571457|30571 460|30615305|30617115|30617250|30617696|30617756|30617859|30617873|30617899|30617953|30626925|30626967|30626972|30646 957|30647005|30647017|30647019|30647575|30647653|30647694|30647768|30647801 |30647843|30672735|30672742|30672748|30672 763|30672766|30672771 |30672816|30672888|30673006|30673073|30673172|30679257|30686633|30686782|30686861 |30686919|30686 939|30686945|30686959|30687420|30687569|30687679|30690880|30691019|30691088|30691241 |30717310|30717452|30717466|30717 534|30717629|30717662|30720195|30720260|30720884|30720888|30720899|30721044|30721485|30721698|30721701 |30742648|30742 670|30742678|30742687|30742705|30742859|30742871 |30742905|30742910|30743121 |30743124|30743878|30744250|30744281 |30884 530|30884789|30908104|30908106|30908115|30908363|30908382|30914310|30914417|30914431 |30914436|30914483|30914516|30955 466|30955593|30955816|31158173|31158226|31158309|31158323|31158372|31158501131158568|31403494|31403646|31403780|31403 837|31492167|31493951 |31494457|31497939|31498342|31541146|31542168|31542300|31547519|31580819|31580822|31581066|31581 084|31620915|31621046|31652128|31652143|31652172|31652577|31652918|31653140|31653195|31660419|31660521 |31660590|31660 862|31664982|31665061 |31665138|31665176|31665178|31665968|31666126|31681312|31681316|31681514|31681595|31702833|31702 974|31702983|31703018|31703197|31703204|31703260|31703398|31703436|31703438|31729753|31729768|31730011131730057|31730 225|31730238|31730260|31730281 |31730332|31735138|31735411 |31739750|31739825|31740022|31740038|31740076|31740145|31740 173|31740179|31740184|31795533|31795535|31795593|31795658|31795693|31795770|31795774|31806828|31806833|31806843|31806 917|31821763|31827796|31827894|31827901 |31834822|31834860|31834879|31835145|31835466|31862587|31862793|31863119|31863 143|31898243|31898509|31901752|31901757|31901763|31901788|31901795|31902323|31902329|31902482|31958792|31958804|31958 809|31958846|31958990|31959004|31959016|31959024|31959112|31959208|31971967|31972020|31972088|31972107|31972233|31972 338|31972463|31972466|31972499|31972573|31972575|31972629|31972631 |31972769|31972774|32127768|32127779|32127804|32128 183|32128202|32130300|32130308|32154066|32154659|32154707|32154751 |32175904|32195527|32195708|32196033|32196037|32196 370|32196433|32196466|32196477|32196605|32196636|32797088|32838712|32838846|32843870|32843917|32843924|32843991 |32844 587|32844884|32844886|32853083|32853085|32853116|32853222|32853417|32853512|32853522|32853801 |32853828|32853862|32853

[0291] 57

[0292] CAN DMS: \1015053120\1931 |32894496|32894556|32894652|32894744|32894770|32953103|32968120|32968275|32968292|32968638|32968878|32970408|32971 558|32971649|32971952|32972000|32972011132972035|32972197|32972232|32972277|32972306|32972323|32972328|32972435|32972 526|32972529|32972535|32972591 |32972607|32972614|32973019|32973022|32973024|32973257|33161611 |33161642|33161790|33192 485|33199850|33199966|33199995|33200215|33200672|33200675|33200677|33200805|33200847|33204690|33204795|33207867|33207 911 |33208310|33208490|33208512|33208565|33208570|33208662|33208830|33208833|33213368|33213616|33248418|33248506|33248 615|33248658|33248835|33248841 |33248983|33249255|33249375|33249416|33249549|33249591 |33249644|33249775|33271483|33271 666|33271669|33271771133272101133272104|33272152|33272200|33272247|33276998|33277011133277199|33277404|33288763|33288 768|33289318|33289335|33289724|33298926|33299154|33299184|33299301 |33299366|33299491 |33299512|33299581 |33299692|33299 758|33299772|33299795|33299865|33299923|33313150|33313430|33313721 |33313728|33313737|33313740|33313799|33313803|33323 136|33323172|33323188|33323236|33323532|33323579|33323586|33323623|33391353|33391370|33391389|33391646|33391663|33391 741 |33391757|33391766|33391819|33391993|33392009|33392012|33392040|33392056|33392065|33410528|33410563|33410568|33411 159|33411273|33411488|33417979|33417987|33418152|33418263|33418265|33418280|33418296|33418326|33418331 |33418347|33418 358|33418371 |33418391 |33425830|33425869|33426025|33428159|33428383|33454125|33454303|33454318|33454325|33454523|33454 535|33454603|33454617|33454626|33454629|33454640|33454649|33454699|33571308|33580203|33620501 |33621242|33621395|33711 386|33711802|33788901 |34196486|34224202|34224228|34236682|34236774|34237888|34248893|34249375|34249395|34392835|34392 968|34425621 |34426198|34426213|34426254|34527347|34696922|34696926|34697257|34757339|34757367|34757511134757582|34791 868|34888062|34888108|34889143|34889241 |35259140|35259451 |35259609|35259738|35297866|35342765|35468246|35468270|35468 421 |35688813|35728082|35776578|35920774|35921108|35921270|36027588|36027590|36027853|36027899|36028282|36196281 |36442 723|36442731 |36442742|36442757|36442970|36442980|36443174|36443200|36547230|36547397|36593949|36594181 |36594188|36678 706|36678763|36680518|36875025|36875089|36885833|36886091 |36985918|36986186|36986362|36986473|37102824|37169962|37169 977|37171177|37257637|37353897|37499989|37500007|37500009|37698570|37819276|37819433|37819963|38640048|38640248|38703 009|38703080|38703191 |38703196|39114826|39115261 |41072012|41072243|41072493|41072504|41073110|41545995|41787254|41787 275|41787294|41787656|41787661 |41895392|41895532|41895703|41921155|41941442|41941794|41941914|41942215|42048933|42048 939|42048957|42050424|42050490|42050609|42453505|42547816|42564131 |42564164|42771283|42771311 |42783122|42783506|42879 554|42890809|42890972|42929005|42929321 |42929493|42929561 |42929860|42979313|42984286|43013986|43014210|43014212|43014 312|43021539|43021619|43021629|43053930|43059387|43059545|43059661 |43076501 |43171060|43171089|43171115|43171139|43171 632|43181999|43229507|43229527|43368981 |43369711 |43427671 |43477536|43516635|43516889|43517070|43576034|43576115|43576 263|43629288|43629415|43629575|43629923|43636070|43687656|44073311 |44073433|44073448|44223467|44238090|44238176|44246 360|44257365|44265298|44313347|44387550|45377238|45377864|45378030|45421798|45422123|45422134|47309944|47309947|47477 575|49463298|49463310|52284709|52284897|52361956|52420005|52420160|52576925|52664226|52664268|52664381 |52670953|52670 956|52671130|52671145|53061795|53061852|53061988|53064853|53065253|53065308|53065488|53347820|53348230|53348361 |53348 956|53349073|53793819|53794279|53795185|57046459|57089975|57089981 |57089986|57090109|57172301 |57172445|57172684|57222 077|57222290|57222463|57317523|57317623|57317718|63573197|63635950|63636159|63636267|63636615|70413257|70667642|70667 683|70667709|70667715|70667845|70667848|73262981 |73263285|73263384|73451956|73461707|73461723|73461768|73462217|73520 285|73521041 |73521044|73521063|73521195|73653726|73653911 |73654052|73695927|75284754|75284997|79077844|79078346|79078 352|79078359|79078382|79078390|79078517|79078729|79078764|79233781 |80004439|80004563|80004598|82247732|82247852|83065 829|83065835|83067646|83067649|83067666|83067729|83067896|83193288|83859558|83859737|84227697|85593744|85593951 |85594 014|85594049|85594063|85643729|85678794|87155233|87155242|87155354|87155520|87155767|87322668|87473161 |87589936|87589 941 |87590120|87702081 |87702260|89080699|89080715|89081403|89117988|89145728|89146045|89352746|89352750|89352972|89352 987|89638404|89638583|89638663|89638690|89638790|89638834|89819788|89819799|89819810|89819843|89829837|89830085|90296 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250317|136289877|136289958|136289960|136290415|136792187|136793065|137219478|137219486|137867183|137868195|138403586 |138404068|138404094|138773328|138987586|138988184|139028497|139028930|139029176|139030060|139134943|139135063|13913 51111139374524|139374535|139374700|139374722|139374730|139374879|142147054|1421471811142147209|142147213|142147217|1 42147219|142147225|142147295|142946456|142947634|143060599|143060690|143450474|143450784|143450878|143537149|1438430 83|143843255|143843263|143843390|144064124|144064669|144095609|144095693|144095713|144095716|144150296|144150427|144 215933|144216469|144284940|145735634|145735657|145814970|145964203|145964278|145964288|145964408|148746525|148747022 |148747248|148747303|149316745|149546008|149546072|149546217|149546219|149566160|149566437|149648638|149717820|14971 8264|149746478|149746602|149749933|149863780|149863833|149864062|149864352|149864363|149864365|150866203|151390449|1 51391411 |151391624|151452158|151452232|151452934|152302169|152302252|152982996|152983053|152983101 |152983160|1529831 66|152983170|152983372|152983678|152983684|152983736|152983749|154733401 |155314651 |156687005|156777333|156779144|156 779847|157380861 |157981880|157982006|158168081 |158168151 |158168404|158168416|158560409|158644160|158644370|158644748

[0293] 58

[0294] CAN DMS: \1015053120\1|158644806|158644952|158818132|158818197|158819309|158819522|158819534|158869806|159692781 |159693200|159726827|15972 6970|159727009|159727765|159761773|159761786|159761799|159761809|159788836|159788871 |159969010|159969075|160992023|1 60992094|163414219|163414363|166275873|166342554|166382970|166383100|166383212|166383218|166383271 |166383403|1663836 90|166956003|166956453|166956727|166956788|166999030|166999216|169701732|169701986|169702064|169702218|169723009|169 7242211169724837|169725069|169751505|169751536|1697517111169751754|170290915|170306363|170306648|170306659|170306662 |170306832|170553143|170554208|170554355|170584637|170584727|170584775|170584857

[0295] chr7:

[0296] 520014|520032|520038|726686|726747|72719118134011816563|816658|975346|975530|975599|993268|1044526|1138158|1138247|113 8265|1138392|1160205|1160211 |1160267|1160300|1160499|1504300|1504370|1504383|1530771 |1531469|1532616|2232757|2233105|2 233139|2241982|2242137|2242139|2242150|2242289|2314409|2314431 |2354754|2403441 |2519789|2520058|2520193|2555202|255562 112555692|2555700|2555704|2555803|2559067|2843895|2844387|2844445|2844524|3043699|3043704|4641946|4682747|4775455|4775 520|4775536|4775588|4775709|5045965|5190107|5190112|5423036|5423509|5424119|5424280|5494781 |5513792|5529436|5529761 |55 30229|5530646|5592778|5592793|5781468|5781596|5781663|5781676|5898596|6009244|6059157|6059277|6059283|6081625|6104496| 6104738|6104741 |6105426|6105483|6105537|6348932|6348989|6349064|6349107|63491111644788116448108|6484179|6484255|65310 53|6577384|6589884|6590559|6615489|6637153|663720116706927|7182429|756739117968502|7968611110939959|10940145|10940272| 10940370|10973899|10974094|16644696|16644879|16645281 |16753713|17940648|19708786|19708843|19709040|21427051 |21428092| 21945659|21945971 |21945995|21946010|21946088|21946117|22082994|22822889|22822895|22823002|22854305|22854459|23014293| 23105357|23105593|23105641 |23105689|23105692|23106536|23181678|23181735|23181811 |23181999|23182060|23182360|23299241 | 23299252|23299278|23299616|23531692|23532026|23532074|23532144|23597193|23597634|23597937|24573507|25125316|25125355| 25125451 |25179991 |25180173|25180357|26200720|26200823|26200850|26200903|26201055|26201281 |26398614|26398622|27161052| 27662797|27663166|28180879|28180881 |28927042|30134980|30134990|30284219|30284229|30284302|30286024|30478581 |30478790| 30478891 |30478917|30594495|30594509|30594542|30594623|30594771 |30594777|30595165|30595598|32490435|32490533|32495577| 32891186|32891766|32892272|33062823|33109502|33109505|33109510|33109525|33109531 |33109665|33129403|33933054|35038092| 35537619|35694550|35694813|35695195|35695198|35800875|35800903|35800924|35801096|36367458|36389861 |36389867|38177996| 38178227|38178230|38178295|38178319|38908933|39566178|39566206|39566681 |39623331 |39623399|39623455|39733241 |39733337| 39733345|39733459|39733476|39733557|39949945|39950124|39950261 |39950268|39950933|40134014|40135054|41943196|42911958| 42912023|42912194|42912215|42932311 |42932357|42932391 |42932571 |43582979|43729517|43839010|43869445|43869625|43869651 | 43869769|43926652|44019305|44044439|44082311144082471144082604|44082711144123542|44123672|44490637|44490640|44490815| 44490886|44490922|44582231 |44582304|44582398|44606342|44606476|44606504|44748658|44748671 |44748832|44749316|44796128| 44796130|44796510|44796514|44796542|44796545|44848091 |44848144|44848156|44848181 |44848263|44848265|44884999|44885189| 44885513|44986660|44986749|44999999|45000008|45000066|45111449|45768954|47979258|50304273|50304735|50308659|50450354| 50450450|54759371154759401155366256|55366387|55571893|55572238|55572703|55572789|55964408|55964911156051538|560516911 56051755|56052148|56064126|56106514|56106606|56106618|56106683|64307463|64313962|64563172|64666566|64794667|65373870| 65750920|65750982|65872937|65982262|65982431 |66075916|66114946|66205143|66205228|66205250|66493621 |66592376|66628687| 66628899|66628902|66654492|66655055|66740483|66740495|66844894|66844966|66921502|66921512|66921872|66995348|66996905| 67302259|67302723|67302852|70694344|70694354|72829309|72829311172829354|73005751173005755|73005775|73521382|73521856| 73522284|73522351 |73522550|73557871 |73557889|73578392|73607192|73667729|73683410|73683556|73683586|73683593|73683630| 73683635|73683637|73739299|73739302|74083715|74083721 |74083764|74083769|74174146|74174348|74174653|74254409|74254547| 74254570|74254607|74254680|74289198|74657437|74657555|74658671 |74964725|75073781 |75073889|75073914|75093134|75486025| 75486350|75486392|75528112|75739019|75739258|75739759|75878970|75915041 |75915197|75994048|75994380|75994669|75994778| 76047931 |76048096|76048190|76302425|76302690|76303534|76303560|76303660|76317944|76318211 |76358293|76359002|76359042| 76359108|76379923|76380155|76393053|76393364|76393610|76549254|77537028|77537893|77537899|77696188|77696381 |77696386| 77798413|77798536|77798915|77798925|77799017|77799020|77799344|77799347|77799362|77799502|78020013|87059783|87152015| 87219695|87219697|87220169|87220528|87345428|87345545|87345606|87345640|87345645|87875786|87875814|87876223|87876468| 87934210|88219886|88220204|88220231 |88220433|90346620|90403494|91263579|91264348|91940529|91940731 |91940983|91941186| 92245900|92245920|92245978|92447420|92447582|92447713|92447717|92528237|92528362|92528625|92528659|92528678|92528741 | 92528979|92589965|92590401 |92834020|92834029|92836764|93232191194004281194004513|94004531196322167|96709712|96709937| 97972274|97972368|98106814|98107048|98107541 |98251976|98252411198281259|98281544|98281572|98870415|98878875|98879192| 99143734|99143976|99144360|99325743|99325757|99325960|99374565|99374574|99375110|99408717|99408769|99408796|99438705| 99438720|99438873|99438878|99438889|99438911 |99439133|99465883|99466293|99472690|99472787|99472789|99472861 |99472866| 99473513|99500012|99500263|99500386|99504574|99504628|99504690|99504824|99552004|99552109|99558255|99558503|99558739| 99616867|99616911 |99616925|99617009|99617104|100015562|100015582|100015621 |100050127|100081413|100088773|100088830|1 00101176|100101365|100101383|100101538|100101934|100101987|100119437|100119621 |100148791 |100148894|100158516|1001773 12|100336098|100336174|100428730|100428830|100436315|100436618|100477779|100478937|100478998|100479129|100483354|100 483735|100483774|100483896|100483912|100493632|100493741 |100538894|100585920|100585994|100586342|100612322|100612363 |100612374|100612720|100673208|100673594|100673605|100673700|100674600|100675080|100694268|100694282|100706106|10070 6112|100706216|100852498|100852538|100852746|100874885|100874944|100875143|100875433|100889559|100889669|100889951 |1 01085873|101154252|101217496|101217802|101218071|101244424|101245019|101245088|101245181 |101252300|101252523|1013219 17|101816012|102396381 |102396434|102433500|102464748|102464754|102464758|102464897|102465306|103074674|103075112|103 075118|103149170|103297546|103344750|105013463|105013594|105014057|105014248|105014260|105014273|105388938|105389038 |105389052|105522314|105522408|105522431 |105532217|106111943|106112402|106112474|106112504|106112541 |106284205|10628 5091 |107044570|107044576|107044578|107044588|107563857|107563954|107564136|107580143|107580523|107743354|107743668|1 07743742|107743800|107744113|107744122|107891041|108526243|108526359|108569606|108569617|108569771 |108569807|1085698 60|108570005|108570547|108570627|111562394|112206091 |112206417|112206443|112206447|112206453|112206484|112206638|112 206650|112206860|112450068|112450293|112450459|112450903|112790311 |112790476|112939702|113118689|116862339|116862571 |116862725|116863074|118184360|120950490|121396480|123748286|123748919|124929659|124929993|124930027|127392455|12739

[0297] 59

[0298] CAN DMS: \1015053120\12458|127585289|127585565|127585723|127588423|127588478|127588785|127651874|127652104|128343823|128343846|128343912|1 28361582|128409630|128409809|128409814|128409831|128409926|128410061 |128455923|128456211 |128739198|128739270|1287392 76|128862679|128862730|128937969|128938110|129054338|129054616|129055033|129055107|129055302|129144362|129144549|129 144595|129144658|129188619|129188734|129188744|129189141 |129224834|129224837|129502443|129611509|129611578|129611804 |129611993|129952479|130051419|130070279|130070594|130205500|130205528|130205537|130441178|130441183|130441222|13066 8653|130669088|131106250|131109945|1311101511131327347|131327776|131327786|131327793|131327920|131556637|131556894|1 33082057|133082179|133252878|133252957|133252994|133253055|134316548|134317113|134317164|134459154|134459303|1346466 27|134646661 |134646772|134986606|135170644|135170653|135170888|135170914|135170923|135170998|135171022|135211475|135 211541 |135211595|135211911 |135510292|135557875|135557935|135558487|138001548|138001753|138460286|138460786|138461173 |139109085|139109687|139133805|139231495|139340228|139340399|139340533|139341055|139341074|139341089|139359628|13935 9699|139359842|139359878|139360051 |139360061 |139500123|139500165|139500239|139778220|140062683|140177304|140398162|1 40478739|140478996|140672955|140673229|140673233|140696838|140697103|140924257|140924668|140924670|141701803|1417382 26|141738350|141738648|142855152|143263409|143288117|143288152|143288350|143380497|143381544|143902084|144835999|148 698961 |148884284|148966949|148983174|149028730|149028870|149090918|149091236|149126123|149126770|149147512|149147977 |149195767|149196138|149239555|149239792|149262207|149460539|149460644|149460712|149498001 |149624968|149773195|14977 3254|149838263|149838272|149838289|149838405|149873903|149873928|149874018|149874022|149874057|150368128|150368445|1 50368912|150369067|150379249|150379271 |150379346|150379557|150405180|151057985|151058093|151058134|151058147|1510582 33|151058248|151059305|151059372|151059404|151059422|151059513|151083423|151083570|151172787|151227187|151227268|151 227358|151227364|151232303|151232419|151232427|151232595|151248521 |151248783|151248851 |151341856|151519908|151519921 |151519940|152435988|152464957|152676225|152676254|152759615|152759661 |152759730|152759942|155003560|155297680|15529 7684|155298002|155298004|155298093|155380337|155644174|155644334|155644414|155644453|155645122|156893130|156893132|1 56893292|156893294|156893354|156893429|156950202|157138688|157139065|157336897|157336958|157336972|157336975|1587048 48|158704874|158829094|158829637|158829691 |158829695|158856451 |158856552|158857005

[0299] chr8:

[0300] 731291 |731352|731354|731449|731577|1764164|6406268|6406650|6406672|6708057|6708292|6708306|6708329|6708346|6708355|670 8443|8386331 |8386609|8893815|9002756|9002944|9003125|9150936|9555891 |9555895|9555905|9555935|9555947|10839507|1083985 5|10840188|11284386|11284487|11284563|11467157|11867595|11868090|11868434|11902552|12754862|12755302|12755630|1275578 1 |12755796|17246692|17246964|17247026|17247343|17922554|17924080|17924108|18084059|18084730|18084935|18085017|1821026 1 |19817264|19817711 |20197072|20197086|20197182|20197188|20197445|20197501 |21919337|21919550|21919552|21920430|2206664 2|22089306|22109223|22142028|22142074|22156616|22165483|22245198|22245200|22245211 |22367504|22367646|22441058|2244106 5|22441073|22441628|22578907|22604597|22604610|22604612|22604942|22604980|22668802|22669142|22669192|22669225|2269328 4|22693318|22693648|22999989123068965123069272123069349123225056123225297123246524|2324656912324682112328819112345763 6|23457784|23457788|23457815|23457863|23472526|23529043|23529110|25458851 |25458976|25458978|26291354|26291357|2629147 7|26291539|26291784|26382793|26382808|26577792|26577838|26577918|27274569|27310775|27311393|27325580|27326356|2759239 0|27772582|27774488|27774588|28092783|28093108|28093284|28386304|28386436|28401324|28401976|28402191 |28402471 |2841187 9|28701300|28889936|29262970|29263489|29351023|30082482|30083063|30095146|30095296|30095548|30095848|30156197|3015636 3|30657820|30657847|30658309|30727916|30728111130728118|30812332|30812755|31033464|31033486|31034193|31034202|3103425 7|33472790|33473205|33473286|33473317|33485057|33485076|33485125|33485146|33485163|33513148|33513175|33566832|3356713 5|37695613|37695618|37695760|37736317|37736332|37736401 |37736586|37736655|37737035|37737078|37762593|37797157|3784969 0|37849767|37849804|37899507|37899732|38030195|38030382|38030385|38030431 |38104979|38105315|38105402|38105447|3810545 9|38105501 |38105790|38105799|38176400|38176649|38176668|38176874|38231269|38231347|38231530|38231643|38231918|3823192 6|38232044|38269038|38269363|38269374|38269410|38269425|38382391 |38383376|38386165|38386306|38386351 |38386389|3838709 7|38466224|38787421 |38787890|38996529|38996543|38996551 |38996808|38996857|38996885|41490311 |41490969|41529118|4152923 5|41529345|41577950|41578179|41578183|41578657|41828474|41828593|42051051 |42051297|42051938|42152854|42152976|4215357 2|42271134|42338021 |42391753|42541093|42541625|42542016|42542123|42542131 |42843052|42843388|42843579|42896494|4289652 1 |42896619|42897192|42897967|43056144|43056165|43056865|43093339|43093404|43093544|43093725|47261018|47960798|4796097 3|48008278|48008502|51899147|51899151 |51899625|52713304|52714379|52714809|52715068|53842859|53843019|53843025|5384312 1 |53843294|53843401153843481154022465|54022521154102081154102083|54135197|54135205|54135231 |54135412|55772968|5577315 4|55773574|55773576|55773787|56074009|56074636|56074647|56074668|56074731 |56211788|56993607|58552960|58552967|5855303 6|58553208|58553219|58553221 |58659045|58659402|58659659|58659892|58659908|59118981 |59119273|60653880|60678640|6067864 5|60678839|60909869|63168442|63168539|65633998|65644695|65841629|65842044|66113232|66113685|66113756|66113876|6643907 6|66613044|66613266|66613337|66712522|66775171 |66775202|67064299|67064436|67343648|70402797|70404395|70668876|7300879 1173008851173294296|73294731173294948|73294964|73878817173879064|73879066173879150|73972221173972224|7397236617397603 4|73976242|73976332|73976362|74350322|74350437|79767743|79767753|79767891 |80030143|80030383|80485554|80486267|8057824 9|81112227|81280366|81280369|81686266|81721342|81841858|85107189|85107408|85177246|85177265|85177951 |85220414|8522054 6|85220608|85220737|85245609|86342516|86342522|86342582|86342590|86342869|86508195|86508508|86508671 |86508873|8990311 1 |89984374|89984720|90001198|90001226|90001445|90001459|90002099|91040589|91070270|91070551 |93741013|9374102119374103 8|93741049|93741190|93916627|93916976|93917011 |93917802|93991585|94553561 |94553573|94553725|94719743|94823316|9489521 4|94895431 |94895463|94949264|94949529|94949531 |95024947|95024966|95024971 |95134495|95269171 |95269276|95269472|9526973 2|96234985|96235406|96235637|96261791197644031197644339|98045689|98045702|98046196|98117252|98117255|9811771119817019 4|98170213|99893199|99893650|99893734|99893834|100157994|100158299|100158337|100158349|100309392|100309982|100310290| 100310485|100310563|100559867|100721384|100722518|100950721 |100950729|100951905|100952958|100953175|100953185|101126 468|101126636|101126783|101205341 |101205685|101205991 |101206137|102124473|102238533|102238901 |102238939|102412598|10 2601116|102653973|102654685|102655853|102655862|102806975|102810670|102863393|102864183|102864373|102864593|10302086 6|103021093|103021522|103414460|103414841 |103415427|108248670|108248760|108248888|109333627|109334156|109334435|1095 39479|109539655|109539736|109539747|109539764|109540068|109540187|116755792|116755872|116766343|116766370|116766447|

[0301] 60

[0302] CAN DMS: \1015053120\1116766490|116766513|116874945|119833138|119855932|119855937|119855944|119856114|1198739111119874660|120445412|122781 584|122782061 |123042156|123042338|123042436|123157504|123240730|123241295|123274495|123274506|123274655|123395953|12 3396481 |123396721 |123416645|123541210|123541238|123541248|123541342|123541353|123541360|123768450|123768611 |12376867 1 |123768970|124372486|124372607|124372889|124474629|124474717|124474728|124474816|124998452|125091750|125429511 |1254 29755|125429818|125430230|125430339|127735152|127735762|127735842|127735846|127735861 |127736235|127736916|127737168| 127738625|129939829|129939832|129939891 |129940084|130016744|130358168|131904159|132775196|132775235|132775292|132775 677|133297494|133297695|133570062|133571170|134712528|134712678|134713631 |140458368|140458535|140464023|140464694|14 0511110|140511343|140634798|140636106|141128226|141417830|141418039|142669441 |142669907|142727014|142727648|14324684 8|143291282|143291399|143334597|143334855|143334952|143334990|143541363|143541545|143541689|143597176|143597180|1435 98113|143609729|143609731 |143609740|143617460|143617667|143635853|143636355|143684407|143684499|143684674|143815385| 143815400|143828998|143829292|143829312|143829574|143829578|143840909|143841024|143939310|143942307|143942459|143942 578|143942660|143944017|143952167|143953058|1439750211143975112|143989896|143990018|144078363|144078509|144078585|14 4078954|144094658|144094962|144094975|144095491 |144104116|144104204|144104383|144104405|144104411 |144104470|14410447 2|144104798|144291242|144291781 |144291783|144326702|144326955|144358123|144358487|144358491 |144358731 |144358887|1443 73726|144373909|144374640|144408903|144409372|144409382|144428279|144428532|144428643|144428698|144428707|144444804| 144462804|144462823|144465405|144466199|144466244|144466246|144466393|144509262|144509274|144517529|144517962|144518 028|144518441 |144522362|144755744|144787284|144787388|144787485|144787519|144791942|144791987|144798554|144798654|14 4799274|144852846|144853071 |144853094|144853448|144901430|144901477|144902130|145052094

[0303] chr9:

[0304] 2015064|2015788|2016340|2844307|4679784|4793178|4985123|5450410|6008054|6412991 |6413544|6413852|6414096|6758546|15422 591 |15510463|15510859|19127551 |19379996|19409654|20621889|20684769|26892481 |26956304|27528434|27573819|32384460|32384 912|32526425|32526494|33025351 |33025489|33167079|33167136|33817859|34126837|34329108|34458460|34458535|34523232|34612 677|35071969|35072640|35096657|35103353|35617309|35690931 |35732501 |35732572|35748389|35748806|35815222|36136930|36191 187|36191538|36258603|36487141 |36572904|37079532|37422917|37466351 |37785023|37801322|70420520|71769159|72364645|74951 925|74952445|74952579|74953114|75087690|75087920|75088703|76394822|77177731 |78236146|78236517|79571503|79572755|79572 940|83707810|83980349|83981366|85940824|86354592|86354842|88388221 |89310970|90801867|91193393|91423504|92115620|92140 471 |92293557|92293770|92325741 |92326185|92670178|93095422|93134467|93451846|93453770|93566778|94374525|94726654|94726 658|94726671 |96418150|96418952|96449934|96778042|96778127|96778170|97633131 |97633816|97696935|97697552|97982857|97983 072|98056402|98056947|98119121 |98192412|98255761 |98255777|99821287|99906833|100352387|100352850|100352876|104764206|1 05448324|105558046|105558226|105694358|108934483|108934806|110256974|112333240|112333254|112334201 |112379575|1123799 21 |112487457|112718259|112750776|112751202|113221356|114505392|114587713|114611237|120793305|120793615|120877161 |121 075567|121202167|121268175|121699133|122264679|122264794|122264970|122904907|122904970|122905259|122932021 |123930255 |124771519|124862005|124868996|124869365|124869841 |124869888|125200683|125240976|125261748|125747893|127424457|12745 1030|127451522|127716099|127916967|127922050|127980743|128127923|128128005|128128283|128276323|128340931 |128371591 |1 28420217|128420450|128420960|128456173|128505086|128552220|128552263|128552629|128552877|128553216|128656878|1286901 77|128771699|128787264|128829503|128829770|128829883|128881654|128882033|128947482|128948235|129028220|129080800|129 111384|129174659|129642132|129803239|129824256|129834941 |129835979|130042001 |130043476|130579433|130579768|130693822 |130693849|1307127011130712706|130713236|131125818|131277144|131394760|131531138|131739739|1322425411132406886|13267 0454|132670933|132770244|133121544|133144624|133163738|133163894|133356058|133356507|133356950|133376156|133460201 |1 34066900|134067600|134068542|134135818|134164580|134165130|134165341 |135906757|135907895|135960653|136410764|1364392 31 |136439944|136483491 |136644640|136712397|136728249|136791349|136799956|136849268|136849350|136886757|136943906|136 944911 |136949869|136992363|137028635|137028950|137070532|137070624|137070711 |137087130|137087208|137114528|137114943 |137129660|137188807|137205922|137255031 |137255223|137255545|137590395|137590525|137606228|137618661 |137619564 chr10:

[0305] 987961 |988228|988344|988353|1048489|1049098|1049204|1049288|1049295|1056373|1056414|1056895|3172760|3782839|3785167|37 85413|3785426|3785432|3785560|5666711 |5666802|5666834|5684503|5684687|5684714|5684720|5813046|5813622|5813712|5814029| 5889858|5890007|5890012|5890065|5890566|5977563|5978046|6088898|6088904|6089265|6144686|6144700|6144705|6144831 |61449 96|6200784|6201828|6201917|6202723|6202991 |6920173|6920223|7409352|7410280|7410853|7787508|7787948|7788088|7818391 |781 8548|7818580|7818583|781859117818783|11164850|11164875|11165944|11611238|11611933|11611986|12042757|12042955|12042974 |12042976|12042978|12068737|12068956|12069642|12129398|12129446|12129667|12129676|12195802|12195873|12195913|12196366 |12196377|12348908|13100126|13161447|13161479|13349149|13349182|13349488|13349535|13586849|14604245|14837982|14838575 |14878333|14878464|14878911 |14953626|14954046|14954197|14954223|14954225|14954338|14954384|14959345|14959408|15096980 |15097057|15097415|15097417|15097817|15168319|15860325|15860332|16817471 |16817475|17201267|17201439|17201601 |17228301 |17229520|17229995|17230220|17230617|17617396|17617545|17643951 |17644108|18651475|18651696|18651716|18651721 |18651737 |18651799|18651803|18651835|18659129|18659193|18659244|18659267|18659288|21494926|21495001 |21496768|21516871 |22003539 |22003639|22003747|22003887|22003904|22229241 |22316118|22316250|22316253|22316263|22316272|22320700|22320968|22321065 |22341422|22436956|22713669|22714321 |22714330|22714724|23439002|23439055|25016149|26438140|26438332|26438996|26697451 |26697455|26860420|27100605|27100692|27154389|27154401 |27155558|27155770|27155969|27240862|27241162|27242188|27242278 |27242302|27504187|27504189|27504195|27504326|27504512|28303011 |28532301 |28532307|28532325|28532452|28532753|28532785 |28533034|28533455|28534162|30348904|30349110|30349346|30433573|30433807|30433844|30434171 |30434418|30434683|31031956 |31031959|31031974|31319734|31320422|31320953|31321031 |31760008|31928619|31928637|31929003|31929293|32055676|32056069 |32056492|32056513|32056625|32346886|32347384|32347454|32347479|32378777|32958559|32958604|32958617|35090302|35090413 |35090415|35090703|35126678|35127052|35127435|35127444|35337046|37857586|37857623|37857965|37976665|37976742|37976836 |38010575|42782402|42782414|42782465|42782818|43138359|43138510|43138513|43407889|43407897|43420615|43436540|43437001 |43437018|43455711 |43606366|43606397|43606514|43648575|43648863|43648997|44959126|44959496|44959534|44959650|44959656

[0306] 61

[0307] CAN DMS: \1015053120\1|44959666|44959693|44959797|44975114|45000867|45001004|45001028|45001034|45419197|45594537|45594958|45595074|45727026 |45972104|46284504|46284726|48306487|48306503|48307331 |48656356|49539121 |49539155|49539268|49539282|50623919|50623923 |50624089|50624169|51699943|56361246|58268032|58269324|58269695|58334946|58334972|58335119|58385161 |58385296|58385331 |58385368|58385373|59906523|60778284|60778290|60778355|60778421 |61901737|61903511162804401162804684|62804708|62804796 |62816472|62816502|62816754|62818141 |63133084|63133127|63133146|63133156|63133251 |63269220|63465436|63630503|67764036 |67764086|67884446|67884641 |67885180|67885419|68075195|68075368|68331853|68332110|68333067|68407005|68407016|68407254 |68407258|68471871168527284|68527449|68720974|68721055|68721135|68721148|68721162|68721165|68827060|68827363|68827393 |68827397|68827447|68900791 |68900945|68956076|68956202|69123774|69123802|69123970|69124195|69124495|69180149|69180231 |69180233|69180257|69318598|69318616|69318750|69408697|70146554|70170556|70170761 |70233460|70233462|70233534|70382168 |70382548|70382762|70382764|70382775|70382777|70478650|70815847|70815849|71773547|71773692|71773711 |71850988|71851316 |71889115|72087501 |72216307|72261218|72273861 |72274095|72319601 |72319777|72354293|72692174|73095643|73096528|73096977 |73096983|73096989|73097088|73167984|73168078|73168097|73168105|73168124|73246704|73247268|73247320|73247395|73247493 |73252385|73252540|73252886|73414090|73414191 |73414232|73495428|73496031 |73496104|73772411 |73772959|73781910|73785603 |73785643|73785749|73811576|73910939|73911035|73911145|73998053|73998056|73998059|74151030|74176460|74176504|74176577 |74826033175111547175111556175210411175211019175211243175211294|75236041175295083178033895178303304|78973906178974008 |79067576|79347334|79347488|79347490|79347751 |79348133|79445661 |79445787|80078564|80078621 |80078717|80078827|80205415 |80205704|84139336|84328711 |86521813|86521815|86521819|87094001 |87818149|87818356|87818419|87818430|87862032|87862035 |87862163|87862227|87862291 |87862624|87862727|87862774|87863365|87863579|87863584|87863596|87863600|88880082|88880310 |88880652|89207400|89251910|89251938|89252045|89302145|89414542|89414769|89701350|89701437|89701444|90857805|91162623 |91163468|91164080|91220506|91220870|91410044|91410242|91798214|91798432|91798548|91798700|91908594|91908821 |91923831 |91923857|91923946|92240813|92291087|92291150|92291481 |92573590|92574051 |92574186|92574464|92574470|92591750|92592943 |92592969|92593003|92593186|92593574|92690040|92690299|92848283|92848575|92848836|93482354|93496584|93496591 |93496602 |94545497|94545631 |94545723|95656636|95656809|95656837|95656908|95656936|95693881 |95693917|95694216|95694218|95694227 |95907842|95907920|96043629|96043768|96044380|96375328|96375433|96513753|96513957|96513962|96585909|96720367|96720706 |96720986|96832023|96833080|97318945|97319061 |97319326|97334634|97334986|97401305|97426172|97426244|97445788|97446017 |97446197|97446209|97446219|97497851 |97497942|97498542|97499072|97687031 |97687196|97687328|97687335|97687455|97687459 |97714394|97736938|97737103|97869700|98134681 |98135001 |98268563|98446642|98447066|99620577|99620587|99732042|99732187 |99732258|99732690|99732861 |100185723|100186008|100186140|100186142|100186360|100229590|100229604|100229616|10026724 5|100286611 |100286695|100286717|100346997|100529772|100535813|100535835|100535867|100912536|100912611 |100969306|1009 69324|100969618|100987361 |100987392|100987404|100987418|100987423|100997164|100999435|101031119|101031271 |101060285| 101061011 |101213781 |101353767|101353911 |101570387|101818615|101818769|101818777|101839860|102056239|102056241 |102065 340|102065453|102065811 |102114552|102115213|102120357|102120372|102120662|102120803|102120919|102120951 |102132762|10 2132905|102132944|102132966|102133076|102152054|102152124|102152394|102152822|102245487|102245733|102394071 |10239454 11102394543|102394742|102399743|102421551 |102432396|102432562|102461243|102461256|102461277|102461467|102502626|1025 02744|102502857|102504020|102504035|102504257|102642799|102644297|102713897|102714439|102714447|102854244|102854379| 102918409|103193428|103193441 |103351187|103351200|103351207|103351294|103367913|103368256|103396513|103396520|103396 533|103396692|103493959|103693127|103917925|103967062|103967490|103967665|104121934|104121936|104121996|104122068|10 4122070|104122072|104254866|104255135|104255292|104268792|104268870|104269170|110007621 |110207499|110207536|11021128 1 |110225806|110226364|110304472|110305015|110305258|110567343|110567476|110567523|110567653|110567662|110567842|1108 71826|110872034|110919011 |110919248|110919889|112183639|112376295|112446753|112446932|113679125|113679157|113679498| 113679547|113854549|113854782|113855197|113855296|114174158|114174221 |114174278|114174674|114174789|114304713|114822 710|114938135|117174984|1173752011117375470|1173756211118046364|118046949|118046993|118047005|118342380|118754775|11 8755276|118755299|118755302|119029647|119079895|1190804311119080934|119165323|1191655811119165796|119165813|11916583 011191787011119178762|119178885|119178966|119542756|119597167|119686665|119872810|119872812|119872917|119873128|1198 73551 |119873553|119892725|119892757|119892776|119892868|121927865|121928095|121928182|121928331 |121975143|121975197| 122954278|122980277|122980447|122980659|123008745|123009092|123154122|123154194|123154208|123154932|123994870|124461 705|124461918|124461922|124462149|124743799|124744414|124744674|124744762|124791803|124792014|124792240|124801666|12 4801880|124802192|124916552|124916741 |124916753|124916881 |124916937|124917538|124917981 |125719431 |125719435|12571947 5|125719537|125719654|125823462|125823472|125823534|128125841 |128126110|128126255|128212092|129467206|130136274|1301 36329|130136468|132332039|132332076|132332082|132332225|132397357|132397363|133144129|133308805|133373350|133373564| 133378424|133378458|133378534|133378546|133378672|133378693|133378722|133378728|133394199|133520301

[0308] chr11 :

[0309] 2074121207425120752912075311208514|20866112363091236658|236908|268923|268976|3563131450288|506908|5069111506924|506932| 507006|507014|507300|507302|507341 |507426|535387|535396|537432|537476|537558|560868|560921 |560926|560951 |576230|576298| 576342|576489|577089|615945|616009|616038|6954611695492|695533|695543|695585|695873|695891 |695893|696207|74711117473011 747458|747461 |776838|777775|777833|798041 |798350|798364|804954|809279|809282|809449|809742|809905|809907|810109|832821 | 842744|842748|842764|842945|842963|842977|910944|911002|926062|926082|926106|1309363|1309369|1309549|1309577|1309610|1 574775|1694188|1763890|1764177|1764184|1947086|1947413|2377291 |2377296|2377303|2377357|2400740|2400901 |2400904|240092 012401026|24011611240117112401195|2888485|29021801290220612902268|290231712902348|29920791299231112992398|2992403|2992 42112992426|299256112992579|2992712|2992738|299278113057394|3057622|3379344|379761113797623137976251379762913797665137 97680|3797923|3797926|3808257|3808439|3808530|3808594|3840282|3841761 |3855557|3855592|6234721 |6234849|6234861 |6390164| 6390256|6390385|6390594|6474032|6481343|6481399|6481402|6481418|6481425|6481460|6481465|6481484|6481588|6481760|66034 35|6603523|6603546|6603635|6603642|6604026|6612243|6612267|6612273|6612435|6612508|6683436|6683519|6683593|6683631 |668 37511826398118682337|8682827|8682934|8689017|8911060|8911204|8964430|8964670|8964832|9265522|9314067|9314402|9314584|9 314813|9314839|9314929|9384570|9460919|9573659|9573667|9573669|9574736|9614342|9614398|9663974|9664015|9758167|102942 07|10294212|10294214|10294367|10302822|10305591110307818|10308021110308229|10450612|10540926|10541199|10751097|107511

[0310] 62

[0311] CAN DMS: \1015053120\102|10751231 |10751234|10808683|10809087|10809090|10809108|10809159|10809425|10809666|10857386|10858116|10858481 |108586 03|10931242|13463311 |13463429|13668914|14358784|14381215|14499879|14499945|14520001 |14520368|14520375|14520394|145205 90|14520747|14891805|16738399|16738683|17077672|17077752|17077799|17207940|17207976|17208115|17276437|17276501 |172767 17|17276721 |17353456|17353566|17389316|17389524|18013115|18013146|18013210|18013589|18106116|18322118|18322211 |183226 90|18322820|18394303|18394677|18396210|18396220|18396232|18396285|18396293|18527076|18527118|18634372|18634432|186345 31 |18634534|18634618|18634873|18698811 |19240704|19241077|19241455|19241744|20387067|20387387|20387709|20387760|226257 63|22625854|22625864|22625882|22625917|22625940|22829345|27363149|27363261 |27363367|27506595|27506918|28108319|303230 16|30323052|31369760|31369786|31509588|31509630|32090911 |32583733|32583735|32583737|32892444|32894277|33039254|330393 64|33039522|33039842|33161253|33161605|33161717|33257538|33257541 |33257545|33257706|33258466|33736312|33736326|337746 79|33774682|33774711 |34051478|34051615|34051777|34105289|34105384|34105493|34174476|34358018|34359148|34915794|349161 00|34916231 |34916464|34916467|35662940|35821958|36289449|36289457|36289477|36510364|43311952|43358745|43358801 |433588 43|43358934|43358976|43680530|43680553|43680563|43680578|43681187|43942544|43942600|44095637|44565604|45340197|453713 92|45772092|45804345|45805055|45847328|45847405|45847442|45847498|45885603|45917992|45918507|46119656|46119835|462392 44|46333080|46380985|46381116|46381866|46617131 |46617489|46617715|46617904|46700371 |46700784|46701121 |46846278|471767 64|47214950|47249004|47269179|47269939|47394984|47408388|47408393|47408633|47426560|47426562|47426619|47565247|475653 24|47565659|47565947|47578728|47578961 |47578976|47579125|47579420|47642698|47642739|47714911 |47767025|47767257|477673 76|47767556|47767603|47848423|47848562|47980388|47980402|57325071 |57335491 |57335583|57335687|57335914|57335940|575157 47|57515990|57530828|57567578|57567667|57567981 |57568078|57568112|57568133|57568257|57657375|57657509|57657689|576577 70|57667214|57668027|57712522|57712526|57712552|57712835|57741546|58579615|59142629|59142683|59142685|59142762|591429 97|59144763|59171799|59172221 |59550530|59615595|59615730|59616355|59668765|59754614|59755349|59755354|59810694|598108 78|60841935|60841941 |60906660|60906692|60906825|60906870|60913828|60914124|60914237|60914537|60914558|61161437|611615 32|61161629|61161728|61295365|61332971 |61333028|61333053|61333055|61333322|61361902|61361963|61392660|61429518|614295 41 |61430012|61430017|61680175|61792098|61792260|61792490|61792520|61792528|61792822|61792883|61792894|61793327|618164 84|61816640|61817144|61891118|61891854|61967276|61967664|61967666|61967843|61967855|62124253|62574002|62574091 |625916 15|62591765|62592137|62601409|62601922|62612750|62612858|62621784|62646550|62646591 |62646711 |62646764|62646789|626532 98|62653304|62653364|62664921 |62665158|62665173|62665297|62671581 |62671619|62671662|62671802|62671813|62671842|626786 49|62678820|62678868|62678926|62679123|62679130|62679183|62679252|62679265|62706187|62706389|62726537|62727091 |627282 89|62728505|62728509|62728976|62754283|62754437|62761518|62761741 |62771266|62771275|62771378|62787209|62787390|627916 28|62791908|62791965|62805435|62805622|62832189|62832550|62841829|62842085|62855513|62855947|62855955|62855958|628559 62|62856072|62880766|62881460|63671643|63671685|63671735|63681283|63681292|63681463|63681868|63768349|63768858|638136 47|63814159|63838791 |63838814|63839040|63839247|63938288|63938807|63974567|63974653|63985966|63986401 |64166012|641663 06|64166524|64185628|64185927|64225960|64225977|64226443|64226823|64230248|64234522|64234524|64234823|64234826|642408 56|64240877|64240902|64240952|64241951 |64247117|64247126|64251745|64251771 |64270044|64271606|64284715|64284728|642847 54|64285657|64285888|64286009|64300323|64304617|64304664|64305221 |64305438|64305482|64305585|64305663|64317558|643175 69|64317631 |64317659|64317993|64318022|64318076|64318211 |64318246|64358985|64449272|64723161 |64723200|64723264|647233 36|64723338|64742994|64743852|64744560|64744727|64745817|64778832|64778879|64803365|64810583|64810674|64810701 |648445 00|64844633|64878106|64878830|64878977|64917199|64917253|64924613|64924736|65013827|65014003|65014370|65027361 |650273 81 |65027516|65040871 |65040895|65041019|65083846|65084023|65084025|65084034|65084100|65084133|65084311 |65084316|650843 30|65096486|65111681165111902|65111926|65117598|65117687|65117753|65117766|65117777|65117864|65122063|65122172|651221 79|65122196|65122316|65122409|65134408|65134478|65134606|65134621 |65181377|65181518|65261590|65261721 |65261912|652619 43|65262013|65262179|65262604|65314893|65314898|65333685|65333696|65354736|65354741 |65354970|65386447|65386482|653869 17|65422754|65477139|65477419|65477650|65497378|65497585|65497589|65498500|65525195|65540320|65540774|65540952|655581 23165570072165570302165570308|65570442165572585|65572811165573011165574190|65574791165575647|65575872|655760821656138 86|65614139|65614343|65615690|65616235|65638031 |65638289|65652713|65663040|65663073|65663397|65711838|65711943|657122 07|65720470|65720719|65720841 |65780453|65817919|65818223|65818269|65858243|65858246|65858491 |65859688|65873572|658737 03|65888517|65890988|65900453|65900527|65919189|65919191 |65961460|65961547|65961606|65961672|65961685|65961693|660019 93|66002047|66002145|66002218|66052156|66052271 |66052377|66052595|66070124|66070525|66257440|66257458|66257470|662574 78|66257496|66257589|66257668|66257702|66258234|66267666|66267958|66267966|66268178|66268461 |66268480|66268515|662685 34|66268544|66268546|66268549|66278015|66278023|66278029|66278041 |66278089|66278093|66278247|66278461 |66289101 |662891 16|66289268|66289280|66289357|66289473|66345195|66345291 |66466877|66479650|66479866|66480327|66480329|66480349|664803 98|66480500|66510649|66510689|66546058|66546067|66546078|66546202|66546207|66546383|66593021 |66593024|66593028|666165 64|66638440|66638507|66677970|66678362|66694842|66727852|66843276|66843311 |66843313|66857370|66982194|67119858|672400 82|67240097|67266233|67266328|67266330|67266778|67288767|67288975|67317416|67317708|67317808|67317963|67353495|673536 41 |67353652|67373608|67391608|67391821 |67391825|67391918|67392022|67392299|67401599|67401791 |67402046|67402060|674210 50|67421202|67428330|67428370|67428373|67428522|67429035|67464845|67469262|67469268|67469399|67482889|67482972|674829 74|67483147|67508514|67508656|67508674|67508705|67508852|67583505|67583800|67606917|67607131 |67629943|67805528|680307 45|68030825|68120511 |68120818|68121136|68121380|68121488|68121595|68212733|68272201 |68313202|68460603|68460755|684607 60|68461300|68841735|68842122|68842129|68903769|68904018|69675423|69675447|69675546|70270457|71448344|71448346|714486 62|71452807|71453052|71453066|71453143|71453216|71928211 |71928502|71928641 |71928702|71928707|71928760|71928874|720804 99|72080509|72080517|72080534|72080857|72102986|72103174|72103362|72103410|72103412|72103451 |72112704|72112797|721128 41 |72223232|72223616|72223661 |72224805|72752185|72752373|72781901 |72793663|72794056|72814128|72814718|73142279|731424 81 |73308292|73308482|73308513|73308632|73376510|73376670|73376690|73598217|73598219|73598224|73598242|73761152|737611 60|73761164|73761172|73761178|73761362|73761372|73761424|73761455|73788089|73876677|73876870|73982747|74170973|741710 82|74171103|74171127|74171426|74398684|74398859|74493118|74493568|74592485|74592741 |74748780|74748816|74948825|749489 93|74949107|74949111 |74949116|74949145|74949210|74949213|74949215|74949491 |74988863|74988877|74988900|74988916|753994 05|75399699|75399782|75525736|75562142|75768634|75814716|76381267|76381385|76444723|76444877|76444996|76444998|764450 00|76445006|76445012|76445353|76671105|76721941 |76783132|76783182|76861069|77066816|77066834|77066946|77589515|775897

[0312] 63

[0313] CAN DMS: \1015053120\118|77637805|77637828|77637879|77637913|77820807|77821128|77821136|77821154|77994621 |77994782|77994786|78046337|780795 67|78079750|78079965|78139604|78188682|78188730|78188732|78188735|78188852|78188864|78188977|78417650|82901604|830719 97|83072025|83072481183157091183193715|83193726|83194059|83194667|83286371183286425|85628564|85647962|856479711858549 23|85854932|85854934|85855147|86068987|86069303|86244647|86244724|86302135|87037843|87037871 |93543426|93661515|936616 31 |93661643|93662106|93741466|93741480|93741539|93741569|93784144|93784241 |93784370|93784963|94128685|94128873|941288 94|94128907|94129428|94129550|94129583|94493825|94493840|94493940|94493943|94494017|94494214|94544285|94973666|949736 69|95089569|95089680|95090103|95231109|95231130|95231339|95231352|95788980|95789782|95789835|95789903|95789921 |957902 94|95790300|95790321 |95790423|95790477|95790878|95791163|95924160|96343307|96389794|96390006|96390032|102317449|10234 7050|102347344|102453208|103092185|103092190|103092303|103092319|106022128|106076971 |106077371 |106077460|106077485|1 06077505|106077689|106077798|106077849|106077977|106078088|107565759|107565774|108009303|108009326|108121392|1081215 08|108121524|108121526|108221977|108222596|108222675|108222686|108222692|108222712|108222953|108223027|108223194|108 467511 |108467541 |108467551 |108498488|108498504|110296831 |110296837|110296843|110296860|110296866|110296877|110429908 |111602017|111602330|111602484|111602637|111602656|111766462|111766582|111871472|111878829|111878890|111879039|11187 9081 |111879450|111926828|111936884|111937043|111937239|112025774|112074057|112074166|112074253|112086694|112086708|1 12086718|112086764|112086770|112086772|112086858|112086872|112226327|112226333|112226350|112280109|113773830|1137738 411113875734|114400520|114400606|114400614|114400634|114400907|114439280|114439305|114439310|114439329|116772707|116 772787|116772995|116773017|116773019|116773024|116773028|116773087|117098247|117098577|117144008|117144175|117178796 |117178820|117179237|117233037|117327811 |117327843|117327860|118145532|118145575|118171783|118359484|118359609|11835 9626|118401286|118401316|118401736|118401985|1184363511118436357|1185309511118530978|118531086|118565998|118566063|1 18572209|118572525|118572596|118791414|118791459|118791462|118925716|118930022|118930244|118997543|118997912|1189979 44|118997946|118998054|118998085|118998166|119018408|119018499|1190308911119030900|119057368|119057389|119067558|119 067748|119067758|119067764|119067885|119084899|119084925|119084998|119095420|119095423|119095476|119095584|119095603 |119095609|119095672|119095793|119102235|119102328|119107187|119107366|119107481 |119107488|119121419|119121547|11912 1568|119121703|119149412|119149437|119169092|119317158|119317169|119321264|1193343311119334504|119381500|11938173111 19728717|119728910|120210789|120210798|121024092|121292185|121292685|121452003|121655555|122655647|122656030|1226564 31 |123062150|123062320|123063406|123301811 |123430463|123741710|124622715|124622815|124622838|124622843|124673822|124 718462|124739920|124762185|124762349|124800009|124800342|124800372|124800523|124800530|124800554|124953930|124953933 11249539611125569327|125569334|125592573|125592765|125625687|125625970|1258875511125887734|125887736|125888211112590 32211125903230|125903240|126062806|126211560|126211578|126211590|126211746|126211753|126211768|126211777|12621188111 26211904|126268834|126268837|126268881 |126268883|126268907|126269048|126269147|126283038|126283064|126283070|1263037 55|126303915|126304066|126355402|128522207|128693723|128694979|128695273|129751050|129895717|130002108|130002895|130 002931 |130002990|130069954|130213240|134223603|134224356|134224477|134224610|134252967|134253316|134253545|134253770 chr12:

[0314] 388996|389302|389312|389710|401945|459945|751314|751354|752549|752621 |949881 |949885|990657|990819|990843|991219|991222| 1594003|1594538|1690905|1690924|1690939|1690970|1691239|2004269|2004498|2004580|2004583|2004621 |2052964|2691743|26917 53|2794823|2794827|2794841 |2794927|2794930|2794945|2795746|2795987|2796199|2812699|2812873|2877182|2877187|2877192|287 7261 |2890623|2890667|2890674|2890828|2890831 |2890868|2890960|4271105|4272305|4272417|4272554|4272565|4272933|4272946|4 272948|4272957|4273005|4320833|4321360|4538394|4538459|4538690|4649035|4649084|4649106|4649330|6278707|6278811 |645152 3|6451662|6452381 |6470664|6470691 |6470726|6470958|6471091 |6493986|65343911653458116535190|6568243|6568444|6568485|6606 564|6607400|6663191 |6689238|6689590|6723803|6723972|6724057|6753020|6828947|6851355|6851400|6852023|6852045|6852269|68 52782|6867245|6867252|6867323|6867467|6867496|6867920|6868058|6872496|6891217|6904699|6904723|6914363|6924465|6938087| 6970313|6970716|6970873|6970954|7018419|7018476|7018709|7018712|7018873|7019040|7109347|7130058|7130332|7130335|71896 32|7971031 |8026450|8026461 |8032481 |8032743|8032745|8082210|8697771 |8697774|8697789|8949665|8949687|8949912|8950032|964 7871 |9647873|9648152|9648222|9869836|10212842|10213097|10613554|10613665|10613693|10750330|11648974|11649283|11650036 |11650265|12334566|12350255|12357006|12357029|12357133|12357136|12561875|12562094|12562126|12562877|12611697|12611818 |12611858|12611983|12612215|12717529|12718025|12718990|12725821 |12725845|12725953|12786817|12813290|12813337|12813351 |13044426|13044616|13101116|13101469|14770110|14771098|14771142|14771171114803308|14803636|14803646|14803767|15882028 |15882045|15882227|15882243|15882340|15882348|15911206|15911260|15911348|21501761 |21501811 |21657918|22544380|22544546 |22544710|22544732|22624993|22625086|25195039|25251003|25251028|25251218|25251255|25251366|25251510|25386263|25386678 |25958888|26114136|26114353|26122378|26122728|26126227|26126510|26126611 |26832248|26832479|26833569|26833870|26833892 |26938345|26938444|26938918|27014144|27022347|27022424|27022456|27022535|27022557|27022596|27333142|27524086|27710772 |27710779|27780056|29380631 |29381225|30696025|30754662|30754665|30754915|31326203|31326205|31326207|31326214|31326255 |31326257|31326384|31590948|31591109|31659319|31659402|31959169|31959228|32106610|32106769|32107084|32107157|32399592 |32399831 |32679402|32679527|32755593|32755998|32756007|38316622|42144389|42144734|42144825|42145004|42145011 |42145013 |42145018|42145038|42145099|42238001 |42238523|42326048|43806104|43806440|43806504|45215482|45216196|45216288|45216912 |45216921 |45726826|45728023|45728950|45729786|45730324|45989818|45990670|45990676|45990762|45990815|45992103|46371352 |46372754|46372760|46372765|46383407|47705736|47759145|47759148|47759168|47759341 |47772969|47773579|47813000|47813065 |47820030|47963544|47963611 |48105763|48105774|48106072|48106077|48106289|48157070|48157573|48157691 |48682265|48682301 |48682366|48682470|48716775|48717070|48814984|48852074|48852334|48852338|48852389|48865704|48865943|48957470|48957548 |48978204|48999443|48999461 |49018798|49019089|49059928|49060978|49069942|49070021 |49070135|49070205|49089933|49110525 |49130758|49131350|49131457|49131751 |49189260|49234573|49234675|49234737|49264405|49264638|49264642|49265019|49322864 |49322914|49323009|49323080|49346998|49366613|49366823|49367095|49539012|49539077|49539189|49568128|49568138|49568176 |49623004|49623201 |49623489|49623604|49707244|49707571 |49707573|49707576|49707647|49741339|49742002|49828459|49843023 |49843167|49843182|49967162|49967169|49967618|50025601 |50025616|50025658|50025692|50057531 |50057533|50085118|50085220 |50111737|50111971 |50112053|50112079|50112081 |50112174|50112451 |50283472|50283496|50283498|50400702|50400917|50504978 |50504980|50763855|50763900|50763989|51026117|51026560|51048273|51048279|51083289|51083575|51083630|51238892|51239206

[0315] 64

[0316] CAN DMS: \1015053120\1|51239266|51270461 |51270626|51424717|51424897|51591226|51591230|52006866|52006879|52023835|52025769|52033138|52033359 |52037067|52037393|52051209|52051492|52069893|52069956|53006213|53006215|53006325|53006402|53047591 |53079423|53079495 |53079515|53079599|53079623|53079659|53079694|53097849|53098066|53180543|53180550|53180740|53180755|53181360|53220291 |53220703|53220716|53251947|53251991 |53268124|53295590|53299658|53299669|53299701 |53300041 |53300165|53321710|53321716 |53344775|53344916|53379516|53380011 |53380028|53380044|53441593|53442117|53451958|53452007|53452083|53452088|53500634 |53500889|53501499|53501507|53675989|53676330|53676347|53676510|53727105|53727538|53751690|53752057|54214924|54281100 |54281203|54281258|54324763|54324822|54391219|54391271 |54984870|55716015|55716108|55729174|55729186|55817736|55817792 |55818040|55818459|55829548|55829680|55926996|55927118|55927131 |55927134|55927140|55927816|55927946|55928060|55931946 |55931952|55932013|55932083|55932283|55973905|56041796|56041883|56104544|56105307|56116515|56116577|56116586|56118148 |56118624|56128167|56128477|56128568|56128669|56129486|56152521 |56152531 |56157858|56189339|56190291 |56221748|56222041 |56224282|56224349|56224370|56224412|56224415|56258279|56258488|56258501 |56266696|56266842|56267112|56267135|56267204 |56267309|56300384|56300402|56316312|56360102|56360142|56449166|56449232|56449367|56468460|56468566|56468586|56630005 |56646111 |56646277|56688328|56688386|56688395|56725276|56725369|56725480|56751713|56752084|56752546|56752548|57006148 |57006417|57078613|57088120|57088745|57088755|57088766|57088807|57088979|57089730|57089848|57110604|57111746|57112099 |57112578|57128339|57216708|57216903|57229669|57229942|57229976|57229992|57240686|57430539|57431106|57459952|57462221 |57488073|57488141 |57520623|57520932|57633272|57693789|57693898|57744940|57752203|57752565|57752567|57752570|57772178 |57772530|57772610|57782736|57845351 |57845541 |57847004|57847026|57847034|57847113|57865299|57941050|57941362|57941719 |59596339162260376162260431162466671162603511162603632163779830163779892163779999164222220164222246164222431164222589 |64451937|64452146|64452430|64610014|64759421 |64759429|64759461 |65169379|65169549|65170120|66130801 |66169636|66302497 |66302574|66302756|67069478|67069501 |67268945|67269312|67269699|67989423|68332647|68610485|68687118|68746036|68746049 |68746234|68746238|68746807|68807916|69239539|69240074|69240237|69240407|69470468|69585383|69585439|69585782|69739207 |69739269|69739274|69739287|70242838|70243441 |70243444|70243613|70366090|70366134|70366140|71663601 |71663910|71686044 |71686348|71754636|71754735|71755073|71839544|71839772|74537774|74537980|75330132|75330157|75330237|75330242|75330348 |75511447|75511682|75511766|76031734|76085104|76559167|76559356|76559763|76559917|76560015|76763868|76763898|76763989 |77065700|77066060|82358393|82358536|88035601 |88141986|88142361 |89351896|89352551 |89352574|89352641 |89352835|89525981 |89525994|89526020|89526035|89526038|89526056|89526264|89708700|89709742|89709810|92144970|92146267|92928751 |92929449 |92929500|92929797|93378435|93442163|93442188|93442276|93442279|93442354|93442360|93442389|93467548|93467642|93467723 |93569777|93570919|93571009|93571011 |93591761 |93677518|93677670|94102137|94148214|94149673|94459869|94459872|94459882 |94460231 |94460239|95003549|95003653|95003811195073201195073347|95073746|95073748|95217145|95217343|95217509|95217656 |95218084|95473986|95473999|95474021 |95474032|95474057|95858806|95858960|95859159|95943163|95943322|96035966|96194345 |96194347|96194425|96195173|96399264|96489603|96907044|96907075|96907351 |96907476|98503974|98515189|98515514|98515744 |98516339|98516360|98593433|98593439|98593469|98593580|98593881 |98644170|98644512|98644773|98644799|98644988|98644990 |98645409|98645800|100142322|100142653|100142890|100143037|100199645|100199677|100200956|100267015|100267103|1002671 49|100267867|101407463|1014077211101407823|101408052|1016974411101697480|101697546|101877115|101877417|102062117|102 062183|102119999|102120003|103930792|103956726|103965470|103965651 |103965700|103965833|104064119|104064295|104064347 |104064374|104138113|104456798|104456938|104456989|104457538|104458131 |104458373|104458668|105107751 |105107754|10510 8017|105235740|105235977|105236020|105236281 |105236285|105330532|105330632|105330648|105331040|106247708|106248216|1 06302206|106302220|106303387|106357870|106357885|106358054|106774711 |106774855|106955759|106955761 |106987184|1076857 26|107760593|107761140|108515143|108560663|108562336|108562413|108562513|108731621 |108731628|108731633|108857505|108 857935|109052523|109052581 |109052915|109093438|109093474|109093669|109097523|109097579|109098033|109098135|109098193 |109477346|109573497|109573521 |109573530|109573557|109573647|109573741 |109573769|109713873|109714133|109714342|109...

Claims

CLAIMS:

1. A method of assessing survival risk of a human subject with haematological cancer or an age-related non-malignant disease comprising:a) providing a sample from the subject comprising DNA that includes at least 1000 of the 31744 differentially methylated regions (DMRs) set forth in Table 1.b) determining an epigenetically stable loci (ESL) profile based on the methylation status of the at least 1000 DMRs; andc) categorizing the subject as having either low survival risk or high survival risk, each being associated with high DNA methylation instability (DMI) or low DMI respectively, wherein the subject has high DMI if the ESL profile has methylated DMRs exceeding a predetermined threshold and the subject has low DMI if the ESL profile has methylated DMRs below the predetermined threshold.

2. The method of claim 1 , wherein the predetermined threshold is the median DMI of a reference cohort.

3. The method of claim 1 or 2, wherein the DMI is determined as the standard deviation of ESL p-values within the sample.

4. The method of any one of claims 1-3, wherein the ESL profile comprises at least 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, or 10000 of 31744 DMRs in Table 1.

5. The method of any one of claims 1-3, wherein the ESL profile comprises at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98% or 99% of the 31744 DMRs in Table 1.

6. The method of any one of claims 1-5, wherein the ESL profile comprises the top DMRs ranked by recurrence in Table 1.

7. The method of any one of claims 1-3, wherein the ESL profile comprises all of the 31744 DMRs in Table 1.

8. The method of any one of claims 1-3, wherein the ESL profile consists of all of the 31744 DMRs in Table 1.

9. The method of any one of claims 1-8, wherein the methylation status is determined using methylation bead array.

10. The method of any one of claims 1-8, wherein the methylation status is determined using methylation sequence conduced following enzymatic or chemical conversion of methylated or unmethylated cytosines.

11. The method of any one of claims 1-10, wherein the haematological cancer is leukemia, lymphoma, myeloma, myelodysplastic syndrome, or myeloproliferative neoplasm.

12. The method of any one of claims 1-10, wherein the age-related disease is a cardio vascular disease.

13. The method of claim 12, wherein the cardio vascular disease is coronary artery disease, cerebrovascular disease, myocardial infarction, heart failure, hypertension, arrhythmia, cardiomyopathy, peripheral artery disease, deep vein thrombosis, pulmonary embolism, or aortic aneurysms / dissection.

14. The method of any one of claims 1-13, wherein the sample is blood, plasma, urine, saliva, cerebrospinal fluid, bone marrow aspirate, lymph node, or pleural fluid.

15. The method of claim 14, wherein the sample is blood plasma.

16. The method of any one of claims 1-15, wherein if the subject is categorized as high risk, the method further comprises treating the haematological cancer or age-related disease.

17. The method of claim 16, wherein the treatment is aggressive therapy.

18. A computer-implemented method for assessing survival risk of a human subject with haematological cancer or an age-related disease, the method comprising:a) receiving, at at least one processor, data reflecting the subject’s methylation status of at least 1000 of the 31744 differentially methylated regions (DMRs) set forth in Table 1;b) constructing, at the at least one processor, an epigenetically stable loci (ESL) profile based on the methylation status of the at least 1000 DMRs;c) categorizing, at the at least one processor, the subject as having high DNA methylation instability (DMI) or low DMI, wherein the subject has high DMI if the ESL profile has methylated DMRs exceeding a predetermined threshold and the subject has low DMI if the ESL profile has methylated DMRs below the predetermined threshold.

19. A computer program product for use in conjunction with a computer having a processor and a memory connected to the processor, the computer program product comprising a computer readable storage medium having a computer mechanism encoded thereon, wherein the computer program mechanism may be loaded into the memory of the computer and cause the computer to carry out the method of any one of claims 1-15.

20. A method of assessing risk of a human subject developing a haematological cancer or an age-related disease comprising:a) providing a sample from the subject comprising DNA that includes at least 1000 of the 31744 differentially methylated regions (DMRs) set forth in Table 1.b) determining an epigenetically stable loci (ESL) profile based on the methylation status of the at least 1000 DMRs; andc) categorizing the subject as having either low risk or high risk, each being associated with high DNA methylation instability (DMI) or low DMI respectively, wherein the subject has high DMI if the ESL profile has methylated DMRs exceeding a predetermined threshold and the subject has low DMI if the ESL profile has methylated DMRs below the predetermined threshold.

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