Patent Publication Number: US-2016222448-A1

Title: Method to estimate the age of tissues and cell types based on epigenetic markers

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit under 35 U.S.C. Section 119(e) of co-pending U.S. Provisional Patent Application Ser. No. 61/883,875, entitled “METHOD TO ESTIMATE THE AGE OF TISSUES AND CELL TYPES BASED ON EPIGENETIC MARKERS” filed Sep. 27, 2013, the contents of which are incorporated herein by reference. 
    
    
     SEQUENCE LISTING 
     This application contains a Sequence Listing which has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Sep. 26, 2014, is named G&amp;C30435.276-WO-U1 SL.txt and is 119,130 bytes in size. 
     BACKGROUND OF THE INVENTION 
     (Note: This application references a number of different publications as indicated throughout the specification by reference numbers enclosed in brackets, e.g., [x]. A list of these different publications ordered according to these reference numbers can be found below in the section entitled “REFERENCES”.) 
     From the moment of conception, we begin to age. A decay of cellular structures, gene regulation, and DNA sequence ages cells and organisms. An increasing body of evidence suggests that many manifestations of aging are epigenetic [1, 2]. DNA methylation patterns have been found to change with increasing age and contribute to age-related diseases. Methylation in promoter regions is generally accompanied by gene silencing and loss of methylation or loss of the proteins that bind to certain methylated cytosine DNA nucleotides. This can lead to diseases in humans, for example, Immunodeficiency Craniofacial Syndrome and Rett Syndrome (see, e.g. Bestor (2000) Hum. Mol. Genet. 9:2395-2402). DNA methylation may be gene-specific or occur genome-wide. 
     One particular type of epigenetic control is the cytosine-5 methylation within Cytosine-phosphate-Guanine (CpG) dinucleotides (also known as DNA methylation or “DNAm”). Age-related DNA hypomethylation has long been observed in a variety of species including salmon [3], rats [4], and mice [5]. More recent studies have shown that many CpGs are subject to age-related hypermethylation or hypomethylation [6-14]. Previous studies have shown that age-related hypermethylation occurs preferentially at CpG islands [8], at bivalent chromatin domain promoters that are associated with key developmental genes [15], and at Polycomb-group protein targets [10]. The epigenomic landscape varies markedly across tissue types [16-18] and many age-related changes depend on tissue type [8, 19]. Some studies have suggested that age-dependent CpG signatures may be defined independently of sex, tissue type, disease state, and array platform [10, 13-15, 20-22]. 
     While there are articles that describe age predictors based on DNA methylation (DNAm) levels in specific tissues (e.g. saliva or blood [23, 24]), it is not yet known whether age can be predicted irrespective of tissue type using a single predictor. Articles that describe age-related changes in various tissues (e.g. blood, saliva, and brain [13, 21, 23, 24, 90, 91]) typically only focus on the biological impact of aging. For example, various DNA CpG methylation markers have been included in a list of aging-related genes by Teschendorff et al. [10], who showed that these markers correlated with age. However, Teschendorff et al. [10] did not investigate brain tissue and saliva and further did not build (multivariate) predictors of age. There have also been publications describing age predictors based on DNA methylation levels (see, e.g. Bockland et al. [23], Koch et al. [21], Hannum et al. [24]). Notably, however, Hannum et al. [24] found that computing a DNA methylation-based age predictor for different tissues gave basically no overlap, e.g. blood-derived predictive CpGs were different from those from other tissues. 
     Thus, there is a need for an age predictor based on DNA methylation levels that can accurately predict age across a broad spectrum of human tissues/cell types. 
     SUMMARY OF THE INVENTION 
     In one aspect of the present invention, a method is provided for estimating the chronological and/or biological age of an individual&#39;s tissue or cell sample by measuring the methylation of specific DNA Cytosine-phosphate-Guanine (CpG) methylation markers attached to the individual&#39;s DNA. Optionally, the measured methylation levels are transformed. In one or more embodiments, the method comprises forming a linear combination of a predetermined set of CpG methylation markers (or optionally, forming a linear combination of the transformed methylation levels), which is then transformed to an age estimate using a calibration function. The linear combination of the CpGs, referred to as “clock CpGs” (or of the transformed methylation levels), can be interpreted as an epigenetic clock. The resulting predicted age is referred to as the “DNA methylation (DNAm) age”. In one embodiment, the age is estimated based on a set of 354 CpG methylation markers (see Table 3 below). In other embodiments, the age is estimated based on a set of 110, 38, 17 or 6 CpG methylation markers (see Tables 4, 5, 6, and 7, respectively). The sets of 110, 38, 17, and 6 CpGs are subsets of methylation markers taken from the set of 354 CpG methylation markers shown in Table 3. 
     In another aspect of the present invention, a multi-tissue age predictor is provided that uses a set of CpG methylation markers for estimating age. An advantage of the multi-tissue age predictor lies in its wide applicability: for most tissues it does not require any adjustments or offsets. The invention allows for the comparison of the ages of different parts of the human body. Furthermore, the multi-tissue age predictor and CpG methylation markers allow for easily accessible tissues (e.g. blood, saliva, buccal cells, epidermis) to be used to measure age in inaccessible tissues (e.g. brain, kidney, liver). For example, the methods disclosed herein can be used to estimate the age of inaccessible human brain tissue by measuring the age of more accessible tissues such as blood, saliva, skin or adipose tissue. In further aspects, the sample comprises tissue culture cells or pluripotent stem cells (e.g. induced pluripotent stem (iPS) cells). Thus, in some aspects, a method of the embodiments can be used to determine the passage number or amount of time in culture for a population of tissue culture cells. In additional aspects, a method of the embodiments can be used to assess the differentiation status (or the pluripotency) of a population of cells comprising pluripotent stem cells (e.g. iPS cells). 
     In one or more embodiments, a method is provided comprising a first step of extracting genomic DNA from a sample. In a second step, the DNAm levels at multiple loci in the genome are measured. In specific instances, this results in thousands of quantitative measurements per sample. Each measurement measures the extent of methylation at a particular genomic location (CpG). The more CpGs measured allows for normalization of the data, though in certain embodiments, the DNAm levels of only 354, 110, 38, 17 or 6 CpG methylation markers are measured (see, Table 3-7 respectively). A third step comprises calculating the (weighted) average of the (optionally, transformed) DNAm levels across the measured CpGs. In certain instances, the result is a real number that lies between −4 and 4. The DNAm level of each CpG is multiplied by a coefficient value (of a regression model) and the individual products are summed up. In a fourth step, the weighted average is transformed to a new scale, such as a number that measures DNAm age in years. In this instance, age zero corresponds to age at birth and a prenatal sample results in a negative age. A monotonic, non-linear transformation is used. 
     The method may further comprise an additional step after the second step, wherein the measurements are normalized/transformed such that the two peaks of their frequency distribution are located at the same two locations as that of a gold standard measurement. The result is the same as that of the second step but the values are slightly changed. The peaks of the frequency distribution correspond to values for completely methylated or un-methylated CpGs, respectively. This normalization step is possible because most CpGs are either perfectly methylated or un-methylated. In one exemplary implementation, the gold standard is based on the average DNAm value across 715 blood samples. 
     The present invention can be used to study the effects of medication, food compounds and/or special diets on the biological age of humans or chimpanzees (which may serve as model organisms since DNAm age is also applicable to chimpanzee tissues). Since DNA methylation patterns change with increasing age and contribute to age-related diseases, the CpGs can be used as biomarkers of chronological age (e.g. for forensic applications). The invention can also be used for determining and/or increasing an individual&#39;s likelihood of longevity, in particular, by determining and decreasing an individual&#39;s likelihood of developing an age-related disease (e.g. cancer). This is accomplished, for example, by diagnosing and determining the existence or likelihood of disease (e.g. cancer) or providing an assay for identifying a compound which counters the age-related increase or decrease of methylation in the CpG markers disclosed herein. 
     In a further embodiment there is provided a method for determining age of a biological sample comprising selectively measuring the methylation levels of a set of methylation markers in genomic DNA of the biological sample, said set of methylation markers comprising markers in least 6 of the genes listed in Table 3 (SEQ ID NO: 1-354) and determining the age of the sample based on said methylation levels. In some aspects, the set of methylation markers may comprise markers in at least or at most 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345, 350, or 354 of the genes listed in Table 3. In further aspects, the set of methylation markers may comprise markers in at least or at most 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345, 350, or 354 of the CpG positions listed in Table 3. 
     In a further aspect, a method of the embodiments comprises selectively measuring the methylation levels of a set of methylation markers in genomic DNA of the biological sample, said set of methylation markers comprising markers in least 6 of the genes listed in Table 4 and determining the age of the sample based on said methylation levels. In some aspects, the set of methylation markers may comprise markers in at least or at most 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105 or 110 of the genes listed in Table 4. In further aspects, the set of methylation markers may comprise markers in at least or at most 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105 or 110 of the CpG positions listed in Table 4. 
     In yet a further aspect, a method of the embodiments comprises selectively measuring the methylation levels of a set of methylation markers in genomic DNA of the biological sample, said set of methylation markers comprising markers in least 3 of the genes listed in Table 5 and determining the age of the sample based on said methylation levels. In some aspects, the set of methylation markers may comprise markers in at least or at most 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 or 38 of the genes listed in Table 5. In further aspects, the set of methylation markers may comprise markers in at least or at most 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 or 38 of the CpG positions listed in Table 5. 
     In yet still a further aspect, a method of the embodiments comprises selectively measuring the methylation levels of a set of methylation markers in genomic DNA of the biological sample, said set of methylation markers comprising markers in least 3 of the genes listed in Table 6 and determining the age of the sample based on said methylation levels. In some aspects, the set of methylation markers may comprise markers in at least or at most 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17 of the genes listed in Table 6. In further aspects, the set of methylation markers may comprise markers in at least or at most 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17 of the CpG positions listed in Table 6. 
     In still a further aspect, a method of the embodiments comprises selectively measuring the methylation levels of a set of methylation markers in genomic DNA of the biological sample, said set of methylation markers comprising markers in least 2 of the genes listed in Table 7 and determining the age of the sample based on said methylation levels. In some aspects, the set of methylation markers may comprise markers in at least or at most 2, 3, 4, 5 or 6 of the genes listed in Table 7. In further aspects, the set of methylation markers may comprise markers in at least or at most 2, 3, 4, 5 or 6 of the CpG positions listed in Table 7. 
     In some aspects, the biological sample is a solid tissue, blood, urine, fecal or saliva sample that comprises genomic DNA. In particular aspects, the biological sample is a blood sample. 
     In further aspects, selectively measuring the methylation levels of a set of methylation markers in genomic DNA, further comprises transforming the measured methylation marker levels. In certain aspects of the embodiments determining the age of the biological sample comprises applying a statistical prediction algorithm to the measured methylation marker levels (or the transformed methylation marker levels). In certain aspects, applying a statistical prediction algorithm comprises (a) obtaining a linear combination of the methylation marker levels (or the transformed methylation marker levels), and (b) applying a transformation to the linear combination to determine the age of the biological sample. For example, obtaining a linear combination of the methylation marker levels can comprise obtaining weighted average of the methylation marker levels (or a weighted average of the transformed methylation marker levels). In further aspects, applying a transformation to the linear combination comprises applying a logarithmic and/or linear transformation to the linear combination. 
     In a further aspect determining the age of the biological sample comprises applying a linear regression model to predict sample age based on a weighted average of the methylation marker levels plus an offset. 
     In still further aspects, the set of methylation markers for use accordingly to the embodiments may comprise methylation markers in all of the gene or at all of the CpG positions of Table 3, Table 4, Table 5, Table 6 or Table 7. In certain aspects, the set of methylation markers may comprise markers in or near the NHLRC1 (SEQ ID NO: 357), GREM1 (SEQ ID NO: 356), SCGN (SEQ ID NO: 358) or EDARADD (SEQ ID NO: 355) genes. In one embodiment, probes cg22736354 (SEQ ID NO: 158) near gene NHLRC1, cg21296230 near gene GREM1 (SEQ ID NO: 354), cg06493994 (SEQ ID NO: 46) near gene SCGN, and/or cg09809672 (SEQ ID NO: 252) near gene EDARADD are used. 
     In some aspects the age of an individual is determined based on the age of the biological sample. For example, the age of individual can be determined by determining the age of biological sample from a peripheral tissue sample (e.g., a blood or saliva sample) from the individual. A method may further comprise, for instance, reporting the age of the sample or of the individual, e.g., by preparing a written, oral or electronic report. 
     In another embodiment there is provided a tangible computer-readable medium comprising computer-readable code that, when executed by a computer, causes the computer to perform operations comprising receiving information corresponding to methylation levels of a set of methylation markers in a biological sample, said markers comprising markers in at least 2 of the genes listed in Table 3, Table 4, Table 5, Table 6 or Table 7 and determining the age of the biological sample by applying a statistical prediction algorithm to the measured methylation marker levels. In some aspects, the set of methylation markers may comprise markers in at least, or at most, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345, 350, or 354 of the genes listed in Table 3, Table 4, Table 5, Table 6 or Table 7. In further aspects, the set of methylation markers may comprise markers at least, or at most, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345, 350, or 354 of the CpG positions listed in Table 3, Table 4, Table 5, Table 6 or Table 7. In some aspects, determining the age of the biological sample may further comprise comparing the measured methylation marker levels to reference marker levels. The reference levels may, optionally, be stored in said tangible computer-readable medium. In certain aspects, determining the age of the biological sample may comprise applying a linear regression model to predict sample age based on a weighted average of the methylation marker levels plus an offset. 
     In some aspects the receiving information may comprise receiving from a tangible data storage device information corresponding to the methylation levels of the set of methylation markers in the biological sample. In other aspects the receiving information may further comprise receiving information corresponding to methylation levels of a set of methylation markers in a biological sample, said markers comprising markers in at least, or at most, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345, 350, or 354 of the genes listed in Table 3, Table 4, Table 5, Table 6 or Table 7. 
     Further aspects of the tangible computer-readable medium may comprise computer-readable code that, when executed by a computer, causes the computer to perform one or more additional operations comprising: sending information corresponding to the methylation levels of the set of methylation markers in the biological sample to a tangible data storage device. 
     In certain aspects of the embodiments measuring methylation marker comprises, performing methylation specific PCR (MSP), real-time methylation specific PCR, methylation-sensitive single-strand conformation analysis (MS-SSCA), quantitative methylation specific PCR (QMSP), PCR using a methylated DNA-specific binding protein, high resolution melting analysis (HRM), methylation-sensitive single-nucleotide primer extension (MS-SnuPE), base-specific cleavage/MALDI-TOF, PCR, real-time PCR, Combined Bisulfite Restriction Analysis (COBRA), methylated DNA immunoprecipitation (MeDIP), a microarray-based method, pyrosequencing, or bisulfite sequencing. For example, measuring a methylation marker can comprise performing array-based PCR (e.g., digital PCR), targeted multiplex PCR, or direct sequencing without bisulfite treatment (e.g., via a nanopore technology). In some aspects, determining methylation status comprises methylation specific PCR, real-time methylation specific PCR, quantitative methylation specific PCR (QMSP), or bisulfite sequencing. In certain aspects, a method according to the embodiments comprises treating DNA in or from a sample with bisulfite (e.g., sodium bisulfite) to convert unmethylated cytosines of CpG dinucleotides to uracil. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Referring now to the drawings in which like reference numbers represent corresponding parts throughout: 
         FIG. 1 : Univariate predictor of age in blood tissue from multiple independent studies. The predictor of true (chronological) age is highly accurate: Median absolute deviation between predicted and true age is only 7.2 years. Correlation between true and predicted age is 0.76. 
         FIG. 2 : Univariate linear predictor of age in brain tissues (using samples from temporal cortex, frontal cortex, and PONS). The predictor of true (chronological) age is highly accurate: Median absolute deviation between predicted and true age is only 6.1 years. Correlation between true and predicted age is 0.88. 
         FIG. 3 : Univariate linear predictor of age by brain region (frontal cortex, temporal cortex, PONS and overall). 
         FIG. 4 : Multivariate predictor of age in whole blood tissue from multiple independent studies. The multivariate predictor of true (chronological) age is highly accurate: Median absolute deviation between predicted and true age is only 5.4 years. Correlation between true and predicted age is 0.90. 
         FIG. 5 : Multivariate predictor of age in brain tissues (using samples from temporal cortex, frontal cortex, and PONS). The multivariate predictor of true (chronological) age is highly accurate: Median absolute deviation between predicted and true age is only 5.9 years. Correlation between true and predicted age is 0.89. 
         FIG. 6 : Multivariate predictor of age by brain region (e.g. frontal cortex, temporal cortex, PONS and overall). 
         FIG. 7 : Multivariate predictor of age in saliva tissue. The multivariate predictor of true (chronological) age is highly accurate: Median absolute deviation between predicted and true age is only 4.9 years. Correlation between true and predicted age is 0.67. 
         FIG. 8 : Multivariate predictor of age in whole blood tissue from multiple independent studies. The multivariate predictor of true (chronological) age is highly accurate: Median absolute deviation between predicted and true age is only 5.1 years. Correlation between true and predicted age is 0.91. 
         FIG. 9 : Multivariate predictor of age in brain tissues (using samples from temporal cortex, frontal cortex, and PONS). The multivariate predictor of true (chronological) age is highly accurate: Median absolute deviation between predicted and true age is only 5.8 years. Correlation between true and predicted age is 0.90. 
         FIG. 10 : Multivariate predictor of age by brain region (frontal cortex, temporal cortex, PONS and overall). 
         FIG. 11 : Multivariate predictor of age in saliva tissue. The multivariate predictor of true (chronological) age is highly accurate: Median absolute deviation between predicted and true age is only 4.4 years. Correlation between true and predicted age is 0.71. 
         FIG. 12 : Multivariate predictor of age in brain tissues (using samples from temporal cortex, frontal cortex, and PONS). The multivariate predictor of true (chronological) age is highly accurate: Median absolute deviation between predicted and true age is only 8.2 years. Correlation between true and predicted age is 0.84. 
         FIG. 13 : Multivariate predictor of age by brain region (frontal cortex, temporal cortex, PONS and overall). 
         FIG. 14 : Multivariate predictor of age in saliva tissue. The multivariate predictor of true (chronological) age is highly accurate: Median absolute deviation between predicted and true age is only 4.2 years. Correlation between true and predicted age is 0.72. 
         FIG. 15 : Although the markers work particularly well in saliva and brain, they also work quite well in blood tissue. The multivariate predictor of true (chronological) age is highly accurate: Median absolute deviation between predicted and true age is only 6.1 years. Correlation between true and predicted age is 0.988. 
         FIG. 16 : Each column corresponds to different embodiments of the multi-tissue age predictor. The first and second rows show the results in the training data sets and test sets respectively. Each dot corresponds to a human subject and is colored and labeled according to the data set (Table 1 in Horvath 2013). Each panel reports the median error and correlation coefficient between predicted age and chronological age. The first column (panels A, F) shows how one embodiment of the multi-tissue age predictor (based on 354 CpGs, Table 3) performs in the training data (A) and test data (F). The second column (panels B,G) shows the performance of another embodiment of the multi-tissue age predictor based on a “shrunken” subset of 110 CpGs. Similarly, columns three, four, and five report the results of other embodiments of the multi-tissue age predictor based on 38, 17, and 6 CpGs, respectively. Even 6 CpGs (panel J) lead to a very high correlation 0.89 in the test data but the error rate (8.9 years) is substantially higher than that (3.6 years, panel F) observed for the predictor that uses 354 CpGs. 
         FIG. 17 : Chronological age (y-axis) versus DNAm age (x-axis) in the test data. (A) Across all test data, the age correlation is 0.96 and the error is 3.6 years. Results for (B) CD4 T cells measured at birth (age zero) and at age 1 (cor=0.78, error=0.27 years), (C) CD4 T cells and CD14 monocytes (cor=0.90, error=3.7), (D) peripheral blood mononuclear cells (cor=0.96, error=1.9), (E) whole blood (cor=0.95, error=3.7), (F) cerebellar samples (cor=0.92, error=5.9), (G) occipital cortex (cor=0.98, error=1.5), (H) normal adjacent breast tissue (cor=0.87, error=13), (I) buccal epithelium (cor=0.83, error=0.37), (J) colon (cor=0.85, error=5.6), (K) fat adipose (cor=0.65, error=2.7), (L) heart (cor=0.77, error=12), (M) kidney (cor=0.86, error=4.6), (N) liver (cor=0.89, error=6.7), (0) lung (cor=0.87, error=5.2), (P) muscle (cor=0.70, error=18), (Q) saliva (cor=0.83, error=2.7), (R) uterine cervix (cor=0.75, error=6.2), (S) uterine endometrium (cor=0.55, 11), (T) various blood samples composed of 10 Epstein Barr Virus transformed B cell, three naive B cell, and three peripheral blood mononuclear cell samples (cor=0.46, error=4.4). Samples are colored by disease status: brown for Werner progeroid syndrome, blue for Hutchinson-Gilford progeria, and turquoise for healthy control subjects. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     In the description of embodiments, reference may be made to the accompanying figures which form a part hereof, and in which is shown by way of illustration a specific embodiment in which the invention may be practiced. It is to be understood that other embodiments may be utilized and structural changes may be made without departing from the scope of the present invention. 
     All publications mentioned herein are incorporated herein by reference to disclose and describe aspects, methods and/or materials in connection with the cited publications. Publications cited herein are cited for their disclosure prior to the filing date of the present application. Nothing here is to be construed as an admission that the inventors are not entitled to antedate the publications by virtue of an earlier priority date or prior date of invention. Further, the actual publication dates may be different from those shown and require independent verification. 
     Many of the techniques and procedures described or referenced herein are well understood and commonly employed by those skilled in the art. Unless otherwise defined, all terms of art, notations and other scientific terms or terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this invention pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art. 
     The term “epigenetic” as used herein means relating to, being, or involving a modification in gene expression that is independent of DNA sequence. Epigenetic factors include modifications in gene expression that are controlled by changes in DNA methylation and chromatin structure. For example, methylation patterns are known to correlate with gene expression. 
     The term “nucleic acids” as used herein may include any polymer or oligomer of pyrimidine and purine bases, preferably cytosine, thymine, and uracil, and adenine and guanine, respectively. The present invention contemplates any deoxyribonucleotide, ribonucleotide or peptide nucleic acid component, and any chemical variants thereof, such as methylated, hydroxymethylated or glucosylated forms of these bases, and the like. The polymers or oligomers may be heterogeneous or homogeneous in composition, and may be isolated from naturally-occurring sources or may be artificially or synthetically produced. In addition, the nucleic acids may be DNA or RNA, or a mixture thereof, and may exist permanently or transitionally in single-stranded or double-stranded form, including homoduplex, heteroduplex, and hybrid states. 
     The terms “oligonucleotide” and “polynucleotide” as used herein refers to a nucleic acid ranging from at least 2, preferable at least 8, and more preferably at least 20 nucleotides in length or a compound that specifically hybridizes to a polynucleotide. Polynucleotides of the present invention include sequences of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) which may be isolated from natural sources, recombinantly produced or artificially synthesized and mimetics thereof. 
     The term “methylation marker” as used herein refers to a CpG position that is potentially methylated. Methylation typically occurs in a CpG containing nucleic acid. The CpG containing nucleic acid may be present in, e.g., in a CpG island, a CpG doublet, a promoter, an intron, or an exon of gene. For instance, in the genetic regions provided herein the potential methylation sites encompass the promoter/enhancer regions of the indicated genes. Thus, the regions can begin upstream of a gene promoter and extend downstream into the transcribed region. 
     The term “genome” or “genomic” as used herein is all the genetic material in the chromosomes of an organism. DNA derived from the genetic material in the chromosomes of a particular organism is genomic DNA. 
     The term “gene” as used herein refers to a region of genomic DNA associated with a given gene. For example, the region can be defined by a particular gene (such as protein coding sequence exons, intervening introns and associated expression control sequences) and its flanking sequence. It is, however, recognized in the art that methylation in a particular region is generally indicative of the methylation status at proximal genomic sites. Accordingly, determining a methylation status of a gene region can comprise determining a methylation status of a methylation marker within or flanking about 10 bp to 50 bp, about 50 to 100 bp, about 100 bp to 200 bp, about 200 bp to 300 bp, about 300 to 400 bp, about 400 bp to 500 bp, about 500 bp to 600 bp, about 600 to 700 bp, about 700 bp to 800 bp, about 800 to 900 bp, 900 bp to lkb, about 1 kb to 2 kb, about 2 kb to 5 kb, or more of a named gene, or CpG position. 
     The phrase “selectively measuring” as used herein refers to methods wherein only a finite number of methylation marker or genes (comprising methylation markers) are measured rather than assaying essentially all potential methylation marker (or genes) in a genome. For example, in some aspects, “selectively measuring” methylation markers or genes comprising such markers can refer to measuring no more than 1,000, 900, 800, 700, 600, 500, 400 or 354 different methylation markers or genes comprising methylation markers. 
     The term “probes” as used herein are oligonucleotides capable of binding in a base-specific manner to a complementary strand of nucleic acid. The term “probe” as used herein refers to a surface-immobilized molecule that can be recognized by a particular target as well as molecules that are not immobilized and are coupled to a detectable label. 
     The term “label” as used herein refers, for example, to colorimetric (e.g. luminescent) labels, light scattering labels or radioactive labels. Fluorescent labels include, inter alia, the commercially available fluorescein phosphoramidites such as Fluoreprime™ (Pharmacia™), Fluoredite™ (Millipore™) and FAM™ (ABI™) (see, e.g. U.S. Pat. Nos. 6,287,778 and 6,582,908). 
     The term “primer” as used herein refers to a single-stranded oligonucleotide capable of acting as a point of initiation for template-directed DNA synthesis under suitable conditions for example, buffer and temperature, in the presence of four different nucleoside triphosphates and an agent for polymerization, such as, for example, DNA or RNA polymerase or reverse transcriptase. The length of the primer, in any given case, depends on, for example, the intended use of the primer, and generally ranges from 15 to 30 nucleotides. A primer need not reflect the exact sequence of the template but must be sufficiently complementary to hybridize with such template. The primer site is the area of the template to which a primer hybridizes. The primer pair is a set of primers including a 5′ upstream primer that hybridizes with the 5′ end of the sequence to be amplified and a 3′ downstream primer that hybridizes with the complement of the 3′ end of the sequence to be amplified. 
     The term “complementary” as used herein refers to the hybridization or base pairing between nucleotides or nucleic acids, such as, for instance, between the two strands of a double stranded DNA molecule or between an oligonucleotide primer and a primer binding site on a single stranded nucleic acid to be sequenced or amplified. Complementary nucleotides are, generally, A and T (or A and U), or C and G. Two single stranded RNA or DNA molecules are said to be complementary when the nucleotides of one strand, optimally aligned and compared and with appropriate nucleotide insertions or deletions, pair with at least about 80% of the nucleotides of the other strand, usually at least about 90% to 95%, and more preferably from about 98 to 100%. Alternatively, complementarity exists when an RNA or DNA strand will hybridize under selective hybridization conditions to its complement. Typically, selective hybridization will occur when there is at least about 65% complementary over a stretch of at least 14 to 25 nucleotides, preferably at least about 75%, more preferably at least about 90% complementary. See, M. Kanehisa, Nucleic Acids Res. 12:203 (1984), incorporated herein by reference. 
     The term “hybridization” as used herein refers to the process in which two single-stranded polynucleotides bind non-covalently to form a stable double-stranded polynucleotide; triple-stranded hybridization is also theoretically possible. Factors that can affect the stringency of hybridization, including base composition and length of the complementary strands, presence of organic solvents and extent of base mismatching, the combination of parameters is more important than the absolute measure of any one alone. Hybridization conditions suitable for microarrays are described in the Gene Expression Technical Manual, 2004 and the GeneChip Mapping Assay Manual, 2004, available at Affymetrix.com. 
     The term “array” or “microarray” as used herein refers to an intentionally created collection of molecules which can be prepared either synthetically or biosynthetically (e.g. Illumina™ HumanMethylation27 microarrays). The molecules in the array can be identical or different from each other. The array can assume a variety of formats, for example, libraries of soluble molecules; libraries of compounds tethered to resin beads, silica chips, or other solid supports. 
     The term “solid support”, “support”, and “substrate” as used herein are used interchangeably and refer to a material or group of materials having a rigid or semi-rigid surface or surfaces. In many embodiments, at least one surface of the solid support will be substantially flat, although in some embodiments it may be desirable to physically separate synthesis regions for different compounds with, for example, wells, raised regions, pins, etched trenches, or the like. According to other embodiments, the solid support(s) will take the form of beads, resins, gels, microspheres, or other geometric configurations. See U.S. Pat. No. 5,744,305 for exemplary substrates. 
     In the following description, embodiments utilizing a linear combination are discussed. Those of skill in the art understand that this aspect of the invention is not limited to linear combinations and is merely a typical example. For example, a product or ratio may be used instead. Such a product would be mathematically equivalent to forming a linear combination of log transformed methylation levels. 
     DESCRIPTION OF ILLUSTRATIVE ASPECTS OF THE INVENTION 
     As disclosed herein, a number of locations have been identified in the human genome for which the percentage of DNA methylation is linearly correlated with age. By measuring the DNA methylation at just a few of the 3 billion nucleotides in an individual&#39;s genome, the present invention allows for accurate estimations of the individual&#39;s chronological age. While previous studies have shown that DNA methylation in certain parts of the genome changes with age, the present invention identifies loci where methylation is continuously correlated with age, over a range of at least 5 decades. This allows for a highly accurate prediction of an individual&#39;s age. In certain embodiments of the invention, the link between age and this chemical change in the DNA is so strong that it is possible to estimate the age of an individual by examining, for example, just two spots in the genome of the individual (see Bockland et al., et al. (2011) PLoS ONE 6(6): e14821. doi:10.1371/journal.pone.0014821). In addition, certain aspects of this invention have been confirmed by other studies (see, e.g. Koch et al., (2011) AGING, Vol. 3, No 10, pp 1,018-1,027). A related publication (United States Application Publication No. 2014/0228231) filed by Eric Vilain et al. on Aug. 14, 2014 and titled “Method to Estimate Age of Individual Based On Epigenetic Markers in Biological Sample,” is incorporated by reference in its entirety herein. A publication “DNA methylation age of human tissues and cell types” by Steve Horvath (Horvath (2013) Genome Biology 14:R115) is also incorporated by reference in its entirety herein. 
     The present invention relates to methods for estimating the chronological and/or biological age of an individual human tissue or cell type sample based on measuring DNA Cytosine-phosphate-Guanine (CpG) methylation markers that are attached to our DNA. In a general embodiment of the invention, a method is disclosed comprising a first step of choosing a biological cell or tissue sample (e.g. whole blood, individual blood cells, saliva, brain). In a second step, genomic DNA is extracted from the collected tissue of the individual for whom an age prediction is desired. In a third step, the methylation levels of the methylation markers near the specific clock CpGs are measured. In a fourth step, a statistical prediction algorithm is applied to the methylation levels to predict the biological or chronological age. One basic approach is to form a weighted average of the clock CpGs, which is then transformed to DNAm age using a calibration function. A detailed description of the data pre-processing, data normalization, age prediction steps is provided in Example 8. 
     One embodiment focuses on forming a linear combination of 354 CpGs (Table 3, SEQ ID NO: 1-354), which is then transformed to an age estimate using a calibration function. The weighted average of the degree of cytosine methylation at these 354 locations is significantly correlated with age, including but not limited to, human brain tissue (frontal cortex, temporal cortex, PONS), blood tissue (whole blood, cord blood and blood cells), liver, adipose, skin, kidney, prostate, muscle, and saliva tissue. The linear combination of the 354 CpGs (which are referred to as clock CpGs) can be interpreted as an epigenetic clock. The resulting predicted age is referred to as DNA methylation (DNAm) age. In other embodiments, a linear combination of 110, 38, 15 or 6 CpGs are used (Tables 4-7 respectively), which are subsets of the 354 CpGs. In specific instances, these subsets or sub-clocks were determined by increasing the threshold of the penalty term in a penalized regression model. In further embodiments of the invention, these sequences can include either translated or untranslated 5′ regulatory regions; and optionally are within 1 kilobase (5′ or 3′) of the specific GC loci that are identified herein. 
     In a further embodiment there is provided a method for determining age of a biological sample comprising selectively measuring the methylation levels of a set of methylation markers in genomic DNA of the biological sample, said set of methylation markers comprising markers in least 6 of the genes listed in Table 3 and determining the age of the sample based on said methylation levels. In some aspects, the set of methylation markers may comprise markers in at least or at most 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345, 350, or 354 of the genes listed in Table 3. In further aspects, the set of methylation markers may comprise markers in at least or at most 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345, 350, or 354 of the CpG positions listed in Table 3. 
     In a further aspect, a method of the embodiments comprises selectively measuring the methylation levels of a set of methylation markers in genomic DNA of the biological sample, said set of methylation markers comprising markers in least 6 of the genes listed in Table 4 and determining the age of the sample based on said methylation levels. In some aspects, the set of methylation markers may comprise markers in at least or at most 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105 or 110 of the genes listed in Table 4. In further aspects, the set of methylation markers may comprise markers in at least or at most 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105 or 110 of the CpG positions listed in Table 4. 
     In yet a further aspect, a method of the embodiments comprises selectively measuring the methylation levels of a set of methylation markers in genomic DNA of the biological sample, said set of methylation markers comprising markers in least 3 of the genes listed in Table 5 and determining the age of the sample based on said methylation levels. In some aspects, the set of methylation markers may comprise markers in at least or at most 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 or 38 of the genes listed in Table 5. In further aspects, the set of methylation markers may comprise markers in at least or at most 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 or 38 of the CpG positions listed in Table 5. 
     In yet still a further aspect, a method of the embodiments comprises selectively measuring the methylation levels of a set of methylation markers in genomic DNA of the biological sample, said set of methylation markers comprising markers in least 3 of the genes listed in Table 6 and determining the age of the sample based on said methylation levels. In some aspects, the set of methylation markers may comprise markers in at least or at most 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17 of the genes listed in Table 6. In further aspects, the set of methylation markers may comprise markers in at least or at most 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17 of the CpG positions listed in Table 6. 
     In still a further aspect, a method of the embodiments comprises selectively measuring the methylation levels of a set of methylation markers in genomic DNA of the biological sample, said set of methylation markers comprising markers in least 2 of the genes listed in Table 7 and determining the age of the sample based on said methylation levels. In some aspects, the set of methylation markers may comprise markers in at least or at most 2, 3, 4, 5 or 6 of the genes listed in Table 7. In further aspects, the set of methylation markers may comprise markers in at least or at most 2, 3, 4, 5 or 6 of the CpG positions listed in Table 7. 
     In another aspect of the invention, a set of four methylation markers are disclosed that continuously relate to age in human blood, brain tissue, and saliva. Specifically, DNA methylation markers near the following genes: NHLRC1, GREM1, SCGN have highly significant positive correlations with age in multiple human tissues. Methylation markers near gene EDARADD have a highly significant negative correlation with age in multiple tissues. In one embodiment, the methylation markers comprise of probes cg22736354 (SEQ ID NO: 158) near gene NHLRC1, cg21296230 near gene GREM1 (SEQ ID NO: 354), cg06493994 (SEQ ID NO: 46) near gene SCGN, and cg09809672 (SEQ ID NO: 252) near gene EDARADD. Methods for estimating age are provided which involve one to four of these markers. In these methods, biological cell or tissue sample is collected from an individual. Genomic DNA is extracted from the collected tissue and the methylation level of the methylation markers near at least one of the NHLRC1 (SEQ ID NO: 357), GREM1 (SEQ ID NO: 356), SCGN (SEQ ID NO: 358), and EDARADD (SEQ ID NO: 355) genes are measured. A statistical prediction algorithm is applied to the measured methylation levels to determine the biological or chronological age of the individual. 
     Embodiments of the invention include methods where observations of cytosine methylation in genomic DNA from a biological sample are used to predict the chronological age of the individual from which a sample is derived. Other embodiments of these methods comprise calculating a theoretical biological age (bio-age) of the individual based on the degree/amount of cytosine methylation observed in the sequence and then comparing the theoretical bio-age of the individual to an actual chronological age of the individual. In this way, information useful to determine a level of risk of an age-related disease in the individual is obtained. Optionally for example, the theoretical bio-age of the individual is compared to an actual chronological age to determine if the theoretical bio-age is greater than the actual chronological age; and the method further includes providing an individualized treatment to the individual to bring the theoretical bio-age closer to the actual chronological age of the individual. 
     DNAm age is a valuable biomarker for studying human development, aging, and cancer and can be used as a surrogate marker for evaluating rejuvenation therapies. The most salient feature of DNAm age is its applicability to a broad spectrum of tissues and cell types. DNAm age has been found to accurately predict age in various sources of DNA, including: adipose tissue/fat, blood (whole blood, cord blood, blood cells, peripheral blood mononuclear cells, B cells, T cells, monocytes), brain tissue (frontal cortex, temporal cortex, PONS), breast, buccal cells/epithelium, cartilage, cerebellum, colon, cortex (pre-frontal-, frontal-, occipital-, temporal cortex), epidermis, fibroblasts (e.g. dermal fibroblasts), gastric tissue, glial cells, head/neck tissue, kidney, lung, liver, mesenchymal stromal cells, neurons, pancreas, pons, prostate, saliva, stomach, thyroid, uterine cervix, and many other tissues/cell types. After incorporating an offset, it has also been found to perform well in heart tissue. Furthermore, DNAm age of easily accessible fluids/tissues (e.g. saliva, buccal cells, blood, skin) can serve as a surrogate marker for inaccessible tissues (e.g. brain, kidney, liver). Further, DNAm age can be used to compare the ages of different parts of the human body, e.g. to find diseased organs or tissues. 
     In another aspect of the present invention, a method is provided for estimating age in multiple tissues (e.g. whole blood, individual blood cells, saliva or brain tissue). In a further aspect, as shown below, easily accessible tissues (e.g. blood, saliva, buccal cells, epidermis) can be used to measure age in inaccessible tissues (e.g. brain). In one embodiment of the present invention, a method is provided for estimating of the chronological and/or biological age of an individual&#39;s human brain based on measuring DNA CpG methylation markers that are attached to the individual&#39;s DNA. Generally, human brain tissue from living individuals is not accessible and available for such measurements. However, as disclosed herein, a small set of DNA methylation markers can be measured in more accessible tissues, such as blood or saliva samples, to estimate the age-related methylation changes in the brain and other tissues. Thus, one is able to accurately predict an individual&#39;s age in the brain tissue based on blood or saliva measurements. Illustrative embodiments of this aspect of the invention include, for example, a method of predicting the age of a human by observing the methylation status of a plurality of markers such as at least 6, 17, 38, 100 markers (see, e.g. Tables 3-6) in biological sample from a human, comparing the methylation status observed in to methylation patterns observed in a population of individuals of differing ages (e.g. using a statistical prediction algorithm), and then predicting age of human from whom sample was obtained based upon the information obtained in this comparison step. 
     Many articles have described age-related changes in various human tissues, e.g. blood, saliva, and brain. However, these studies have never attempted to build a predictor of age in multiple tissues or cell types at the same time (e.g. combining brain and blood data). Instead, the studies have only focused on creating large lists of age-related CpG markers in various tissues for the sake of studying the biological impact of aging on individual CpGs. Currently, only three publications describe age predictors based on DNA methylation levels (Bockland et al. [23], Koch et al. [21], Hannum et al. [24]) but these publications focus on individual tissues or fluids (e.g. blood or saliva). Notably, Hannum et al. [24] found that computing a DNA methylation-based age predictor for different tissues gave basically no overlap, e.g. blood-derived predictive CpGs were different from those from other tissues. Comparison studies show that the age predictor of the present invention greatly outperforms the predictors by Bockland et al. [23] and Koch et al. [21]. A direct comparison with the predictor of Hannum et al. [24] was not possible because their predictor included additional covariates (data batch, gender and body mass index). The multi-tissue predictor provided herein only uses the clock CpGs, i.e. it does not require additional covariates. 
     CpGs/genes overlapping with the subclocks (110, 38, 17, and 6 CpGs shown in Tables 4, 5, 6, and 7 respectively) for Hannum/Bell include: 110/38/17/6-IP08 (alias: RANBP8) and NHLRC1; 110/38/17-KLF4, SCGN, RHBDD1, and C16orf65; 110/38-MGC16703 (alias: P2RX6) and FZD9; 38-BRUNOL6; 110-ABCA17P (alias: ABCA3), PIPDX, ABHD14B, EDARADD, GRP25, F1132110 (alias: ZNF8048) and LAG3. 
     In another aspect of the present invention, a very simple and cost-effective kit is provided for estimating DNAm age based on the clock CpGs. In some embodiments of the invention, the kit comprises a methylation microarray (see, e.g. U.S. Patent Application Publication No. 2006/0292585, the contents of which are incorporated by reference). In one embodiment, the kit is used to estimate the chronological and biological age of brain tissue or blood tissue utilizing measurements in blood or saliva. Microfluidics devices can be applied to easily accessible tissues/fluids such as blood, buccal cells, or saliva. Optionally, the kit comprises a plurality of primer sets for amplifying at least two genomic DNA sequences. In some embodiments of the invention, the kit further comprises a probe or primer used to perform a DNA fingerprinting analysis. Such kits of the invention can further include a reagent used in a genomic DNA polymerization process, a genomic DNA hybridization process, and/or a genomic DNA bisulfite conversion process. In one exemplary implementation, a kit is provided for obtaining information useful to determine the age of an individual, the kit comprising a plurality of primers or probes specific for at least one genomic DNA sequence in a biological sample, wherein the genomic DNA sequences comprises a CG loci identified in  FIG. 4 . The invention is may also be provided in a fully developed software package or web-based program. For example, a user may access a webpage and upload their DNA methylation data. The program then emails the results, including the predicted age (DNAm age), to the user. 
     DNA methylation of the methylation markers (or markers close to them) can be measured using various approaches, which range from commercial array platforms (e.g. from Illumina™) to sequencing approaches of individual genes. This includes standard lab techniques or array platforms. A variety of methods for detecting methylation status or patterns have been described in, for example U.S. Pat. Nos. 6,214,556, 5,786,146, 6,017,704, 6,265,171, 6,200,756, 6,251,594, 5,912,147, 6,331,393, 6,605,432, and 6,300,071 and US Patent Application publication Nos. 20030148327, 20030148326, 20030143606, 20030082609 and 20050009059, each of which are incorporated herein by reference. Other array-based methods of methylation analysis are disclosed in U.S. patent application Ser. No. 11/058,566. For a review of some methylation detection methods, see, Oakeley, E. J., Pharmacology &amp; Therapeutics 84:389-400 (1999). Available methods include, but are not limited to: reverse-phase HPLC, thin-layer chromatography, SssI methyltransferases with incorporation of labeled methyl groups, the chloracetaldehyde reaction, differentially sensitive restriction enzymes, hydrazine or permanganate treatment (m5C is cleaved by permanganate treatment but not by hydrazine treatment), sodium bisulfite, combined bisulphate-restriction analysis, and methylation sensitive single nucleotide primer extension. 
     The methylation levels of a subset of the DNA methylation markers disclosed herein are assayed (e.g. using an Illumina™ DNA methylation array, or using a PCR protocol involving relevant primers). To quantify the methylation level, one can follow the standard protocol described by Illumina™ to calculate the beta value of methylation, which equals the fraction of methylated cytosines in that location. The invention can also be applied to any other approach for quantifying DNA methylation at locations near the genes as disclosed herein. DNA methylation can be quantified using many currently available assays which include, for example: 
     a) Molecular break light assay for DNA adenine methyltransferase activity is an assay that is based on the specificity of the restriction enzyme DpnI for fully methylated (adenine methylation) GATC sites in an oligonucleotide labeled with a fluorophore and quencher. The adenine methyltransferase methylates the oligonucleotide making it a substrate for DpnI. Cutting of the oligonucleotide by DpnI gives rise to a fluorescence increase. 
     b) Methylation-Specific Polymerase Chain Reaction (PCR) is based on a chemical reaction of sodium bisulfite with DNA that converts unmethylated cytosines of CpG dinucleotides to uracil or UpG, followed by traditional PCR. However, methylated cytosines will not be converted in this process, and thus primers are designed to overlap the CpG site of interest, which allows one to determine methylation status as methylated or unmethylated. The beta value can be calculated as the proportion of methylation. 
     c) Whole genome bisulfite sequencing, also known as BS-Seq, is a genome-wide analysis of DNA methylation. It is based on the sodium bisulfite conversion of genomic DNA, which is then sequencing on a Next-Generation Sequencing (NGS) platform. The sequences obtained are then re-aligned to the reference genome to determine methylation states of CpG dinucleotides based on mismatches resulting from the conversion of unmethylated cytosines into uracil. 
     d) The Hpall tiny fragment Enrichment by Ligation-mediated PCR (HELP) assay is based on restriction enzymes&#39; differential ability to recognize and cleave methylated and unmethylated CpG DNA sites. 
     e) Methyl Sensitive Southern Blotting is similar to the HELP assay but uses Southern blotting techniques to probe gene-specific differences in methylation using restriction digests. This technique is used to evaluate local methylation near the binding site for the probe. 
     f) ChIP-on-chip assay is based on the ability of commercially prepared antibodies to bind to DNA methylation-associated proteins like MeCP2. 
     g) Restriction landmark genomic scanning is a complicated and now rarely-used assay is based upon restriction enzymes&#39; differential recognition of methylated and unmethylated CpG sites. This assay is similar in concept to the HELP assay. 
     h) Methylated DNA immunoprecipitation (MeDIP) is analogous to chromatin immunoprecipitation. Immunoprecipitation is used to isolate methylated DNA fragments for input into DNA detection methods such as DNA microarrays (MeDIP-chip) or DNA sequencing (MeDIP-seq). 
     i) Pyrosequencing of bisulfite treated DNA is a sequencing of an amplicon made by a normal forward primer but a biatenylated reverse primer to PCR the gene of choice. The Pyrosequencer then analyses the sample by denaturing the DNA and adding one nucleotide at a time to the mix according to a sequence given by the user. If there is a mismatch, it is recorded and the percentage of DNA for which the mismatch is present is noted. This gives the user a percentage methylation per CpG island. 
     In certain embodiments of the invention, the genomic DNA is hybridized to a complimentary sequence (e.g. a synthetic polynucleotide sequence) that is coupled to a matrix (e.g. one disposed within a microarray). Optionally, the genomic DNA is transformed from its natural state via amplification by a polymerase chain reaction process. For example, prior to or concurrent with hybridization to an array, the sample may be amplified by a variety of mechanisms, some of which may employ PCR. See, for example, PCR Technology: Principles and Applications for DNA Amplification (Ed. H. A. Erlich, Freeman Press, NY, N.Y., 1992); PCR Protocols: A Guide to Methods and Applications (Eds. Innis, et al., Academic Press, San Diego, Calif., 1990); Mattila et al., Nucleic Acids Res. 19, 4967 (1991); Eckert et al., PCR Methods and Applications 1, 17 (1991); PCR (Eds. McPherson et al., IRL Press, Oxford); and U.S. Pat. Nos. 4,683,202, 4,683,195, 4,800,159, 4,965,188, and 5,333,675. The sample may be amplified on the array. See, for example, U.S. Pat. No. 6,300,070, which is incorporated herein by reference. 
     Any statistical approach can be used to relate the methylation levels to age, e.g. a transformed version of chronological age can be regressed on the CpG markers using a (penalized) linear regression model (such as elastic net regression) as described herein. Using conventional regression model/analysis tools and methodologies known in the art, a number of age prediction models are contemplated for use with specific genomic DNA samples and/or specific analysis techniques and/or specific individual populations (see, e.g., statistical package R version 2.11.1 in citation as discussed in R Development Core Team (2005) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL www.R-project.org). In one embodiment, an identity transformation may be used, wherein chronological age is simply regressed on the CpGs. In other embodiments, the chronological age (the dependent variable in a penalized regression model) is transformed. In illustrative experiments, this transformation has been found to lead to an age predictor that is substantially more accurate (in relation to error) and that requires substantially fewer CpGs than one without the transformation. Additionally, one can form a weighted average of the CpGs. 
     In another embodiment, a linear regression model may predict age based on a weighted average of the methylation levels plus an offset. To identify the weights for the weighted average, one can use the regression coefficients of a regression model. In another embodiment, one can standardize each methylation marker so that it has a mean zero and variance. A weighted average of the standardized methylation levels is then formed where the weights are chosen to equal their correlation with age in a training data set times the standard deviation of the ages that is expected in the test data set. In one or more embodiments, the transformation of the dependent variable (i.e. chronological age) is a piecewise transformation: for ages between say 0 and 20, a logarithmic transformation is used. For ages older than 20, a linear transformation is used. Additionally, the dependent variables (CpGs) are “normalized” to a chosen gold standard (e.g. the mean methylation level in the training data or the mean methylation levels in blood tissue) using an adaptation of the BMIQ algorithm by Teschendorff. Further details are provided in Example 8. This normalization step ensures that future test data resemble those of the training data. 
     For example, in one training data set disclosed herein, methylation markers cg22736354 (SEQ ID NO: 158), cg21296230 (SEQ ID NO: 354), cg06493994 (SEQ ID NO: 46), and cg09809672 (SEQ ID NO: 252) near genes NHLRC1, GREM1, SCGN, and EDARADD have correlations r=−0.47, 0.80, 0.71, and 0.76, respectively (see Examples). In the training data set, the standard deviation of age was 24 and the mean value was 45. After forming this weighted average of the standardized methylation levels, the expected mean age in the test data set (e.g. 45) is added to arrive at the final prediction of the chronological and/or the biological age of the individual. While the prediction is based on the chosen tissue, it also applies to other tissues. Therefore, easily accessible tissues such as blood or saliva tissue can be used to predict the age of brain tissue or other inaccessible tissues. 
     In addition to the illustrative models disclosed herein, other models can, for example, customize the coefficient values (weights) for different tissues and/or cell lineages. Furthermore, in addition to tissue type, such coefficients can be weighted in data sets from different populations. For example, if a model is applied to pediatric patients only, then one set of coefficients can be used. Alternatively, if a model is applied exclusively to older people (e.g. greater than 50 years), another set of coefficients can be used. Alternatively, coefficients can be fixed, for example, when a model is broadly applied to people of ages from 10 to 100 etc. Coefficient values in various models can also reflect the specific assay that is used to measure the methylation levels (e.g. as the variance of the methylation levels of individual probes may affect the coefficient). For example, for beta values measured on Illumina™ methylation microarray platforms there can be one set of coefficients, while for other methylation measures (e.g. using sequencing technology) there can be another set of coefficients etc. Other values may also be used instead, such as M values (transformed versions of beta values). Furthermore, methylation levels may be replaced by values that adjust for the methylation levels of a background or by mean methylation levels of a set benchmark of CpGs. In practicing certain embodiments of the invention, one can collect a reference data set (e.g. of 100 individuals of varying ages) using specific technology platform(s) and tissue(s) and then design a specific multivariate linear model fit to this reference data set to estimate the coefficients (e.g. using least squares regression). The resultant multivariate model can then be used for predicting ages on test patients. In this way, different mathematical models can be adapted for analyzing methylation patterns in a wide variety of contexts. 
     In addition to using art accepted modeling techniques (e.g. regression analyses), embodiments of the invention can include a variety of art accepted technical processes. For example, in certain embodiments of the invention, a bisulfite conversion process is performed so that cytosine residues in the genomic DNA are transformed to uracil, while 5-methylcytosine residues in the genomic DNA are not transformed to uracil. Kits for DNA bisulfite modification are commercially available from, for example, MethylEasy™ (Human Genetic Signatures™) and CpGenome™ Modification Kit (Chemicon™). See also, WO04096825A1, which describes bisulfite modification methods and Olek et al. Nuc. Acids Res. 24:5064-6 (1994), which discloses methods of performing bisulfite treatment and subsequent amplification. Bisulfite treatment allows the methylation status of cytosines to be detected by a variety of methods. For example, any method that may be used to detect a SNP may be used, for examples, see Syvanen, Nature Rev. Gen. 2:930-942 (2001). Methods such as single base extension (SBE) may be used or hybridization of sequence specific probes similar to allele specific hybridization methods. In another aspect the Molecular Inversion Probe (MIP) assay may be used. 
     Furthermore, the methods provided for estimating age may involve relatively few markers. In one or more certain embodiments, the methods involve between 1 to 4 markers. For example, DNA methylation markers near the following genes: NHLRC1 (SEQ ID NO: 357), GREM1 (SEQ ID NO: 356), SCGN (SEQ ID NO: 358) have highly significant positive correlations with age in multiple human tissues. Methylation markers near gene EDARADD (SEQ ID NO: 355) have a highly significant negative correlation with age in multiple tissues. By way of illustration, genes and corresponding Illumina™ Methylation probe IDs are provided. For example, the following probe identifiers from an Illumina™ methylation array platform denote suitable markers: i) probe cg22736354 (SEQ ID NO: 158) near gene NHLRC1, ii) probe cg21296230 (SEQ ID NO: 354) near gene GREM1, and iii) probe cg06493994 (SEQ ID NO: 46) near gene SCGN have positive correlations with age in multiple tissues; iv) probe cg09809672 (SEQ ID NO: 252) near gene EDARADD has a negative correlation with age in multiple tissues. 
     The methods for estimating an individual&#39;s age can be used for both diagnostic and prognostic purposes. The biomarkers for aging can be used to study the effect of medication, food compounds and/or special diets on the wellness and biological age of humans. They can also be used as biomarkers of vitality or youthfulness. For example, the biomarkers for aging can be used to determine chronological age (e.g. for forensic applications). They can also be used for determining and increasing an individual&#39;s likelihood of longevity and of retaining cognitive function during aging. 
     In certain embodiments the methods of the invention can be used to provide valuable information in forensic investigations (e.g. where the identity of the individual from which the DNA is derived is unknown). In one embodiment, the methods disclosed herein can be applied to forensic applications involving the prediction of chronological age. The methylation levels of the epigenetic markers (clock CpGs) are measured. In certain embodiments, the methylation levels of one or more of the four methylation markers near genes EDARADD, NHLRC1, GREM1, and SCGN in blood or saliva are measured. In one embodiment, probes cg22736354 (SEQ ID NO: 158) near gene NHLRC1, cg21296230 (SEQ ID NO: 354) near gene GREM1, cg06493994 (SEQ ID NO: 46) near gene SCGN, and/or cg09809672 (SEQ ID NO: 252) near gene EDARADD are used. A statistical prediction method (e.g. based on linear regression) is then applied to predict the age of the individual. The age predictive models disclosed can be applied in a variety of contexts. For instance, the ability to predict an individual&#39;s age can be used by forensic scientists to estimate a suspect&#39;s age based on a biological sample alone. In embodiments of the invention designed for forensic use, a practitioner could, for example, submit a biological sample to a lab. In the lab, DNA prepared from the sample could then be analyzed to determine the percentage of methylation at one or more of the loci identified herein. The results could be inputed in a regression model, such as those disclosed herein, to predict the age of the suspect. In certain instances, the suspect&#39;s age can be predicted to an average accuracy of 3 to 5 years. 
     Such embodiments of the invention can be combined with other forensic analysis procedures, for example by also performing a DNA fingerprinting analysis on the genomic DNA. DNA fingerprinting (also known as DNA profiling) using short tandem repeats (STRs) is one method for human identification in forensic sciences, finding applications in different circumstances such as determination of perpetrators of violent crime, resolving paternity, and identifying remains of missing persons or victims of mass disaster. The FBI and the forensic science community typically use 13 separate STR loci (the core CODIS loci) in routine forensic analysis. (CODIS refers to the Combined DNA Index System that was established by the FBI in 1998). Illustrative DNA fingerprinting methodologies are disclosed, for example, in U.S. Pat. Nos. 7,501,253, 7,238,486, 6,929,914, 6,251,592, and 5,576,180). 
     In another embodiment, the methods disclosed herein can be applied to medical applications involving the prediction of the biological age. The age is predicted according to the methods described. This predicted value is interpreted as the biological age (DNA methylation age). The prediction then is contrasted with the known chronological age of the individual. If the predicted age is higher than the chronological age, it indicates that the person appears older (or more impaired or more at risk of an age related disease) than his or her peers from the same age group, i.e. shows evidence of age acceleration. 
     In addition, a measurement of relevant methylation patterns in genomic DNA from white blood cells or skin cells also provides a tool in routine medical screening to predict the risk of age-related diseases as well as to tailor interventions based on the epigenetic biological age instead of the chronological age. In some embodiments of the invention, one can compare the predicted age of the individual with the actual chronological age of the individual, for example as part of a diagnostic procedure for an age associated pathology (e.g. one that compares an individual&#39;s chronological age with an apparent biological age in view of their DNA methylation patterns). Such methods can be useful in clinical interventions that are predicated on an epigenetic biological age rather than an actual chronological age. In one embodiment, a biological sample can be collected in a routine health check and sent to the lab for methylation pattern analysis (e.g. as described above). If the predicted age of the patient is higher than the real age, the patient can be at an increased risk of age-related diseases, and dietary intervention, or specific drugs, could be prescribed to reduce this “genetic age”. As noted above, embodiments of the invention include methods of obtaining information useful to determine a level of risk of an age-related disease in an individual (e.g. Alzheimer&#39;s disease or Parkinson&#39;s disease). 
     Furthermore, since DNAm age allows one to contrast the ages of various tissues/cell types from the same individual, it can be used to identify diseased tissue (e.g. cancer tissue often shows evidence of severe positive or negative age acceleration). The biomarkers for aging can also be used for determining and decreasing an individual&#39;s likelihood of developing an age-related disease, e.g. cancer, dementia. Methods are provided for diagnosing and determining the existence or likelihood of cognitive deficits in the elderly resulting from senescence or age-related disease. Accordingly, such methods allow for the determination of patients who are most likely to be at risk of age-related cognitive decline and allow these patients to be targeted for more intensive study or prophylaxis. 
     In a further embodiment, the methods disclosed herein can be applied to assess the efficacy of a treatment or compound (e.g. rejuvenation or curing an age-related impairment, enhancing memory function or cognition). As an example, the biomarkers for aging can be used in studying patients who, although not elderly, are afflicted by a brain disease that typically occurs in the elderly (e.g. early onset dementia). A determination is made regarding whether administration of the treatment or compound affects the predicted age. An effective treatment would lower the predicted age since the individual appears rejuvenated and younger. 
     An assay is provided for identifying a compound that increases memory function and/or decreases a subject&#39;s likelihood of developing an age-related cognitive decline. The assay comprises identifying a compound which counters the age-related increase or decrease of methylation in the identified markers. Age prediction methodologies are also relevant to healthcare applications. For example, significant DNA methylation differences are known to be associated with specific age-related disorders, for example in comparisons between the brains of people diagnosed with late-onset Alzheimer&#39;s disease and brains from controls. In this context, the identification of specific loci highly correlated with age can be used to enhance the understanding of aging in health and disease. In certain embodiments of the invention, age prediction methodologies can be used as part of clinical interventions tailored for patients based on their “bio-age”—a result of the interaction of genes, environment, and time—rather than their chronological age. For example, if a person&#39;s predicted age is higher than their real age, specific interventions could be designed to return the genome to a “younger” state. Age prediction methodologies can also pave the way for interventions based on specific epigenetic marks associated with disease, as occurs in certain cancer treatments. 
     As described in detail in the Example section below, specific age-related methylation markers have been identified and validated using further assays and additional samples. Additionally, illustrative age prediction analysis models have been designed and tested, for example by using a leave-one-out analysis where one subject from a model is systematically removed and the model is used to predict the subject&#39;s age. Since the real age of this subject is already known, such methods provide ways to validate various model designs. 
     EXAMPLES 
     As shown in the illustrative examples below, the relationship between DNA methylation and age has been validated in 5 independent whole blood data sets, 3 brain methylation data sets and 2 saliva data sets. These findings are highly significant and have been carefully validated. 
     For Examples 1-4, publicly available data was used (see e.g. Gene Expression Omnibus database). Brain methylation data came from Gibbs J R et al. (2010) (Gibbs J R, van der Brug M P, Hernandez D G, Traynor B J, Nalls M A, et al. (2010) Abundant Quantitative Trait Loci Exist for DNA Methylation and Gene Expression in Human Brain. PLoS Genet 6(5): e1000952. doi:10.1371/journal.pgen.1000952). The authors obtained frozen brain tissue from frontal cortex (FCTX), pons (PONS) and temporal cortex (TCTX) from 150 subjects (total 450 tissue samples). Using the Illumina™ 27 k methylation array they assayed 27,578 CpG methylation sites in each of the brain regions. However, the authors did not study age effects. Further, they did not relate the brain methylation data to blood methylation data. The publicly available blood and saliva methylation used the same Illumina™ methylation array and are described in the following Table 1. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Table 1. Description of public DNA methylation data sets used for the invention 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Set 
                 Sample 
                   
                 Sample 
                 Mean 
                 Age 
                 Methylation 
                   
                 GSE 
               
               
                 No 
                 size 
                 Tissue 
                 characteristics 
                 Age 
                 Range 
                 Assay 
                 Reference 
                 number 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 191 
                 WB 
                 Type 1 diabetics 
                 44 
                 24-74 
                 Infin 27k 
                 Teschendorff 2010 
                 GSE20067 
               
               
                 2 
                 93 
                 WB 
                 Healthy older women 
                 63 
                 49-74 
                 Infin 27k 
                 Rakyan 2010 
                 GSE20236 
               
               
                 3 
                 534 
                 WB 
                 postmenopausal 
                 66 
                 49-91 
                 Infin 27k 
                 Teschendorff 2010, 
                 GSE19711 
               
               
                   
                   
                   
                 women from the 
                   
                   
                   
                 Song 2009 
                   
               
               
                   
                   
                   
                 ovarian cancer UKOPS 
                   
                   
                   
                   
                   
               
               
                 4 
                 133 
                 FCTX 
                 FCTXbrain 
                 48 
                  15-101 
                 Infin 27k 
                 Gibbs 2010 
                 GSE15745 
               
               
                 5 
                 127 
                 TCTX 
                 TCTXbrain 
                 49 
                  15-101 
                 Infin 27k 
                 Gibbs 2010 
                 GSE15745 
               
               
                 6 
                 125 
                 PONS 
                 PONSbrain 
                 47 
                  15-101 
                 Infin 27k 
                 Gibbs 2010 
                 GSE15745 
               
               
                 7 
                 114 
                 CRBLM 
                 CRBLM brain 
                 48 
                 16-96 
                 Infin 27k 
                 Gibbs 2010 
                 GSE15745 
               
               
                 8 
                 69 
                 Saliva 
                 Saliva 
                 35 
                 21-55 
                 Infin 27k 
                 Bockland 2011 
                 GSE28746 
               
               
                 9 
                 168 
                 cord blood 
                 newborns, cordblood 
                 0 
                 0-0 
                 Infin 27k 
                 Adkins 2011 
                 GSE27317 
               
               
                   
                   
                 buffy coat 
                   
                   
                   
                   
                   
                   
               
               
                 10 
                 50 
                 CD14+ CD4+ 
                 sorted CD4+ T-cells 
                 36 
                 16-69 
                 Infin 27k 
                 Rakyan 2010 
                 GSE20242 
               
               
                   
                   
                   
                 and CD14+ 
                   
                   
                   
                   
                   
               
               
                   
                   
                   
                 monocytes 
                   
                   
                   
                   
                   
               
               
                 11 
                 185 
                 Saliva 
                 Saliva from alcoholics 
                 32 
                 21-55 
                 Infin 27k 
                 Liu 2010 
                 GSE34035 
               
               
                   
               
               
                 (WB) Whole blood, 
               
               
                 FCTX (Frontal Cortex), 
               
               
                 TCTX (Temporal Cortex), 
               
               
                 CRBLM (Cerebellum), 
               
               
                 (NA) not available 
               
            
           
         
       
     
     For the identification of age-related methylation markers across multiple tissues, Stouffer&#39;s meta-analysis Z statistic (implemented in the metaAnalysis R function in the Weighted correlation network analysis (WGCNA) R package) was used to identify methylation markers that consistently relate to age across all data sets (see Table 2). 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Table: P-values from a meta analysis relating age to methylation levels across multiple tissues. 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Gene Sym 
                 Probe ID 
                 pValueAllTissues 
                 pValueBood 
                 pValueBrain 
                 pValueSaliva 
                 cor with age 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 SOGN 
                 cg06493994 
                 2.05E−119 
                 3.72E−23 
                 2.33E−121 
                 1.64E−18 
                 0.76 
               
               
                 EDARADD 
                 cg09809672 
                 2.69E−87  
                 3.18E−39 
                 1.52E−40  
                 3.50E−28 
                 −0.47 
               
               
                 GREM1 
                 cg21296230 
                 4.16E−105 
                 4.78E−22 
                 1.71E−108 
                 7.27E−16 
                 0.71 
               
               
                 NHLRC1 
                 cg22736354 
                 8.13E−146 
                 3.52E−27 
                 8.51E−165 
                 6.50E−11 
                 0.80 
               
               
                   
               
            
           
         
       
     
     Example 1 
     Linear Regression Predictor Involving Only 1 Methylation Marker Accurately Predicts Age in Blood, Brain and Saliva 
     A univariate linear regression predictor based on a single methylation probe was examined. A single methylation probe corresponding to Illumina™ probe ID cg22736354 (SEQ ID NO: 158) (close to gene NHLRC1) was used in the univariate linear regression model. As shown in  FIGS. 1-3 , using a single cytosine marker in gene NHLRC1, the linear regression model-based prediction of age was found to correlate with the true age in brain tissue (correlation coefficient=0.88, p-value=6.8×E-126) and blood tissue (cor=0.76,p=3.6E-174). In particular, Probe ID: cg22736354 (SEQ ID NO: 158), located near the gene with gene symbol NHLRC1, had a highly significant positive correlation with age in the considered brain regions and in blood. 
     Example 2 
     A Multivariate Regression Predictor Involving 2 Methylation Markers Accurately Predicts Age in Blood, Brain and Saliva 
     A multivariate regression predictor based on two methylation probes was examined. Methylation probes corresponding to Illumina™ probe IDs cg09809672 (SEQ ID NO: 252, close to gene EDARADD) and cg22736354 (SEQ ID NO: 158, close to gene NHLRC1) were used in the multivariate linear regression model. As shown in  FIGS. 4-7 , using just the two cytosines near genes NHLRC1 and EDARADD, the multivariate linear regression model based prediction of age had a correlation larger than 0.90 with age in blood and brain tissue and it also correlated highly with age in saliva tissue. The median absolute difference (deviation) between predicted age and true age was 5.1 years. In particular, Probe ID: cg09809672 (SEQ ID NO: 252), located near the gene with gene symbol EDARADD, had a negative correlation with age and Probe ID: cg22736354 (SEQ ID NO: 158), located near the gene with gene symbol NHLRC1, had a positive correlation with age. 
     Example 3 
     A Multivariate Regression Predictor Involving 4 Methylation Markers Accurately Predicts Age in Blood, Brain and Saliva 
     A multivariate regression predictor based on four methylation probes was examined. Methylation probes corresponding to Illumina™ probe IDs cg09809672 (SEQ ID NO: 252, close to gene EDARADD), cg22736354 (SEQ ID NO: 158, close to gene NHLRC1), cg21296230 (SEQ ID NO: 354, close to gene GREM1), and cg06493994 (SEQ ID NO: 46, close to gene SCGN) were used in the multivariate linear regression model. As shown in  FIGS. 8-11 , using the four cytosines near genes EDARADD, NHLRC1, GREM1, SCGN, the multivariate linear regression model based prediction of age had a correlation larger than 0.90 with age in blood and brain tissue and that correlate with age in saliva tissue. The median absolute difference (deviation) between predicted age and true age was around 5.1 years. In particular, probe ID: cg09809672 (SEQ ID NO: 252), located near the gene with gene symbol EDARADD, had a negative correlation with age and Probe IDs: cg22736354 (SEQ ID NO: 158), cg21296230 (SEQ ID NO: 354), and cg06493994 (SEQ ID NO: 46), located near the genes with gene symbols NHLRC1, GREM1, and SCGN, respectively, had a positive correlation with age. 
     Example 4 
     Two Saliva Based Methylation Markers can be Used to Predict the Age of Brain Tissue 
     Methylation markers near the gene EDARADD (e.g. methylation probe cg09809672, SEQ ID NO: 252) and gene SCGN (e.g. probe cg06493994, SEQ ID NO: 46) were used in predicting brain age. As shown in  FIGS. 12-15 , the predicted age in brain tissue had a correlation of 0.4 with the true age (median deviation=8.2 years). In saliva, the correlation was 0.72 and median deviation was only 4.2 years. In blood tissue, the correlation was 0.88 and median deviation was 6.1 years. Thus, the predictor is particularly well suited for predicting brain age based on saliva samples. Probe ID: cg09809672 (SEQ ID NO: 252), located near the gene with gene symbol EDARADD, had a negative correlation with age and Probe ID: cg06493994 (SEQ ID NO: 46), located near the gene with gene symbol SCGN (also known as SEGN; SECRET; setagin; DJ501N12.8) had a positive correlation with age. 
     Example 5 
     DNA Methylation Age of Human Tissues and Cell Types 
     A collection of publicly available DNA methylation data sets is used for defining and evaluating an age predictor. The demonstrated accuracy across most tissues and cell types justifies its designation as a multi-tissue age predictor. Its age prediction, referred to as DNAm age, can be used as biomarker for addressing a host of questions arising in aging research and related fields. For example, interventions used for creating induced pluripotent stem cells are shown to reset the epigenetic clock to zero. 
     Using 82 Illumina™ DNA methylation array data sets (n=7844) involving 51 healthy tissues and cell types, a multi-tissue predictor of age is provided which allows one to estimate the DNA methylation (DNAm) age of most tissues and cell types. DNAm age has the following properties: a) it is close to zero for embryonic and induced pluripotent stem (iPS) cells, b) it correlates with cell passage number, c) it gives rise to a highly heritable measure of age acceleration, and d) it is applicable to chimpanzee tissues. 354 clock CpGs were characterized in terms of chromatin states and tissue variance (Table 3). The application of DNAm age to 32 additional cancer DNA methylation data sets (comprised of n=5826 samples) shows that all cancer tissues exhibit significant age acceleration (on average 36.2 years). Low age acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations. Mutations in steroid receptors greatly accelerate DNAm age in breast cancer. The multi-tissue predictor of age has been applied to colorectal cancer, glioblastoma multiforme, AML, and cancer cell lines. 
     Description of the (Non-Cancer) DNA Methylation Data Sets 
     A large DNA methylation data set was assembled by combining publicly available individual data sets measured on the Illumina™ 27K or Illumina™ 450K array platform (Cancer Genome Atlas (TCGA) data sets). In total, n=7844 non-cancer samples from 82 individual data sets were analyzed, which assess DNA methylation levels in 51 different tissues and cell types. Although many data sets were collected for studying certain diseases (Example 8), they largely involved healthy tissues. In particular, cancer tissues were excluded from this first large data set since it is well known that cancer has a profound effect on DNA methylation levels [6, 7, 24-26]. The Cancer Genome Atlas (TCGA) data sets involved normal adjacent tissue from cancer patients. Details on the individual data sets and data pre-processing steps are provided in Example 7 (Materials and methods) and Example 8. The first 39 data sets were used to construct (“train”) the age predictor. Data sets 40-71 were used to test (validate) the age predictor. Data sets 72-82 served other purposes e.g. to estimate the DNAm age of embryonic stem and iPS cells. The criteria used for selecting the training sets are described in Example 8. Briefly, the training data were chosen i) to represent a wide spectrum of tissues/cell types, ii) to involve samples whose mean age (43 years) is similar to that in the test data, and iii) to involve a high proportion of samples (37%) measured on the Illumina™ 450K platform since many on-going studies use this recent Illumina™ platform. 21369 CpGs (measured with the Infinium type II assay), which were present on both Illumina™ platforms (Infinium 450K and 27K), were studied. There were fewer than 10 missing values across the data sets. 
     The Multi-Tissue Age Predictor Used for Defining DNAm Age 
     To ensure an unbiased validation in the test data, only the training data was used to define the age predictor. As detailed in Example 7 (Materials and methods) and Example 8, a transformed version of chronological age was regressed on the CpGs using a penalized regression model (elastic net). The elastic net regression model automatically selected 354 CpGs (Table 3, Example 9). Since their weighted average (formed by the regression coefficients) amounts to an epigenetic molecular clock, the 354 CpGs are referred to as clock CpGs. 
     Predictive Accuracy Across Different Tissues 
     Several measures of predictive accuracy were initially considered since each measure has distinct advantages. The first, referred to as “age correlation”, is the Pearson correlation coefficient between DNAm age (predicted age) and chronological age. It has the following limitations: it cannot be used for studying whether DNAm is well calibrated, it cannot be calculated in data sets whose subjects have the same chronological age (e.g. cord blood samples from newborns), and it strongly depends on the standard deviation of age (as described below). The second accuracy measure, referred to as (median) “error”, is the median absolute difference between DNAm age and chronological age. Thus, a test set error of 3.6 years indicates that DNAm age differs by less than 3.6 years in 50% of subjects. The error is well suited for studying whether DNAm age is poorly calibrated. Average age acceleration, defined by the average difference between DNAm age and chronological age, can be used to determine whether the DNAm age of a given tissue is consistently higher (or lower) than expected. 
     According to these three accuracy measures, the multi-tissue age predictor has been found to perform remarkably well in most tissues and cell types. A high accuracy in the training data (age correlation 0.97, error=2.9 years) was demonstrated in exemplary experiments and its performance assessment (age correlation=0.96, error=3.6 years,  FIG. 17 ) in the test data is notably unbiased. Note that the age predictor performs well in heterogeneous tissues (e.g. whole blood, blood peripheral blood mononuclear cells, cerebellar samples, occipital cortex, buccal epithelium, colon, adipose, liver, lung, saliva, uterine cervix) as well as in individual cell types such as CD4 T cells and CD14 monocytes ( FIG. 17C ) and immortalized B cells ( FIG. 17T ). 
     The age predictor is particularly accurate in data sets comprised of adolescents and children, e.g. blood ( FIG. 17B ), brain data ( FIG. 17F ,G), and buccal epithelium ( FIG. 17I ). 
     The DNAm Age of Blood and Brain Cells 
     Human blood cells have different life spans: while CD14+ monocytes (myeloid lineage) only live several weeks, CD4+ T-cells (lymphoid lineage) represent a variety of cell types that can live from months to years. An interesting question is whether blood cell types have different DNAm ages. In one experiment, it was found that DNAm age does not vary significantly across sorted blood cells from healthy male subjects. These results combined with the fact that the age predictor works well in individual cell types ( FIG. 17 ) strongly suggest that DNAm age does not reflect changes in cell type composition but rather intrinsic changes in the methylome. This conclusion is also corroborated by the finding that DNAm age is highly related to chronological age in glial cells and neurons and various brain regions. 
     DNAm Age and Progeria 
     DNAm age can be used to study whether cells from patients with accelerated aging diseases such as progeria (including Werner progeroid syndrome, Hutchinson-Gilford progeria, HGP) truly look old at an epigenetic level. An exemplary experiment has demonstrated that progeria disease status is not related to DNAm based age acceleration in Epstein-Barr-Virus transformed B cells ( FIG. 17T ). But the study of accelerated aging effects in HGP should be repeated for vascular smooth muscle, the tissue that is most compromised in HGP. 
     Tissues where DNAm Age is Less Accurately Calibrated 
     In certain experiments, DNAm age was found to be less accurately calibrated (i.e. leads to a higher error) in breast tissue ( FIG. 17H ), uterine endometrium ( FIG. 17S ), dermal fibroblasts, skeletal muscle tissue ( FIG. 17P ), and heart tissue ( FIG. 17L ). The biological reasons that could explain the less accurate calibration can only be speculated. It may be possible that the higher error in breast tissue may reflect hormonal effects or cancer field effects in this normal adjacent tissue from cancer samples. Note that the lowest error (7.5 years) in breast tissue is observed in normal breast tissue, i.e. in samples from women without cancer. The menstrual cycle and concomitant increases in cell proliferation may explain the high error in uterine endometrium. Myosatellite cells may effectively rejuvenate the DNAm age of skeletal muscle tissue. Similarly, the recruitment of stem cells into cardiomyocytes for new cardiac muscle formation could explain why human heart tissue tends to have a low DNAm age. Carefully designed studies will be needed to test these hypotheses. 
     The Age Correlation in a Data Set is Determined by the Standard Deviation of Age 
     In the following, non-biological reasons that affect the accuracy (age correlation) of the age predictor are described. To address how well the age predictor works in individual data sets, two different approaches were used. First, the age predictor was applied to individual data sets. An obvious limitation of this approach is that it leads to biased results in the training data sets. 
     The second approach, referred to as leave-one-data-set-out cross validation (LOOCV) analysis, leads to unbiased estimates of the predictive accuracy for each data set. As suggested by its name, this approach estimates the DNAm age for each data set (considered as test data set) separately by fitting a separate multi-tissue age predictor to the remaining (left out) data sets. 
     Data sets differ greatly with respect to the median chronological age and the standard deviation (SD), which is defined as the square root of the variance of age. Some data sets only involve samples with the same age (SD=0) while others involve both young and old subjects. As expected, the SD is found to be significantly correlated (r=0.49, p=4E-5) with the corresponding LOOCV estimate of the age correlation. In contrast, the sample size of the data set has no significant relationship with the age correlation. 
     A host of technical artefacts could explain differences in predictive accuracy (e.g. variations in sample processing, DNA extraction, DNA storage effects, batch effects, and chip effects. 
     DNAm Age of Multiple Tissues from the Same Subject 
     The following addresses whether solid tissues can be found whose DNAm age differs substantially from chronological age. As a first step, the mean DNAm age per tissue is compared with the corresponding mean chronological age. As expected, mean DNAm age per tissue is highly correlated (cor=0.99) with mean chronological age. But breast tissue shows evidence of significant age acceleration. 
     A more interesting analysis is to compare the DNAm ages of tissues collected from the same subjects. DNAm age does not change significantly across different brain regions (temporal cortex, pons, frontal cortex, cerebellum) from the same subjects. Although the limited sample sizes per tissue (mostly one sample per tissue per subject) in this illustrative experiment did not allow for rigorous testing, these data can be used to estimate the coefficient of variation of DNAm age (i.e. the standard deviation divided by the mean). Note that the coefficient of variations for the first and second adult male are relatively low (0.12 and 0.15) even though the analysis involved several tissues that were not part of the training data, e.g. jejunum, penis, pancreas, esophagus, spleen, pancreas, lymph node, diaphragm. The coefficient of variation in the adult female is relatively high (0.21) which reflects the fact that her breast tissue shows signs of substantial age acceleration. 
     It remains to be seen how well DNAm age performs in tissues and DNA sources that were not represented in the training data set. It is anticipated that it also performs well in several other human tissues. As expected, no significant age correlation was found in sperm. The DNAm age of sperm is significantly lower than the chronological age of the donor. 
     DNAm Age is Applicable to Chimpanzees 
     It is important to study whether there are inter-primate differences when it comes to DNAm age. These studies may not only help in identifying model organisms for rejuvenating interventions but might explain differences in primate longevity. While future studies could account for sequence differences, it is straightforward to apply the DNAm age estimation algorithm to Illumina™ DNA methylation data sets 72 [27] and 73 [28]. Strikingly, the DNAm age of heart-, liver-, and kidney tissue from chimpanzees (Pan troglodytes) is aligned with that of the corresponding human tissues. Further, the DNAm age of blood samples from two extant hominid species of the genus pan (commonly referred to as chimpanzee) is highly correlated with chronological age. While DNAm age is applicable to chimpanzees, its performance appears to be diminished in gorillas, which may reflect the larger evolutionary distance. 
     DNAm Age of Induced Pluripotent Stem (iPS) Cells and Stem Cells 
     The billions of cells within an individual can be organized by genealogy into a single somatic cell tree that starts from the zygote and ends with differentiated cells. Cells at the root of this tree should be young. This is indeed the case: embryonic stem cells have a DNAm age close to zero in 5 different data sets. Induced pluripotent stem (iPS) cells are a type of pluripotent stem cell artificially derived from a non-pluripotent cell (typically an adult somatic cell) by inducing a set of specific genes. Since iPS cells are similar to ES cells, it is hypothesized that the DNAm age of iPS cells should be significantly younger than that of corresponding primary cells. This hypothesis is confirmed in three independent data sets. No significant difference in DNAm age could be detected between embryonic stem (ES) cells and iPS cells. 
     Effect of Cell Passaging on DNAm Age 
     Most cells lose their proliferation and differentiation potential after a limited number of cell divisions (Hayflick limit). It is hypothesized that cell passaging (also known as splitting cells) increases DNAm age. This hypothesis is confirmed in three independent data sets. A significant correlation between cell passage number and DNAm age can be also observed when restricting the analysis to iPS cells or when restricting the analysis to embryonic stem cells. 
     Comparing the Multi-Tissue Predictor with Other Age Predictors 
     The multi-tissue predictor disclosed greatly outperforms existing predictors described in other articles [21, 23]. See Example 8 for a comparison of the multi-tissue predictor versus existing predictors. While further gains in accuracy can perhaps be achieved by focusing on a single tissue and considering more CpGs, the major strength of the multi-tissue age predictor lies in its wide applicability: for most tissues it will not require any adjustments or offsets. A “shrunken” version of the multi-tissue predictor (Examples 8 and 9), based on 110 CpGs (selected from the 354 clock CpGs) has also been found to be highly accurate in the training data (cor=0.95, error=4 years) and test data (cor=0.95, error=4.2 years). 
     What is Known about the 354 Clock CpGs? 
     An Ingenuity Pathway analysis of the genes that co-locate with the 354 clock CpGs (Table 3) shows significant enrichment for cell death/survival, cellular growth/proliferation, organismal/tissue development, and cancer. 
     The 354 clock CpGs can be divided into two sets according to their correlation with age. The 193 positively and 160 negatively correlated CpGs get hypermethylated and hypomethylated with age, respectively. DNA methylation data measured across many different adult and fetal tissues is used to study the relationship between tissue variance and age effects. While the DNA methylation levels of the 193 positively related CpGs vary less across different tissues, those of the 160 negatively related CpGs vary more across tissues than the remaining CpGs on the Illumina™ 27K array. To estimate “pure” age effects, a meta-analysis method was used that implicitly conditions on data set, i.e. it removes the confounding effects due to data set and tissue type. The clock CpGs include those with the most significant meta-analysis p-value for age irrespective of whether the meta-analysis p-value was calculated using only training data sets or all data sets. While positively related markers don&#39;t show a significant relationship with CpG island status, negatively related markers tend to be over-represented in CpG shores (p=9.3E-6). 
     Significant differences between positive and negative markers exist when it comes to Polycomb-group protein binding: positively related CpGs are over-represented near Polycomb-group target genes (reflecting results from [10, 14]) while negative CpGs show no significant relationship. 
     Chromatin State Analysis 
     Chromatin state profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. It provides a systematic means of detecting cis-regulatory elements (given the central role of chromatin in mediating regulatory signals and controlling DNA access) and can be used for characterizing non-coding portions of the genome, which contribute to cellular phenotypes [29]. While individual histone modifications are associated with regulator binding, transcriptional initiation, enhancer activity, combinations of chromatin modifications can provide even more precise insight into chromatin state [29]. Ernst et al (2011) distinguish six broad classes of chromatin states, referred to as promoter, enhancer, insulator, transcribed, repressed, and inactive states. Within them, active, weak and poised promoters (states 1-3) differ in expression levels, while strong and weak enhancers (states 4-7) differ in expression of proximal genes. The 193 positively related CpGs are more likely to be in poised promoters (chromatin state 3 regions) while the 160 negatively related CpGs are more likely to be either in weak promoters (chromatin state 2) or strong enhancers (chromatin state 4). 
     Age Acceleration is Highly Heritable 
     Several authors have found that DNA methylation levels are under genetic control [24, 26, 30-32]. Since many age-related diseases are heritable, it is interesting to study to whether age acceleration (here defined as difference between DNAm age and chronological age) is heritable as well. The broad sense heritability of age acceleration is estimated using Falconer&#39;s formula, H 2 =2(cor(MZ)-cor(DZ)), in two twin data sets that included both monozygotic (MZ) and dizygotic (DZ) twins. 
     An illustrative experiment estimating the heritability of age acceleration found that the broad sense heritability of age acceleration was 100% in newborns and 39% in older subjects, which suggests that non-genetic factors become more relevant later in life. 
     Aging Effects on Gene Expression (Messenger RNA) Levels 
     Since DNA methylation is an important epigenetic mechanism for regulating gene expression levels (messenger RNA abundance), it is natural to wonder how age-related DNAm changes relate to those observed in gene expression levels. It has been found that there is very little overlap. Further, age effects on DNAm levels have not been found to affect genes known to be differentially expressed between naive CD8 T cells and CD8 memory cells. These non-significant results reflect the fact that the relationship between DNAm levels and expression levels is complex [33, 34]. 
     Age Effects on Individual CpGs 
     In this example, for each CpG, the median DNAm level in subjects younger than 35 and in subjects older than 55 is examined (Example 9). The age-related change in beta values is typically small (the average absolute difference across the 354 CpGs is only 0.032). The weak age effect on individual clock CpGs can also be observed in a heat map that visualizes how the DNAm levels change across subjects. Few vertical bands in the heat map suggest that the clock CpGs are relatively robust against tissue and data set effects. 
     The Changing Ticking Rate of the Epigenetic Clock 
     The linear combination of the 354 clock CpGs (resulting from the regression coefficients) varies greatly across ages. There is a logarithmic dependence until adulthood which slows to a linear dependence later in life (see formula in Example 8). The rate of change is interpreted as the ticking rate of the epigenetic clock. Using this terminology, it has been found that organismal growth (and concomitant cell division) leads to a high ticking rate which slows down to a constant ticking rate (linear dependence) after adulthood. 
     DNAm Age does not Measure Mitotic Age or Cellular Senescence 
     Since epigenetic somatic errors in somatic replications appear to be readily detected as age-related changes in methylation [35, 36], it is a plausible hypothesis that DNAm age measures the number of somatic cell replications. In other words, that it measures mitotic age (which assigns a cell copy number to every cell) [35, 37]. While DNAm age is correlated with cell passage number and the clock ticking rate is highest during organismal growth, it is clearly different from mitotic age since it tracks chronological age in non-proliferative tissue (e.g. brain tissue) and assigns similar ages to both short and long lived blood cells. 
     One explanation is that DNAm age is a marker of cellular senescence. This turns out to be wrong as can be seen from the fact that DNAm age is highly related to chronological age in immortal, non-senescent cells, e.g. immortalized B cells ( FIG. 17T ). Further, DNAm age and cell passage number are highly correlated in ES cells which are also immortal [38]. 
     Example 6 
     Model: DNAm Age Measures the Work Done by an Epigenetic Maintenance System 
     It is proposed that DNAm age measures the cumulative work done by a particular kind of epigenetic maintenance system (EMS), which helps maintain epigenetic stability. While epigenetic stability is related to genomic stability, it is useful to distinguish these two concepts. If the EMS model of DNAm age is correct then this particular kind of EMS appears to be inactive in the perfectly young ES cells. Maintenance methyltransferases are likely to play an important role. In physics, “work” is defined by the integral of power over time. Using this terminology, it is hypothesized that the power (defined as rate of change of the energy spent by this EMS) corresponds to the tick rate of the epigenetic clock. This model would explain the high tick rate during organismal development since a high power is required to maintain epigenetic stability during this stressful time. At the end of development, a constant amount of power is sufficient to maintain stability leading to a constant tick rate. 
     If this EMS model of DNAm age is correct then DNAm age should be accelerated by many perturbations that affect epigenetic stability. Further, age acceleration should have some beneficial effects given the protective role of the EMS. In particular, the EMS model of DNAm age entails the following testable predictions. First, cancer tissue should show signs of positive or negative accelerated age, reflecting the actions of the EMS. Second, many mitogens, genomic aberrations, and oncogenes, which trigger the response of the EMS, should be associated with accelerated DNAm age. Third, high age acceleration of cancer tissue should be associated with fewer somatic mutations given the protective role of the EMS. Fourth, mutations in TP53 should be associated with a lower age acceleration of cancer tissue if one further assumes that p53 signaling helps trigger the EMS. All of these model predictions turn out to be true as will be shown in the following cancer applications. 
     DNAm Age of Cancer Tissue Versus Tumor Morphology 
     A large collection of cancer data sets was assembled comprising n=5826 cancer samples from 32 individual cancer data sets (Example 10). Details on the cancer data sets can be found in Example 8. While some cancer tissues show relatively large correlations between DNAm age and patient age, the correlation between DNAm age and chronological age tends to be weak. Some cancer types exhibit increased age acceleration while others exhibit negative age acceleration. Tumor morphology (grade and stage) has only a weak relationship with age acceleration in most cancers: only 4 out of 33 hypothesis tests led to a nominally (p&lt;0.05) significant result. Only the negative correlation between stage and age acceleration in thyroid cancer remains significant after applying a Bonferroni correction. 
     Cancer Tissues with High Age Acceleration Exhibit Fewer Somatic Mutations 
     Strikingly, the number of mutations per cancer sample tends to be inversely correlated with age acceleration, which may reflect that DNAm age acceleration results from processes that promote genome stability. Specifically, a significant negative relationship between age acceleration and the number of somatic mutations can be observed in the following seven affected tissues/cancers: bone marrow (AML data from TCGA), breast carcinoma (BRCA data), kidney renal cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), ovarian cancer (OVAR), prostate (PRAD), and thyroid (THCA). Similar results can also be observed in several breast cancer types. 
     TP53 Mutations are Associated with Lower Age Acceleration 
     Strikingly, TP53 was among the top 2 most significant genes in 4 out of the 13 cancer data sets whose mutation has the strongest effect on age acceleration. Further, TP53 mutation is associated with significantly lower age acceleration in five different cancer types including AML, breast cancer, ovarian cancer, and uterine corpus endometrioid. Further, marginally significant result can be observed in lung squamous cell carcinoma and colorectal cancer (below). Only one cancer type (GBM) was found where mutations in TP53 are associated with a nominally significant increased age acceleration. Overall, these results suggest that p53 signaling can trigger processes that accelerate DNAm age. 
     Somatic Mutations in Steroid Receptors Accelerate DNAm Age in Breast Cancer 
     In the following, DNAm age changes across different breast cancer types are shown. Somatic mutations in steroid receptors have a pronounced effect on DNAm age in breast cancer samples: samples with a mutated estrogen receptor (ER) or mutated progesterone receptor (PR) exhibit a much higher age acceleration than ER- or PR-samples in four independent data sets. In contrast, HER2/neu amplification has no significant relationship with age acceleration. Age acceleration differs greatly across different breast cancer types: Luminal A tumors (typically ER+ or PR+, HER2−, low Ki67), show the highest positive age acceleration. Luminal B tumors (typically ER+ or PR+, HER2+ or HER2− with high Ki67) show a similar effect. The lowest age acceleration can be observed for basal-like tumors (often triple negative ER−, PR−, HER2−) and HER2 type tumors (typically HER2+, ER−, PR−). 
     Proto-Oncogenes Affect DNAm Age in Colorectal Cancer 
     Colorectal cancer samples with a BRAF (V600E) mutation are associated with an increased age acceleration whereas samples with a K-RAS mutation have a decreased age acceleration. Echoing previous results, TP53 mutations appear to be associated with decreased age acceleration. Promoter hypermethylation of the mismatch repair gene MLH1 leads to the most significant increase in age acceleration, which supports the EMS model of DNAm age. The CpG island methylator phenotype, defined by exceptionally high cancer-specific DNA hypermethylation [39], is also significantly associated with age acceleration, which may reflect its association with MLH1 hypermethylation and BRAF mutations. 
     DNAm Age in Glioblastoma Multiforme (GBM) 
     In general, the CpG island methylator phenotype and age acceleration measure different properties as can be seen in glioblastoma multiforme. 
     Interestingly, age acceleration in GBM samples is highly significantly associated with certain mutations in H3F3A, which encodes the replication-independent histone variant H3.3. These mutations are single-nucleotide variants (SNV) changing lysine 27 to methionine (K27M) or changing glycine 34 to arginine (G34R) [40]. The fact that GBMs with a G34R mutation in H3F3A have a much higher age acceleration than those with a K27M mutation makes sense since each H3F3A mutation defines an epigenetic subgroup of GBM with a distinct global methylation pattern and acts through a different set of genes [40]. Lysine 27 is a critical residue of histone 3 variants, and methylation at this position (H3K27me), which may be mimicked by the terminal CH3 of methionine substituted at this residue [40], is commonly associated with transcriptional repression [41] while H3K36 methylation or acetylation typically promotes gene transcription [42]. G34-mutant cells exhibit increased RNA polymerase II binding, increased gene expression, most notably that of the oncogene MYCN [43]. Both H3F3A mutations are mutually exclusive with IDH1 mutations, which characterize a third mutation-defined subgroup [44]. Age acceleration in GBM samples is also associated with the following genomic aberrations: TP53 mutation, ATRX mutation, chromosome 7 gain, chromosome 10 loss, CDKN2A del, and EGFR amplification. Reflecting these results for individual markers, age acceleration varies significantly across the GBM subtypes defined in [44]. 
     DNAm Age of Cancer Cell Lines. 
     Using seven publicly available cell line data sets (Example 10), the DNAm age of 59 different cancer cell lines (from bladder, breast, gliomas, head/neck, leukemia, and osteosarcoma) was estimated. Across all cell lines, it was found that DNAm age does not have a significant correlation with the chronological age of the patient from whom the cancer cell line was derived. However, a marginally significant age correlation can be observed across osteosarcoma cell lines (cor=0.41, p=0.08). Overall, DNAm age acceleration varies greatly across the cancer lines (Example 11): the highest values can be observed for AML cell lines (KG1A: 182 years, HL-60: 177 years); the lowest values for head/neck squamous cell carcinoma cell line (UPCI SCC47: 6 years) and two breast cancer cell lines (SK-BR-3: 8 years, MDA-MB-468: 11 years). 
     Conclusions 
     Through the generosity of hundreds of researchers, an unprecedented collection of DNA methylation data from healthy tissues, cancer tissues, and cancer cell lines were analyzed. The healthy tissue data allowed for the development of a multi-tissue predictor of age (mathematical details are provided in Example 8). Relevant software can be accessed from [45]. A brief software tutorial is also presented in Example 8. The basic approach of the multi-tissue predictor of age is to form a weighted average of 354 clock CpGs (Table 3), which is then transformed to DNAm age using a calibration function. The calibration function reveals that the epigenetic clock has a high tick rate until adulthood after which it slows to a constant tick rate. 
     It is proposed that DNAm age measures the cumulative work done by an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer-, and aging research. This EMS model of DNAm age leads to several testable model predictions which have been validated using cancer data. But irrespective of the validity of the EMS model, the findings in cancer are interesting in their own right. Overall, high age acceleration is associated with fewer somatic mutations in cancer tissue. Mutations in TP53 are associated with lower DNAm age. To provide a glimpse of how DNAm age can inform cancer research, DNAm age has been related to several widely used genomic aberrations in breast cancer, colorectal cancer, glioblastoma multiforme, and acute myeloid leukemia. 
     DNAm age is a promising marker for studying human development, aging, and cancer. It may become a useful surrogate marker for evaluating rejuvenation therapies. The most salient feature of DNAm age is its applicability to a broad spectrum of tissues and cell types. Since it allows one to contrast the ages of different tissues from the same subject, it can be used to identify tissues that show evidence of accelerated age due to disease (e.g. cancer). It is likely that the DNAm age of easily accessible fluids/tissues (e.g. saliva, buccal cells, blood, skin) can serve as surrogate marker for inaccessible tissues (e.g. brain, kidney, liver). It is noteworthy that DNAm age is applicable to chimpanzee tissues. Given the high heritability of age acceleration in young subjects, it is expected that age acceleration will mainly be a relevant measure in older subjects. Using a relatively small data set, no evidence was found that a premature aging disease (progeria) is associated with accelerated DNAm age ( FIG. 17T ). Example 8, further describes if DNAm age fulfills the biomarker criteria developed by the American Federation for Aging Research. 
     Future research will need to clarify whether DNAm age is only a marker of aging or relates to an effector of aging. In conclusion, the epigenetic clock described here is likely to become a valuable addition to the telomere clock. 
     Example 7 
     Materials and Methods 
     Definition of DNAm Age Using a Penalized Regression Model 
     Using the training data sets, a penalized regression model (implemented in the R package glmnet [46]) is used to regress a log transformed version of chronological age on 21369 CpG probes which a) were present both on the Illumina™ 450K and 27K platform and b) had fewer than 10 missing values. The alpha parameter of glmnet was chosen to 0.5 (elastic net regression) and the lambda value was chosen using cross validation on the training data (lambda=0.0226). DNAm age was defined as predicted age. Mathematical details are provided in Example 8. 
     Short Description of the Healthy Tissue Data Sets 
     All data are publicly available. Many data sets involve normal adjacent tissue from The Cancer Genome Data Base (TCGA). Details on the individual data sets can be found in Example 8. Briefly, relevant citations include: Data sets 1 and 2 (whole blood samples from a Dutch population) were generated by Roel Ophoff [14]. Data set 3 (whole blood) consists of whole blood samples from a recent large scale study of healthy individuals [24]. The authors used these and other data to estimate human aging rates and developed a highly accurate predictor of age based on blood data. Data set 4 leukocyte samples from healthy male children from Children&#39;s Hospital Boston [47]. Data set 5 peripheral blood leukocytes samples [48]. Data set 6 cord blood samples from newborns [30]. Data set 7 cerebellum samples were provided by C. Liu and C. Chen (GEO identifier GSE38873). Data set 8, 9, 10, 13 cerebellum, frontal cortex, pons, temporal cortex samples obtained from the same subjects [49]. Data set 11 prefrontal cortex samples from healthy controls [22]. Data set 12 neuron and glial cell samples from [50]). Data set 14 normal breast tissue samples [51]. Data set 15 buccal cells involved 109 fifteen-year-old adolescents from a longitudinal study of child development [52]. Data set 16 buccal cells from 8 different subjects [15]). Data set 17 buccal cells from monozygotic (MZ) and dizygotic (DZ) twin pairs from the Peri/postnatal Epigenetic Twins Study (PETS) cohort [53]. Data set 18 cartilage (chondrocyte) samples from [54]. Data set 19 normal adjacent colon tissue from TCGA. Data set 20 colon mucosa samples from [55]. Data set 21 dermal fibroblast samples from [21]. Data set 22 epidermis samples from [56]. Data set 23 gastric tissue samples from [57]. Data set 24 head/neck normal adjacent tissue samples from the TCGA data base (HNSC data). Data set 25 heart tissue samples from [58]. Data set 26 normal adjacent renal papillary tissue from TCGA (KIRP data). Data sets 27 normal adjacent tissue from TCGA (KIRC data). Data set 28 normal adjacent liver samples from [59]. Data set 29 normal adjacent lung tissue from TCGA data base (LUSC data). Data set 30 normal adjacent lung tissue samples from TCGA (LUAD data). Data set 31 from TCGA (LUSC). Data set 32 mesenchymal stromal cells isolated from bone marrow [60]. Data set 33 placenta samples from mothers of monozygotic and dizygotic twins [61]. Data set 34 prostate samples from [62]. Data set 35 normal adjacent prostate tissue from TCGA (PRAD data). Data set 36 male saliva samples from [63]. Data set 37 male saliva samples from [23]. Data set 38 stomach from TCGA (STAD data). Data set 39 thyroid TCGA (THCA data). Data set 40 WB from type 1 diabetics from [10, 64]. Data set 41 WB from [15]. Data sets 42 and 43 involve whole blood samples from women with ovarian cancer and healthy controls, respectively. These are the samples from the United Kingdom Ovarian Cancer Population Study [10, 64]. Data set 44 WB from [65]. Data set 45 leukocytes from healthy children of the Simons Simple Collection [47]. Data set 46 peripheral blood mononuclear cells from [66]. Data set 47 peripheral blood mononuclear cells from [67]. Data set 48 cord blood samples from newborns provided by N Turan and C Sapienza (GEO GSE36812). Data set 49 cord blood mononuclear cells from [68]. Data set 50 cord blood mononuclear cells from [61]. Data set 51 CD4 T cells from infants [69]. Data set 52 CD4+ T cells and CD14+ monocytes from [15]. Data set 53 immortalized B cells and other cells from progeria, Werner syndrome patients, and controls [70]. Data set 54 and 55 are brain samples from [71]. Data set 56 and 57 breast tissue from TCGA (27K and 450K platform, respectively). Data set 58 buccal cells from [72]. Data set 59 colon from TCGA (COAD data). Data set 60 fat (adipose) tissue from [73]. Data set 61 human heart tissue from [27]. Data set 62 kidney (normal adjacent) tissue from TCGA (KIRC). Data set 63 liver (normal adjacent tissue) from TCGA data base (LIHC data). Data set 64 lung from TCGA. Data set 65 muscle tissue from [73]. Data set 66 muscle tissue from [74]. Data set 67 placenta samples from [75]. Data set 68 female saliva samples [63]. Data set 69 uterine cervix samples from [51, 76]. Data set 70 uterine endometrium (normal adjacent) tissue from TCGA (UCEC data). Data set 71 various human tissues from the ENCODE/HAIB Project (GEO GSE40700). Data set 72 chimpanzees and human tissues from [27]. Data set 73 great ape blood samples from [28]. Data set 74 sperm samples from [77]. Data set 75 sperm samples from [78]. Data set 76 vascular endothelial cells from human umbilical cords from [61]. Data sets 77 and 78 (special cell types) involved human embryonic stem cells, iPS cells, and somatic cell samples measured on the Illumina™ 27K array and Illumina™ 450K array, respectively [79]. Data set 79 reprogrammed mesenchymal stromal cells from human bone marrow (iP-MSC), initial MSC, and embryonic stem cells [80]. Data set 80 human ES cells and normal primary tissue from [81]. Data set 81 human ES cells from [82]. Data set 82 blood cell type data from [83]. 
     Description of the Cancer Data Sets 
     All data are publicly available as can be seen from the column that reports GSE identifiers from the Gene Expression Omnibus (GEO) database and other online resources. Most cancer data sets came from the TCGA data base. Data set 3 glioblastoma multiforme from [44]. Data set 4 breast cancer from [84]. Data set 5 breast cancer from [85]. Data set 6 breast cancer from [51]. Data set 10 colorectal cancer from [39]. Data set 23 prostate cancer from [62]. Data set 30 urothelial carcinoma from [86]. More details of the cancer tissue and cancer cell line data sets can be found in Examples 8 and 10. 
     DNA Methylation Profiling and Normalization Steps 
     All of the public Illumina™ DNA data were generated by following the standard protocol of Illumina™ methylation assays, which quantifies DNA methylation levels by the β value. A detailed description of the pre-processing and data normalization steps is provided in Example 8. 
     Meta Analysis for Measuring Pure Age Effects (Irrespective of Tissue Type) 
     The metaAnalysis R function in the WGCNA R package [87] is used to measure pure age effects as detailed in Example 8. 
     Analysis of Variance for Measuring Tissue Variation 
     To measure tissue effects in the training data, analysis of variance (ANOVA) is used to calculate an F statistic as follows. First, a multivariate regression model was used to regress each CpG (dependent variable) on age and tissue type. The analysis adjusted for age since the different data sets have very different mean ages. Next, ANOVA based on the multivariate regression model was used to calculate an F statistic, F.tissueTraining, for measuring the tissue effect in the training data. This F statistic measures the tissue effect after adjusting for age in the training data sets. The F statistic was not translated into a corresponding p-value since the latter turned out to be extremely significant for most CpGs. F.tissueTraining is shown to be highly correlated with an independent measure of tissue variance (defined using adult somatic tissues from data set 77). 
     Characterizing the CpGs Using Sequence Properties 
     Occupancy counts for Polycomb-group target (PCGT) genes was studied since they have an increased chance of becoming methylated with age compared to non-targets [10]. Toward this end, the occupancy counts of Suz12, Eed, and H3K27me3 published in [88] were used. To obtain the protein binding site occupancy throughout the entire nonrepeat portion of the human genome, Lee et al. 2006 isolated DNA sequences bound to a particular protein of interest (for example, Polycomb-group protein SUZ12) by immunoprecipitating that protein (chromatin immunoprecipitation) and subsequently hybridizing the resulting fragments to a DNA microarray. More details on the chromatin state data from [29] can be found in Example 8. 
     Abbreviations 
     AML—acute myeloid leukemia (AML),
 
BLCA—bladder urothelial carcinoma,
 
CBMC—cord blood mononuclear cell
 
CESC—cervical squamous cell carcinoma and endocervical adenocarcinoma
 
COAD—colon adenocarcinoma
 
CpG: Cytosine phospate Guanin
 
ES—embryonic stem
 
EMS—epigenetic maintenance system
 
GBM—glioblastoma multiforme
 
GEO—Gene Expression Omnibus data base
 
HNSC—head/neck squamous cell carcinoma
 
HUVEC cell—human umbilical vascular endothelial cells
 
iPS—induced pluripotent cell
 
KIRC—kidney renal clear cell carcinoma
 
KIRP—kidney renal papillary cell carcinoma
 
LIHC—liver hepatocellular carcinoma
 
LOO—leave one data set out
 
MSC—mesenchymal stromal cell
 
OVAR—ovarian serous cystadenocarcinoma
 
PBMC—peripheral blood mononuclear cell
 
PRAD—prostate adenocarcinoma
 
READ—rectum adenocarcinoma
 
SARC—sarcoma
 
     TCGA—The Cancer Genome Atlas 
     THCA—thyroid carcinoma
 
SCM—skin cutaneous melanoma
 
UCEC—uterine corpus endometrioid carcinoma
 
WB—whole blood
 
     Example 8 
     Materials and Methods Supplement 
     (Note: This example references an additional number of different publications as indicated throughout by reference numbers enclosed in braces, e.g., {x}. A list of these different publications ordered according to these reference numbers can be found in the section below entitled “Example 8 References”.) 
     The following reasons may explain the remarkable accuracy of the age predictor in the test data sets. First, measurements from Illumina™ DNA methylation arrays (Methods) are known to be less affected by normalization issues than those from gene expression (mRNA) arrays and even non-normalized beta-values (Methods) turn out to be highly correlated with corresponding measures found using pyrosequencing {1-3}. Second, the penalized regression model automatically selected CpGs that are relatively robust since it was trained on data sets from different labs and platforms. Third, the large number of data sets helped average out spurious results and artifacts. Fourth, age has a profound effect on the DNAm levels of tens of thousands of CpGs as shown by many authors {4-13}. 
     The results of this article do not contradict previous studies that have noted age-related DNA methylation changes which occur in a tissue specific manner, e.g. {14, 15}. Instead, the results of this article demonstrate that one can use a couple of hundred CpGs for forming an age predictor that a) performs remarkably well across a broad spectrum of human tissues and b) the resulting DNAm age estimate is biologically meaningful. 
     Description of the Healthy Tissue and Cell Line Data Sets 
     Data sets 1 and 2 (whole blood samples from a Dutch population) are comprised of schizophrenics and healthy control subjects measured on the Illumina™ 27K and 450K array platform, respectively. These data from Dr. Roel Ophoffs lab were formerly used to find co-methylation modules related to age {13}. The current study has a different aim, namely the development of an age predictor based on methylation levels. Since schizophrenia status had a negligible effect on age relationships {13}, it was ignored in this analysis. Further, it turned out that schizophrenia status was not related to DNAm age. GEO identifier of the data is GSE41037. 
     Data set 3 (whole blood) consists of whole blood samples from a recent large scale study of healthy individuals {16}. The authors used these data (and additional data) to estimate human aging rates and developed a highly accurate predictor of age based on blood data. 
     Data set 4 (leukocytes from healthy male children from Children&#39;s Hospital Boston) consists of 72 peripheral blood leukocyte samples from healthy males (mean age 5, range 1-16) {17}. 
     Data set 5 (peripheral blood leukocytes) from a DNAm study of Crohn&#39;s disease and ulcerative colitis {18}. Illumina™ 450K were used on 48 samples of peripheral blood leukocyte (PBL) DNA from discordant MZ twin pairs (CD: 3; UC: 3) and treatment-naive pediatric cases of IBD (CD: 14; UC: 8), as well as controls (n=14). I ignored disease status in the analysis. I did not find significant evidence that disease status affects DNAm age in this moderately sized data set. 
     Data set 6 (cord blood from newborns) is comprised of cord blood samples from 216 subjects (of age zero) {19}. 
     Data set 7 (cerebellum) is comprised of postmortem cerebellum brains. The data were provided by C. Liu and C. Chen (GEO identifier GSE38873). 
     Data set 8, 9, 10, 13 (cerebellum, frontal cortex, pons, temporal cortex) consist of brain tissue samples obtained from the same subjects whose mean age was 49 (range 15-101) {20}. These subjects, who had donated their brains for research, were of non-Hispanic, Caucasian ethnicity, and none had a clinical history of neurological or cerebrovascular disease, or a diagnosis of cognitive impairment during life. Demographics, tissue source and cause of death for each subject are reported in {20}. Unbiased removal of potential outliers (as described in the section on sample pre-processing) reduced the number of retained samples. 
     Data set 11 (prefrontal cortex from healthy controls) consists of 108 samples (mean age 26, ranging from samples before birth up to age 84) {21}. These post-mortem human brains from non-psychiatric controls were collected at the Clinical Brain Disorders Branch (National Institute of Mental Health). The DNAm data are publicly available from the webpage of the standalone package BrainCloudMethyl, which can be downloaded from the following URL: 
     http://braincloud.jhmi.edu/Methylation32/BrainCloudMethyl.htm 
     Data set 12 (neuron and glial cells) from {22}. The authors developed a cell epigenotype specific model for the correction of brain cellular heterogeneity bias and applied it to study age, brain region and major depression. After performing fluorescence activated cell sorting (FACS) of neuronal nuclei in post mortem frontal cortex 58 samples (29 major depression and 29 matched control samples) followed by Illumina™ HM450 microarray based DNAm profiling, the authors characterized the extent of neuron and glia specific DNAm variation independent of disease status and identified significant cell type specific epigenetic variation at 51% of loci. I ignored disease status in the analysis. I found no evidence that disease status accelerated age in this data set. 
     Data set 14 (breast) consists of normal breast tissue from 23 females (mean age 48, range 19-75) downloaded from GEO {23}. 
     Data set 15 (buccal cells) involved 109 fifteen-year-old adolescents from a longitudinal study of child development {24}. While the authors found that DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children&#39;s early lives, parental stress was ignored. All samples have the same chronological age (15 years). 
     Data set 16 (buccal cells) involved 8 different subjects. Rakyan et al (2010) confirmed that these buccal cell preparations contained very little, if any, leukocyte contamination, hence showing that the measured methylation profiles were predominantly from buccal cells {25}. 
     Data set 17 (buccal cells) from {26}. The authors applied the Illumina™ 450K platform to buccal swabs from 10 monozygotic (MZ) and 5 dizygotic (DZ) twin pairs from the Peri/postnatal Epigenetic Twins Study (PETS) cohort. In this longitudinal study, DNAm profiles were generated at birth (age 0) and at age 1.5 years (18 months). 
     Data set 18 (cartilage, chondrocytes) from {27}. The authors analyzed human articular chondrocytes from osteoarthritic patients and healthy cartilage samples. I did not find a relationship between disease status and accelerated DNAm age. 
     Data sets 19 (colon, normal tissue) consists of samples downloaded from TCGA data base measured on the Illumina™ 27K array. 
     Data set 20 (colon mucosa) from {28}. Crohn&#39;s disease, ulcerative colitis, and normal colon mucosa samples were measured on the Illumina™ Infinium HumanMethylation450 BeadChip v1.1. Samples came from 9 Crohn&#39;s disease affected, 5 ulcerative colitis affected, and 10 normal individuals. I did not detect a significant relationship between disease status and DNAm age acceleration. 
     Data set 21 (dermal fibroblasts) consists of 14 female fibroblast samples (mean age 32, range 6-73). The samples came from different locations on the human body (5 abdomen, 2 arm, 2 breast, 3 ear, and 2 leg samples) {2}. The single blepharoblast sample was removed from this data set since hierarchical clustering (based on the Euclidean distance, single linkage) indicated that it was an outlier. 
     Data set 22 (epidermis) came from a study that evaluated the epigenetic effects of aging and chronic sun exposure {29}. I used the 10 epidermal samples collected using suction blistering. 
     Data set 23 (gastric tissue) from {30}. The Illumina™ HumanMethylation27 BeadChip was used to obtain DNAm profiles across 27,578 CpGs in 203 gastric tumors and 94 matched non-malignant gastric samples. I focused on matched control samples. 
     Data set 24 (head/neck normal adjacent tissues) measured on the Illumina™ 450K platform from the TCGA data base (HNSC data). 
     Data set 25 (heart tissue) {31}. The authors generated DNAm profiles from human left ventricular myocardium DNA in order to study alterations in cardiac DNAm in human dilated cardiomyopathy (DCM). There were n=8 controls (patients after heart transplantation) and n=9 patients with idiopathic DCM. I ignored disease status in the analysis. I could find no significant evidence that disease status affects DNAm age in this small data set. 
     Data sets 26 (renal papillary, normal tissue) consists of 44 samples (mean age 66) downloaded from TCGA data base (KIRP) measured on the Illumina™ 450K array. 
     Data sets 27 (adjacent normal tissue, kidney measured on the Illumina™ 450K array) from TCGA (Kidney Clear Cell Renal Carcinoma, KIRC). 
     Data set 28 (liver) consists of normal adjacent tissue samples from Taiwanese hepatocellular carcinoma subjects {32}. The data were downloaded from GEO (GSE37988). 
     Data set 29 (lung squamous cells from normal adjacent tissue) consists of samples downloaded from TCGA data base (normal from LUSC) that were measured on the Illumina™ 27K array. 
     Data set 30 (lung normal adjacent lung tissue, Illumina™ 27K) from the Cancer Genome Atlas (TCGA) data base (http://tcga-data.nci.nih.gov/), LUAD. 
     Data sets 31 (lung squamous cells from normal adjacent tissue measured on the Illumina™ 450K) from the TCGA data base (normal samples from LUSC). 
     Data set 32 (mesenchymal stromal cells from bone marrow) consists of 16 female samples (mean age 53, range 21-85) {33}. The MSC from human bone marrow were either isolated from bone marrow aspirates or from the caput femoris upon hip fracture of elderly donors {33}. Due to sample size constraints, cell passage status (reflecting short versus long term culture) was ignored. 
     Data set 33 (placenta) from mothers of monozygotic and dizygotic twins {34}. Since placenta only develops during pregnancy, its chronological age was set to zero. 
     Data set 34 (prostate) consists of 69 normal prostate samples (mean age 61) {35}. 
     Data set 35 (prostate, normal adjacent tissue) measured on the Illumina™ 450K platform from the TCGA data base (PRAD data). 
     Data set 36 (saliva from alcoholic males) is from {36} as data set 68, but involves 131 male samples (again with mean age 32, range 21-55). Thus, I split the original data by gender. 
     Data set 37 (saliva from healthy men) involved 69 healthy male samples (mean age 35, range 21-55). We used these twin pairs and triplets to develop a saliva based predictor of age {3}. Since all twins were monozygotic, I could not use these data to estimate heritability with Falconer&#39;s formula. 
     Data sets 38 (stomach normal adjacent tissue measured on the Illumina™ 27K array) consists of 41 samples (mean age 69) downloaded from TCGA data base (STAD data). 
     Data set 39 (thyroid, normal adjacent tissue) measured on the Illumina™ 450K platform from the TCGA data base (THCA data). 
     Data set 40 (WB from type 1 diabetics) consists of samples from 191 subjects (mean age 44, range 24-74) {12, 37}. Since all subjects had type 1 diabetes, disease status was ignored. These data were downloaded from GEO (GSE20067). 
     Data set 41 (WB from healthy females) consists of 93 whole blood samples from women whose mean age was 63 (range 49-74) {25}. The samples were collected from different healthy females (both twin pairs and singletons). 
     Data set 42 (WB from postmenopausal women) consists of 262 whole blood samples from women with ovarian cancer (mean age 66, range 49-91). These are the cases from the UKOPS data (see data set 43). These samples were used since ovarian cancer did not have a global effect on blood methylation levels {12, 37}. 
     Data set 43 (WB from healthy postmenopausal women) consists of 269 whole blood samples from women with a mean of 65 (range 52-78) {12, 37}. While the data come from the United Kingdom Ovarian Cancer Population Study (UKOPS), it is important to emphasize that the samples come from healthy age matched controls of ovarian cancer patients. The data were downloaded from GEO (GSE19711). 
     Data set 44 (WB from rheumatoid arthritis) from a differential DNAm study of rheumatoid arthritis {38}. The authors found DNAm could serve as an intermediary of genetic risk in rheumatoid arthritis. I ignored disease status in the analysis. I did find that the whole blood of rheumatoid arthritis patients showed evidence of negative age acceleration compared to controls. While the large sample size led to a statistically significant (p=0.0049) finding, the effect size (age difference of 1.2 years) appears to be negligible. 
     Data set 45 (leukocytes from healthy children of the Simons Simple Collection) consists of peripheral blood leukocyte samples from 386 healthy (mostly male) subjects (mean age 10, range 3-17). These are healthy siblings of subjects with autism spectrum disorder (ASD) {17}. 
     Data set 46 (peripheral blood mononuclear cells from newborns and nonagenarians) {39} can be downloaded from GEO GSE30870. 
     Data set 47 (peripheral blood mononuclear cells) collected from a community-based cohort stratified for early-life socioeconomic status {40}. The data were downloaded from GEO (GSE37008). The authors found that psychosocial factors, such as perceived stress, and cortisol output were associated with DNAm patterns, as was early-life socioeconomic status. But none of these factors turned out to be related to DNAm age which justified that these covariates were ignored in this study. 
     Data set 48 (cord blood samples from newborns) comes from a study that related DNAm data to birth weight. Incidentally, DNAm age did not appear to be correlated with birth weight. No citation appears to be available for these data that were submitted to GEO (GSE36812) by N Turan and C Sapienza. 
     Data set 49 (cord blood mononuclear cells) comes from a study that investigated the effects of periconceptional maternal micronutrient supplementation on infant blood methylation patterns from offspring of Gambian women enrolled into a randomized, double blind controlled trial {41}. No significant relationship between DNAm age and micronutrient supplementation status could be observed. 
     Data set 50 (cord blood mononuclear cells) is from monozygotic and dizygotic twins {34} but twin status was ignored in our analysis. 
     Data set 51 (CD4 T cells from infants) consisted of sorted CD4+ T cell samples. The authors used the data to investigate the dynamics and relationship between DNAm and gene expression during early T-cell development {42}. The mononuclear cells were collected from 24 infants at birth (n=12) and resampled at 12 months (n=12). CD4+ cells were purified and the DNA analyzed using Illumina™ Inf450K arrays. The data were downloaded from GEO (GSE34639). 
     Data set 52 (CD4+ T cells and CD14+ monocytes) consisted of sorted CD4+ T-cells and CD14+ monocytes from blood of an independent cohort of 25 healthy subjects {25}. 
     Data set 53 (immortalized B cells) and other cells from progeria and Werner syndrome patients and controls {43}. The Hutchinson-Gilford Progeria Syndrome (HGP) and Werner Syndrome are two premature aging diseases showing features of common aging. Mutations in LMNA and WRN genes are associated to disease onset; however for a subset of patients the underlying causative mechanisms remains elusive. In this study, the authors aimed to evaluate the role of epigenetic alteration on premature aging diseases by performing genome-wide DNAm profiling of HGP and WS patients. The authors analyzed Epstein-Bar virus (EBV) immortalized B cells, naive B-cells, and peripheral blood mononuclear cells. The authors found aberrant DNAm profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome {43}. In this relatively small data set, I found no evidence that these premature aging diseases accelerate DNAm age in immortalized B cells. Future studies could evaluate whether premature aging diseases are associated with accelerated DNAm age in other tissues or cell types. Interestingly, chronological age continued to be highly correlated with DNAm age in these immortalized B cells which suggests that immortalization via EBV does not have a major effect on DNAm age. 
     Data set 54 (cerebellar samples) and data set 55 (occipital cortex samples) from autism cases and controls {44}. The authors collected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues. Here we ignored autism disease status. Incidentally, we could not detect an association between autism status and DNAm age. 
     Data set 56 (breast, normal adjacent tissue, Illumina™ 450K) consists of normal breast tissue samples from 90 female breast cancer cases (mean age 57, range 28-90) from TCGA, but unlike data set 57 these samples were assayed on the Illumina™ 450K platform. 
     Data set 57 (breast, normal adjacent tissue, Illumina™ 27K) consists of normal breast tissue samples from 27 female breast cancer cases (mean age 55, range 35-88) from the Cancer Genome Atlas (TCGA) data base (http://tcga-data.nci.nih.gov/). 
     Data set 58 (buccal cells) from {45}. The authors performed a longitudinal study of DNA methylation at birth and age 18 months in DNA from buccal swabs from 10 monozygotic (MZ) and 5 dizygotic (DZ) twin pairs from the Peri/postnatal Epigenetic Twins Study (PETS) cohort. 
     Data sets 59 (colon) normal adjacent tissue measured on the Illumina™ 450K array, downloaded from TCGA (COAD data). 
     Data set 60 (adipose) from monozygotic Twins Discordant for Type 2 Diabetes. {46}. Monozygotic twins discordant for type 2 diabetes constitute an ideal model to study environmental contributions to type 2 diabetic traits. The authors aimed to examine whether global DNAm differences exist in major glucose metabolic tissues from twelve 53-80 year-old monozygotic discordant twin pairs. DNAm was measured by the Illumina™ HumanMethylation27 BeadChip in 22 (11 pairs) skeletal muscle and 10 (5 pairs) subcutaneous adipose tissue biopsies. Diabetes status was ignored in my analysis. I could find no significant evidence that disease status affects DNAm age in this small data set. 
     Data set 61 (heart tissue) consists of only 6 human male samples (mean age 61, range 55-71) {47}. Clearly, larger sample sizes will be needed to evaluate this tissue. 
     Data set 62 (kidney) normal adjacent tissue from clear cell renal carcinoma consists of samples downloaded from the TCGA data base (KIRC) that were measured on the Illumina™ 27K platform. 
     Data set 63 (liver normal adjacent tissues) measured on the Illumina™ 450K platform from the TCGA data base (LIHC data). 
     Data sets 64 (lung, normal adjacent tissue) measured on the Illumina™ 450K arrays. The data consists of samples downloaded from TCGA data base (normal from LUAD). 
     Data set 65 (muscle) from monozygotic Twins Discordant for Type 2 Diabetes {46}. Monozygotic twins discordant for type 2 diabetes constitute an ideal model to study environmental contributions to type 2 diabetic traits. The authors aimed to examine whether global DNAm differences exist in major glucose metabolic tissues from twelve 53-80 year-old monozygotic discordant twin pairs. DNAm was measured by the Illumina™ HumanMethylation27 BeadChip in 22 (11 pairs) skeletal muscle and 10 (5 pairs) subcutaneous adipose tissue biopsies. Diabetes status was ignored in my analysis. I could find no significant evidence that disease status affects DNAm age in this small data set. 
     Data set 66 (muscle) tissue from healthy men who were 24 years old. These data came from an epigenetic analysis of healthy young men following a control and high-fat overfeeding diet {48}. These data came from a randomized cross-over design, where all subjects received both treatments (control and high-fat overfeeding diet). Biopsies were obtained from 23 different individuals amounting to 22 samples following the control diet and 22 samples following the high-fat overfeeding diet (paired n=21). The resulting 44 samples were analyzed using the Illumina™ 27K platform. Diet status was ignored in my analysis. I could find no significant evidence that diet affects DNAm age in this relatively small data set. 
     Data set 67 (placenta) from {49}. DNA from 20 third trimester early onset preeclampsia placentas and 20 gestational age matched controls. 
     Data sets 68 (saliva) from alcoholic females involved 52 samples (mean age 32, range 21-55) {36}. 
     Data set 69 (uterine cervix) involved cytologically normal cells from the uterine cervix of 152 women {23, 50}. 
     Data set 70 (uterine endometrium normal adjacent tissue) measured on the Illumina™ 450K platform from the TCGA data base (UCEC data). 
     Data set 71 (various human tissues) from the ENCODE/HAIB Project. These Illumina™ 27K data were downloaded from GEO GSE40700. 
     Data set 72 (chimpanzees and humans) from {47} The authors used the Illumina™ 27K array to compare DNAm profiles in the following human and chimpanzee tissue samples: 6 human livers, 6 human kidneys, 6 human heart, 6 chimpanzee livers, 6 chimpanzee kidneys, and 6 chimpanzee hearts. 
     Data set 73 (ape blood) from {51}. The authors applied the Illumina™ 450K arrays to blood derived DNA from humans, chimpanzees, bonobos, gorillas and orangutans. Since ages were not available for humans and orangutans, I focused on chimpanzees, bonobos, gorillas for whom ages were available. 
     Data set 74 (sperm) from {52}. The authors performed a genome-wide analysis of sperm DNA isolated from 21 men with a range of semen parameters presenting to a tertiary male reproductive health clinic. DNAm was measured with the Illumina™ Infinium array at 27,000 CpG loci. 
     Data set 75 (sperm) from {53}. The authors applied the 450K platform to DNA derived from 26 normal sperm samples. 
     Data set 76 (vascular endothelial cells from human umbilical cords) from monozygotic and dizygotic twins {34}. 
     Data sets 77 and 78 (special cell types) involved human embryonic stem cells, iPS cells, and somatic cell samples measured on the Illumina™ 27K array and Illumina™ 450K array, respectively {54}. Although no specific age information was available, these two valuable data sets could be used a) to compare adult somatic tissues versus fetal somatic tissues, b) to compare the DNAm ages of different tissues from the same individual ( FIG. 3 ), c) to assess the variance of methylation probes across adult somatic tissues and fetal somatic tissues, d) to study how the DNAm age of iPS cells compares to that of somatic primary tissue and primary cell lines ( FIG. 6 ), e) to evaluate how cell passaging effects DNAm age ( FIG. 6 ). Data set 78 contained multiple tissue samples from two adults. For data set 78, the following tissues and sample sizes were available: Adipose (n=2 samples), Adrenal (n=4), Aorta (2), Bladder (2), Blood (2), Brain (3), Breast (1), Colon (1), Diaphragm (2), Duodenum (1), human embryonic stem (ES) cells (118), Gallbladder (1), Heart (2), iPS (46), Kidney (2), Liver (1), Lung (4), Lymph Node (2), Ovary (2), Pancreas (2), Prostate (1), Skeletal Muscle (2), Skin (1), Small Intestine (1), Somatic Primary Cell Line (49), Spleen (3), Stomach (4), Tongue (1) Ureter (2). For data set 52, the following sample sizes were available {54} Adipose (2), Adrenal (5), Bladder (2), Blood (2), Brain (5), ES (19), Heart (5), iPSC (29), Kidney (5), Liver (4), Lung (7), Lymph Node (2), Pancreas (2), Skeletal Muscle (2), Somatic Primary Cell Line (22), Spleen (5), Stomach (6), Thymus (2), Tongue (2), Ureter (2). 
     Data set 79 (reprogrammed mesenchymal stromal cells from human bone marrow (iP-MSC), initial MSC, and embryonic stem cells) {55}. The authors reprogrammed mesenchymal stromal cells from human bone marrow (iP-MSC) and compared their DNAm profiles with initial MSC and embryonic stem cells (ESCs) using the Illumina™ 450K array. The data were downloaded from GEO (GSE37066). 
     Data set 80 (hESC and normal primary tissue) from {56}. The authors extracted DNA from the following well-characterized human embryonic stem cell (hESC) lines: SHEF-1, SHEF-4, SHEF-5, SHEF-7, H7, H14, H14S9, H7S14, HS181 and 13. The authors used DNA from human normal primary tissues provided by Biochain (Hayward, Calif., USA). 
     Data set 81 (hESC) from {57}.DNA derived from H9, H13C, SHEF2 hESC cultured in two different media. The medium was not significantly related with DNAm age estimate. 
     Data set 82 (blood cell type data) {58} Six healthy male blood donors, age 38±13.6 years, were included in the study. From each individual, global DNAm levels were analyzed in whole blood, peripheral blood mononuclear cells (PBMC) and granulocytes as well as for seven isolated cell populations (CD4+ T cells, CD8+ T cells, CD56+NK cells, CD19+ B cells, CD14+ monocytes, neutrophils, and eosinophils), n=60 samples analyzed in total. The data were downloaded from GEO (GSE35069). 
     Criteria guiding the choice of the training sets 
     The choice of training data sets was guided by the following criteria: First, the training data should represent a wide spectrum of tissues and cell types. In this example, the training data involved blood (whole blood, cord blood, PBMCs), brain (cerebellum, frontal cortex, pons, prefrontal cortex, temporal cortex, neurons and glial cells), breast, buccal epithelium, cartilage, colon, dermal fibroblasts, epidermis, gastric tissue, head/neck tissue, heart, kidney, liver, lung, mesenchymal stromal cells, prostate, saliva, stomach, thyroid, etc. 
     Second, the individual training sets (that make up the combined training set) should have a similar age distribution. The training data should contain a high proportion of samples (37%) measured on the Illumina™ 450K platform since many on-going studies use this recent Illumina™ platform. Incidentally, 34% of test set samples were measured on the 450K platform. Here I only studied 21369 probes measured with the Infinium type II assay which satisfied the following criteria: a) they were present on both Illumina™ platforms (Infinium 450K and 27K) and b) had fewer than 10 missing values. 
     Description of the Cancer Data Sets 
     Data set 3 (glioblastoma multiforme, GBM) measured on the Illumina™ 450K array from {59} (GEO identifier GSE36278). 
     Data set 4 (breast cancer) measured on the Illumina™ 27K array from {60} (GEO identifier GSE31979). 
     Data set 5 (breast cancer) measured on the Illumina™ 27K array from {61}(GEO identifier GSE20712). 
     Data set 6 (breast cancer) measured on the Illumina™ 27K array from {23} (GEO identifier GSE33510). 
     Data set 10 (colorectal cancer) measured on the Illumina™ 27K array from {62} (GEO identifier GSE25062). 
     Data set 23 (prostate cancer) measured on the Illumina™ 27K array from {35} (GEO identifier GSE26126). 
     Data set 30 (urothelial carcinoma) measured on the Illumina™ 27 L array from {63}. 
     All other cancer data sets came from the TCGA data base. In particular, acute myeloid leukemia (AML), bladder urothelial carcinoma (BLCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), colon adenocarcinoma (COAD), head/neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LIHC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver ovarian serous cystadenocarcinoma (OVAR), prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), sarcoma (SARC), thyroid carcinoma (THCA), skin cutaneous melanoma (SKCM), uterine corpus endometrioid carcinoma (UCEC). 
     DNAm Profiling and Pre-Processing Steps 
     Full experimental methods and detailed descriptions of these public data sets can be found in the original references. The following briefly summarizes the main steps. Methylation analysis was performed either using the Illumina™ Infinium Human Methylation27 BeadChip {64} or the Illumina™ Infinium HumanMethylation450 BeadChip. The Illumina™ HumanMethylation27 BeadChips measures bisulfite-conversion-based, single-CpG resolution DNAm levels at 27,578 different CpG sites within 5′ promoter regions of 14,475 well-annotated genes in the human genome. Data from the two platforms were merged by focusing on the roughly 26 k CpG sites that are present on both platforms. The HumanMethylation27 BeadChip mainly represents specific CpG that are located near gene promoter regions. 
     All of the public data were generated by following the standard protocol of Illumina™ methylation assays, which quantifies DNAm levels by the β value using the ratio of intensities between methylated (signal A) and un-methylated (signal B) alleles. Specifically, the β value was calculated from the intensity of the methylated (M corresponding to signal A) and un-methylated (U corresponding to signal B) alleles, as the ratio of fluorescent signals β=Max(M,0)/[Max(M,0)+Max(U,0)+100]. Thus, β values range from 0 (completely un-methylated) to 1 (completely methylated) {65}. 
     The mean inter-array correlation was used to measure how similar (correlated) a given sample is compared to the remaining samples of the data set. To ensure high quality data without technical artifacts, non-cancer samples were only used if their mean inter-array correlation was larger than 0.90 and if their maximum DNAm level (across all probes) was larger than 0.96. This filtering step was not applied to the cancer samples since it is well known that cancer greatly affects the DNAm levels. It is worth mentioning that my results would barely change if all samples had been used. 
     Normalization Methods for the DNA Methylation Data 
     I carried out several normalization steps to ensure that these data are comparable. While quantile normalization is often used in gene expression studies, it is less frequently used in DNAm studies. Before explaining my unbiased normalization strategy, I briefly provide some background. The Illumina™ 450K platforms uses 2 different chemical assays. The Infinium I and Infinium II assays for the assessment of the DNAm status of more than 480,000 cytosines distributed over the whole genome. The older Illumina™ 27K platform only uses the Infinium II assays. Several authors have noted that the data generated by the two chemical assays used by the 450K platform are not entirely compatible {66}. Dedeurwaerder et al (2011) showed that their correction technique called ‘peak-based correction’, which rescales type II probes on the basis of type I probes greatly improved the signal in Illumina™ Inf450K data. Similarly, Maksimovic et al (2012) showed that their subset-quantile within array normalization (SWAN) substantially improves the results for the Illumina™ 450K platform {67}. Unfortunately, I could not adopt the SWAN normalization here since it requires idat input files, which were not available for many of the data sets. 
     Teschendorff et al (2012) developed a model-based intra-array normalization strategy for the 450K platform, called BMIQ (Beta MIxture Quantile dilation), which adjusts beta-values of type II probes into a statistical distribution characteristic of type I probes{68}. 
     My own studies support the claim of these authors that normalizing type II probes so that they correspond to type I probes is a very useful pre-processing step for any study using the Illumina™ 450K platform. I could not adopt these techniques directly since my study only involves type II probes from the 27K platform. About 26000 CpGs from the 27K platform are also represented on the 450K platform and have the same probe identifier. Therefore, it is straightforward to merge data from the two platforms as long as one restricts attention to these overlapping probes. The age predictor was trained on the roughly 21368 type II probes that a) are shared between the Illumina™ 27K and the 450K platforms and b) had &lt;=10 missing values across the training data. However, I adopted the idea underlying these articles as follows. Instead of using type I probes as gold standard for rescaling type II probes, I created another gold standard by forming the mean DNAm value in the largest single study of this article (data set 1, i.e. whole blood samples from {13}). Next, I adapted the BMIQ R function from Teschendorff et al (2013) {68} so that it would rescale the overlapping 21 k probes of each array so that their distribution matched that of the new gold standard. My empirical studies showed that this pre-processing step improved the accuracy of the resulting age predictor especially when it comes to the median error. Even though only the 21 k CpGs that overlap between the Illumina™ 27K and 450K array used in this illustrative example, it can be applied to any set of CpGs (e.g. all CpGs on the 450K array). 
     Explicit Details on the Definition of DNAm Age 
     Based on the training set data, I found that it is advantageous to transform age before carrying out an elastic net regression analysis. Toward this end, I used the following novel function F for transforming age (though it is contemplated that other transformations may also possibly be used):
         F(age)=log(age+1)-log(adult.age+1) if age&lt;=adult.age.   F(age)=(age-adult.age)/(adult.age+1) if age&gt;adult.age.       

     The parameter adult.age was set to 20 for humans (different values can also be chosen) and 15 for chimpanzees. Note that F satisfies the following desirable properties: it
         i) is a continuous, monotonically increasing function (which can be inverted),   ii) has a logarithmic dependence on age until adulthood (here set at 20 years),   iii) has a linear dependence on age after adulthood (here set to 20),   iv) is defined for negative ages (i.e. prenatal samples) by adding 1 (year) to age in the logarithm,   v) it has a continuous first derivative (slope function). In particular the slope at age=adult.age is given by 1/(adult.age+1).       

     The function F is visualized by a red line. As expected, the red line passes through the weighted average of the CpGs (i.e. the linear part of the regression model). The inverse of the function F, denoted by inverse.F, is used to transform the linear part of the regression model into DNAm age. 
     An elastic net regression model (implemented in the glmnet R function) was used to regress a transformed version of age on the roughly 21 k beta values in the training data. The elastic net regression results in a linear regression model whose coefficients b 0 , b 1 , . . . , b 354  relate to transformed age as follows 
         F (chronological age)= b   0   +b   1   CpG   1   + . . . +b   354   CpG   354 +error 
     The coefficient values can be found in Example 9. Based, on the coefficient values from the regression model, DNAmAge is estimated as follows 
         DNAm Age=inverse. F ( b   0   +b   1   CpG   1   + . . . +b   354   CpG   354 ) 
     Thus, the regression model can be used to predict to transformed age value by simply plugging the beta values of the selected CpGs into the formula. The linear part, (i.e. the weighted average of the selected CpGs) is visualized as a red line. 
     The glmnet function requires the user to specify two parameters (alpha and beta). Since I used an elastic net predictor, alpha was set to 0.5. But the lambda value of 0.02255706 was chosen by applying a 10 fold cross validation to the training data (via the R function cv.glmnet). 
     The following R code provides details on the analysis. 
     library(glmnet) 
     # use 10 fold cross validation to estimate the lambda parameter 
     # in the training data 
     glmnet.Training CV=cv.glmnet(datMethTraining, F(Age), nfolds=10,alpha=alpha,family=“gaussian”) 
     # The definition of the lambda parameter: 
     lambda.glmnet.Training=glmnet.Training CV$lambda.min 
     # Fit the elastic net predictor to the training data 
     glmnet.Training=glmnet(datMethTraining, F(Age), family=“gaussian”, alpha=0.5, nlambda=100) 
     # Arrive at an estimate of of DNAmAge 
     DNAmAgeBasedOnTraining=inverse.F(predict(glmnet.Training,datMeth,type=“response”,s=lambda.glmnet.Training)) 
     Chromatin State Data Used 
     While specific histone modifications correlate with regulator binding, transcriptional initiation and elongation, enhancer activity and repression, combinations of chromatin modifications can provide even more precise insight into chromatin state {69}. Here I used the chromatin state data from {69}. The authors profiled nine human cell types, including common lines designated by the ENCODE consortium and primary cell types. These consisted of embryonic stem cells (H1 ES), erythrocytic leukemia cells (K562), B-lymphoblastoid cells (GM12878), hepatocellular carcinoma cells (HepG2), umbilical vein endothelial cells (HUVEC), skeletal muscle myoblasts (HSMM), normal lung fibroblasts (NHLF), normal epidermal keratinocytes (NHEK), and mammary epithelial cells (HMEC). 
     Ernst et al (2011) distinguish six broad classes of chromatin states, referred to as promoter, enhancer, insulator, transcribed, repressed, and inactive states. Within them, active, weak and poised promoters (states 1-3) differ in expression levels, strong and weak candidate enhancers (states 4-7) differ in expression of proximal genes, and strongly and weakly transcribed regions (states 9-11) also differ in their positional enrichments along transcripts. Similarly, Polycomb-repressed regions (state 12) differ from heterochromatic and repetitive states (states 13-15), which are also enriched for H3K9me3. It will be interesting to map the 354 clock CpGs to the states of individual cell lines. Since the number of profiled cell lines keeps expanding and warrants a comprehensive analysis, reporting results for individual cell lines is beyond the scope of this article. Instead, I provide a broad overview by averaging the results across the 9 cell lines mentioned by Ernst 2011. Specifically, the y-axis reports the mean number of cell lines (out of 9 cell lines) for which the CpGs were in the chromatin state mentioned in the title. 
     Comparing the Multi-Tissue Predictor with Other Age Predictors 
     Several recent publications describe age predictors based on DNA methylation levels {2, 3, 16}. Hannum et al (2012) found that computing a DNAm based age predictor for different tissues gave basically no overlap, e.g. blood-derived predictive CpGs were different from those from other tissues {16}. This suggests that an optimal age predictor for one tissue may be sub-optimal for another. I don&#39;t disagree with these results. Instead, I show that one can build a multi-tissue age predictor which can be used for addressing a wide range of questions arising in aging research. While slight gains in accuracy can probably be achieved by focusing on a single tissue and considering more CpGs, the major strength of the proposed multi-tissue age predictor lies in its wide applicability: for most tissues it will not require any adjustments or offsets. The proposed multi-tissue age predictor greatly outperforms the predictors by {2, 3} as detailed below. I could not directly evaluate the predictor by {16} since a) only seven out of its 71 CpGs are represented on the Illumina™ 27K platform, b) it included gender and body mass index as covariates. However, I was able to evaluate the performance of a sparse version of the published predictor by using the seven overlapping CpGs that could be found on both Illumina™ platforms. In the following, I provide more details. To provide an unbiased comparison, I constructed each predictor in an analogous fashion in the training data, i.e. its coefficient values were estimated using the same penalized regression approach. Thus, the predictors only differed with respect to the sets of CpGs that were considered in the penalized regression model. While this does not allow me to assess the performance of the published predictors directly, it provides a completely unbiased comparison of the age predictors. Using the coefficient values from the respective publications would have biased the comparison against them since most were constructed on significantly smaller training data sets (often involving a single tissue) or using a single Illumina™ platform. 
     I evaluated the performance of each age predictor a) across the training data sets and b) across the test data sets. Since I constructed each predictor using the training data sets, the estimated accuracy in the training set is overly optimistic. I also defined a “shrunken” version of my multi-tissue age predictor, which only involves a subset of 110 CpGs from the 354 CpGs. As indicated by its name, the shrunken predictor is defined by using a more stringent shrinkage parameter (50 times that of the original model) in the penalized regression model. The shrunken predictor is highly accurate in the training data (cor=0.95, error=4 years) and test data (cor=0.95, error=4.2 years). Coefficient values of the multi-tissue predictor and its shrunken version can be found in Example 9. I find that my multi-tissue age predictor greatly outperforms the predictors by {2, 3}. Even when I use the same penalized regression approach for re-training their CpGs, both predictors lead to high errors in training and test data (&gt;14 years) and much lower age correlations (&lt;=0.56). Hannum et al (2012) proposed an age predictor based on 71 CpGs {16}. The authors built a predictive model of aging using a penalized regression method (elastic net) but it differs from the current analysis in the following aspects. First, the aging model from {16} was trained on whole blood, which is a noteworthy advantage when it comes to the design of practical diagnostics and for testing blood samples collected from other studies. Second, it also included clinical parameters such as gender and body mass index as covariates. Third, it is based on CpGs from the Illumina™ 450K arrays while my predictor only involves CpGs from the Illumina™ 27K array. Since only seven of the 71 CpG markers from {16} can be found on the Illumina™ 27K array, I could not carry out a direct comparison across the many tissues considered here. Instead, I was only able to evaluate the performance of a very sparse version of the published predictor by using the seven overlapping CpGs (cg04474832, cg05442902, cg06493994, cg09809672, cg19722847, cg21296230, cg22736354) that could be found on both Illumina™ platforms. The resulting sparse version performs well in the training data (age cor=0.82, error=8.0 years) and in the test data (cor=0.86, error=8.0 years). 
     In conclusion, a sparse version of the predictor from {16}(based on 7 CpGs) works best among predictors with fewer than 10 CpGs. The proposed multi-tissue predictor suggests that a couple of hundred CpGs will be needed to accurately predicted age across multiple tissue types and the two Illumina™ platforms. 
     Meta Analysis for Finding Age-Related CpGs 
     To measure pure age effects in the marginal analysis, I used the metaAnalysis R function in the WGCNA R package {70}. This function allowed to calculate two p-values: pValueHighScale and pValueLowScale for finding consistently positively and negatively age related CpGs, respectively. Thus, CpGs with a low pValueHighScale have a consistently high age correlation in the individual data sets. Since this meta analysis method conditions on the data sets, the p-values are not confounded by data set or tissue. I used the signed logarithm (base 10) of the meta analysis p-value in scatter plots. The sign was chosen so that CpGs with positive (negative) age correlations lead to positive (negative) log p-values. It is shown that the meta analysis p-value based on the training data sets is highly correlated with a corresponding meta analysis p-value calculated using all training and test sets. The high correlation shows that little information is lost by focusing on the training data. The most significant age-related CpGs found in all data can already be found using the training data alone. 
     Variation of Age Related CpGs Across Somatic Tissues 
     Since the age predictor performs well across a wide spectrum of tissues, I hypothesized that many of the 354 CpGs used for estimating DNAm age vary little across tissues and that many of them correlate highly with age. 
     To test this hypothesis, I first defined three different measures of tissue variance. The first measure of tissue variance used analysis of variance (ANOVA) across the training data sets. Toward this end, I used a multivariate regression model to regress each CpG (dependent variable) on age and tissue type. The regression model included age as covariate since the analysis needed to adjust for the fact that different data sets had different age distributions. ANOVA allowed me to calculate an F statistic for tissue effect which takes on a large value for CpGs that vary greatly across the different training set tissues. The second and third measure of tissue variance were defined using the adult somatic tissues and the fetal somatic tissues, respectively, from {54} (data set 77). As an aside, I mention that the mean DNAm age (predicted age) of fetal somatic tissues is close to zero, i.e. it is much lower than that of adult somatic tissues in this data set, which again validates the age predictor. The adult- and the fetal measure of tissue variance of each CpGs is defined by its variance across the adult and somatic tissue samples from {54}, respectively. I find that the adult and the fetal tissue variance measures are highly correlated (cor=0.8) which indicates that these measures are robustly defined and change little with age. Since the data from Nazor et al (data set 77) were not part of the training data, these measures could be used to validate the F-statistic measure of tissue variance. I find a high correlation between the adult measure of tissue variance and the F statistic (cor=0.73) which shows that these measures of tissue variance are highly reproducible. I also defined a stringent measure of age variation for each CpG using a meta analysis approach. The meta analysis calculated age correlations in each training data set separately and next aggregated the correlation test p-values resulting in a meta analysis p-value. Different from the construction of the age predictor, the meta analysis approach explicitly conditioned on each data set. Thus, a CpG has a significant meta analysis p-value if it consistently correlates with age irrespective of tissue type, data set effect, or Illumina™ platform version. It did not really matter that I calculated the meta analysis p-value using the training data alone since the resulting p-value is highly correlated (cor=0.97) with the analogous p-value that results from using all data sets. 
     To address the question how the tissue variation of a CpG relates to its age variation, I plotted tissue variance versus age variance. Using the ANOVA F statistic for tissue effect, I find the that CpGs with high positive or negative age correlations do not vary much across the somatic adult tissues. A completely analogous result can be observed when using the somatic variance measures involving the adult and fetal tissues from Nazor et al (data 77). CpGs that vary little across tissues appear to be more susceptible to aging effects. Conversely, CpGs that vary greatly across tissues are less affected by aging effects which might reflect that they are actively protected against aging effects. 
     Studying Age Effects Using Gene Expression Data 
     The publicly available microarray data sets involved mainly healthy individuals (in particular no cancer samples were considered). 
     To estimate the age effect on gene expression levels, I analyzed multiple independent publicly available microarray data sets. Blood microarray data sets involving mainly healthy control individuals (referred to as SAFHS {71}, Chaussabel {72} and NOWAC {73} data) and the CD8 T cell microarray data Cao {74}. To assess whether a gene was differentially expressed between naive CD8+ T cells and antigen exposed CD8+ T cells, I used the data from Willinger et al {75, 76}). In the following I provide more details. 
     The data from a study of post-menopausal women (the NOWAC data). In my largest data set, the San Antonio Family Heart Study (SAFHS) data set, individuals were ascertained from probands meeting two criteria: 1) having a living spouse and 2) having six first-degree relatives 16 years or older in the San Antonio area—excluding parents. While this data set was used to study cardiovascular phenotypes, the data was obtained without selection bias towards these traits, and therefore can be considered a random sampling. 
     I obtained the San Antonio Family Heart Study (SAFHS) blood data set, which was previously analyzed by Goring, et al {71}. This data set was derived from lymphocytes; RNA was hybridized to Illumina™ Sentrix Human Whole Genome (WG-6) Series I BeadChips with probe sets corresponding to 18,544 genes. Quantile normalization was applied to the raw data. This data set consisted of 1,084 samples: 452 males and 632 females between ages 15 and 94 after outlier removal. Specifically, outlier detection and removal was performed using an iterative process of removing outliers with average interarray correlation (IAC)&lt;2 SD below the mean until visual inspection of the cluster dendrogram and plot of the mean IAC revealed no further outliers. This analysis was completely unbiased and agnostic to chronological age. Toward this end, I used our recently developed sampleNetwork R function described in {77} 
     The Chaussabel data set was originally published by Pankla, et al. {72} and was used to study melioidosis. 67 whole blood samples were hybridized to Illumina™ Sentrix Human-6 V2 BeadChip arrays with 12,483 genes. Background subtraction and average normalization was performed using Illumina™ BeadStudio version 2 software, and standard normalization for one-color array data was performed using Gene-Spring GX7.3 software (Agilent Technologies) by the original authors. This data set consisted of 35 men and 32 women between the ages of 18 and 74. I also used healthy postmenopausal women from the Norwegian Women and Cancer (NOWAC) study {73}. The whole blood data were measured using AB Human Genome Survey Microarray V2.0 with 16,753 genes. For sets of technical replicates, arrays with the least number of probes with a S/N&gt;3 were excluded. Arrays with less than 40% of probes with a S/N≧3 were removed. Probes with an S/N≧3 in less than 50% of samples were excluded. Log (base 2) transformation, quantile normalization and imputation was performed. I furthermore excluded samples using an iterative process of removing samples with average interarray correlation &lt;2 SD ultimately resulting in 245 samples. Age ranges of {48,53), {53,58) and {58,63} were given, and I used for the analysis corresponding ages of 50, 55 and 60. 
     In the CD8+ T cell data set from Cao, et al. {74} Affymetrix HG-U133A_2 Gene Arrays were used to explore the expression profiles of three male and six female donors whose ages ranged from 23 to 81. Microarray Suite Version 5.0 (MAS 5.0; Affymetrix) was used to quantify the expression levels of 12,483 genes. In the CD8+ T cell data set from Willinger et al {75, 76}, Affymetrix HG-U133 plus 2.0 arrays (log transformed MASS data) were used to explore the expression profiles of human CD8+ naive T cells (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) CD8+ T cells. TN can be regarded as peripheral stem cells, while TEM and TEMRA are differentiated cells with effector function. For each T cell type, the original data set contained 4 replicates (i.e. there were 16 arrays). Since one of the central memory samples had very low interarray correlation with the other samples, I removed this potential outlier from the analysis. A Student t-test of differential expression was used to compare expression levels in naive CD8+ cells versus the memory T cells. 
     The first brain data set was previously analyzed by Lu, et al. {78}. 30 frontal lobe samples were hybridized to Affymetrix HG-U95Av2 oligonucleotide arrays with 8,760 genes. Arrays were normalized by Lu, et al. using dChip V1.3 software, and after using the aforementioned iterative process of removing samples with average interarray correlation &lt;2 SD below the mean I obtained 25 samples. This data set consisted of 16 men and 9 women between ages 26 and 91. 
     The second cortical brain data set was previously analyzed by Myers, et al. {79}. The Illumina™ HumanRef-8 Expression BeadChip was utilized, and expression profiles were rank-invariant normalized using Illumina™ BeadStudio software. I utilized a iterative normalization process and removed 25 samples for a total of 168 samples and 19,880 genes. This data set consisted of 92 men and 76 women between ages 65 and 100. The third cortical brain data set was previously analyzed by Oldham, et al. {80}. Affymetrix HG-U95Av2 microarrays were used. Quantile normalization was utilized. Ultimately I identified 7763 genes in 67 individuals. This data set consisted of 48 men and 19 women between ages 22 and 81. The kidney data sets were previously analyzed by Rodwell, et al. {81}. I utilized data from HG-U133A high-density oligonucleotide arrays; Rodwell, et al. normalized data using the dChip program according to the stable invariant set, and I further processed using the normalization and iterative outlier removal process. These normalization and outlier detection procedures resulted in 63 kidney cortex samples and 52 kidney medulla samples. There were 12,606 genes in both data sets. The kidney cortex data set consisted of 35 men and 26 women between ages 27 and 87, and the kidney medulla data set consisted of 29 men and 23 women between ages 29 and 92. 
     The muscle data set was previously analyzed by Zahn, et al. {82}. 81 samples were hybridized to Affymetrix HG-U133 2.0 Plus high-density oligonucleotide arrays. The authors used the DChip program to normalize the data. I omitted 10 samples using the iterative normalization and outlier removal process, resulting in 71 samples and 19,621 genes. This data set consisted of 39 men and 32 women between ages 16 and 89. 
     Meta Analysis Applied to Gene Expression Data 
     In the following, I describe how I obtained the Pearson correlation coefficient, the corresponding t-test statistic Z in each data set, the metaZ statistics summarizing correlation test statistics across multiple data, a corresponding empirical p-value (pMetaZ). I denote by r s  the Pearson correlation coefficient (e.g. between age and the gene expression profile) in the s-th data set. The Student t-test statistic for testing whether the correlation is different from zero is given by 
     
       
         
           
             
               Z 
               s 
             
             = 
             
               
                 
                   
                     
                       m 
                       s 
                     
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                 · 
                 
                   r 
                   s 
                 
               
               
                 
                   1 
                   - 
                   
                     r 
                     s 
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     where m s  denotes the number of observations (i.e. microarrays, individuals) in the s-th data set. This Z statistic is equivalent to the Wald test statistic resulting from a univariate regression model where age is regressed on the gene expression profile. To combine multiple correlation test statistics across the data sets, I used the metaZ statistic 
     
       
         
           
             metaZ 
             = 
             
               
                 
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                     s 
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                     1 
                   
                   
                     no 
                     . 
                     
                         
                     
                      
                     dataSets 
                   
                 
                  
                 
                   
                     w 
                     s 
                   
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                     Z 
                     s 
                   
                 
               
               
                 
                   
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                       dataSets 
                     
                   
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                       ( 
                       
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     where w s  denotes a weight associated with the s-th data set. All data sets received a weight of w s =1 but the weight had a negligible effect. Under the null hypothesis of zero correlation, metaZ follows an approximate normal distribution under weak assumptions, which will be outlined in the following. First, metaZ follows approximately a standard normal distribution if each individual Z, follows approximately a standard normal distribution since the data sets are independent. Second, even if individual Z statistics do not follow a normal distribution, one can invoke the central limit theorem if many independent data sets are being considered.
 
Names of the Genes Whose Mutations are Associated with Age Acceleration
 
     Mutations in the following genes either increase or decrease DNAm age. 
     AKAP9—A kinase (PRKA) anchor protein (yotiao) 9 
     CHD7—chromodomain helicase DNA binding protein 7 [ Homo sapiens]   
     CTNND2—catenin (cadherin-associated protein), delta 2 
     DMBT1—deleted in malignant brain tumors 1 
     DSG3—desmoglein 3 
     FAM123C—family with sequence similarity 123C 
     FAT4—FAT atypical cadherin 4 
     GATA3—GATA binding protein 3 
     KCNB1—potassium voltage-gated channel, Shab-related subfamily, member 1 
     LEPR—leptin receptor 
     MACF1—microtubule-actin crosslinking factor 1 
     MB21D1—Mab-21 domain containing 1 
     MGAM—maltase-glucoamylase (alpha-glucosidase) 
     MUC17—mucin 17, cell surface associated 
     MYH7—myosin, heavy chain 7, cardiac muscle, beta 
     RELN—reelin 
     THOC2—THO complex 2 
     TMEM132D—transmembrane protein 132D 
     TTN—titin 
     TP53—tumor protein p53 
     U2AF1—U2 small nuclear RNA auxiliary factor 1 
     Is DNAm Age a Biomarker of Aging? 
     The American Federation for Aging Research proposed the following criteria for a biomarker of aging (reviewed in {83-85}): 
     1. It must predict the rate of aging. 
     2. It must monitor a basic process that underlies the aging process, not the effects of disease. 
     3. It must be able to be tested repeatedly without harming the person. 
     4. It must be something that works in humans and in laboratory animals. 
     I will address these criteria in reverse order. DNAm age probably meets criterion 4 if chimpanzees are acceptable as lab animals (given my results in  FIG. 4 ). There is a good chance that it meets criterion 3 (given my results in blood, saliva, buccal cells, skin) and criterion 2 (see my EMS model of DNAm age and the vast literature on aging effects on DNA methylation levels). Large cohort studies will be very valuable for addressing criterion 1. These studies need to test whether a measure of DNAm based age acceleration will, in the absence of disease, better predict functional capability than chronological age {86}. 
     Example 8 
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     Example 9 
     Coefficient Values for the DNAm Age Predictor 
     This example provides information on the multi-tissue age predictor defined using the training set data. The multi-tissue age predictor uses 354 CpGs of which 193 and 160 have positive and negative correlations with age, respectively. The table also represents the coefficient values for the shrunken new predictor that is based on a subset of 110 CpGs (a subset of the 354 CpGs). Although this information is sufficient for predicting age, the software posted on [45] is recommended. The table reports a host of additional information for each CpG including its variance, minimum value, maximum value, and median value across all training and test data. Further, it reports the median beta value in subjects younger than 35 and in subjects older than 55. 
     Example 10 
     Description of Cancer Data Sets 
     This example describes 32 publicly available cancer tissue data sets and 7 cancer cell line data sets. Column 1 reports the data number and corresponding color code. Other columns report the affected tissue, Illumina™ platform, sample size n, proportion of females, median age, age range (minimum and maximum age), relevant citation (TCGA or first author with publication year), and public availability. None of these data sets were used in the construction of estimator of DNAm age. The table also reports the age correlation, cor(Age,DNAmage), median error, and median age acceleration. The epigenetic clock was applied to many different cancer types and cancer data sets. The last columns of Example 10 show that DNAm age has only a weak relationship with chronological age in cancer tissue. 
     Example 11 
     Cancer Lines and DNAm Age 
     This example reports the DNAm age and age acceleration for 59 cancer cell lines. The epigenetic clock was applied to many different cancer cell lines. It turns out that the DNAm age changes greatly across cell lines. 
     CONCLUSION 
     This concludes the description of the preferred embodiment of the present invention. The foregoing description of one or more embodiments of the invention has been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of the above teaching. It is intended that the scope of the invention be limited not by this detailed description, but rather by the claims appended hereto. 
     All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes. 
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         65. Liu Y, Aryee M J, Padyukov L, Fallin M D, Hesselberg E, Runarsson A, Reinius L, Acevedo N, Taub M, Ronninger M, et al: Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis.  Nat Biotech  2013, 31:142-147. 
         66. Heyn H, Li N, Ferreira H J, Moran S, Pisano D G, Gomez A, Diez J, Sanchez-Mut J V, Setien F, Carmona F J, et al: Distinct DNA methylomes of newborns and centenarians.  Proceedings of the National Academy of Sciences  2012, 109:10522-10527. 
         67. Lam L L, Emberly E, Fraser H B, Neumann S M, Chen E, Miller G E, Kobor M S: Factors underlying variable DNA methylation in a human community cohort.  Proceedings of the National Academy of Sciences  2012, 109:17253-17260. 
         68. Khulan B, Cooper W N, Skinner B M, Bauer J, Owens S, Prentice A M, Belteki G, Constancia M, Dunger D, Affara N A: Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia.  Human Molecular Genetics  2012, 21:2086-2101. 
         69. Martino D, Maksimovic J, Joo J H, Prescott S L, Saffery R: Genome-scale profiling reveals a subset of genes regulated by DNA methylation that program somatic T-cell phenotypes in humans.  Genes Immun  2012, 13:388-398. 
         70. Heyn H, Moran S, Esteller M: Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome.  Epigenetics  2013, 8:28-33. 
         71. Ginsberg M R, Rubin R A, Falcone T, Ting A H, Natowicz M R: Brain Transcriptional and Epigenetic Associations with Autism.  PLoS ONE  2012, 7:e44736. 
         72. Martino D, Loke Y, Gordon L, Ollikainen M, Cruickshank M, Saffery R, Craig J: Longitudinal, genome-scale analysis of DNA methylation in twins from birth to 18 months of age reveals rapid epigenetic change in early life and pair-specific effects of discordance.  Genome Biology  2013, 14:R42. 
         73. Ribel-Madsen R, Fraga M F, Jacobsen S, Bork-Jensen J, Lara E, Calvanese V, Fernandez A F, Friedrichsen M, Vind B F, Højlund K, et al: Genome-Wide Analysis of DNA Methylation Differences in Muscle and Fat from Monozygotic Twins Discordant for Type 2 Diabetes.  PLoS ONE  2012, 7:e51302. 
         74. Jacobsen S C, Brons C, Bork-Jensen J, Ribel-Madsen R, Yang B, Lara E, Hall E, Calvanese V, Nilsson E, Jorgensen S W, et al: Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men.  Diabetologia  2012, 55:3341-3349. 
         75. Blair J D, Yuen R K C, Lim B K, McFadden D E, von Dadelszen P, Robinson W P: Widespread DNA hypomethylation at gene enhancer regions in placentas associated with early-onset pre-eclampsia.  Molecular Human Reproduction  2013. 
         76. Teschendorff A, Jones A, Fiegl H, Sargent A, Zhuang J, Kitchener H, Widschwendter M: Epigenetic variability in cells of normal cytology is associated with the risk of future morphological transformation.  Genome Medicine  2012, 4:24. 
         77. Pacheco S E, Houseman E A, Christensen B C, Marsit C J, Kelsey K T, Sigman M, Boekelheide K: Integrative DNA Methylation and Gene Expression Analyses Identify DNA Packaging and Epigenetic Regulatory Genes Associated with Low Motility Sperm.  PLoS ONE  2011, 6:e20280. 
         78. Krausz C, Sandoval J, Sayols S, Chianese C, Giachini C, Heyn H, Esteller M: Novel Insights into DNA Methylation Features in Spermatozoa: Stability and Peculiarities.  PLoS ONE  2012, 7:e44479. 
         79. Nazor Kristopher L, Altun G, Lynch C, Tran H, Harness Julie V, Slavin I, Garitaonandia I, Müller F-J, Wang Y-C, Boscolo Francesca S, et al: Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and Their Differentiated Derivatives.  Cell stem cell  2012, 10:620-634. 
         80. Shao K, Koch C, Gupta M K, Lin Q, Lenz M, Laufs S, Denecke B, Schmidt M, Linke M, Hennies H C, et al: Induced Pluripotent Mesenchymal Stromal Cell Clones Retain Donor-derived Differences in DNA Methylation Profiles.  Mol Ther  2012. 
         81. Calvanese V, Fernández A F, Urdinguio R G, Suárez-Alvarez B, Mangas C, Pérez-Garcia V, Bueno C, Montes R, Ramos-Mejia V, Martinez-Camblor P, et al: A promoter DNA demethylation landscape of human hematopoietic differentiation.  Nucleic Acids Research  2012, 40:116-131. 
         82. Ramos-Mejia V, Fernández A, Ayllon V, Real P, Bueno C, Anderson P, Martin F, Fraga M, Menéndez P: Maintenance of human embryonic stem cells in mesenchymal stem cell-conditioned media augments hematopoietic specification.  Stem Cells Dev  2012, 21:1549-1558. 
         83. Reinius L E, Acevedo N, Joerink M, Pershagen G, Dahlén S-E, Greco D, Söderhäll C, Scheynius A, Kere J: Differential DNA Methylation in Purified Human Blood Cells: Implications for Cell Lineage and Studies on Disease Susceptibility.  PLoS ONE  2012, 7:e41361. 
         84. Fackler M J, Umbricht C B, Williams D, Argani P, Cruz L-A, Merino V F, Teo W W, Zhang Z, Huang P, Visvananthan K, et al: Genome-wide Methylation Analysis Identifies Genes Specific to Breast Cancer Hormone Receptor Status and Risk of Recurrence.  Cancer Research  2011, 71:6195-6207. 
         85. Dedeurwaerder S, Desmedt C, Calonne E, Singhal S K, Haibe-Kains B, Defrance M, Michiels S, Volkmar M, Deplus R, Luciani J, et al: DNA methylation profiling reveals a predominant immune component in breast cancers.  EMBO Molecular Medicine  2011, 3:726-741. 
         86. Lauss M, Aine M, Sjödahl G, Veerla S, Patschan O, Gudjonsson S, Chebil G, Lövgren K, Fernö M, Månsson W, et al: DNA methylation analyses of urothelial carcinoma reveal distinct epigenetic subtypes and an association between gene copy number and methylation status.  Epigenetics  2012, 7:858-867. 
         87. Langfelder P, Mischel P S, Horvath S: When is hub gene selection better than standard meta-analysis?  PLoS ONE  2013, 8:e61505. 
         88. Lee T I, Jenner R G, Boyer L A, Guenther M G, Levine S S, Kumar R M, Chevalier B, Johnstone S E, Cole M F, Isono K-i, et al: Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells.  Cell  2006, 125:301-313. 
         89. Miller J A, Cai C, Langfelder P, Geschwind D H, Kurian S M, Salomon D R, Horvath S: Strategies for aggregating gene expression data: The collapseRows R function.  BMC Bioinformatics  2011, 12:322. 
         90. Teschendorff A E, Menon U, Gentry-Maharaj A, Ramus S J et al. Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer.  Genome Res  2010 Apr.; 20(4):440-6. PMID: 20219944 
         91. Rakyan V K, Down T A, Maslau S, Andrew T et al. Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains.  Genome Res  2010 Apr.; 20(4):434-9. PMID: 20219945 
         92. Gibbs J R, van der Brug M P, Hernandez D G, Traynor B J, Nalls M A, Lai S L, Arepalli S, Dillman A, Rafferty I P, Troncoso J, Johnson R, Zielke H R, Ferrucci L, Longo D L, Cookson M R, Singleton A B. Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.  PLoS Genet.  2010 May 13; 6(5):e1000952. 
         93. Bocklandt S, Lin W, Sehl M E, Sanchez F J, Sinsheimer J S, et al. 2011 Epigenetic Predictor of Age.  PLoS ONE  6(6): e14821 
         94. Pacheco S E, Houseman E A, Christensen B C, Marsit C J et al. Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm.  PLoS One  2011; 6(6):e20280. PMID: 21674046 
         95. Song H, Ramus S J, Tyrer J, Bolton K L, Gentry-Maharaj A, Wozniak E,Anton-Culver H, Chang-Claude J, Cramer D W, DiCioccio R, et al. 2009. A genome-wide association study identifies a new ovarian cancersusceptibility locus on 9p22.2 . Nat Genet  41: 996-1000 
         96. Adkins R M, Thomas F, Tylaysky F A,  Julia  Krushkal (2011) Parental ages and levels of DNA methylation in the newborn are correlated.  BMC Med Genet.  2011; 12: 47. 
         97. Liu J, Morgan M, Hutchison K, Calhoun V D. A study of the influence of sex on genome wide methylation.  PLoS One  2010 Apr. 6; 5(4):e10028. PMID: 20386599 
         98. Adkins, R M, Krushkal, J, Tylaysky, F A and Thomas, F (2011), Racial differences in gene-specific DNA methylation levels are present at birth.  Birth Defects Research Part A: Clinical and Molecular Teratology,  91: 728-736. doi: 10.1002/bdra.20770 
         99. Teschendorff A E, Menon U, Gentry-Maharaj A, Ramus S J et al.  Age - dependent    
         DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer.  Genome Res  2010 Apr.; 20(4):440-6. PMID: 20219944 
         100. Rakyan V K, Down T A, Maslau S, Andrew T et al. Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains.  Genome Res  2010 Apr.; 20(4):434-9. PMID: 20219945″ 
         101. Bocklandt S, Lin W, Sehl M E, Sanchez F J, Sinsheimer J S, Horvath S, Vilain E (2011) Epigenetic Predictor of Age.  PLoS ONE  6(6): e14821 
       
    
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Listing of 354 CpGs Set 
               
               
                 This Table provides sequence and methylation residue information 
               
               
                 (in brackets) for the 354 clock CpGs of the present invention. 
               
               
                 Further explanations of these sequences can be found, for example, 
               
               
                 on the Illumina ™ website, under Technical Note: Epigenetics - CpG 
               
               
                 Loci Identification (Search: “res.illumina.com/documents/products/ 
               
               
                 technotes/technote_cpg_loci_identification.pdf”). Briefly, these 
               
               
                 354 CpGs correspond to Illumina probes specified by so called 
               
               
                 Cluster CG numbers (see Table 1 in the Illumina ™ Techical Notes). 
               
               
                 For convenience, the genomic coordinates of these clock CpGs and 
               
               
                 the gene names are also provided. 
               
            
           
           
               
               
               
               
               
               
            
               
                 SEQ 
                   
                   
                   
                   
                   
               
               
                 ID 
                   
                 Sequence with the CpG 
                 Chro- 
                   
                   
               
               
                 NO. 
                 Probe 
                 site marked with [ ] 
                 mosome 
                 Position 
                 Gene 
               
               
                   
               
               
                   1 
                 cg00075967 
                 GGTGTGGCCAGGAGCCACCCCCACCCC 
                 15 
                  74495354 
                 STRA6 
               
               
                   
                   
                 CGCACCTGACTTCACACACATACCTGC 
                   
                   
                   
               
               
                   
                   
                 CTTCAG[CG]CCTGCCCCAGAGCTCCCA 
                   
                   
                   
               
               
                   
                   
                 AGCCCCTGCCCGCCACATCTGCAGTGC 
                   
                   
                   
               
               
                   
                   
                 CGCACACAGACAGGA 
                   
                   
                   
               
               
                   
               
               
                   2 
                 cg00374717 
                 AAACCTTACAGAAACATGAAGCCCTCA 
                 17 
                  66303145 
                 ARSG 
               
               
                   
                   
                 ACCATCTGCTACTCAGTTATTCGGGGC 
                   
                   
                   
               
               
                   
                   
                 TGACGG[CG]GCTTCTAGAACATCCAGG 
                   
                   
                   
               
               
                   
                   
                 TGTTCTGCAGATGCGAGAACTCATCCT 
                   
                   
                   
               
               
                   
                   
                 GTAGTCACCAGATGG 
                   
                   
                   
               
               
                   
               
               
                   3 
                 cg00864867 
                 AGTACAAGACCGTATTATTTGAGAGAA 
                 12 
                  80085268 
                 PAWR 
               
               
                   
                   
                 AGTCTCGAACGCTGCTGGCTAAGGGGA 
                   
                   
                   
               
               
                   
                   
                 AAAGTG[CG]ATAACTTGTGATGATTCA 
                   
                   
                   
               
               
                   
                   
                 GGGAATGACTAGACAGGATGGGAAAA 
                   
                   
                   
               
               
                   
                   
                 TACCCACGTGTCTCTT 
                   
                   
                   
               
               
                   
               
               
                   4 
                 cg00945507 
                 TGGGATTACAGACGTGAGCCACCGCGC 
                  7 
                  54827677 
                 SEC61G 
               
               
                   
                   
                 CCGGCCATGTTTCCTTTTAGCAATGGA 
                   
                   
                   
               
               
                   
                   
                 GCATAA[CG]GGATCTGAGGAACAATAT 
                   
                   
                   
               
               
                   
                   
                 AACTCAGGAAGAGCTGATGGAACATT 
                   
                   
                   
               
               
                   
                   
                 AAGACGTGTTACAACT 
                   
                   
                   
               
               
                   
               
               
                   5 
                 cg01027739 
                 CCTTAACTGTAGCTAAGCTTCCACTCTT 
                  9 
                 131842738 
                 DOLPP1 
               
               
                   
                   
                 AAGTATCAATTAAGCTTCTCTGTTCAG 
                   
                   
                   
               
               
                   
                   
                 TCCAG[CG]TTTAGGGCGCCTACTGCGC 
                   
                   
                   
               
               
                   
                   
                 GCCCCGCCCCACACACTTTTGACAAAA 
                   
                   
                   
               
               
                   
                   
                 AGGTCGCCTGCTCT 
                   
                   
                   
               
               
                   
               
               
                   6 
                 cg01353448 
                 GCCCAGCCTCGGTGAGCACACACGCCC 
                  7 
                  31726912 
                 C7orf16 
               
               
                   
                   
                 TCCCTGTCTCTCGCCTTCGCTTCCCTGC 
                   
                   
                   
               
               
                   
                   
                 ATCTG[CG]CTGATTGGTAAGTGCTTCA 
                   
                   
                   
               
               
                   
                   
                 GATTTTTACTCCAAGAACTTTTGTGGTG 
                   
                   
                   
               
               
                   
                   
                 AGAAAAGCAAGTT 
                   
                   
                   
               
               
                   
               
               
                   7 
                 cg01584473 
                 CAGGGACCAAAGGTCTCTGGCACCCAT 
                  7 
                 100663367 
                 MUC17 
               
               
                   
                   
                 TTATTTATCAGTTTCCTTCTCTGAGGCT 
                   
                   
                   
               
               
                   
                   
                 CATTT[CG]CCAGCTCCTCTGGGGGTGA 
                   
                   
                   
               
               
                   
                   
                 CAGGCAAGTGAGACGTGCTCAGAGCTC 
                   
                   
                   
               
               
                   
                   
                 CGATGCCAAGGCCA 
                   
                   
                   
               
               
                   
               
               
                   8 
                 cg01644850 
                 ACAGCACCTCAGAATACAAGTTCGCAG 
                 19 
                  58193231 
                 ZNF551 
               
               
                   
                   
                 AGGTCAAAGCAGTGGACACACTCCGA 
                   
                   
                   
               
               
                   
                   
                 AGAGCTC[CG]TGGAGTTTTGGAAACTA 
                   
                   
                   
               
               
                   
                   
                 CATTATCCAGAGTGCAGAGCGCAAAAC 
                   
                   
                   
               
               
                   
                   
                 GGCGGCGGAGTTGAGC 
                   
                   
                   
               
               
                   
               
               
                   9 
                 cg01656216 
                 CATGTGCATAATACTGTGGAAATTAGT 
                 10 
                  31273710 
                 ZNF438 
               
               
                   
                   
                 AAACAGTCACAAACAAGTGATTCATAT 
                   
                   
                   
               
               
                   
                   
                 TCAGGG[CG]CAGCCTTTTTGACAGGAA 
                   
                   
                   
               
               
                   
                   
                 AACAGTAATCAAGAGTTTGGGATTTGA 
                   
                   
                   
               
               
                   
                   
                 AGATTTTTAAAAGGA 
                   
                   
                   
               
               
                   
               
               
                  10 
                 cg01873645 
                 TTGGTTTTCTTTCCCCTCATCCTTTTGC 
                  9 
                  74526649 
                 FAM108B 
               
               
                   
                   
                 CTGCTCCCGGCGAGGGGTGGCTTTGAT 
                   
                   
                 1; C9orf85 
               
               
                   
                   
                 TTCGG[CG]ATGAGCTCCCAGAAAGGCA 
                   
                   
                   
               
               
                   
                   
                 ACGTGGCTCGTTCCAGACCTCAGAAGC 
                   
                   
                   
               
               
                   
                   
                 ACCAGAATACGTTT 
                   
                   
                   
               
               
                   
               
               
                  11 
                 cg01968178 
                 CTGCAGCGGCCCCGTTTGCAGGGCAGG 
                  2 
                  86565038 
                 REEP1 
               
               
                   
                   
                 GACCCGGGTGCTGCCCCACCCTCAGCG 
                   
                   
                   
               
               
                   
                   
                 TTCCAG[CG]GAGAAACTGAAGTCCGAA 
                   
                   
                   
               
               
                   
                   
                 CCTGAACCTCGGGAATCTGTCTGCACC 
                   
                   
                   
               
               
                   
                   
                 TGTCTAGGTGGGATG 
                   
                   
                   
               
               
                   
               
               
                  12 
                 cg02085507 
                 CTGGGGGAGGGAAGGCAGGATGCGGT 
                 19 
                   6739192 
                 TRIP10 
               
               
                   
                   
                 GCGGGAGTTAATGGACCTGGCCTTGGC 
                   
                   
                   
               
               
                   
                   
                 GAAGGCG[CG]TCCTGGGTTGGATCGAA 
                   
                   
                   
               
               
                   
                   
                 ACCCTCTCATCCGCCCTGTGGCCGGAG 
                   
                   
                   
               
               
                   
                   
                 GGACCAGACCATTAGT 
                   
                   
                   
               
               
                   
               
               
                  13 
                 cg02154074 
                 TGGGGAACGCGAGTGGGGACAGGGGG 
                  2 
                  74756234 
                 HTRA2; 
               
               
                   
                   
                 GCCTTCAGCTGGGCCCCAGGGAACCGC 
                   
                   
                 AUP1 
               
               
                   
                   
                 CCCGTGG[CG]CTCTCGGCCTCGCTCTC 
                   
                   
                   
               
               
                   
                   
                 ACTCACGGTGCTACAGGTGGTAAGCAA 
                   
                   
                   
               
               
                   
                   
                 ATTGACTATGTTGTGG 
                   
                   
                   
               
               
                   
               
               
                  14 
                 cg02217159 
                 TATTTCCGATGACCTACATCTCAGGGA 
                  6 
                  62996697 
                 KHDRBS2 
               
               
                   
                   
                 CGCAGTAGGATGTTCATTGATAAACAA 
                   
                   
                   
               
               
                   
                   
                 ATAAAG[CG]GCTCGAAGAAATATTGTG 
                   
                   
                   
               
               
                   
                   
                 CAGAGACATGATTGAGGTGTACAATCA 
                   
                   
                   
               
               
                   
                   
                 TTAGGATATTGAATT 
                   
                   
                   
               
               
                   
               
               
                  15 
                 cg02331561 
                 CAGCGGCGGTAGCCGAGCGAGGGCGC 
                 16 
                   2391081 
                 ABCA17P; 
               
               
                   
                   
                 GGTGGCCTCTGACAGGAATGACTCTGC 
                   
                   
                 ABCA3 
               
               
                   
                   
                 GCACGTG[CG]TTTCGCAGCAGTGGAAG 
                   
                   
                   
               
               
                   
                   
                 TCTTCACACCCGGAAACTCGACTTTGG 
                   
                   
                   
               
               
                   
                   
                 CCGTTTCTCCATTTCT 
                   
                   
                   
               
               
                   
               
               
                  16 
                 cg02332492 
                 CGGGGCAGCTGTCAGTGAAGCTCTACG 
                  9 
                 139840678 
                 C8G 
               
               
                   
                   
                 GTATGTGGGGGCCAGCCTCTGTGACCA 
                   
                   
                   
               
               
                   
                   
                 GGCAGG[CG]CTCAAGCTCTGCACACTC 
                   
                   
                   
               
               
                   
                   
                 ACTGGGCCACCCCGAGGGGCTGGGTG 
                   
                   
                   
               
               
                   
                   
                 AGCCCATGGGGACACA 
                   
                   
                   
               
               
                   
               
               
                  17 
                 cg02364642 
                 GGGTCGCTGTGCCTGTCCCCGTGTGAT 
                 12 
                  58005758 
                 GEFT 
               
               
                   
                   
                 CCGAAAAGTGCTGGCAAAATGCGGCT 
                   
                   
                   
               
               
                   
                   
                 GCTGCTT[CG]CCCGGGGGGGACGTGGT 
                   
                   
                   
               
               
                   
                   
                 GAGTGCCAGGTCGAGAGGGTCCAGTGT 
                   
                   
                   
               
               
                   
                   
                 TGAGTGGGGGGCGGGC 
                   
                   
                   
               
               
                   
               
               
                  18 
                 cg02388150 
                 AACCTATGAAAATAAACAAAAGCTGCT 
                  8 
                  41165699 
                 SFRP1 
               
               
                   
                   
                 CCAAGCATTCTCTCGGCCTTTCTGAACT 
                   
                   
                   
               
               
                   
                   
                 TTCTA[CG]CTTTGGGTTTTTGTTTTTTCC 
                   
                   
                   
               
               
                   
                   
                 TCCCGTCTCAGAGGTTAAAAACTTCGA 
                   
                   
                   
               
               
                   
                   
                 TAGGGACTCGGA 
                   
                   
                   
               
               
                   
               
               
                  19 
                 cg02479575 
                 GAGGGACAGCTCTCCACCGACCGAAG 
                 19 
                   4769653 
                 MIR7-3; 
               
               
                   
                   
                 GAGGAGAATGCTATTTATTTCAGCACC 
                   
                   
                 C19orf30 
               
               
                   
                   
                 AAATATC[CG]GACAGCGCCTCTCGGGA 
                   
                   
                   
               
               
                   
                   
                 GGTCCGAGAAGAGAACCGCGATCTGTT 
                   
                   
                   
               
               
                   
                   
                 TCAGCACCGGGGCTCA 
                   
                   
                   
               
               
                   
               
               
                  20 
                 cg02489552 
                 CTCCTCCCCCCACCTCTGGAATTCCACC 
                 19 
                  15121531 
                 CCDC105 
               
               
                   
                   
                 TCCCTTGTTGCGCCCATCGCTATGGTG 
                   
                   
                   
               
               
                   
                   
                 ACGGG[CG]CTCTCAGTACACTGTCTCT 
                   
                   
                   
               
               
                   
                   
                 ACAGGCCAGGAAAGAGTTGTGTGTCTT 
                   
                   
                   
               
               
                   
                   
                 TGGGGTCCCTTCCG 
                   
                   
                   
               
               
                   
               
               
                  21 
                 cg02580606 
                 AACCTAAATTTTGGGAGCACCTACTCT 
                 17 
                  39526726 
                 KRT33B 
               
               
                   
                   
                 GCATGAAGCACTGTGCTCCATGCCTGT 
                   
                   
                   
               
               
                   
                   
                 GCACAG[CG]TGACTCTGTCATTGGTGA 
                   
                   
                   
               
               
                   
                   
                 TGGGTCCTGCTTGCTGAGCCTCCACTG 
                   
                   
                   
               
               
                   
                   
                 TGCACCAGGCACAGT 
                   
                   
                   
               
               
                   
               
               
                  22 
                 cg02654291 
                 GCCTCGAAGAGCATTATGGCCGTAGAT 
                  9 
                  86572014 
                 C9orf64 
               
               
                   
                   
                 CTGGGTGCTGAGGACTGAGCCACCCCC 
                   
                   
                   
               
               
                   
                   
                 AGACTG[CG]ACATGGGCGGCGGTGCCT 
                   
                   
                   
               
               
                   
                   
                 CCTTCCCCAAGCCCCAGGGAGTGTTTT 
                   
                   
                   
               
               
                   
                   
                 TTTGTTTGTTTTGTT 
                   
                   
                   
               
               
                   
               
               
                  23 
                 cg02827112 
                 AATTGTTGCGGCCTAACAATGAAGCGC 
                  4 
                  95129403 
                 SMARCA 
               
               
                   
                   
                 AGCCATAACAGTCCTGAGCCACTGGCA 
                   
                   
                 D1 
               
               
                   
                   
                 TGTTTG[CG]GGCCCTTTATTGCCTTGGG 
                   
                   
                   
               
               
                   
                   
                 AATAAACTGCTGTGGCATTGTATCGTA 
                   
                   
                   
               
               
                   
                   
                 TATTGTTTTCATGG 
                   
                   
                   
               
               
                   
               
               
                  24 
                 cg02972551 
                 ACCCTTTCCTGTGAGATTCTTCCGCCAA 
                  2 
                  86668068 
                 KDM3A 
               
               
                   
                   
                 GTGGAAGGCTCATCTTCGGTCGACAGC 
                   
                   
                   
               
               
                   
                   
                 CTACG[CG]GTTGAAGAACAATCCAGTA 
                   
                   
                   
               
               
                   
                   
                 GGCACTTATAGCTCAGGGTCTCGCCAT 
                   
                   
                   
               
               
                   
                   
                 TCAGTCTTATCTAT 
                   
                   
                   
               
               
                   
               
               
                  25 
                 cg03103192 
                 AAGCTAGAAGTAAGAAGTACTGAAAT 
                  4 
                  52917271 
                 SPATA18 
               
               
                   
                   
                 TTTAGTTACAAGTTTCATACAGGTAAA 
                   
                   
                   
               
               
                   
                   
                 CCCAAGG[CG]CTACAAATGAAGAATTA 
                   
                   
                   
               
               
                   
                   
                 AAGGAATGAAAGGCGAAAGAATAAAG 
                   
                   
                   
               
               
                   
                   
                 GGGCCAAAGAGGTGATC 
                   
                   
                   
               
               
                   
               
               
                  26 
                 cg03167275 
                 GCCTGGACGGTGTTAGTCTCCTGGAAG 
                 21 
                  18886093 
                 CXADR 
               
               
                   
                   
                 CAGCTCGCCCAGGCAGGAGCTGCTAAC 
                   
                   
                   
               
               
                   
                   
                 CAGACG[CG]CATTGTGAAGGAGACCGT 
                   
                   
                   
               
               
                   
                   
                 GGAAAATCAAAAGTGGGTTCCTGCAA 
                   
                   
                   
               
               
                   
                   
                 AAATGTAGCATTGGTT 
                   
                   
                   
               
               
                   
               
               
                  27 
                 cg03270204 
                 AAGAGAGTGGGCCCGCCTTCAGGGTCT 
                  6 
                  30851638 
                 DDR1 
               
               
                   
                   
                 GGGGCCTTCCAGGTTGGGTCGTAGGGG 
                   
                   
                   
               
               
                   
                   
                 CGGGAG[CG]CACAGGCTGCGAGAGAG 
                   
                   
                   
               
               
                   
                   
                 GAGCAAAGGTTGGTGGAGGGAGAAGA 
                   
                   
                   
               
               
                   
                   
                 GCAGTCTGGGGCCTGGC 
                   
                   
                   
               
               
                   
               
               
                  28 
                 cg03565323 
                 TTTCCTAGAGGAAGAATGGGCAGGGA 
                 17 
                  16472866 
                 ZNF287 
               
               
                   
                   
                 AGATGTGGGTCTAAAGGCAGAAAGAC 
                   
                   
                   
               
               
                   
                   
                 TTAATGTG[CG]GTTTCGGGCTTTACTGT 
                   
                   
                   
               
               
                   
                   
                 GCATACATACTAACTGTGAAAGGTTTT 
                   
                   
                   
               
               
                   
                   
                 CACTTCCTCCTCAGGA 
                   
                   
                   
               
               
                   
               
               
                  29 
                 cg03588357 
                 GCCAGCGCGCACGCAGATGGCGGGGT 
                 14 
                  91720173 
                 GPR68 
               
               
                   
                   
                 GGCCTGGGGAGGTCTTCGGGTCCCTTC 
                   
                   
                   
               
               
                   
                   
                 CTGGGAA[CG]CAGGGCCAAGTTGTGCT 
                   
                   
                   
               
               
                   
                   
                 CCGATTCCACGCCCCCCCCACCCACGT 
                   
                   
                   
               
               
                   
                   
                 CGGGCACACGCAGCCC 
                   
                   
                   
               
               
                   
               
               
                  30 
                 cg03760483 
                 ACAGCCGGCTCTACCGCTCTGCTCGCA 
                 17 
                   6899297 
                 ALOX12 
               
               
                   
                   
                 GGTTTGGGCTAGTCTGGGGCGGGGACT 
                   
                   
                   
               
               
                   
                   
                 TGGGAG[CG]CCTAAAACTTGCGAGGA 
                   
                   
                   
               
               
                   
                   
                 GGGCGGGGCCGCAGACCGGTCCTTTAA 
                   
                   
                   
               
               
                   
                   
                 AGGTTGGAAGTGGCCC 
                   
                   
                   
               
               
                   
               
               
                  31 
                 cg04084157 
                 AGGGTGCCTGCCTCTCCCGGCCTGCGC 
                  7 
                 100809049 
                 VGF 
               
               
                   
                   
                 CTGCGCGCTGGGGCCTTCGGCTGAAGG 
                   
                   
                   
               
               
                   
                   
                 GGTGTG[CG]CTAGCGGAGCTCCGGGAA 
                   
                   
                   
               
               
                   
                   
                 ATGAATGAATGAATGAATGAATGAAAT 
                   
                   
                   
               
               
                   
                   
                 GCTGAAGCGGGCAGG 
                   
                   
                   
               
               
                   
               
               
                  32 
                 cg04126866 
                 CTCCACCAACAGGAGCTCCTTGAGGCG 
                 10 
                  85932763 
                 C10orf99 
               
               
                   
                   
                 AGGCACAGTGTCTTCTGTGTCCCTGGA 
                   
                   
                   
               
               
                   
                   
                 GCCAAG[CG]CATGGCTCAGCCCAGGTC 
                   
                   
                   
               
               
                   
                   
                 ACGTGTCCAGTGAATGGGTGGCATCTG 
                   
                   
                   
               
               
                   
                   
                 AGCCTCCTGCACCTG 
                   
                   
                   
               
               
                   
               
               
                  33 
                 cg04528819 
                 GCAGCCCGGGAAGGGGCATTGGTGGC 
                  7 
                 130418315 
                 KLF14 
               
               
                   
                   
                 GCTTGGCAGCAGGTGTGACAGACCTCC 
                   
                   
                   
               
               
                   
                   
                 TCCGGGG[CG]CCTGATCCGCGGCGGGG 
                   
                   
                   
               
               
                   
                   
                 GCGGGGCCTGCCCCTAGGGCCCCTCCA 
                   
                   
                   
               
               
                   
                   
                 GAGAACCCACCAGAGG 
                   
                   
                   
               
               
                   
               
               
                  34 
                 cg04836038 
                 CTCTGCGGGGACAGAGGTCTCAGGAA 
                 13 
                  99739382 
                 DOCK9 
               
               
                   
                   
                 AGTAGCCTTTATTTATGTGGCACCGAT 
                   
                   
                   
               
               
                   
                   
                 CGGAACC[CG]CGGCCGGCCAGGCGGA 
                   
                   
                   
               
               
                   
                   
                 CCTGGACGGAGCGTCCCTGCTCGGAAC 
                   
                   
                   
               
               
                   
                   
                 CTGGCGCGGGGCGCCGC 
                   
                   
                   
               
               
                   
               
               
                  35 
                 cg05250458 
                 TTAATTGGCTTGTGCCTCTTATTTTACT 
                 19 
                   9473565 
                 ZNF177 
               
               
                   
                   
                 CTAATGCAATGAATAAAGACAGTCCCA 
                   
                   
                   
               
               
                   
                   
                 GCCTT[CG]CCCTAAGGGAGCAGGAGCA 
                   
                   
                   
               
               
                   
                   
                 CCTGCGATGCCCCGTTCCCAAGTCCTC 
                   
                   
                   
               
               
                   
                   
                 AGGGCGAATCCGCC 
                   
                   
                   
               
               
                   
               
               
                  36 
                 cg05294243 
                 GATGTCTCCAGGCACCCCCGACCTGGG 
                 19 
                  51569106 
                 KLK13 
               
               
                   
                   
                 CTTGGCCCTCTGCTTGGGGCGGAGCTT 
                   
                   
                   
               
               
                   
                   
                 CCAGGA[CG]TGCTGGGACCTAGGTCTG 
                   
                   
                   
               
               
                   
                   
                 ACCCCGCCCAAGGCAGAGTTGAACCCA 
                   
                   
                   
               
               
                   
                   
                 CTGTGAACTTTCAGG 
                   
                   
                   
               
               
                   
               
               
                  37 
                 cg05365729 
                 ACATAATACACGCTCAATTAAAGCTGC 
                  8 
                  23262073 
                 LOXL2 
               
               
                   
                   
                 CGAATGAAAGTGTTCAGAAACTTGCAC 
                   
                   
                   
               
               
                   
                   
                 CCATCT[CG]CCTGGGTTTCACCTCCCTT 
                   
                   
                   
               
               
                   
                   
                 TTCCTGTAGGGGGAAAACCGATCCTGA 
                   
                   
                   
               
               
                   
                   
                 ACCAGTAAATAAAC 
                   
                   
                   
               
               
                   
               
               
                  38 
                 cg05675373 
                 AAGGAGGAGATGGCCAAGGGCGAGGC 
                  1 
                 110754257 
                 KCNC4 
               
               
                   
                   
                 GTCGGAGAAGATCATCATCAACGTGGG 
                   
                   
                   
               
               
                   
                   
                 CGGCACG[CG]ACATGAGACCTACCGCA 
                   
                   
                   
               
               
                   
                   
                 GCACCCTGCGCACCCTACCGGGAACCC 
                   
                   
                   
               
               
                   
                   
                 GCCTCGCCTGGCTGGC 
                   
                   
                   
               
               
                   
               
               
                  39 
                 cg05755779 
                 CCTGGTACTATTTCTTTTGCAAATTCAG 
                  8 
                 120079625 
                 COLEC10 
               
               
                   
                   
                 AGTCTGGGTCTGGATATTGATAGCCGT 
                   
                   
                   
               
               
                   
                   
                 CCTAC[CG]CTGAAGTCTGTGCCACACA 
                   
                   
                   
               
               
                   
                   
                 CACAATTTCACCAGGACCCAAAGGTGA 
                   
                   
                   
               
               
                   
                   
                 GGAAAGAAAACCAC 
                   
                   
                   
               
               
                   
               
               
                  40 
                 cg05921699 
                 AAGAATTCCAGTAAAGAGCTGATCATG 
                 19 
                  42380725 
                 CD79A 
               
               
                   
                   
                 GTTCTCACTCCTTGAATACCAGGAACA 
                   
                   
                   
               
               
                   
                   
                 CCATCT[CG]TATCACATAATGAGACAG 
                   
                   
                   
               
               
                   
                   
                 GGAGACATTCTGGTCCTCATCTCACAG 
                   
                   
                   
               
               
                   
                   
                 ATGAAAAATGTCAAG 
                   
                   
                   
               
               
                   
               
               
                  41 
                 cg05960024 
                 CAAGGAAAGTAGCAGATCATTACCCA 
                  4 
                  56376020 
                 CLOCK 
               
               
                   
                   
                 AGTATTTTTATAATTCCTTGTCCTATGC 
                   
                   
                   
               
               
                   
                   
                 TTCCAC[CG]GTACACTGCAAATTCCAC 
                   
                   
                   
               
               
                   
                   
                 CCAACCATGATTAAGGGAAAAGAAAC 
                   
                   
                   
               
               
                   
                   
                 AAAGATAGCATACCTT 
                   
                   
                   
               
               
                   
               
               
                  42 
                 cg06121469 
                 CCAGTCCCACTCTGCTTAACTGCTCTG 
                 15 
                  44956098 
                 SPG11 
               
               
                   
                   
                 GCATGCTTGAAGGCCTAGCTTAGCGTA 
                   
                   
                   
               
               
                   
                   
                 GCAGGC[CG]TTGCAGCCGTTCTCGCTC 
                   
                   
                   
               
               
                   
                   
                 TGTGGCATTGCTCTTTGCCTTCTTGGTC 
                   
                   
                   
               
               
                   
                   
                 CAGCTGCCTCCAGC 
                   
                   
                   
               
               
                   
               
               
                  43 
                 cg06144905 
                 CTGACCTCACCACCCACCAGGGAGGTG 
                 17 
                  27369780 
                 PIPOX 
               
               
                   
                   
                 GGTCTTATTCTGGGCATCGTGCCAAGT 
                   
                   
                   
               
               
                   
                   
                 TCTTAG[CG]GGGCCCTCTAGAATCTCT 
                   
                   
                   
               
               
                   
                   
                 AAAGCAAATCAGGCTGAAGAGGGGAA 
                   
                   
                   
               
               
                   
                   
                 AACCAGCAGGGGGAGG 
                   
                   
                   
               
               
                   
               
               
                  44 
                 cg06361108 
                 GGTCAGCGTTCCGCGGGGGAGACTTCC 
                 16 
                   2478781 
                 CCNF 
               
               
                   
                   
                 CAGCGTCAGCTCCGACCTCCTCTTTCTC 
                   
                   
                   
               
               
                   
                   
                 TACCA[CG]ATCCCGGCCAGCATCCCCG 
                   
                   
                   
               
               
                   
                   
                 CCCAGCAGCGGCTCAGCCACAAACCCA 
                   
                   
                   
               
               
                   
                   
                 AGGGTCTCCACCTG 
                   
                   
                   
               
               
                   
               
               
                  45 
                 cg06462291 
                 TCTCTCCGCATTAATGGCCTCTGGCAG 
                 12 
                 104235479 
                 NT5DC3 
               
               
                   
                   
                 TCTAATTAATGGCAGTCTGGACCTCCC 
                   
                   
                   
               
               
                   
                   
                 CTGGAT[CG]TGGGGCCCCTCTGAGACG 
                   
                   
                   
               
               
                   
                   
                 TCCCCGATCCCCAGCTTAAATTTATCC 
                   
                   
                   
               
               
                   
                   
                 AGGAGGACCTGTGAG 
                   
                   
                   
               
               
                   
               
               
                  46 
                 cg06493994 
                 GGAGAGCAAGTCAAGAAATACGGTGA 
                  6 
                  25652602 
                 SCGN 
               
               
                   
                   
                 AGGAGTCCTTCCCAAAGTTGTCTAGGT 
                   
                   
                   
               
               
                   
                   
                 CCTTCCG[CG]CCGGTGCCTGGTCTTCGT 
                   
                   
                   
               
               
                   
                   
                 CGTCAACACCATGGACAGCTCCCGGGA 
                   
                   
                   
               
               
                   
                   
                 ACCGACTCTGGGGCG 
                   
                   
                   
               
               
                   
               
               
                  47 
                 cg06557358 
                 AGCATCGAGACAGCGGGCGAACGGGC 
                 17 
                  32907002 
                 TMEM132 
               
               
                   
                   
                 GTCCGGGGACAGGGTGGGGGCGGCGG 
                   
                   
                 E; 
               
               
                   
                   
                 GGAGGAGG[CG]TCGGAGACTCTGAAC 
                   
                   
                 C17orf102 
               
               
                   
                   
                 CCCAGAAAAGTTCAAGGTTTGTGCAGG 
                   
                   
                   
               
               
                   
                   
                 TTCCCCCAGGGAAGGCGA 
                   
                   
                   
               
               
                   
               
               
                  48 
                 cg06738602 
                 ACTTCATTGTTTGGTGAGTTGCTTTGCT 
                 14 
                  52780634 
                 PTGER2 
               
               
                   
                   
                 TTGCTCGTTGCCCCGATCTTCTGTGTAT 
                   
                   
                   
               
               
                   
                   
                 TCTG[CG]CAGACCCCGCAAGTGCTCCT 
                   
                   
                   
               
               
                   
                   
                 GCACTCCCTCCCAGCCCTCTGCTGGGG 
                   
                   
                   
               
               
                   
                   
                 CTTAACGCTTCCC 
                   
                   
                   
               
               
                   
               
               
                  49 
                 cg06810647 
                 TGCCGCGGGGGAGAGGAACCCCTCGC 
                 16 
                   1665094 
                 CRAMP1L 
               
               
                   
                   
                 CCCAGCCGGGCTCCACCCTAGCTCACC 
                   
                   
                   
               
               
                   
                   
                 CATCCCG[CG]GCCTACACTGAGGCTCT 
                   
                   
                   
               
               
                   
                   
                 CAATTTGGGTGGCACTTATGGGGCATG 
                   
                   
                   
               
               
                   
                   
                 TGTCCCCTCTCTCCTT 
                   
                   
                   
               
               
                   
               
               
                  50 
                 cg06952310 
                 TGGCATGGGCTAGAGAATAAAATGAG 
                 19 
                  19327990 
                 NCAN 
               
               
                   
                   
                 AATAGATTTTAAAAGGTCTTTGAACAG 
                   
                   
                   
               
               
                   
                   
                 TCAAAAG[CG]AACAGGATACCTAAGA 
                   
                   
                   
               
               
                   
                   
                 GGTTATTTTTAGTCATTGTCAGCAGAA 
                   
                   
                   
               
               
                   
                   
                 GCTGGAGATTCCCGCCT 
                   
                   
                   
               
               
                   
               
               
                  51 
                 cg06993413 
                 GAGGCGCGGGGTGGAGACTGGGCCGA 
                 15 
                  65810204 
                 DPP8 
               
               
                   
                   
                 GCAGGGGATAGAGATGAACTCCAGAA 
                   
                   
                   
               
               
                   
                   
                 AGGAACAG[CG]ACTTGCTGAAAGTCAC 
                   
                   
                   
               
               
                   
                   
                 AGGGCAAAATGTGGCGCGTCTGTAGTC 
                   
                   
                   
               
               
                   
                   
                 AATAAATAATATATATT 
                   
                   
                   
               
               
                   
               
               
                  52 
                 cg07285276 
                 GGCCTCAGGTCTTTCTCCCAAATAGCA 
                  9 
                 134613015 
                 RAPGEF1 
               
               
                   
                   
                 GAGAACTCAAATGAAGAGTCATTTCAT 
                   
                   
                   
               
               
                   
                   
                 TCCCAG[CG]GTTTGGGCAGCTCATGGG 
                   
                   
                   
               
               
                   
                   
                 ATGACAGGCAACTTTTTCCTTTTTTTAA 
                   
                   
                   
               
               
                   
                   
                 AAAAAGAGGCCCAG 
                   
                   
                   
               
               
                   
               
               
                  53 
                 cg07291563 
                 CGCTACGCGAAGGGGAGGAGCTGGTC 
                 19 
                  48949441 
                 GRWD1 
               
               
                   
                   
                 ATGGACGAGGAGGCCTATGTGCTCTAC 
                   
                   
                   
               
               
                   
                   
                 CACCGAG[CG]CAGACTGGTAGGGCTG 
                   
                   
                   
               
               
                   
                   
                 AGTCCGGACTCCAGGGTCCTGAGGTGG 
                   
                   
                   
               
               
                   
                   
                 CTGATCCCGAGCCTTTA 
                   
                   
                   
               
               
                   
               
               
                  54 
                 cg07337598 
                 GGCTGTGTTTAGACCTGAGGGAGCCAG 
                  1 
                 150953943 
                 ANXA9 
               
               
                   
                   
                 CTGTGAGGCTGGAGCAGTTGCTGCATG 
                   
                   
                   
               
               
                   
                   
                 GCGGGG[CG]GGGGCTCCACAGGGCTG 
                   
                   
                   
               
               
                   
                   
                 TTCACCTGCTGCTCTGTGCAGAGACAG 
                   
                   
                   
               
               
                   
                   
                 CCTCAAGTCCAGCTGC 
                   
                   
                   
               
               
                   
               
               
                  55 
                 cg07455279 
                 GGTAACAGAGCACTGTGAGAGCCCGC 
                 19 
                  54605703 
                 NDUFA3 
               
               
                   
                   
                 AGAAAGCTCCTAACCCATCTGGGATGA 
                   
                   
                   
               
               
                   
                   
                 GACCTAG[CG]CTTCCAGGACGAGCCGA 
                   
                   
                   
               
               
                   
                   
                 TGTTGAGCTGAGACCTCGAAGGACAGG 
                   
                   
                   
               
               
                   
                   
                 TTAGTCATTCACCTTC 
                   
                   
                   
               
               
                   
               
               
                  56 
                 cg07595943 
                 CTTCGGCTTCTCAGGGCGCTGACGACG 
                 16 
                  84224901 
                 ADAD2 
               
               
                   
                   
                 ACGGCAGTCGTAGGAAGCCCCGCCTGG 
                   
                   
                   
               
               
                   
                   
                 CTGCAT[CG]TTGCAGATCAGCCCCCAG 
                   
                   
                   
               
               
                   
                   
                 CCCCGCCCCTGGCGACCGCTACCCGCC 
                   
                   
                   
               
               
                   
                   
                 CAGGCCCAAAGTGCC 
                   
                   
                   
               
               
                   
               
               
                  57 
                 cg08030082 
                 GGCGAGGGTGAAGTTACCTGCGTGCGT 
                  2 
                  25391839 
                 POMC 
               
               
                   
                   
                 GCTGGGGCTGGCATCTGCCTGGTTCGC 
                   
                   
                   
               
               
                   
                   
                 ATTTGG[CG]GTAAATATCACCGTCTGC 
                   
                   
                   
               
               
                   
                   
                 ACACGGGGAGGCCTCCGATTTCCCCAT 
                   
                   
                   
               
               
                   
                   
                 TGTTTGGAAACTGTG 
                   
                   
                   
               
               
                   
               
               
                  58 
                 cg08090772 
                 TCTTACTCCGTGGGAAAATGGCCCTGA 
                  8 
                  67344640 
                 ADHFE1 
               
               
                   
                   
                 GCCCGACTGGCTTGAGGCTTAGACAGG 
                   
                   
                   
               
               
                   
                   
                 TGACCC[CG]CGAAGCGGGTGGGCAGG 
                   
                   
                   
               
               
                   
                   
                 CGCGGCCGAGGGGCGGGAGGCGGGCA 
                   
                   
                   
               
               
                   
                   
                 GCCTCCGTGATTGGCCG 
                   
                   
                   
               
               
                   
               
               
                  59 
                 cg08124722 
                 CTTCCAGCAGAATTTGGGATCAGGGTG 
                 17 
                  32597714 
                 CCL7 
               
               
                   
                   
                 ATCAAAGACAGGAGGCTTCTGGGGAT 
                   
                   
                   
               
               
                   
                   
                 GGGTGTG[CG]GGCTGTTTCCAGATACC 
                   
                   
                   
               
               
                   
                   
                 GGGAGACCCAGAATCTGGTCTGTGGAA 
                   
                   
                   
               
               
                   
                   
                 GCCCAGCTTCCAGAAA 
                   
                   
                   
               
               
                   
               
               
                  60 
                 cg08251036 
                 ATCTTGTTCACTGTTCAGTCACCAGGG 
                  2 
                 135008923 
                   
               
               
                   
                   
                 CCTGATGGCCGCTCATGCTCAATATAG 
                   
                   
                   
               
               
                   
                   
                 ACTTGG[CG]CGGAGCGGAGTGGAGGA 
                   
                   
                   
               
               
                   
                   
                 AGGAAAGAGGGCAGGTGCTAGTTGGC 
                   
                   
                   
               
               
                   
                   
                 TGGCCTGCAGTTAGAAG 
                   
                   
                   
               
               
                   
               
               
                  61 
                 cg08370996 
                 CCCTCCCGCGCCCCCCTTTTTAGCATAT 
                 15 
                  96874031 
                 NR2F2 
               
               
                   
                   
                 TTGATCACTTTGATTCTCTGTTCTTTTCT 
                   
                   
                   
               
               
                   
                   
                 CTC[CG]CGGTGTGTGTGTGCGTGCGCG 
                   
                   
                   
               
               
                   
                   
                 CGTGTGTGTTTTCTTCTTCTCCTCCTCC 
                   
                   
                   
               
               
                   
                   
                 TCTCCCCGAGT 
                   
                   
                   
               
               
                   
               
               
                  62 
                 cg08413469 
                 GCTGCGTCCTGGGGCTCCAGTAGCTGG 
                  1 
                  68962940 
                 DEPDC1 
               
               
                   
                   
                 CGCGGGCTGGGGTGGGCTGGGCTGGCC 
                   
                   
                   
               
               
                   
                   
                 TGGGAC[CG]CCTCGATGGGACAGGCTC 
                   
                   
                   
               
               
                   
                   
                 GGGTTTCCCTGGCGCTGTTTCTCCCTCC 
                   
                   
                   
               
               
                   
                   
                 TGCGGTCTACGGCG 
                   
                   
                   
               
               
                   
               
               
                  63 
                 cg08434234 
                 AGGTGCCCAACTCCGCGGAAGCGCCCC 
                  7 
                 137531173 
                 DGKI 
               
               
                   
                   
                 TTGCTGGGTAGAAGAGTGGGTCTCCCG 
                   
                   
                   
               
               
                   
                   
                 CCGCGG[CG]CACCTGTCTCGGCTGCCG 
                   
                   
                   
               
               
                   
                   
                 GCTCCCCGCACCTACCTGTACGAGACC 
                   
                   
                   
               
               
                   
                   
                 TGCTTCCGGAAAGTT 
                   
                   
                   
               
               
                   
               
               
                  64 
                 cg08771731 
                 TGAAAGCGATCCAAACACAGCCAGAG 
                  5 
                  17216434 
                 LOC28569 
               
               
                   
                   
                 GGCGCCAAAATGCCGCAAATAAAAGT 
                   
                   
                 6; BASP1 
               
               
                   
                   
                 TCCAAAGG[CG]TCAACTGGCTTTTGCG 
                   
                   
                   
               
               
                   
                   
                 GGAAGGTAAAATTGGCTTTTGTGTAAT 
                   
                   
                   
               
               
                   
                   
                 CAAAGAGCTACCGTTGT 
                   
                   
                   
               
               
                   
               
               
                  65 
                 cg08965235 
                 ACCCACGCGGAAGCCGGAGCCCGTGA 
                 11 
                  65325158 
                 LTBP3 
               
               
                   
                   
                 GCGTGTCTGTGCTGTGGCCGTTCTCTCC 
                   
                   
                   
               
               
                   
                   
                 GATGAG[CG]TCATGTTGGAGCCCTGCT 
                   
                   
                   
               
               
                   
                   
                 GACAACTGTCCCGACACTGGCCCTTGA 
                   
                   
                   
               
               
                   
                   
                 GACAGGTCCGCTTGC 
                   
                   
                   
               
               
                   
               
               
                  66 
                 cg09019938 
                 CTGGAGTTGGATCAGAAGGACGAACT 
                 10 
                  52834498 
                 PRKG1 
               
               
                   
                   
                 GATCCAGAAGCTGCAGAACGAGCTGG 
                   
                   
                   
               
               
                   
                   
                 ACAAGTAC[CG]CTCGGTGATCCGACCA 
                   
                   
                   
               
               
                   
                   
                 GCCACCCAGCAGGCGCAGAAGCAGAG 
                   
                   
                   
               
               
                   
                   
                 CGCGAGCACCTTGCAGGG 
                   
                   
                   
               
               
                   
               
               
                  67 
                 cg09118625 
                 GCAGGGCGGGCAGAAGCCGCAACCGC 
                  1 
                  68512971 
                 DIRAS3 
               
               
                   
                   
                 TTCAGCAGCTTCTGTTCCTTGGAGCCA 
                   
                   
                   
               
               
                   
                   
                 AAGCTGG[CG]TTACCCATCGTTGGGAT 
                   
                   
                   
               
               
                   
                   
                 TCGGAGGGGAGATACGTGCACAAGTTC 
                   
                   
                   
               
               
                   
                   
                 TCCCACACTTAGCTGG 
                   
                   
                   
               
               
                   
               
               
                  68 
                 cg09191327 
                 GCTCCGTGCTCCCGGCTGAGGCCCTGG 
                  9 
                 133540108 
                 PRDM12 
               
               
                   
                   
                 TGCTCAAGACCGGGCTGAAGGCGCCG 
                   
                   
                   
               
               
                   
                   
                 GGACTGG[CG]CTGGCCGAGGTTATCAC 
                   
                   
                   
               
               
                   
                   
                 CTCCGACATCCTGCACAGCTTCCTGTA 
                   
                   
                   
               
               
                   
                   
                 CGGCCGCTGGCGCAAC 
                   
                   
                   
               
               
                   
               
               
                  69 
                 cg09418283 
                 GGAGCTTGTAGGGGACGAGGCGTAGG 
                 12 
                  80084718 
                 PAWR 
               
               
                   
                   
                 GCTGGGATCCGGCTCCCAGGTGTGCCG 
                   
                   
                   
               
               
                   
                   
                 AAGCTGG[CG]CGCGCTCTTCCGCCGCG 
                   
                   
                   
               
               
                   
                   
                 CGGAAAGTGCCGCGGCAAACTCGCGG 
                   
                   
                   
               
               
                   
                   
                 TGCGGAGCTCCAGGCAA 
                   
                   
                   
               
               
                   
               
               
                  70 
                 cg09509673 
                 CCACAACCCCAGCCTCACACCACCAGC 
                 17 
                  40833697 
                 CCR10; 
               
               
                   
                   
                 CCATTTATCTGGAGGACCCCTAGTCTG 
                   
                   
                 CNTNAP1 
               
               
                   
                   
                 AGACAG[CG]CCAAGAATCCTGAATAA 
                   
                   
                   
               
               
                   
                   
                 GCCATAGGATGGCAGAGGCCCATTGCC 
                   
                   
                   
               
               
                   
                   
                 AGGTGGGGAATCCCAT 
                   
                   
                   
               
               
                   
               
               
                  71 
                 cg09785172 
                 GGCTCTTCAGCAGCGAGTGCAGATTGC 
                  4 
                   6271658 
                 WFS1 
               
               
                   
                   
                 TCCCCCGCGGCCGCAGATCTCCCGTTT 
                   
                   
                   
               
               
                   
                   
                 GCGCCG[CG]TTCAGCTGCTCCCGAACA 
                   
                   
                   
               
               
                   
                   
                 ACTTTTCTGCCGGCCCAGAGGCCCCAG 
                   
                   
                   
               
               
                   
                   
                 GGCGTCGCAGCGCCG 
                   
                   
                   
               
               
                   
               
               
                  72 
                 cg09869858 
                 GTTGGATCTGACAATCCCTTCCAGGTT 
                 12 
                  48120416 
                 P11 
               
               
                   
                   
                 CTCAGACTTTAATCTCGAGTTTTCCTGC 
                   
                   
                   
               
               
                   
                   
                 CCATG[CG]CCAGGTTGAACAGTTGCTG 
                   
                   
                   
               
               
                   
                   
                 GTGGGTTAAAGAGAATCCCCCAGCCTG 
                   
                   
                   
               
               
                   
                   
                 TTGCTGTGTAGAGA 
                   
                   
                   
               
               
                   
               
               
                  73 
                 cg09885951 
                 GTAGAGGGCTTGTTTTTAAAATCCATC 
                  1 
                 214776469 
                 CENPF 
               
               
                   
                   
                 CGAAAGGGCCAATCAGACGCGGCAGT 
                   
                   
                   
               
               
                   
                   
                 CTGAGTG[CG]CAGGCGCGGATTGGTCC 
                   
                   
                   
               
               
                   
                   
                 GCAGCTACTTAGAGTGACCAATAGGCG 
                   
                   
                   
               
               
                   
                   
                 TGGAGGTAAGTTTGGT 
                   
                   
                   
               
               
                   
               
               
                  74 
                 cg10281002 
                 TTGGGATGCGATAACTCAGTGCCCTCT 
                 12 
                 114846399 
                 TBX5 
               
               
                   
                   
                 TGCAGACTTGCATAGAAATAATTACTG 
                   
                   
                   
               
               
                   
                   
                 GGTTGT[CG]TGGAGGGGACACGAGAC 
                   
                   
                   
               
               
                   
                   
                 AGAGGGAGTTCTCCGTAATGTGCCTTG 
                   
                   
                   
               
               
                   
                   
                 CGGAGAGAAAGGTCCA 
                   
                   
                   
               
               
                   
               
               
                  75 
                 cg10376763 
                 TCAGGTCTCCTTGGCAGTTCCCCTTCTG 
                  2 
                 217724363 
                 TNP1 
               
               
                   
                   
                 CTGTTCTTGTTGCTGCTTGGTGCTGTGT 
                   
                   
                   
               
               
                   
                   
                 GAAG[CG]CACCAGGGCAGAGCCCGCT 
                   
                   
                   
               
               
                   
                   
                 GGGGGCTCACAAGTGGGAGCGGTAAT 
                   
                   
                   
               
               
                   
                   
                 TGCGATTGGCTGTGG 
                   
                   
                   
               
               
                   
               
               
                  76 
                 cg10377274 
                 AAAAGGAAAAGGAGGAAGTGGAATGC 
                 11 
                 125616888 
                 PATE1 
               
               
                   
                   
                 TGGCTTTTCAGGTGTCGCTTGGCCAAA 
                   
                   
                   
               
               
                   
                   
                 TCTAAAG[CG]TGGCAACTTCAGGAATT 
                   
                   
                   
               
               
                   
                   
                 TCAGGTTGTCCCCATTGTCAGATTCCA 
                   
                   
                   
               
               
                   
                   
                 GGCACCCACAGGTAAG 
                   
                   
                   
               
               
                   
               
               
                  77 
                 cg10486998 
                 CGACCCATCCCGCTAGAATCCGTCCAG 
                 18 
                  74961787 
                 GALR1 
               
               
                   
                   
                 TCTCTGCTCGCGCACCGTGACTTCTAA 
                   
                   
                   
               
               
                   
                   
                 GGGGCG[CG]GATTTCAGCCGAGCTGTT 
                   
                   
                   
               
               
                   
                   
                 TTCGCCTCTCAGTTGCAGCAGAGAAGC 
                   
                   
                   
               
               
                   
                   
                 CCCTGGCACCCGACT 
                   
                   
                   
               
               
                   
               
               
                  78 
                 cg10523019 
                 CTCGCTGCTTCTCCCCTAGTCTTCGGGT 
                  2 
                 227700458 
                 RHBDD1 
               
               
                   
                   
                 CCCTTGAACGCAGGTCGCTTGTTTGCC 
                   
                   
                   
               
               
                   
                   
                 TTACG[CG]TAGTCAGCGGCCAGTGGCT 
                   
                   
                   
               
               
                   
                   
                 ATTTATGGCAGTAAGGAATATTATCCA 
                   
                   
                   
               
               
                   
                   
                 CATTTCACATGGAG 
                   
                   
                   
               
               
                   
               
               
                  79 
                 cg10920957 
                 TACCTGTTGGCCAGGGCGCAGGGCGCA 
                 16 
                  87635473 
                 JPH3 
               
               
                   
                   
                 CGGAATTCGGGTGACTTTGCTCCAAGA 
                   
                   
                   
               
               
                   
                   
                 TACACG[CG]TGTGTCCCGACTCTCACT 
                   
                   
                   
               
               
                   
                   
                 CAATTTATAGGGGAGAGGGACTCGCCA 
                   
                   
                   
               
               
                   
                   
                 AATCCCTGTTTTCTG 
                   
                   
                   
               
               
                   
               
               
                  80 
                 cg11932564 
                 CCCTACACACGGAACTCACCGTCCTTG 
                 22 
                  42322146 
                 TNFRSF13 
               
               
                   
                   
                 TCTCCGTCGGGGGCCTCTGCGGAGGAC 
                   
                   
                 C 
               
               
                   
                   
                 GCGCCG[CG]AAGCCGCCGCTGTCGCCG 
                   
                   
                   
               
               
                   
                   
                 CCTCCAGCTCACCAGACCCACCAGGAC 
                   
                   
                   
               
               
                   
                   
                 CAGCGCCAGGACCAG 
                   
                   
                   
               
               
                   
               
               
                  81 
                 cg12351433 
                 CCCTTCCACACACCCTTCCCTGCCGGC 
                  2 
                  48982957 
                 LHCGR 
               
               
                   
                   
                 CCGCCCCTGCCCTCCCCCTCTTACCGCG 
                   
                   
                   
               
               
                   
                   
                 CACCC[CG]CTGAGTCTGCTCTGCCTTG 
                   
                   
                   
               
               
                   
                   
                 ACCTGCGACAGTGCCCAGTGACCCAAT 
                   
                   
                   
               
               
                   
                   
                 AACCTCCTTCCTGC 
                   
                   
                   
               
               
                   
               
               
                  82 
                 cg12373771 
                 TGGCGATCCAGGAGCACCAGTACAGGT 
                 22 
                  17601381 
                 CECR6 
               
               
                   
                   
                 CGGTGACGGCGATGAGGTACAGGTCC 
                   
                   
                   
               
               
                   
                   
                 AGCAGGC[CG]CCCTGCGCCAGCAGCA 
                   
                   
                   
               
               
                   
                   
                 GCACCACGGACAGCGCCTGGTAGCCCC 
                   
                   
                   
               
               
                   
                   
                 AGCGGCACCTGGGACTG 
                   
                   
                   
               
               
                   
               
               
                  83 
                 cg12768605 
                 TTTGGGACGGCGCGTCCCAAGGGTTTC 
                 19 
                  44324951 
                 LYPD5 
               
               
                   
                   
                 TGGAAGTTGTAACCTGTGCTCCGAGTG 
                   
                   
                   
               
               
                   
                   
                 CGTAGG[CG]CAGGAACCCTTCGGGGG 
                   
                   
                   
               
               
                   
                   
                 AATCCCTTTAGCAGGGAGCGTATATTG 
                   
                   
                   
               
               
                   
                   
                 AAGAGTGCGTGCGGAG 
                   
                   
                   
               
               
                   
               
               
                  84 
                 cg12830694 
                 CCACTGGCCCGGTTCAACGAATATCTA 
                 19 
                  38747796 
                 PPP1R14A 
               
               
                   
                   
                 TTAAGTATCCACTCTATACCAGACACT 
                   
                   
                   
               
               
                   
                   
                 GCTTTA[CG]CTCCAGGGATAGAGCAGG 
                   
                   
                   
               
               
                   
                   
                 GAACAAAACAGACAAAACCAGTCCCA 
                   
                   
                   
               
               
                   
                   
                 CGCAGTTGACAGTTGT 
                   
                   
                   
               
               
                   
               
               
                  85 
                 cg12946225 
                 CCGGCGGGCGGCAAGGCTCCGGGCCA 
                 19 
                   3573751 
                 HMG20B 
               
               
                   
                   
                 GCATGGGGGCTTCGTGGTGACTGTCAA 
                   
                   
                   
               
               
                   
                   
                 GCAAGAG[CG]CGGCGAGGGTCCACGC 
                   
                   
                   
               
               
                   
                   
                 GCGGGCGAGAAGGGGTCCCACGAGGA 
                   
                   
                   
               
               
                   
                   
                 GGAGGTGAGAGTCCCTGC 
                   
                   
                   
               
               
                   
               
               
                  86 
                 cg13038560 
                 GACCTCAAGTGATCCACCGACCTGGGC 
                  2 
                 200819113 
                 C2orf60; 
               
               
                   
                   
                 CTCCCAAAATGTTAGGATTACTGGCAT 
                   
                   
                 C2orf47 
               
               
                   
                   
                 GAACCA[CG]GCGCCCAGCCCATCCGAC 
                   
                   
                   
               
               
                   
                   
                 TTTTGTAACACTCAGAATTGTAGTTTTG 
                   
                   
                   
               
               
                   
                   
                 TTTGTTTGTTTGAG 
                   
                   
                   
               
               
                   
               
               
                  87 
                 cg13216057 
                 TACCTGGGGTGGACCAAGCACAGGTCA 
                 11 
                  12030643 
                 DKK3 
               
               
                   
                   
                 GCCCCCTCCCCTTGGCGTCGGGTCCTA 
                   
                   
                   
               
               
                   
                   
                 CTCGAG[CG]CCCCGCCCCACATCCACC 
                   
                   
                   
               
               
                   
                   
                 AAGAGAGGCTGAGCTCAGCAGAGTCG 
                   
                   
                   
               
               
                   
                   
                 TCCCCTCCCCCGCCGC 
                   
                   
                   
               
               
                   
               
               
                  88 
                 cg13319175 
                 AGAAAGCTCCCTCACCGGCTCCCCTGC 
                  1 
                  19746564 
                 CAPZB 
               
               
                   
                   
                 TCCTGCTCAACAGGCCCTGGTGGCTGC 
                   
                   
                   
               
               
                   
                   
                 AGATGT[CG]TGCCCCCCAGTTGGTTCC 
                   
                   
                   
               
               
                   
                   
                 ATGGTGAACACACTCCAGTAGCGGATT 
                   
                   
                   
               
               
                   
                   
                 ACTTTTGCCCTTTGT 
                   
                   
                   
               
               
                   
               
               
                  89 
                 cg13460409 
                 ATCTCTCACCTTGCTACTTTCTCGGTAG 
                 21 
                  38379570 
                 DSCR6 
               
               
                   
                   
                 CCGTTTCTGTTGTCCCTGGATTGGGGG 
                   
                   
                   
               
               
                   
                   
                 CTCGG[CG]TTCGCTGTCCCTGGGCACC 
                   
                   
                   
               
               
                   
                   
                 AACCCTTTTAAAGACAGTAACGTTGTA 
                   
                   
                   
               
               
                   
                   
                 GGAAATCAAATTAG 
                   
                   
                   
               
               
                   
               
               
                  90 
                 cg13682722 
                 AGTGGTTGGGACCCTGTGAGAACCGGA 
                 14 
                  90798568 
                 C14orf102 
               
               
                   
                   
                 ACTGCGAAAACCGGAGAAGGGAATTG 
                   
                   
                   
               
               
                   
                   
                 TTGACCG[CG]AAAGGGACTAAGGAAA 
                   
                   
                   
               
               
                   
                   
                 TTGGGATTCCAGTTCGACCCCTAAATT 
                   
                   
                   
               
               
                   
                   
                 CACACCATCCTTGCTAA 
                   
                   
                   
               
               
                   
               
               
                  91 
                 cg13836627 
                 CCTCACAGGCTGAGTGGAGTGTTTTGC 
                 15 
                  30113723 
                 TJP1 
               
               
                   
                   
                 AGTCTCAAAGCCTTATCGCTGGCGTGC 
                   
                   
                   
               
               
                   
                   
                 GCATAC[CG]CAGGGAGTGACATCAGAT 
                   
                   
                   
               
               
                   
                   
                 CGAAACTACAGGGTTTCGCCGGGGACC 
                   
                   
                   
               
               
                   
                   
                 AACCACTCCTCCAAA 
                   
                   
                   
               
               
                   
               
               
                  92 
                 cg13854874 
                 AATAATAAATAATAATGAATCCATTCT 
                 21 
                  37757525 
                 CHAF1B 
               
               
                   
                   
                 TCCTTCGGTCGTGGGTCTGGCAGGCAT 
                   
                   
                   
               
               
                   
                   
                 AAATTC[CG]GCCGGGATTCCGACCCCA 
                   
                   
                   
               
               
                   
                   
                 GGGCCAGAGCAGGACTCGCCTTGGCGT 
                   
                   
                   
               
               
                   
                   
                 CTATGAGTGGGCGGG 
                   
                   
                   
               
               
                   
               
               
                  93 
                 cg13899108 
                 GGGCTGAAGAGACCCCCCCCCAACAC 
                 19 
                  18344322 
                 PDE4C 
               
               
                   
                   
                 ACCAGCCCCGAAAACCGTCTGCCGTCC 
                   
                   
                   
               
               
                   
                   
                 CCTATAG[CG]CTGCATGGAAAAGAACC 
                   
                   
                   
               
               
                   
                   
                 AAGACAAGGACTTGGAGTGGAGAAGA 
                   
                   
                   
               
               
                   
                   
                 CAGAAATTGTCCACTGA 
                   
                   
                   
               
               
                   
               
               
                  94 
                 cg13975369 
                 CCATTTGAGGGCAAGGGCTGTGTCTTT 
                  7 
                 130080553 
                 TSGA14 
               
               
                   
                   
                 GGGTACTTCGCTCCTCGCAGTCACAAG 
                   
                   
                   
               
               
                   
                   
                 TACTGG[CG]TGCGTACGCGGGGAGAG 
                   
                   
                   
               
               
                   
                   
                 ATCGCTCCTCAAAACGGGGTCCTGAAC 
                   
                   
                   
               
               
                   
                   
                 GCTGCCCCGCGGCCCC 
                   
                   
                   
               
               
                   
               
               
                  95 
                 cg14258236 
                 GTCTTCCCTCTGAGGACTGGATCCTCA 
                  6 
                  29323330 
                 OR5V1 
               
               
                   
                   
                 AGATGGTGGAGATTATGCAAATGTAGG 
                   
                   
                   
               
               
                   
                   
                 AAAGTA[CG]ATACAAAGGAAAGGAGT 
                   
                   
                   
               
               
                   
                   
                 CCAACCAATGAAGACCCCAGTGGATA 
                   
                   
                   
               
               
                   
                   
                 GCAGTGCCAACTCATTG 
                   
                   
                   
               
               
                   
               
               
                  96 
                 cg14308452 
                 CTGGGGGCCTGTTTGGGAGATGCCACA 
                 19 
                   5784184 
                 PRR22 
               
               
                   
                   
                 AGAACCTTGCCATTGGGGGGCCCCTTT 
                   
                   
                   
               
               
                   
                   
                 GGGGGA[CG]ACATAGATATTGCTTTGG 
                   
                   
                   
               
               
                   
                   
                 GGCCCTGGCTGGGTGATGGATGACACA 
                   
                   
                   
               
               
                   
                   
                 GAGCTTGTCTTTGGG 
                   
                   
                   
               
               
                   
               
               
                  97 
                 cg14329157 
                 TTCCTTTTGGGAAACGCAGTGTGCTAA 
                  2 
                 228736135 
                 WDR69 
               
               
                   
                   
                 AAAAGTGCATGCAGCCCAGGCTGTGGC 
                   
                   
                   
               
               
                   
                   
                 CTAGGC[CG]TCGGTTCCCGGCCATGCC 
                   
                   
                   
               
               
                   
                   
                 TAGCTCCTCTGAGGTCGCCCTTAGTGA 
                   
                   
                   
               
               
                   
                   
                 GGACACGAGGTGCCC 
                   
                   
                   
               
               
                   
               
               
                  98 
                 cg14424579 
                 TAAGCGATAAGGAGTTTCACACGATGT 
                  2 
                  27274309 
                 AGBL5 
               
               
                   
                   
                 CTTTTTATTTCGCAGTTGAGTCCCAGTT 
                   
                   
                   
               
               
                   
                   
                 TCTGC[CG]CTTTATCTTTCCCGCCTCCC 
                   
                   
                   
               
               
                   
                   
                 GGCAGGCAGGCCGTTAACCGTCTTCCG 
                   
                   
                   
               
               
                   
                   
                 GAAGACGCTGCTA 
                   
                   
                   
               
               
                   
               
               
                  99 
                 cg14501253 
                 GAAGGGCCACGCCGAGAGAGGCAGGC 
                  8 
                  12809014 
                 C8orf79 
               
               
                   
                   
                 AACAAGGGCACGGCTGGAGGCCGGAA 
                   
                   
                   
               
               
                   
                   
                 GGTCACCC[CG]TCCCCGGCGGGGCGGG 
                   
                   
                   
               
               
                   
                   
                 CGCGGCCCAGCCTCACTTCCCGGGCAC 
                   
                   
                   
               
               
                   
                   
                 GTTCGGGCGGGGCGATT 
                   
                   
                   
               
               
                   
               
               
                 100 
                 cg14658362 
                 GAAGGGTGGGCTTAGGGCCAGGGGTG 
                  8 
                  30241661 
                 RBPMS 
               
               
                   
                   
                 CAAATCCCTCGGTAAAAGCCGGCAAAC 
                   
                   
                   
               
               
                   
                   
                 TAAAAGT[CG]CACACATCCCAGGTCCC 
                   
                   
                   
               
               
                   
                   
                 GGTCCAGGCCCCGGCGGGGCAGGGTC 
                   
                   
                   
               
               
                   
                   
                 CCCGAAGTCCCGGGGCG 
                   
                   
                   
               
               
                   
               
               
                 101 
                 cg14723032 
                 CTGGGGTTCTAGGCTGGAGCAGGCTTT 
                 17 
                   6460572 
                 PITPNM3 
               
               
                   
                   
                 GTGGACCCCAGCGGCCTGGTGGTGAGC 
                   
                   
                   
               
               
                   
                   
                 AGTACC[CG]CCTTCCACTTCCTAAATC 
                   
                   
                   
               
               
                   
                   
                 GGGATGCAGAGATTCTAGTGGACAGG 
                   
                   
                   
               
               
                   
                   
                 CCTTGTGGTCCGGGGA 
                   
                   
                   
               
               
                   
               
               
                 102 
                 cg14894144 
                 GCGGACAGAGATAGAAAGGCTCTCAG 
                 18 
                  21270554 
                 LAMA3 
               
               
                   
                   
                 AGATCCGAGCCTCACCGCGAACACCCG 
                   
                   
                   
               
               
                   
                   
                 GGGCAAA[CG]ACATTGCGGTGCATGTT 
                   
                   
                   
               
               
                   
                   
                 AAGCAGCATCTTGCAGTGCCTGGCCCT 
                   
                   
                   
               
               
                   
                   
                 TACTCACAGGTCTCAG 
                   
                   
                   
               
               
                   
               
               
                 103 
                 cg14992253 
                 CTGCTGGGCCCAGGTCGGCTCATGAAC 
                  1 
                  32687567 
                 EIF3I; 
               
               
                   
                   
                 CCGCTGCAGGCCGGCGGAGGCCCGCTT 
                   
                   
                 C1orf91 
               
               
                   
                   
                 CAGCAG[CG]GCTGCGTGCCACCCCACA 
                   
                   
                   
               
               
                   
                   
                 GAGCGGCCACCAGCACCAGAGCCAAC 
                   
                   
                   
               
               
                   
                   
                 ACCTGCCCTGAATGCA 
                   
                   
                   
               
               
                   
               
               
                 104 
                 cg15341340 
                 GCAGCGGGATCATAGCTGCTATGGGGC 
                 19 
                  12992237 
                 DNASE2 
               
               
                   
                   
                 TGAGATCCAGGAATCTGTGTCGGGACT 
                   
                   
                   
               
               
                   
                   
                 GCGGGG[CG]CTGGGTTACATCAGAGGC 
                   
                   
                   
               
               
                   
                   
                 CAGGACTGGCACCTGGCGCCTTTCACT 
                   
                   
                   
               
               
                   
                   
                 TCCCTAAACTTGCCT 
                   
                   
                   
               
               
                   
               
               
                 105 
                 cg15381769 
                 GCAGCCTGGGCCCCGCCGCCAGCCGCT 
                  6 
                 128841972 
                 PTPRK 
               
               
                   
                   
                 GCTCGGAGGGAGCGAGCGAGAAAGGG 
                   
                   
                   
               
               
                   
                   
                 GAGCCGG[CG]CAGCTCGCTGCCCTGTT 
                   
                   
                   
               
               
                   
                   
                 CCAGAACTCAGAATTTGAGAGGCGAG 
                   
                   
                   
               
               
                   
                   
                 AGTTCGGTAAGCCGTGC 
                   
                   
                   
               
               
                   
               
               
                 106 
                 cg15547534 
                 CTCCTCCTCTTGAAAACTCTGCTATGGC 
                  7 
                 100034410 
                 C7orf47 
               
               
                   
                   
                 TGAGTTACCCAGAGGAATCTTAGTCCT 
                   
                   
                   
               
               
                   
                   
                 GCTAG[CG]CTGCGATGCCCATTGCCCA 
                   
                   
                   
               
               
                   
                   
                 GTGTGTCAGTCCTCATTCTGGGGCGCC 
                   
                   
                   
               
               
                   
                   
                 AAATGGGGCAGCAT 
                   
                   
                   
               
               
                   
               
               
                 107 
                 cg15661409 
                 TTGTTAATCTTTAATTTAATTAAAGAAT 
                 14 
                  57960976 
                 C14orf105 
               
               
                   
                   
                 TTATCCCCCAAATAGGAAAGAAAGCA 
                   
                   
                   
               
               
                   
                   
                 GCGGAG[CG]GCTAAAGCGTCATTTGAT 
                   
                   
                   
               
               
                   
                   
                 TTTTCTGTCGATGACTTGAGTTGCCTTT 
                   
                   
                   
               
               
                   
                   
                 GAAGGGGGTGAATA 
                   
                   
                   
               
               
                   
               
               
                 108 
                 cg15974053 
                 TGAGGCCGTCGCATCAAATCCTCAATA 
                 19 
                  49339789 
                 HSD17B14 
               
               
                   
                   
                 GAGGCTGGATCCTGGAAGTCCGGCCTC 
                   
                   
                   
               
               
                   
                   
                 GGGGGG[CG]TTGCCAGGAAGGCTAGA 
                   
                   
                   
               
               
                   
                   
                 GACCTGGAAGTTTGTCCCCAGCCCCTC 
                   
                   
                   
               
               
                   
                   
                 CTCCCTCAGACACTCC 
                   
                   
                   
               
               
                   
               
               
                 109 
                 cg15988232 
                 CCTTCTAGTCTCCGGGCAGCCTGGGGA 
                  3 
                  47621127 
                 CSPG5 
               
               
                   
                   
                 GCGGCCTTTAATCCTGGTCCCTTCTCCG 
                   
                   
                   
               
               
                   
                   
                 GGATA[CG]TCGTCCCCCAGGTGTCTCA 
                   
                   
                   
               
               
                   
                   
                 GACCACCAAAACTCAGGTTCCTGGGTA 
                   
                   
                   
               
               
                   
                   
                 GACCAGGGGGGTCT 
                   
                   
                   
               
               
                   
               
               
                 110 
                 cg16150435 
                 TGTGGTCTGTGGCAACAGGTGTCACTT 
                  6 
                  31080529 
                 C6orf15 
               
               
                   
                   
                 GAATGAATGTCCCAGAGGAAGCTGGG 
                   
                   
                   
               
               
                   
                   
                 TGTCTCC[CG]CCCTGGCTCCTTTCCTTG 
                   
                   
                   
               
               
                   
                   
                 ACCTCCCTGCCCCTTCTTGGCCCAGGT 
                   
                   
                   
               
               
                   
                   
                 GTCCTGGCTCACAGC 
                   
                   
                   
               
               
                   
               
               
                 111 
                 cg16241714 
                 GGCACAGCTCCAGGGTGGGCACGGCG 
                  8 
                  48650511 
                 CEBPD 
               
               
                   
                   
                 GCCATGGAGTCGATGTAGGCGCTGAAG 
                   
                   
                   
               
               
                   
                   
                 TCGATGG[CG]CTCTCGTCGTCGTACAT 
                   
                   
                   
               
               
                   
                   
                 GGCGGGGGCGGCGGCGCCTGGCTCGC 
                   
                   
                   
               
               
                   
                   
                 CTAGGGCCCCTGGCTCG 
                   
                   
                   
               
               
                   
               
               
                 112 
                 cg16494477 
                 CTCCCGCCCAGCGATGTATTCAGCGCC 
                  5 
                 170847251 
                 FGF18 
               
               
                   
                   
                 CTCCGCCTGCACTTGCCTGTAAGCGCC 
                   
                   
                   
               
               
                   
                   
                 CGCGCG[CG]GGGCTGCCCACCTTGCCT 
                   
                   
                   
               
               
                   
                   
                 GGCTGTCTGTCCGTATGCCTGTGCCCT 
                   
                   
                   
               
               
                   
                   
                 GTACCTCTGTCTGCC 
                   
                   
                   
               
               
                   
               
               
                 113 
                 cg16547529 
                 CACTGGCTTGTTAACTCTTCAAGGGCA 
                 11 
                  75140681 
                 KLHL35 
               
               
                   
                   
                 GAATTATGGGCACCGAGCCTCTAAAAT 
                   
                   
                   
               
               
                   
                   
                 GTTGAA[CG]AATGACTGAATATCATCA 
                   
                   
                   
               
               
                   
                   
                 AGAGGCAGTACTAAAAGATGATGAAA 
                   
                   
                   
               
               
                   
                   
                 GAATGAATGAGCGGTG 
                   
                   
                   
               
               
                   
               
               
                 114 
                 cg16579101 
                 GCAGAAATGGGAGAAGGTGGCGTCGC 
                 12 
                   6677158 
                 NOP2 
               
               
                   
                   
                 GCGTGTCGGAGGGAACGGCAGAACGC 
                   
                   
                   
               
               
                   
                   
                 ACGCTTGG[CG]TATTATAGTGGGAAAG 
                   
                   
                   
               
               
                   
                   
                 GGCACAGCCTCAACTCAGCACCCGCAA 
                   
                   
                   
               
               
                   
                   
                 CTCACTCAGCACTCCCG 
                   
                   
                   
               
               
                   
               
               
                 115 
                 cg17063929 
                 GCCTGTTGTTGTGGCTGCTGCTGTTCAG 
                 11 
                  89224799 
                 NOX4 
               
               
                   
                   
                 GATGTCCCGGGTGGGAACTTGGAGGCG 
                   
                   
                   
               
               
                   
                   
                 TCCCC[CG]CAGCCTCTACCCAGGCCTG 
                   
                   
                   
               
               
                   
                   
                 CCAGGCTCCAAAATACTGGCAAACATG 
                   
                   
                   
               
               
                   
                   
                 TGAACAATGCTACT 
                   
                   
                   
               
               
                   
               
               
                 116 
                 cg17099569 
                 TTTAACTCAGAGTTCTTAACCTTTTCTG 
                  2 
                 121549866 
                   
               
               
                   
                   
                 CGCCGTGGGCCCCTTGGCAAGCAAGTG 
                   
                   
                   
               
               
                   
                   
                 AAGTT[CG]TGGACTCCTACAATAATGC 
                   
                   
                   
               
               
                   
                   
                 TATAAATGCATAGAAGAAAAGACACA 
                   
                   
                   
               
               
                   
                   
                 GGACTGTGAAAGAAA 
                   
                   
                   
               
               
                   
               
               
                 117 
                 cg17285325 
                 CCGTGTCTGCCTCCCGCTTCCCCGCCTC 
                 22 
                  50968343 
                 TYMP 
               
               
                   
                   
                 GCGACTTGAGCCCCGCCCGTACCTGCT 
                   
                   
                   
               
               
                   
                   
                 TAGGG[CG]CTGCCCTCGCCCGCTTGCT 
                   
                   
                   
               
               
                   
                   
                 CCGGATCCCAGCCCAGGTACCCGGCCT 
                   
                   
                   
               
               
                   
                   
                 CGCCCGCGGGTCGG 
                   
                   
                   
               
               
                   
               
               
                 118 
                 cg17408647 
                 GGGGGGAAGACGGAGACTCTTATACC 
                  7 
                  43769049 
                 C7orf44 
               
               
                   
                   
                 GCGGGAGACTAACCTGTGAGCAACAG 
                   
                   
                   
               
               
                   
                   
                 AAGCACCA[CG]CTACAAAGAGCATGA 
                   
                   
                   
               
               
                   
                   
                 CGAGTTCTTCCAGGCTTGGGAAAGCAC 
                   
                   
                   
               
               
                   
                   
                 GGGTAAATGCCCGCGGTC 
                   
                   
                   
               
               
                   
               
               
                 119 
                 cg17655614 
                 AAACAAAAGAACTCAGCCAAGTGTAA 
                 16 
                  68770944 
                 CDH1 
               
               
                   
                   
                 AAGCCCTTTCTGATCCCAGGTCTTAGT 
                   
                   
                   
               
               
                   
                   
                 GAGCCAC[CG]GCGGGGCTGGGATTCG 
                   
                   
                   
               
               
                   
                   
                 AACCCAGTGGAATCAGAACCGTGCAG 
                   
                   
                   
               
               
                   
                   
                 GTCCCATAACCCACCTAG 
                   
                   
                   
               
               
                   
               
               
                 120 
                 cg17729667 
                 CGCAAATCTCAGGGCGGCTCTGGCCAG 
                 20 
                  25566382 
                 NINL 
               
               
                   
                   
                 TTTGGAGCCTGGGGTGACCCTTGGAGC 
                   
                   
                   
               
               
                   
                   
                 TGACCT[CG]CTGGTCCCTGTCGGAGCC 
                   
                   
                   
               
               
                   
                   
                 CTGCGCGCTGCGGAGCTTGGCGGTTCG 
                   
                   
                   
               
               
                   
                   
                 CAGCTCTCGGGGTAG 
                   
                   
                   
               
               
                   
               
               
                 121 
                 cg17853587 
                 AGTTGCTGGCCTTCCACTTGTCTTCAGG 
                  4 
                 118954386 
                 NDST3 
               
               
                   
                   
                 AGCTGAAACACATGGCATTTGAAAAA 
                   
                   
                   
               
               
                   
                   
                 AACTGG[CG]AACAGAGGAAACTCTTGC 
                   
                   
                   
               
               
                   
                   
                 AGCCTCGCAGCCGCCCTGGTCCAGTGC 
                   
                   
                   
               
               
                   
                   
                 CAACGGCAGGAGCAC 
                   
                   
                   
               
               
                   
               
               
                 122 
                 cg17960516 
                 GAAGGAGCCCCGCCCGCGCCGGCCCTG 
                  4 
                   3465004 
                 DOK7 
               
               
                   
                   
                 GAGTCGCCGGTGTCGCCGCCCTGCCCG 
                   
                   
                   
               
               
                   
                   
                 CGGGCC[CG]CCCTCCTGGCCCAGCCCA 
                   
                   
                   
               
               
                   
                   
                 GGGCCCTGCGAGCTATTTTGAAAGTGA 
                   
                   
                   
               
               
                   
                   
                 CCCTGGGCTGGGGCG 
                   
                   
                   
               
               
                   
               
               
                 123 
                 cg18055007 
                 TCTGGCCGGCCCTGGCGACGGGGCTGC 
                  6 
                  31698226 
                 DDAH2 
               
               
                   
                   
                 AAACGCTTCGTAGACCTCAGAACAGCG 
                   
                   
                   
               
               
                   
                   
                 CAACGG[CG]GACCGGCGGACCGGCAC 
                   
                   
                   
               
               
                   
                   
                 GAAACATAGCAGCCCCACCACAAACA 
                   
                   
                   
               
               
                   
                   
                 TTTCCCTTCTTAATTCC 
                   
                   
                   
               
               
                   
               
               
                 124 
                 cg18180783 
                 AGCCAGGATCTGCCTTTTAACCTCCAT 
                 10 
                  75402320 
                 MYOZ1 
               
               
                   
                   
                 TTGCTGTTGAGATGCTCAGTTCAACCT 
                   
                   
                   
               
               
                   
                   
                 GCTGTG[CG]GGATAGACATCGATGTCT 
                   
                   
                   
               
               
                   
                   
                 CCCTGAGAAGCACATATAGGCTCTCTG 
                   
                   
                   
               
               
                   
                   
                 AGGTTTCTTTTCTTC 
                   
                   
                   
               
               
                   
               
               
                 125 
                 cg18440048 
                 GTAGCCCTGTTCCTGTCTGCCCTCCCCG 
                 22 
                  24093826 
                 ZNF70 
               
               
                   
                   
                 CCCCCACAGAAATAGAGATGAGAAGG 
                   
                   
                   
               
               
                   
                   
                 GGCAGG[CG]AAGAACTAGGAGTGTCT 
                   
                   
                   
               
               
                   
                   
                 GCGAGACCATCCCAGGACCCTGAGCCC 
                   
                   
                   
               
               
                   
                   
                 CCCAACTCTCTGCATC 
                   
                   
                   
               
               
                   
               
               
                 126 
                 cg18573383 
                 GCCGTGAATGGAGTGGAGACTGGCCG 
                 12 
                  75603401 
                 KCNC2 
               
               
                   
                   
                 CAGGTCAGGAGAGCTCACCACTTGAAG 
                   
                   
                   
               
               
                   
                   
                 GTGAAGT[CG]CCCTGCTCGGATTCCAT 
                   
                   
                   
               
               
                   
                   
                 CTGCAGATTTTGTTTCTCCCCCAAATCA 
                   
                   
                   
               
               
                   
                   
                 GCCACTGCTGGAGCT 
                   
                   
                   
               
               
                   
               
               
                 127 
                 cg18983672 
                 GGCAGCCAGAAAGGCAGCTCCAAGTT 
                  1 
                  47881256 
                 FOXE3 
               
               
                   
                   
                 GTGGATTTCCTGGGGGCTCTTCATTTA 
                   
                   
                   
               
               
                   
                   
                 AAGCGGC[CG]CACCACTTTCCACAATT 
                   
                   
                   
               
               
                   
                   
                 CTGTTTTTTCAGAGAATGCTCTCAAGG 
                   
                   
                   
               
               
                   
                   
                 CCTGGAGGGAGGGCAT 
                   
                   
                   
               
               
                   
               
               
                 128 
                 cg18984151 
                 TCCCTTGGCCTCGCTCTCTGCCCAGCCC 
                  3 
                  47555476 
                 C3orf75 
               
               
                   
                   
                 CGGGCTCCTTTTCTCCACACGTGGCTGT 
                   
                   
                   
               
               
                   
                   
                 CAAG[CG]CCTTCTGTATGCCCCACACT 
                   
                   
                   
               
               
                   
                   
                 CCTGGGAGCTTGGGCTACATCGATGAA 
                   
                   
                   
               
               
                   
                   
                 CAAAAACAAAGGA 
                   
                   
                   
               
               
                   
               
               
                 129 
                 cg19008809 
                 GCGCGCGTGCCGCCGCCGCGGGCACTG 
                  3 
                  53080682 
                 SFMBT1 
               
               
                   
                   
                 CGCCCGTTTGCCTGCCCCTCGTCGGGG 
                   
                   
                   
               
               
                   
                   
                 ATCGGG[CG]CTCCCTCTGAGACCTGAA 
                   
                   
                   
               
               
                   
                   
                 AGGGCACCCAAGTGCCCCCTGTCTGCG 
                   
                   
                   
               
               
                   
                   
                 AAGTCCGGCGCGGGC 
                   
                   
                   
               
               
                   
               
               
                 130 
                 cg19167673 
                 TTTTCTCTTTGCAGCGAGGCTGGAGGG 
                 22 
                  39640835 
                 PDGFB 
               
               
                   
                   
                 TGGGCTTTTTTTTTTTTTTTTCCTTTTTG 
                   
                   
                   
               
               
                   
                   
                 CGCG[CG]TATGTATGTGTGTGCGCGCA 
                   
                   
                   
               
               
                   
                   
                 AAGTATCTCTATCTAGGGAATGAAAAA 
                   
                   
                   
               
               
                   
                   
                 TGGGCGCTGGCGG 
                   
                   
                   
               
               
                   
               
               
                 131 
                 cg19273182 
                 GGGCGGGGCTGAGACCTGCGAGAGGC 
                  2 
                  60983417 
                 PAPOLG 
               
               
                   
                   
                 AGGCTGGGAAGCGGCGCCATATTGGC 
                   
                   
                   
               
               
                   
                   
                 GTCGGCCG[CG]CTGTATTGTCATAAAT 
                   
                   
                   
               
               
                   
                   
                 AGAGCCGGTTTTGTGGTGTTTTCACTA 
                   
                   
                   
               
               
                   
                   
                 CTCGGTTGGATGCCTCA 
                   
                   
                   
               
               
                   
               
               
                 132 
                 cg19305227 
                 AAAACATATAATATTTAACTTGAGAGG 
                 15 
                  45544335 
                 SLC28A2 
               
               
                   
                   
                 TGCAGTCCTCCTCTACATTGAGGGCAG 
                   
                   
                   
               
               
                   
                   
                 GCTCAG[CG]AAGGAGGGCCCAAGACA 
                   
                   
                   
               
               
                   
                   
                 TAAAACTAACCAATGGCAGGAAAGCC 
                   
                   
                   
               
               
                   
                   
                 CCCATGCCCCACCCAAG 
                   
                   
                   
               
               
                   
               
               
                 133 
                 cg19346193 
                 ATCCAGCCCATCAGTAAATCCTGTTAT 
                 10 
                 127513190 
                 BCCIP; 
               
               
                   
                   
                 CCAGACATTTCTCAGCACTAATTCTGA 
                   
                   
                 UROS 
               
               
                   
                   
                 GACCAT[CG]TAGTCCACACCTCTATCA 
                   
                   
                   
               
               
                   
                   
                 TCTCTTGCCTGGACTACTATTTAATGTA 
                   
                   
                   
               
               
                   
                   
                 ACAGCTTTTAACCG 
                   
                   
                   
               
               
                   
               
               
                 134 
                 cg19478743 
                 AAGCAGGAGCAGGAGCACGCGGGACC 
                 17 
                   4642647 
                 ZMYND15; 
               
               
                   
                   
                 CGGGCCGCAAGTCCCGTCCCATCTCGG 
                   
                   
                 CXCL16 
               
               
                   
                   
                 GGCTCCG[CG]GACTCTGCGGGGATGGA 
                   
                   
                   
               
               
                   
                   
                 GCCACCTCGCTCTGACTCCCAGACATG 
                   
                   
                   
               
               
                   
                   
                 CTCCGGCGCGTGACGT 
                   
                   
                   
               
               
                   
               
               
                 135 
                 cg19514928 
                 GGGTGCAAACCTTTGGGCATCCAGGGA 
                  1 
                  95583636 
                 TMEM56 
               
               
                   
                   
                 GAGCTTTCTTGTTAGAGCCCACACACA 
                   
                   
                   
               
               
                   
                   
                 ATCGGG[CG]CATCAAGTGGGTAAGTCC 
                   
                   
                   
               
               
                   
                   
                 CCCTCCCCCGCCGCCACCTTCTGAAAC 
                   
                   
                   
               
               
                   
                   
                 AAGTAGCTCTTATTT 
                   
                   
                   
               
               
                   
               
               
                 136 
                 cg19692710 
                 CAAAATAAAACAGAGCCCTGTGAGTCT 
                 11 
                  73661920 
                 DNAJB13 
               
               
                   
                   
                 TCAATTTCCGAGTTGAGTGACCTTTCA 
                   
                   
                   
               
               
                   
                   
                 CAGGGT[CG]CAGAATCAGCCCCAGCTC 
                   
                   
                   
               
               
                   
                   
                 TCCCCCAGTCCTTTCACTGACTCCTCTC 
                   
                   
                   
               
               
                   
                   
                 TGTGGCAGAGCTGA 
                   
                   
                   
               
               
                   
               
               
                 137 
                 cg19945840 
                 GCGCGCCCTGGAGCGGGAGCAGGCGC 
                  1 
                   1168036 
                 SDF4; 
               
               
                   
                   
                 GGCACGGGGACCTGCTGCTGCTGCCCG 
                   
                   
                 B3GALT6 
               
               
                   
                   
                 CGCTGCG[CG]ACGCCTACGAAAACCTC 
                   
                   
                   
               
               
                   
                   
                 ACGGCCAAGGTGCTGGCCATGCTGGCC 
                   
                   
                   
               
               
                   
                   
                 TGGCTGGACGAGCACG 
                   
                   
                   
               
               
                   
               
               
                 138 
                 cg20295671 
                 TCGGACGCAGGCTGGCTGGGCAGGGA 
                 22 
                  22090486 
                 YPEL1 
               
               
                   
                   
                 CACTCGGCCGGCGGGGCTGGCGGTGGT 
                   
                   
                   
               
               
                   
                   
                 GGTCACT[CG]TTCCTCCGGCTCGCGGG 
                   
                   
                   
               
               
                   
                   
                 GATGGGCCGAGGGCGTGCAGGGCCCG 
                   
                   
                   
               
               
                   
                   
                 CAGCTCCAGAGGCTGAG 
                   
                   
                   
               
               
                   
               
               
                 139 
                 cg20305610 
                 GGTTGGGGACGAGGAGGGGGCGCTCC 
                  4 
                  95373302 
                 PDLIM5 
               
               
                   
                   
                 TCGGGCAGGGATGGCTCCTCAGGTGCT 
                   
                   
                   
               
               
                   
                   
                 TTCTGGG[CG]CGGAGCGGCGGAGGTG 
                   
                   
                   
               
               
                   
                   
                 GGAGAGCAGCTTGGGAAAAGGAGCGC 
                   
                   
                   
               
               
                   
                   
                 CCGGAAAAGGGCAGCGCT 
                   
                   
                   
               
               
                   
               
               
                 140 
                 cg20524216 
                 TCGGGGGTGGTGTTAAGCAGGTTATTA 
                  3 
                  47555100 
                 C3orf75 
               
               
                   
                   
                 AGTTCCACGAACATTCCGAGCTCCTGG 
                   
                   
                   
               
               
                   
                   
                 GACTAG[CG]CTCTGGAGGAGAACCCG 
                   
                   
                   
               
               
                   
                   
                 GAGTGCTGCAGAGACGACGGAGGCTG 
                   
                   
                   
               
               
                   
                   
                 GAGAGCAAAACACACCC 
                   
                   
                   
               
               
                   
               
               
                 141 
                 cg20692569 
                 CGACCCGGAGCGCGGGCGCGGGGCTG 
                  7 
                  72848481 
                 FZD9 
               
               
                   
                   
                 CGCCGTGCCAGGCGGTGGAGATCCCCA 
                   
                   
                   
               
               
                   
                   
                 TGTGCCG[CG]GCATCGGCTACAACCTG 
                   
                   
                   
               
               
                   
                   
                 ACCCGCATGCCCAACCTGCTGGGCCAC 
                   
                   
                   
               
               
                   
                   
                 ACGTCGCAGGGCGAGG 
                   
                   
                   
               
               
                   
               
               
                 142 
                 cg20761322 
                 CACCTGGTAGTTGTCTAGCTGCTCTTCG 
                 15 
                  78423564 
                 CIB2 
               
               
                   
                   
                 GTGAAGATGGTCTGCTTGTTCCCCATG 
                   
                   
                   
               
               
                   
                   
                 GTGGC[CG]CCGCGCCGCCGCTCGCCCG 
                   
                   
                   
               
               
                   
                   
                 CCCGGGCTCCGACTCCCATCAGCGGCC 
                   
                   
                   
               
               
                   
                   
                 GCCAGACCCGGAGC 
                   
                   
                   
               
               
                   
               
               
                 143 
                 cg20795863 
                 TTTTCCTTGTGCAGCTTTTGCCCTTCTC 
                  2 
                 233896119 
                 NEU2 
               
               
                   
                   
                 AGTTTTATTTTCTCACATCGTCCTAATA 
                   
                   
                   
               
               
                   
                   
                 TTAA[CG]TTCACTGTGGTTGAATGAAA 
                   
                   
                   
               
               
                   
                   
                 GACTGATAGATTACATTTATTTCTCAA 
                   
                   
                   
               
               
                   
                   
                 AGAAGCTAAGTTT 
                   
                   
                   
               
               
                   
               
               
                 144 
                 cg20828084 
                 GACTCCATATGCCCTAGGGATGTGTTG 
                 15 
                  81070851 
                 KIAA1199 
               
               
                   
                   
                 TGATGAACTTTTCCTACTGGTACTGTTT 
                   
                   
                   
               
               
                   
                   
                 CCTCC[CG]CGAGGGAATGTCTAGACCA 
                   
                   
                   
               
               
                   
                   
                 GCCGCACCTTCTTGCTTTGACCCTTCAG 
                   
                   
                   
               
               
                   
                   
                 AACTTTGGCCTGT 
                   
                   
                   
               
               
                   
               
               
                 145 
                 cg20914508 
                 AGAGCACCAGAGAGAGAGGGAGAGAG 
                  3 
                 115342333 
                 GAP43 
               
               
                   
                   
                 AGAGAGAGCGCTAGAGAGAGGGAGCG 
                   
                   
                   
               
               
                   
                   
                 AGCATGTG[CG]ATGAGCAATAGCTGTG 
                   
                   
                   
               
               
                   
                   
                 GACCTTACAGTTGCTGCTAACTGCCCT 
                   
                   
                   
               
               
                   
                   
                 GGTGTGTGTGAGGGAGA 
                   
                   
                   
               
               
                   
               
               
                 146 
                 cg20947775 
                 CCGCCCGGGGGCGGGTGGAAGGTGGC 
                  4 
                  83720240 
                 SCD5 
               
               
                   
                   
                 TCCCGGGGCAGGGAGCCTGCAGGGCG 
                   
                   
                   
               
               
                   
                   
                 GCTCACAG[CG]CTTCTGCTCTTGTGTGT 
                   
                   
                   
               
               
                   
                   
                 GTGTGACCCCCAAAATGCCTTTTATGG 
                   
                   
                   
               
               
                   
                   
                 TATTTTTCCAGTCCCC 
                   
                   
                   
               
               
                   
               
               
                 147 
                 cg20999813 
                 GGGCCCCGCTTGGGGAGGGCGTGGAG 
                 16 
                  84734014 
                 USP10 
               
               
                   
                   
                 GGCGCCGAAGGGGTTAACCTCCCTGGG 
                   
                   
                   
               
               
                   
                   
                 GCTGGAC[CG]CGGGGCGAGCCCGGGG 
                   
                   
                   
               
               
                   
                   
                 TGTGGAGTGGGGCCCTCCCCGCCGCGC 
                   
                   
                   
               
               
                   
                   
                 CGGCCGGGGGAGGCGGC 
                   
                   
                   
               
               
                   
               
               
                 148 
                 cg21096399 
                 CTGACTGGCCGAGGTGGCAGCGAGGA 
                 11 
                 119188145 
                 MCAM 
               
               
                   
                   
                 GAAGCTGTCCCGGATGCCCGGAGTCGC 
                   
                   
                   
               
               
                   
                   
                 CCCGGGT[CG]AAGCCAGCCAGGCTCAC 
                   
                   
                   
               
               
                   
                   
                 CGCTGCTCAGCCCCTGCCAGCCAATGT 
                   
                   
                   
               
               
                   
                   
                 AGCCCCTAGGGGACCT 
                   
                   
                   
               
               
                   
               
               
                 149 
                 cg21378206 
                 AAATAGGGGAGTCTACACCCTGTGGAG 
                  2 
                 113817043 
                 IL1F5 
               
               
                   
                   
                 CTCAAGATGGTCCTGAGTGGGGCGCTG 
                   
                   
                   
               
               
                   
                   
                 TGCTTC[CG]GTGAGTGTATGAGGCCCT 
                   
                   
                   
               
               
                   
                   
                 GGTTTGGTGGTGTCCTCCGGAGGAAGT 
                   
                   
                   
               
               
                   
                   
                 GAGTTCTGGATAGAC 
                   
                   
                   
               
               
                   
               
               
                 150 
                 cg21460081 
                 CGGGGCGACCCCCTCCTTGCCTCGCTC 
                 17 
                  46656012 
                 HOXB4 
               
               
                   
                   
                 TCTCCGGGATCAGAGAGAGAGCGAGA 
                   
                   
                   
               
               
                   
                   
                 GAGAGAG[CG]CGCGCAGGTTGCGACT 
                   
                   
                   
               
               
                   
                   
                 GGAGGGCCTGTTGGGGCGCTAGGCAG 
                   
                   
                   
               
               
                   
                   
                 AGCGCAAACCCTAGATCC 
                   
                   
                   
               
               
                   
               
               
                 151 
                 cg21801378 
                 CCACGAAGAGCTTGATGGCGTCGTGGT 
                 15 
                  72612125 
                 BRUNOL6 
               
               
                   
                   
                 CCTTCATGGGTACGGCGGGACCGGGGT 
                   
                   
                   
               
               
                   
                   
                 TTAGCC[CG]CTCATGCCGACGCCGCTG 
                   
                   
                   
               
               
                   
                   
                 TCCGCGGTGCTGAAACCCAGGCGCGGG 
                   
                   
                   
               
               
                   
                   
                 CCGGGGCCAGCGGGC 
                   
                   
                   
               
               
                   
               
               
                 152 
                 cg21870884 
                 GGGCCCGCGGCGGCTGGTGGATACCTT 
                  1 
                 200842429 
                 GPR25 
               
               
                   
                   
                 CGTGCTGCACCTGGCGGCAGCTGACCT 
                   
                   
                   
               
               
                   
                   
                 GGGCTT[CG]TGCTCACGCTGCCGCTGT 
                   
                   
                   
               
               
                   
                   
                 GGGCCGCGGCGGCGGCGCTAGGCGGC 
                   
                   
                   
               
               
                   
                   
                 CGCTGGCCGTTCGGCG 
                   
                   
                   
               
               
                   
               
               
                 153 
                 cg22006386 
                 ACACGGGTGCGATCGCAGGCAGAAGC 
                 19 
                  38827378 
                 CATSPER 
               
               
                   
                   
                 AGTACGGGGGAACTTAAGAGGGGGAC 
                   
                   
                 G 
               
               
                   
                   
                 TGTCAAAG[CG]AGAAATAGAAACCAA 
                   
                   
                   
               
               
                   
                   
                 GACCAGGTGAAGAGCAAGAGTGGAAT 
                   
                   
                   
               
               
                   
                   
                 ACAGGGAGGGGGCGGAATA 
                   
                   
                   
               
               
                   
               
               
                 154 
                 cg22289837 
                 TTTTCATGAACAGAGGTACAGCTCAGG 
                  8 
                  86350278 
                 CA3 
               
               
                   
                   
                 GAGTGTGGCTAAATCAGTCCCAGTCTC 
                   
                   
                   
               
               
                   
                   
                 CAGCTC[CG]CGTGAACCTGGGATCCAG 
                   
                   
                   
               
               
                   
                   
                 ACATCTCCTGGATATCTGGCGCTCTCT 
                   
                   
                   
               
               
                   
                   
                 GAGATCCAGCCCTCG 
                   
                   
                   
               
               
                   
               
               
                 155 
                 cg22432269 
                 AGGCCGAGCCGGGAGAGCCCCCGCCC 
                 15 
                  22892697 
                 CYFIP1 
               
               
                   
                   
                 CGGGAGGAAGGGGAGGAGGCCGAGTG 
                   
                   
                   
               
               
                   
                   
                 TTTCCTGG[CG]CATTCCCGGCCAGCCC 
                   
                   
                   
               
               
                   
                   
                 GAGTGACTCACTCGGCCAAGGAAACTC 
                   
                   
                   
               
               
                   
                   
                 CCAGGGCCCGCCCAGGA 
                   
                   
                   
               
               
                   
               
               
                 156 
                 cg22449114 
                 GGGCCTGGGCATTAAGTCAGTGGTTCT 
                 20 
                    590243 
                 TCF15 
               
               
                   
                   
                 GGGCTTGGGGTGCCGCACCCAGCACGA 
                   
                   
                   
               
               
                   
                   
                 ATTCCA[CG]TCGCTTCCCCCTGGCCTCG 
                   
                   
                   
               
               
                   
                   
                 TTGGGGACCCCTGCACCTCTCCGGTTC 
                   
                   
                   
               
               
                   
                   
                 CCGCAGAGGCGCTG 
                   
                   
                   
               
               
                   
               
               
                 157 
                 cg22679120 
                 AAAAAAATTACCGGGCGTAACTGCAC 
                  7 
                   2353402 
                 SNX8 
               
               
                   
                   
                 GCGCCCGTAGTCCCAGCACTTTGGGAG 
                   
                   
                   
               
               
                   
                   
                 GCTAAGG[CG]GAGGATCACTTGAAAG 
                   
                   
                   
               
               
                   
                   
                 AGAGAGAAAAGCAGCTACACATCTAT 
                   
                   
                   
               
               
                   
                   
                 AGATTCGGTTCACAGATG 
                   
                   
                   
               
               
                   
               
               
                 158 
                 cg22736354 
                 TGCGCCAGGGCGGCCACGCAGGCCAG 
                  6 
                  18122719 
                 NHLRC1 
               
               
                   
                   
                 GCAGACCACGTGGCCGCAGGACAGGT 
                   
                   
                   
               
               
                   
                   
                 TGCGCGGG[CG]CCGCTGCTGCCGGTGG 
                   
                   
                   
               
               
                   
                   
                 CCAAACTTCTCAAAGCACACCTTGCAC 
                   
                   
                   
               
               
                   
                   
                 TCGAGCAGGCTGATCTC 
                   
                   
                   
               
               
                   
               
               
                 159 
                 cg22809047 
                 TCACATCTGTCATCTCTCAGGTCATATC 
                  2 
                 101618261 
                 RPL31 
               
               
                   
                   
                 CAACACACTGGGCCACCCACGCACAG 
                   
                   
                   
               
               
                   
                   
                 GGACGA[CG]CGACAGCCCTGTGGCTCC 
                   
                   
                   
               
               
                   
                   
                 ACCGCACAGGACAGCCACGACTGGCA 
                   
                   
                   
               
               
                   
                   
                 ATCCTGTGCCGGCCCT 
                   
                   
                   
               
               
                   
               
               
                 160 
                 cg22901840 
                 GTGCAGGGAAAGCACACCGTGGCTGC 
                  1 
                  68512777 
                 DIRAS3 
               
               
                   
                   
                 AGCCCAGCAACTGGCAGTAGGTATTTT 
                   
                   
                   
               
               
                   
                   
                 CAATGGT[CG]GCAGGTACTCATGACGG 
                   
                   
                   
               
               
                   
                   
                 AAGTTGCCGCTCGCCCACTTGTGCAGC 
                   
                   
                   
               
               
                   
                   
                 AGCGTACTTTTCCCCA 
                   
                   
                   
               
               
                   
               
               
                 161 
                 cg22920873 
                 CGAAGATCCGGCCAATTTGCCCAGCGC 
                  7 
                 139025153 
                 C7orf55 
               
               
                   
                   
                 GCTGTGCTCCGCGACGGCGCATGCCCG 
                   
                   
                   
               
               
                   
                   
                 CTTTTG[CG]CAGGCGCGGGGACTACGG 
                   
                   
                   
               
               
                   
                   
                 CGCAGGCGCGGAGACTATTGCGCAGG 
                   
                   
                   
               
               
                   
                   
                 CAAGCGCGTACGCAGA 
                   
                   
                   
               
               
                   
               
               
                 162 
                 cg23517605 
                 CTCCAGTGCCGGCAGGTGGGAGGGCTG 
                  6 
                   3228365 
                 TUBB2B 
               
               
                   
                   
                 AGGTGGCACAGGCTGCTCCGCCACCTC 
                   
                   
                   
               
               
                   
                   
                 GGACTG[CG]GCTCCTACTCGGCCACTG 
                   
                   
                   
               
               
                   
                   
                 GCCAGAGTCCCTCCAGCCAACTGCCCC 
                   
                   
                   
               
               
                   
                   
                 TGGTGAGACCACCGT 
                   
                   
                   
               
               
                   
               
               
                 163 
                 cg23662675 
                 TGGCTGCCCCGGCAAATCGGAGTGTAA 
                 20 
                  45985596 
                 ZMYND8 
               
               
                   
                   
                 AGCCGCCCCGGATTGGCTGAAACACTT 
                   
                   
                   
               
               
                   
                   
                 CCTGAG[CG]ATTATCTTTGTGAGGCTC 
                   
                   
                   
               
               
                   
                   
                 GGGTGAGCAAGAGCCATCCTGTGCATA 
                   
                   
                   
               
               
                   
                   
                 GAAAAAGACAGGCTA 
                   
                   
                   
               
               
                   
               
               
                 164 
                 cg23941599 
                 CTGAGATCTCGCTGGCTCTTCTCCTCTC 
                  5 
                 114880796 
                 FEM1C 
               
               
                   
                   
                 GGATTTTCGGGGTGCTCCCTTAGGGAA 
                   
                   
                   
               
               
                   
                   
                 TCTTT[CG]GTCCCATCTCAGAGACCCC 
                   
                   
                   
               
               
                   
                   
                 AGAAGGGAAGTGTATTAGTGCGTTTTC 
                   
                   
                   
               
               
                   
                   
                 ACGCTGCTGATAAA 
                   
                   
                   
               
               
                   
               
               
                 165 
                 cg24116886 
                 CTGGTTTATACTGCCACATTCATTCTTG 
                 20 
                    137877 
                 DEFB127 
               
               
                   
                   
                 GAGGTGAGTACATTTCGATCTTGGTCC 
                   
                   
                   
               
               
                   
                   
                 GGCTG[CG]CAGAGAGTCAAAGCAGGA 
                   
                   
                   
               
               
                   
                   
                 AAATCACAGATTCTTCCCAGCAGTCTA 
                   
                   
                   
               
               
                   
                   
                 CAGCCTACACAGCGG 
                   
                   
                   
               
               
                   
               
               
                 166 
                 cg24126851 
                 GCAAGCAATCTTAAAGGAACTGGGAA 
                 11 
                   6678143 
                 DCHS1 
               
               
                   
                   
                 GAGTTCTGACTCCTGTCCTTCTTCCTTA 
                   
                   
                   
               
               
                   
                   
                 GGACTG[CG]AGTAGACTGTGAGAAAA 
                   
                   
                   
               
               
                   
                   
                 ACAGGTTTTCTGGACTTGAGATGTGTA 
                   
                   
                   
               
               
                   
                   
                 CAAATGGCACAAAGAA 
                   
                   
                   
               
               
                   
               
               
                 167 
                 cg24254120 
                 GTTGGAGTGCAGACCCAGTCAGTCTCA 
                 13 
                  34392869 
                 RFC3 
               
               
                   
                   
                 GAATAAGACGAGAAGCCGTTGGAGCA 
                   
                   
                   
               
               
                   
                   
                 TTTTGAG[CG]GAGATGACACCATGTGA 
                   
                   
                   
               
               
                   
                   
                 TTTACTTTCTAGCTGGCTTAAGATTTCT 
                   
                   
                   
               
               
                   
                   
                 CGATGTCATTGTCAT 
                   
                   
                   
               
               
                   
               
               
                 168 
                 cg24262469 
                 CTCTGCAAGCTCCATGAGGACAGGCGT 
                  3 
                 156391694 
                 TIPARP; 
               
               
                   
                   
                 GAAGTTCAGGCTACATGCCTGGTACGT 
                   
                   
                 LOC10028 
               
               
                   
                   
                 AATAGA[CG]CTCTGACAGACATTTGCT 
                   
                   
                 7227 
               
               
                   
                   
                 GAATGAATAAGTTAGTCACTACGGCGT 
                   
                   
                   
               
               
                   
                   
                 TTGTGGGCTTTAAAA 
                   
                   
                   
               
               
                   
               
               
                 169 
                 cg24450312 
                 GGGGCGCGCGAGGGGCGCAGCGCCCG 
                  1 
                 206681158 
                 RASSF5 
               
               
                   
                   
                 GAGGGCTGCCCGGGGGAACCTGGAGC 
                   
                   
                   
               
               
                   
                   
                 CCCCGCCC[CG]GGCCTCCCGACCCGCT 
                   
                   
                   
               
               
                   
                   
                 CGCCCGCTCCGGCCTGGTCTGCAGCAG 
                   
                   
                   
               
               
                   
                   
                 AGACTGCGGCGGCGGCC 
                   
                   
                   
               
               
                   
               
               
                 170 
                 cg24580001 
                 TCTTCTGAAGGATTTGATGCTGGTGCTT 
                 11 
                  64106532 
                 CCDC88B 
               
               
                   
                   
                 TTCAGGTGTGGGTCCTGACAGTGATGT 
                   
                   
                   
               
               
                   
                   
                 TGGGA[CG]GCAGCTAGCCAGACAGCA 
                   
                   
                   
               
               
                   
                   
                 ACTGTACCATGTAAACTCACTTCAGAG 
                   
                   
                   
               
               
                   
                   
                 GTGTAGAATGGGGGC 
                   
                   
                   
               
               
                   
               
               
                 171 
                 cg24834740 
                 GGGATGAGGATGGGGCGGGGAGGTGG 
                 20 
                  37434552 
                 PPP1R16B 
               
               
                   
                   
                 TCCCAGCCTGCTATCACCTAGCTGGGG 
                   
                   
                   
               
               
                   
                   
                 GCCGGGG[CG]CTTTGGCCAAGGGACG 
                   
                   
                   
               
               
                   
                   
                 ATAGCTTGAGATAAATGGGAGTGTGGG 
                   
                   
                   
               
               
                   
                   
                 GACTCTGGAAAGACGGG 
                   
                   
                   
               
               
                   
               
               
                 172 
                 cg25070637 
                 TGCCAATCGGCGTGTAATCCTGTAGGA 
                  8 
                  97505868 
                 SDC2 
               
               
                   
                   
                 ATTTCTCCCGGGTTTATCTGGGAGTCA 
                   
                   
                   
               
               
                   
                   
                 CACTGC[CG]CCTCCTCTCCCCAGTCGC 
                   
                   
                   
               
               
                   
                   
                 CCAGGGGAGCCCGGAGAAGCAGGCTC 
                   
                   
                   
               
               
                   
                   
                 AGGAGGGAGGGAGCCA 
                   
                   
                   
               
               
                   
               
               
                 173 
                 cg25148589 
                 GGGTGAGTGTGTGTGAGTGCATGGGAG 
                  4 
                 158141936 
                 GRIA2 
               
               
                   
                   
                 GGTGCTGAATATTCCGAGACACTGGGA 
                   
                   
                   
               
               
                   
                   
                 CCACAG[CG]GCAGCTCCGCTGAAAACT 
                   
                   
                   
               
               
                   
                   
                 GCATTCAGCCAGTCCTCCGGACTTCTG 
                   
                   
                   
               
               
                   
                   
                 GAGCGGGGACAGGGC 
                   
                   
                   
               
               
                   
               
               
                 174 
                 cg25505610 
                 GAGGCGCCAGCGGGAGGCAACATCAA 
                 11 
                  32605184 
                 EIF3M 
               
               
                   
                   
                 TGCAGTTAGCTACACGGGCCTGAAAAC 
                   
                   
                   
               
               
                   
                   
                 TGGAGGC[CG]CGACAAGCGTCGCTGA 
                   
                   
                   
               
               
                   
                   
                 GTGGAGGCCCAGTAAGTCCCACCCACT 
                   
                   
                   
               
               
                   
                   
                 AGGCCAGCCCGAGCGCG 
                   
                   
                   
               
               
                   
               
               
                 175 
                 cg25552492 
                 GCAGGGGGGCGTCTTGGGGGGCCTCTT 
                  8 
                  22013999 
                 LGI3 
               
               
                   
                   
                 AGCGCTGACTTGCAGCATGAGGCAGA 
                   
                   
                   
               
               
                   
                   
                 AGCCGAG[CG]CGGAGAGCGCCAGCAG 
                   
                   
                   
               
               
                   
                   
                 CCCCGGCCCCGGGCCCCCCCTGGCCCG 
                   
                   
                   
               
               
                   
                   
                 CAGCCCCGCCATGCTGC 
                   
                   
                   
               
               
                   
               
               
                 176 
                 cg25683012 
                 ATCCTCCCAAACTGTGAGCTGGGAACT 
                 12 
                  57030113 
                 BAZ2A 
               
               
                   
                   
                 AGCAAGAATCAAAAAGCCAGTGTATG 
                   
                   
                   
               
               
                   
                   
                 CTTCCTG[CG]AACCACACAGCCTGAAC 
                   
                   
                   
               
               
                   
                   
                 TGCTGTAGGGTGATGTCCCTGTGTGAC 
                   
                   
                   
               
               
                   
                   
                 AGACTGGGGTGGGGAG 
                   
                   
                   
               
               
                   
               
               
                 177 
                 cg25771195 
                 GATAAGCGCCTAATATACATCCCTGCC 
                 16 
                  58163814 
                 C16orf80 
               
               
                   
                   
                 TGTCATTATTCACATTGTGGCATGCAG 
                   
                   
                   
               
               
                   
                   
                 TCAAAG[CG]ACACTCTGAGGAAAATGT 
                   
                   
                   
               
               
                   
                   
                 ATCGCCTTAAATACATTGATTAGAAAA 
                   
                   
                   
               
               
                   
                   
                 TAAGAAAGCCCGAAC 
                   
                   
                   
               
               
                   
               
               
                 178 
                 cg25781123 
                 GGGGAAGCACTCTCTAAACGTTAGCAA 
                  3 
                   9404598 
                 THUMPD3 
               
               
                   
                   
                 ATACCATGGTAGGACACAAGGCCCCTG 
                   
                   
                   
               
               
                   
                   
                 ACTCTC[CG]CTTTCAGCTTACTGAAGA 
                   
                   
                   
               
               
                   
                   
                 TCCTCAAAACCAACAGCACACAGCTTC 
                   
                   
                   
               
               
                   
                   
                 CAGCGCATGCTCCTT 
                   
                   
                   
               
               
                   
               
               
                 179 
                 cg26003813 
                 TTGTTGAGAGGCGGACACTGACTCGGG 
                 16 
                  23689802 
                 PLK1 
               
               
                   
                   
                 AGGTCTGGGGTAGGGCCTGAACGTTTG 
                   
                   
                   
               
               
                   
                   
                 CCTTTG[CG]GTTCTAACAAGCTCTCAG 
                   
                   
                   
               
               
                   
                   
                 GTGATGGCGATGCTACTGTTCCCTGGC 
                   
                   
                   
               
               
                   
                   
                 CCCGAGGTAGAGGAA 
                   
                   
                   
               
               
                   
               
               
                 180 
                 cg26005082 
                 AGCTCTCCACCGACCGAAGGAGGAGA 
                 19 
                   4769660 
                 MIR7-3; 
               
               
                   
                   
                 ATGCTATTTATTTCAGCACCAAATATC 
                   
                   
                 C19orf30 
               
               
                   
                   
                 CGGACAG[CG]CCTCTCGGGAGGTCCGA 
                   
                   
                   
               
               
                   
                   
                 GAAGAGAACCGCGATCTGTTTCAGCAC 
                   
                   
                   
               
               
                   
                   
                 CGGGGCTCAGGACAGT 
                   
                   
                   
               
               
                   
               
               
                 181 
                 cg26045434 
                 GGGCTTCCTAACTTTCAGGTGTCAGAA 
                  8 
                  21987861 
                 HR; HR 
               
               
                   
                   
                 TGTGTGGCCCAGCCCACAGGGGCACGG 
                   
                   
                   
               
               
                   
                   
                 GGAACA[CG]CTCCGTACGGGCACCGCA 
                   
                   
                   
               
               
                   
                   
                 GGCTCGGCTCAGAAATCCCCCGCCACG 
                   
                   
                   
               
               
                   
                   
                 AGTGTCCCCAGACGG 
                   
                   
                   
               
               
                   
               
               
                 182 
                 cg26297688 
                 ATAAGCCACGTCTCTCCTCACCCCTAG 
                 12 
                 107349093 
                 C12orf23 
               
               
                   
                   
                 CACTTAATCACAAAGGCCTGTAGAGAG 
                   
                   
                   
               
               
                   
                   
                 TCCCGA[CG]AGAACTTCTGAGCAGGCC 
                   
                   
                   
               
               
                   
                   
                 CCGCTGTCAGTCCCTGAGGACAGCATG 
                   
                   
                   
               
               
                   
                   
                 CAAGGGAGGTTGACG 
                   
                   
                   
               
               
                   
               
               
                 183 
                 cg26372517 
                 CCGGCGCCTCTGCCCGCAGCGCTCGCC 
                  1 
                  36039159 
                 TFAP2E 
               
               
                   
                   
                 GTCGGGCTAGGGCTCCGCCGCCGCCAC 
                   
                   
                   
               
               
                   
                   
                 GCCTCG[CG]CCCGGCACTCACCGCCCC 
                   
                   
                   
               
               
                   
                   
                 ATGCTGGTGCACACCTACTCCGCCATG 
                   
                   
                   
               
               
                   
                   
                 GTGAGTAGTCTCGGG 
                   
                   
                   
               
               
                   
               
               
                 184 
                 cg26453588 
                 GGCTGCCCACCCGCCCACCCCGCCTGG 
                 22 
                  43506021 
                 BIK 
               
               
                   
                   
                 AAGCTTTCTGATTTCTCTGTTCGCCCCG 
                   
                   
                   
               
               
                   
                   
                 CCAGG[CG]CTGTGGGGTCCGTCTCACC 
                   
                   
                   
               
               
                   
                   
                 AGGTCTGCACGTGAGCCCCCTGCCCCC 
                   
                   
                   
               
               
                   
                   
                 AATCCCTCCCAGTC 
                   
                   
                   
               
               
                   
               
               
                 185 
                 cg26620959 
                 GGTGGGAAGGAAATGTCCCTGAGAGC 
                  6 
                 152958489 
                 SYNE1 
               
               
                   
                   
                 CGGGACGCGCTGCCTCCGCTGCCTGGA 
                   
                   
                   
               
               
                   
                   
                 GGAGCTG[CG]CTGTCCTGCCAGCTAAC 
                   
                   
                   
               
               
                   
                   
                 TTTTGCCCACGGTTTCCACTGCCCGGGT 
                   
                   
                   
               
               
                   
                   
                 GACCTTTCTGAGCGG 
                   
                   
                   
               
               
                   
               
               
                 186 
                 cg26842024 
                 CGACGACGACCTCAACAGCGTGCTGGA 
                 19 
                  16436122 
                 KLF2 
               
               
                   
                   
                 CTTCATCCTGTCCATGGGGCTGGATGG 
                   
                   
                   
               
               
                   
                   
                 CCTGGG[CG]CCGAGGCCGCCCCGGAGC 
                   
                   
                   
               
               
                   
                   
                 CGCCGCCGCCGCCCCCGCCGCCTGCGT 
                   
                   
                   
               
               
                   
                   
                 TCTATTACCCCGAAC 
                   
                   
                   
               
               
                   
               
               
                 187 
                 cg26845300 
                 CGCAACACCCCAGGCGTGGGGCAAAG 
                  6 
                 158243833 
                 SNX9 
               
               
                   
                   
                 ACAGCGGGGTTGCGGGGCTCCTGTCTG 
                   
                   
                   
               
               
                   
                   
                 CCCGGGG[CG]TCGAGAGTTCCTGCCGC 
                   
                   
                   
               
               
                   
                   
                 CCCCTCCCGCCTCATGCACGGAAAGCG 
                   
                   
                   
               
               
                   
                   
                 CCGAGCCACGGCGTGC 
                   
                   
                   
               
               
                   
               
               
                 188 
                 cg27092035 
                 GTGTGACCACGGAACGGCCCTGCTGGT 
                  5 
                 175792880 
                 ARL10 
               
               
                   
                   
                 GCCGGGAGCTTGGGGGGTCGAGGGCTT 
                   
                   
                   
               
               
                   
                   
                 GGCAGC[CG]CAGCGCACAGGCCCCGC 
                   
                   
                   
               
               
                   
                   
                 GCGGGTGGGCGGTCAGAGCCCGGGAA 
                   
                   
                   
               
               
                   
                   
                 CCGAGGAACGGGTGGGT 
                   
                   
                   
               
               
                   
               
               
                 189 
                 cg27169020 
                 GACGGAATGAAATGAAGTGCCCTGGA 
                 15 
                  83954229 
                 BNC1 
               
               
                   
                   
                 GAAGCCAACTGGAGGTGGTGGCCCCG 
                   
                   
                   
               
               
                   
                   
                 AGAGTAGA[CG]CGGAGGGGCTGAGGC 
                   
                   
                   
               
               
                   
                   
                 CGCAGGATCCTGGAGCCCAGGAGCTG 
                   
                   
                   
               
               
                   
                   
                 ACGGAGATCGCCCACAGCT 
                   
                   
                   
               
               
                   
               
               
                 190 
                 cg27319898 
                 GGAATTCCTGATTCCCTGGTGGACCCT 
                  7 
                  88389003 
                 ZNF804B 
               
               
                   
                   
                 GGAAGTTGTCCTTAAATAAATATATCG 
                   
                   
                   
               
               
                   
                   
                 CTGGCC[CG]CGGTTGAGCAGCCACCTC 
                   
                   
                   
               
               
                   
                   
                 GTCAGAGCAGCATGTGGACTGGCTCGC 
                   
                   
                   
               
               
                   
                   
                 CGGGTCCCCTCCGTG 
                   
                   
                   
               
               
                   
               
               
                 191 
                 cg27377450 
                 CTACACAAAGGCGCTCACACTTTATCC 
                 19 
                   7446301 
                   
               
               
                   
                   
                 GAAACAGCAGTGGGGCTTGGGTGCGG 
                   
                   
                   
               
               
                   
                   
                 TGGCTCA[CG]CCTATAATCCCAGCACT 
                   
                   
                   
               
               
                   
                   
                 TTGGGAGGCCGAGGAGGGTGGATCAT 
                   
                   
                   
               
               
                   
                   
                 CTGAGGTCAGGAGTTCA 
                   
                   
                   
               
               
                   
               
               
                 192 
                 cg27413543 
                 GAAACCAAGACTAGGGGCGCGCCGTC 
                  4 
                  83812148 
                 SEC31A 
               
               
                   
                   
                 ACCAGAGACCGGGCCTCAGGCTGGTGC 
                   
                   
                   
               
               
                   
                   
                 GGGGCAG[CG]GAGACCCAGGCTGCGG 
                   
                   
                   
               
               
                   
                   
                 TCCCAGTTTTGGCCTGGGCTCTACCTCA 
                   
                   
                   
               
               
                   
                   
                 AAGCTTAAGGACCGGC 
                   
                   
                   
               
               
                   
               
               
                 193 
                 cg27494383 
                 CAAGCCTAGGAAAGTGCCTCAGGCTGG 
                 15 
                  41805868 
                 LTK 
               
               
                   
                   
                 ACGGTCCCCTGACCGCCAGATAGCACT 
                   
                   
                   
               
               
                   
                   
                 TACCCG[CG]GCTCCGAACCACACCAGC 
                   
                   
                   
               
               
                   
                   
                 AGCTGTCCCCAGCAGCCCATCCCTGTT 
                   
                   
                   
               
               
                   
                   
                 GGGTCCACCCGGCAA 
                   
                   
                   
               
               
                   
               
               
                 194 
                 cg00091693 
                 CTCCTCCTCTGCTGACATGTCACTAGG 
                 17 
                  39041602 
                 KRT20 
               
               
                   
                   
                 ATTGGCACCACAGTCCACCTTGCCTTA 
                   
                   
                   
               
               
                   
                   
                 CTTCCA[CG]CCCCCCGCTTTGTATAGC 
                   
                   
                   
               
               
                   
                   
                 AATATGTTAATATGCTTAATTCAATTCC 
                   
                   
                   
               
               
                   
                   
                 AGAAAATACCACTA 
                   
                   
                   
               
               
                   
               
               
                 195 
                 cg00168942 
                 CTTTGCTTTCTTATCTCCAGCTCACACC 
                 10 
                  35894430 
                 GJD4 
               
               
                   
                   
                 TTTAAGTCTTATGTAGTTAAAGGACAT 
                   
                   
                   
               
               
                   
                   
                 TTATC[CG]CCTCCTTGGAGAACACAGC 
                   
                   
                   
               
               
                   
                   
                 CCTCCAGTGTCTCCTGCAGCCTGGAGC 
                   
                   
                   
               
               
                   
                   
                 CTGGGACATTCTGG 
                   
                   
                   
               
               
                   
               
               
                 196 
                 cg00431549 
                 TAACTGCTGGACCTGACTGTGTTACAC 
                 12 
                  15039025 
                 MGP 
               
               
                   
                   
                 AGGATGCTGCTCTGGTGCAGAAGTTTT 
                   
                   
                   
               
               
                   
                   
                 GGCCAT[CG]TATGCTTGGGGACAGACC 
                   
                   
                   
               
               
                   
                   
                 TGGGCAAAAGCCCACAGAGGAAGTTG 
                   
                   
                   
               
               
                   
                   
                 CCACAAACACATGATC 
                   
                   
                   
               
               
                   
               
               
                 197 
                 cg00436603 
                 CTCACCAGGTCACTGGCTGGAACCCCT 
                 10 
                 135340740 
                 CYP2E1 
               
               
                   
                   
                 GGGGGCCACCATTGCGGGAATCAGCCT 
                   
                   
                   
               
               
                   
                   
                 TTGAAA[CG]ATGGCCAACAGCAGCTAA 
                   
                   
                   
               
               
                   
                   
                 TAATAAACCAGTAATTTGGGATAGACG 
                   
                   
                   
               
               
                   
                   
                 AGTAGCAAGAGGGCA 
                   
                   
                   
               
               
                   
               
               
                 198 
                 cg01027805 
                 CGGTTTGGAGACGGGGGGCGCTGTCGG 
                 14 
                  21566863 
                 ZNF219; 
               
               
                   
                   
                 AGGGAGGGAGGAAGGGAGGGAGCGG 
                   
                   
                 C14orf176 
               
               
                   
                   
                 GGGTGGGG[CG]CACAGAGGATTCCAA 
                   
                   
                   
               
               
                   
                   
                 CAGGAGACTGGAAGAGATTTTGAAAG 
                   
                   
                   
               
               
                   
                   
                 GTCATCTCGTCCTTCCCCC 
                   
                   
                   
               
               
                   
               
               
                 199 
                 cg01234063 
                 AAGCCGGATCCTCTCCGTTCCCTTGGA 
                 11 
                 126226007 
                 ST3GAL4 
               
               
                   
                   
                 GTGAGCAAGCGGGACAGTTCTGCGGA 
                   
                   
                   
               
               
                   
                   
                 AAGTTTC[CG]CCCCCAATCCCCCAGCC 
                   
                   
                   
               
               
                   
                   
                 CTGCGCCCGGACTGAAGCGGCGGCCCC 
                   
                   
                   
               
               
                   
                   
                 CACCTCCAGCATCCTC 
                   
                   
                   
               
               
                   
               
               
                 200 
                 cg01262913 
                 GTTCCAAGAAATCTGCCACCAGCTCCA 
                 21 
                  38580486 
                 DSCR9 
               
               
                   
                   
                 AGCCTCATGTCCTGAAGTGCCACCTCA 
                   
                   
                   
               
               
                   
                   
                 TTCCCG[CG]GGGTGAGCCAGCAGCCTC 
                   
                   
                   
               
               
                   
                   
                 TGAAAAGAGGAAGCCATTGAACAGAT 
                   
                   
                   
               
               
                   
                   
                 CACACTGTGCCTCCCG 
                   
                   
                   
               
               
                   
               
               
                 201 
                 cg01407797 
                 TGATTATATGTACTATTATTATCTCATT 
                 22 
                  29168514 
                 CCDC117 
               
               
                   
                   
                 TTACTACTGTGGAAACTGAGATACGAA 
                   
                   
                   
               
               
                   
                   
                 ACTTG[CG]GAGTGAGGATTTGAACCTA 
                   
                   
                   
               
               
                   
                   
                 GGTCATACTCTTGGCCAGCCAGAGACA 
                   
                   
                   
               
               
                   
                   
                 CCCTAAGCCCCAGC 
                   
                   
                   
               
               
                   
               
               
                 202 
                 cg01459453 
                 GCAAGTTTAAAAGTACTCACAAAATCT 
                  1 
                 169599212 
                 SELP 
               
               
                   
                   
                 AATAGGCAATTCAACATAAAACTCCAT 
                   
                   
                   
               
               
                   
                   
                 GGCTAT[CG]CTGTTCCTCACTTTCTGAA 
                   
                   
                   
               
               
                   
                   
                 CCTTTACCTGCCTGACTTTACTCCATAC 
                   
                   
                   
               
               
                   
                   
                 CACTCCAACTCAC 
                   
                   
                   
               
               
                   
               
               
                 203 
                 cg01485645 
                 CCCCCGCCCGGTCCTGGAAGACCGGGT 
                 17 
                  36862199 
                 MLLT6 
               
               
                   
                   
                 CAGGCATTGTTTTCTTGCCTATTGTTCC 
                   
                   
                   
               
               
                   
                   
                 AGTTC[CG]CGCCCCCCACCCTAAGTTG 
                   
                   
                   
               
               
                   
                   
                 AGGGAGTTTGGGGAGAGTCTAGGGAG 
                   
                   
                   
               
               
                   
                   
                 CAATGAGTGAACTCC 
                   
                   
                   
               
               
                   
               
               
                 204 
                 cg01511567 
                 GTAGTTTTATTGTATCAGACTTAGTACA 
                 11 
                  57103631 
                 SSRP1 
               
               
                   
                   
                 GGGGTGGGGTGGGGGTGTGTATTGGAA 
                   
                   
                   
               
               
                   
                   
                 TGATG[CG]TGCCCGTTTCTCTGCAAAA 
                   
                   
                   
               
               
                   
                   
                 TAGTTTCTATGTCATGGAAAGGAGTCG 
                   
                   
                   
               
               
                   
                   
                 ATGGGACAAGAAGA 
                   
                   
                   
               
               
                   
               
               
                 205 
                 cg01560871 
                 GGTTTTAGCCAGAGAGAAGCGGATGG 
                 10 
                  72545424 
                 C10orf27 
               
               
                   
                   
                 AGGCGGAACGCTGGCAGAGGACGTTG 
                   
                   
                   
               
               
                   
                   
                 GTGGGCTG[CG]TCCCAGCTTCGTCAGC 
                   
                   
                   
               
               
                   
                   
                 CCCACCTGGCCTGACCCCACCACACAG 
                   
                   
                   
               
               
                   
                   
                 GGGTCGGCTTCCATGCA 
                   
                   
                   
               
               
                   
               
               
                 206 
                 cg01570885 
                 GGAGGAGGGTTGGAGAGCAGGGCCGT 
                  6 
                   3849272 
                 FAM50B 
               
               
                   
                   
                 GTTGCAAGGCTCTCTGGGTGGCCACAG 
                   
                   
                   
               
               
                   
                   
                 CAGCTTG[CG]CTGCGCCCACATTGCTT 
                   
                   
                   
               
               
                   
                   
                 CTGCGTGTTTACAGTTGGGCACGAGAA 
                   
                   
                   
               
               
                   
                   
                 GGCTCAGCACGCACGC 
                   
                   
                   
               
               
                   
               
               
                 207 
                 cg01820374 
                 GGGAGGCTCAGTTCCTGGGCTTGCTGT 
                 12 
                   6882083 
                 LAG3 
               
               
                   
                   
                 TTCTGCAGCCGCTTTGGGTGGCTCCAG 
                   
                   
                   
               
               
                   
                   
                 GTAAAA[CG]GGGATGGCGGGAGGGTT 
                   
                   
                   
               
               
                   
                   
                 GACCTCCAGCCCCACAGGAGGGGACC 
                   
                   
                   
               
               
                   
                   
                 AGCAGGGATCTCTGTGG 
                   
                   
                   
               
               
                   
               
               
                 208 
                 cg02047577 
                 AGCCTGCCGGCCTGGTGTGTCTCGGGC 
                 20 
                  62587702 
                 UCKL1AS; 
               
               
                   
                   
                 CGTAGGTGGCGACGTGGGCGAAGGAT 
                   
                   
                 UCKL1 
               
               
                   
                   
                 CAGCGTC[CG]CGCGGGCCGGGGGCGC 
                   
                   
                   
               
               
                   
                   
                 AGCCATGGCGCTCGGAGGCCTCTTTGC 
                   
                   
                   
               
               
                   
                   
                 GGGCCTGGCCGGGCGGC 
                   
                   
                   
               
               
                   
               
               
                 209 
                 cg02071305 
                 TGCCTGATGGATAATCCATCACTTGCT 
                 15 
                  41185973 
                 VPS18 
               
               
                   
                   
                 TTTCTAGTATGAATGGTCTATTTACGGG 
                   
                   
                   
               
               
                   
                   
                 TCCAG[CG]CCCCTGCTGGCTTACGACC 
                   
                   
                   
               
               
                   
                   
                 TTTTCCAGGGCGGGGAGGGGCTGTCCT 
                   
                   
                   
               
               
                   
                   
                 CATCTCTGTGACCC 
                   
                   
                   
               
               
                   
               
               
                 210 
                 cg02275294 
                 GTTTGAATGTTGCTGAAGGACGCTGGT 
                  1 
                 179262462 
                 SOAT1 
               
               
                   
                   
                 TTTCAAACGGTAAGGAATCTCCTGATA 
                   
                   
                   
               
               
                   
                   
                 AAGGCA[CG]AATCTTGGTGTGCAGATA 
                   
                   
                   
               
               
                   
                   
                 AGCCAGCGATTCTTGCTTCTGGCTAGT 
                   
                   
                   
               
               
                   
                   
                 TCTACGTTGTTCCTG 
                   
                   
                   
               
               
                   
               
               
                 211 
                 cg02335441 
                 CCCTGCGAGGGGGAAGGTAATGGTTTC 
                  3 
                 130745948 
                 NEK11; 
               
               
                   
                   
                 AAGCTGCCCGGGCTGGGTTCCGAATCT 
                   
                   
                 ASTE1 
               
               
                   
                   
                 CTAGGA[CG]CCATGGCTGCGATCTCCT 
                   
                   
                   
               
               
                   
                   
                 CGCTTTCCTGGACATCTTACCTCCGGAT 
                   
                   
                   
               
               
                   
                   
                 GTACTCCAGTCTCA 
                   
                   
                   
               
               
                   
               
               
                 212 
                 cg03019000 
                 TGAGCATAGTTGTCACCTTCCCCACCT 
                  3 
                  51704351 
                 TEX264 
               
               
                   
                   
                 CCCACCAAAAGTCCGGGATTTTCACGA 
                   
                   
                   
               
               
                   
                   
                 GGGGAG[CG]TTTTATCTTTGGGCCCCT 
                   
                   
                   
               
               
                   
                   
                 AGAAGAGTGCTTTGTAGTTTGTAGGTC 
                   
                   
                   
               
               
                   
                   
                 CTCAGAAATTTGAGG 
                   
                   
                   
               
               
                   
               
               
                 213 
                 cg03286783 
                 TTTCCCCGCCTCCCAACCGTGAGGTGT 
                 15 
                  44580973 
                 CASC4 
               
               
                   
                   
                 TGGGTTTGGGGGACGCTGGCAGCTGGG 
                   
                   
                   
               
               
                   
                   
                 TTCTCC[CG]GTTCCCTTGGGCAGGTGC 
                   
                   
                   
               
               
                   
                   
                 AGGGTCGGGTTCAAAGCCTCCGGAACG 
                   
                   
                   
               
               
                   
                   
                 CGTTTTGGCCTGATT 
                   
                   
                   
               
               
                   
               
               
                 214 
                 cg03330058 
                 ATAATCGGCCTCCGGTCCCTGAGGATT 
                  3 
                 127392403 
                 ABTB1 
               
               
                   
                   
                 CGGAAACTCCTGACGCAGCTAAAGTGA 
                   
                   
                   
               
               
                   
                   
                 ATCTGG[CG]CTGAGATGCCCCCTCCAT 
                   
                   
                   
               
               
                   
                   
                 GGGCCGGACGCGGAGGGAAGGGGTGC 
                   
                   
                   
               
               
                   
                   
                 CCAGTTGGGTTCTGGG 
                   
                   
                   
               
               
                   
               
               
                 215 
                 cg03578041 
                 TGAATGAATAAAGGGAGCTATTGAAAT 
                 15 
                  71147307 
                 LARP6 
               
               
                   
                   
                 GTCAGGATGTTCTAAAACACTGCCACC 
                   
                   
                   
               
               
                   
                   
                 TTTTCA[CG]TGTAACTTCAAATTGAGTT 
                   
                   
                   
               
               
                   
                   
                 CCATCTCACCTCTCCAAATGTGACCCA 
                   
                   
                   
               
               
                   
                   
                 GAAACTAGGGACAG 
                   
                   
                   
               
               
                   
               
               
                 216 
                 cg03682823 
                 TGGCAGAGCAGGCTGCCTGCCTACTTG 
                  7 
                  94286953 
                 SGCE; 
               
               
                   
                   
                 TGCTTGATTGAAGTGGCGGTGTAGTTG 
                   
                   
                 PEG10 
               
               
                   
                   
                 TGGTGG[CG]CGAATCAGCGTCCAGCAA 
                   
                   
                   
               
               
                   
                   
                 CAGTTTGTGGAAACTGTGGGTTTGCTG 
                   
                   
                   
               
               
                   
                   
                 AGTATGGCGGGGGAA 
                   
                   
                   
               
               
                   
               
               
                 217 
                 cg03891319 
                 ACCATCTCACACTGTCACATACACAAT 
                  3 
                  52016838 
                 ACY1 
               
               
                   
                   
                 CATATCCACTGATAGACTGCACACGCA 
                   
                   
                   
               
               
                   
                   
                 GTGGCA[CG]CTTAAACCGTCACACGTG 
                   
                   
                   
               
               
                   
                   
                 CTCTTGTCCATGCATTCATTCCCATTCT 
                   
                   
                   
               
               
                   
                   
                 AGGCACTGTCCGGG 
                   
                   
                   
               
               
                   
               
               
                 218 
                 cg03947362 
                 CTGCCCCGCGCGAGGGCCTCACCTGTG 
                  2 
                 200820154 
                 C2orf60; 
               
               
                   
                   
                 GGTAGAGGTGCTGCATGAACTGCTCCC 
                   
                   
                 C2orf47 
               
               
                   
                   
                 GAGAAA[CG]CCCTCCAGCCGGGGTACC 
                   
                   
                   
               
               
                   
                   
                 GGGAGGTGCTGCCCGGCCATGGTTGCT 
                   
                   
                   
               
               
                   
                   
                 CACGCCTGCCCTCTT 
                   
                   
                   
               
               
                   
               
               
                 219 
                 cg04005032 
                 GGTGGCGGCCCCGGCACGGCGGCTGCT 
                  3 
                  32022767 
                 OSBPL10; 
               
               
                   
                   
                 GCTGCTGCTACAGCTCCGGACGCCCGG 
                   
                   
                 ZNF860 
               
               
                   
                   
                 GCCGCG[CG]TGCCTGCTCCAAATCCCC 
                   
                   
                   
               
               
                   
                   
                 GGGAAATGCCTGACTCATACAGGAGG 
                   
                   
                   
               
               
                   
                   
                 AAGAGGAGGAGGAGGC 
                   
                   
                   
               
               
                   
               
               
                 220 
                 cg04094160 
                 CTCTGACCAATCACCCTTTGCCTTACA 
                  9 
                  37465712 
                 ZBTB5 
               
               
                   
                   
                 ACATGTAAAACGGTTATCAAATGCCTT 
                   
                   
                   
               
               
                   
                   
                 TTAGGG[CG]GGATTTATCACTAAACTG 
                   
                   
                   
               
               
                   
                   
                 CTCCAGGTTTGGACTATAGAAATGCGG 
                   
                   
                   
               
               
                   
                   
                 CTGTTCGCTGCAACC 
                   
                   
                   
               
               
                   
               
               
                 221 
                 cg04121983 
                 AGCTTACGTCAGTTTCTCGGTGGCAGC 
                 17 
                  73511085 
                 CASKIN2 
               
               
                   
                   
                 GAATTTACTGCCAGAGTCTTGTGGCAT 
                   
                   
                   
               
               
                   
                   
                 GAGATC[CG]CGCAGGCCTGGGGCCCTG 
                   
                   
                   
               
               
                   
                   
                 GCCGGGAACCCCTCACTCCCCAAACGT 
                   
                   
                   
               
               
                   
                   
                 CCCAAGCCCAACCCA 
                   
                   
                   
               
               
                   
               
               
                 222 
                 cg04268405 
                 TGACGTTACGTACTGGAAGTCCCAGGA 
                 10 
                  73723221 
                 CHST3 
               
               
                   
                   
                 GGAATGCCCAGCAAGTGGAATCCAAG 
                   
                   
                   
               
               
                   
                   
                 ACGTTCT[CG]CCTTCTCGGGGACAGGG 
                   
                   
                   
               
               
                   
                   
                 CCATCACCAGGATTCGGAAAGGAACA 
                   
                   
                   
               
               
                   
                   
                 GGGAGGTTCGGTTTGTG 
                   
                   
                   
               
               
                   
               
               
                 223 
                 cg04431054 
                 GATGACCTTGGCTAACTGATCTTATCC 
                  5 
                 126853024 
                 PRRC1 
               
               
                   
                   
                 CTTGGGCCGCTGTGGCACAGGATGAGT 
                   
                   
                   
               
               
                   
                   
                 GAGCTA[CG]CCTGGTAACAAGAGTGCC 
                   
                   
                   
               
               
                   
                   
                 ACTCTCGTGTAAGGGGGCTGCGAAGTA 
                   
                   
                   
               
               
                   
                   
                 GAAAGGAGGCCAGCC 
                   
                   
                   
               
               
                   
               
               
                 224 
                 cg04452713 
                 CCTCTCTACCGCTCATCTAAGGGCGTC 
                  6 
                  56707687 
                 DST 
               
               
                   
                   
                 TCCGGACTGTCGCCCACCCCACCATCC 
                   
                   
                   
               
               
                   
                   
                 TCCCTG[CG]CTGGGGGTACTAAATCCC 
                   
                   
                   
               
               
                   
                   
                 GTGCAAAAAGACCTGGTCCATTCCCAA 
                   
                   
                   
               
               
                   
                   
                 GACTGGTCCAGACAC 
                   
                   
                   
               
               
                   
               
               
                 225 
                 cg04474832 
                 CCAGCCAAGTGGCCTTGATCGTTTTCC 
                  3 
                  52008487 
                 ABHD14B 
               
               
                   
                   
                 CAATGCCCCCGAGCCTGTTTCCTGCCA 
                   
                   
                   
               
               
                   
                   
                 GTAGAG[CG]GGTCAGATGTTGCCAACC 
                   
                   
                   
               
               
                   
                   
                 TCTGCAGAGTAGCAATAAGCAGTAAAC 
                   
                   
                   
               
               
                   
                   
                 GCCACGCTCTGCACA 
                   
                   
                   
               
               
                   
               
               
                 226 
                 cg04999691 
                 GAGGGAGCCGCGGAGGACTGGCAGCT 
                  7 
                 150027050 
                 C7orf29; 
               
               
                   
                   
                 GCAGATGCTGGAGCAGGCCAGCCTGTG 
                   
                   
                 LRRC61 
               
               
                   
                   
                 GCTGGGC[CG]TAGCTTCCTGCTGGCAG 
                   
                   
                   
               
               
                   
                   
                 GCTTCCTGGTATCGAGCAGCTGCCCCA 
                   
                   
                   
               
               
                   
                   
                 GCCTGGAGCAGGCGGC 
                   
                   
                   
               
               
                   
               
               
                 227 
                 cg05442902 
                 GCCAGGTCACCCTCTCACTCTGTGCCT 
                 22 
                  21369010 
                 MGC1670 
               
               
                   
                   
                 CTTAGTTATCTTGCATGCTCTGGTCTTT 
                   
                   
                 3; P2RX6 
               
               
                   
                   
                 GCATA[CG]CTGCTCCCTGCACCAGGAA 
                   
                   
                   
               
               
                   
                   
                 CCTCCATCCCCATCTTTGTCTGCTTGTC 
                   
                   
                   
               
               
                   
                   
                 GAACTTCAGAAAT 
                   
                   
                   
               
               
                   
               
               
                 228 
                 cg05590257 
                 GCAGCCAGCGCAGCACCCAAGGCAGC 
                 17 
                  17109570 
                 PLD6 
               
               
                   
                   
                 GCCTCCAGAGTCAGAGCCAGGCCCACA 
                   
                   
                   
               
               
                   
                   
                 GCCGCCG[CG]GCCGCCACCTGCCAACT 
                   
                   
                   
               
               
                   
                   
                 CAACCGTCCCATGCCGCCGCTAATCCG 
                   
                   
                   
               
               
                   
                   
                 GGACCCACAGCCACGC 
                   
                   
                   
               
               
                   
               
               
                 229 
                 cg05847778 
                 TCGACCTGTCCGCGCAGTGAGTTTCCA 
                  2 
                 170336167 
                 BBS5 
               
               
                   
                   
                 AGATTCCCGAGGGATCTTCAACCCTGT 
                   
                   
                   
               
               
                   
                   
                 AGAGGG[CG]CCGCCGTGCGCGTTAGG 
                   
                   
                   
               
               
                   
                   
                 GACCCGCGGGCGGAGACTGCACCTCCG 
                   
                   
                   
               
               
                   
                   
                 CAGCTCGCGGCCCTGG 
                   
                   
                   
               
               
                   
               
               
                 230 
                 cg05903609 
                 GGGTTACCCGGCCCTCGATAAGGAAAC 
                 17 
                   1587888 
                 PRPF8 
               
               
                   
                   
                 ACTCCGGCCATATCCGGAGAATCTGGG 
                   
                   
                   
               
               
                   
                   
                 GAGCGG[CG]GGATAGAAAAATTCACT 
                   
                   
                   
               
               
                   
                   
                 AACCACAGGCCCGGGCCCACAAGAAG 
                   
                   
                   
               
               
                   
                   
                 CGCAGCAGAAAGGCGTC 
                   
                   
                   
               
               
                   
               
               
                 231 
                 cg06044899 
                 ATATCGGGTTTGTCAGACATGGTTGCG 
                  4 
                  91760229 
                 TMSL3; 
               
               
                   
                   
                 GAGGAAAAGCGGAGCGAGGCGCGCGA 
                   
                   
                 FAM190A 
               
               
                   
                   
                 GTACGAG[CG]AAGTCTGGTCTGCGCAG 
                   
                   
                   
               
               
                   
                   
                 TGGCCACCACCGAGTTGTCGCCATAAT 
                   
                   
                   
               
               
                   
                   
                 ATTTTTAATAATGTTT 
                   
                   
                   
               
               
                   
               
               
                 232 
                 cg06117855 
                 TGGGGAGGGTTTCCTGGACAGAGGTCC 
                  3 
                  45067788 
                 CLEC3B 
               
               
                   
                   
                 TTTGGCTGCTGCCTTAAGACGTGCAGC 
                   
                   
                   
               
               
                   
                   
                 CTGGGC[CG]TGGCTGTCACTGCGTTCG 
                   
                   
                   
               
               
                   
                   
                 GACCCAGACCCGCTGCAGGCAGCAGC 
                   
                   
                   
               
               
                   
                   
                 AGCCCCCGCCCGCGCA 
                   
                   
                   
               
               
                   
               
               
                 233 
                 cg06513075 
                 AGGGGGAGTAATTTCATTTGACGACCA 
                 11 
                  34126714 
                 NAT10 
               
               
                   
                   
                 TATACAGGCCTAATGGGAGCCTGCAAA 
                   
                   
                   
               
               
                   
                   
                 GTACAG[CG]GCCGCAGTCATGGGTAGA 
                   
                   
                   
               
               
                   
                   
                 TTACAGGATTCCCATCTGTAAGATCAG 
                   
                   
                   
               
               
                   
                   
                 TACTGTGGGGGTGGA 
                   
                   
                   
               
               
                   
               
               
                 234 
                 cg06688848 
                 AACGAGCCGGAGAGACTTGATTGGGC 
                 16 
                  57220097 
                 RSPRY1; 
               
               
                   
                   
                 CATTCACGCCTCAGGATGAGGACTGGC 
                   
                   
                 FAM192A 
               
               
                   
                   
                 CAGTCTG[CG]CCTGGAGGGCGGGCCGG 
                   
                   
                   
               
               
                   
                   
                 TCCCGCTGATCACGTGACACGATTTTT 
                   
                   
                   
               
               
                   
                   
                 GAAAGGTGATTGGCTG 
                   
                   
                   
               
               
                   
               
               
                 235 
                 cg06836772 
                 CAGAATAAGTAGAGGAGGACAATTCA 
                  1 
                  57110403 
                 PRKAA2 
               
               
                   
                   
                 AGAGAGCACAGAGCTGCGTGCATTCTC 
                   
                   
                   
               
               
                   
                   
                 CCTGTGC[CG]CGACCTGTATCCAAAAG 
                   
                   
                   
               
               
                   
                   
                 CCTCAGACGAGACTTGAGGAGCTTCCT 
                   
                   
                   
               
               
                   
                   
                 AGAGGCTCTCCTGCCA 
                   
                   
                   
               
               
                   
               
               
                 236 
                 cg06926735 
                 CGTCACAGCCGGTCCCCAGAGCAGGAT 
                 20 
                  48732667 
                 UBE2V1; 
               
               
                   
                   
                 TCCTTCCGGCGCCTGCGCCTGATCACC 
                   
                   
                 TMEM189- 
               
               
                   
                   
                 GCTCTG[CG]CTTGAGCTGATAAACTCA 
                   
                   
                 UBE2V1 
               
               
                   
                   
                 GCTGATGGGATAAGAGTCTTGTTTTAT 
                   
                   
                   
               
               
                   
                   
                 CGGATTTTGGGGAAG 
                   
                   
                   
               
               
                   
               
               
                 237 
                 cg07158339 
                 TACAGGGCTTAACTCATTTTATCCTTAC 
                  9 
                  71650237 
                 FXN 
               
               
                   
                   
                 CACAATCCTATGAAGTAGGAACTTTTA 
                   
                   
                   
               
               
                   
                   
                 TAAAA[CG]CATTTTATAAACAAGGCAC 
                   
                   
                   
               
               
                   
                   
                 AGAGAGGTTAATTAACTTGCCCTCTGG 
                   
                   
                   
               
               
                   
                   
                 TCACACAGCTAGGA 
                   
                   
                   
               
               
                   
               
               
                 238 
                 cg07388493 
                 GGGAGCCAGTGTTCTTTCTCTCCTGTG 
                  1 
                  39491459 
                 NDUFS5 
               
               
                   
                   
                 ACTTTGGTGAAGTCTCTCACCACTCAG 
                   
                   
                   
               
               
                   
                   
                 TGTTGT[CG]TGAGCATGCTAGGCAGAG 
                   
                   
                   
               
               
                   
                   
                 TGCAAGAAAGGAGCAAGAACTCACTA 
                   
                   
                   
               
               
                   
                   
                 ATGGCTAGGCCTTCCC 
                   
                   
                   
               
               
                   
               
               
                 239 
                 cg07408456 
                 GGCCTGGAGACCAGGTGGTTCAGACTC 
                 19 
                  15590532 
                 PGLYRP2 
               
               
                   
                   
                 CATAAACTCTGCCCATTCTCCAGTGAG 
                   
                   
                   
               
               
                   
                   
                 GTGGAC[CG]AGGCAACCCCTCAAGTCC 
                   
                   
                   
               
               
                   
                   
                 TGTCCCTCCCCATAGTGACGGCTCTGT 
                   
                   
                   
               
               
                   
                   
                 AGCCGCTGCTGGCCA 
                   
                   
                   
               
               
                   
               
               
                 240 
                 cg07498421 
                 GATGGTGCTTATGGGGCAGGTTCCCTA 
                 12 
                  94071223 
                 CRADD 
               
               
                   
                   
                 ACAGTCAGGATTCCGGTTGCAGTTTTT 
                   
                   
                   
               
               
                   
                   
                 CTCCCC[CG]CCCCAAAGATACGTGGTT 
                   
                   
                   
               
               
                   
                   
                 GCAGACGTAAGTAACAGGAATCCATCT 
                   
                   
                   
               
               
                   
                   
                 TTCTTTGAAAGTCCT 
                   
                   
                   
               
               
                   
               
               
                 241 
                 cg07663789 
                 TGGTAACACGCTCAGCCGCTGCCACGC 
                  5 
                  32711429 
                 NPR3 
               
               
                   
                   
                 TATTTAAACGCGGGCTATGGATCCAGG 
                   
                   
                   
               
               
                   
                   
                 AACCGG[CG]CGAATCAATGAGATCAA 
                   
                   
                   
               
               
                   
                   
                 ATGCGAGGGAGATGCACCGTCAATTAC 
                   
                   
                   
               
               
                   
                   
                 AAACACTTGGACAAGT 
                   
                   
                   
               
               
                   
               
               
                 242 
                 cg07730301 
                 AGTGGGCCAGCAGTCGGGCCAGAGTC 
                 11 
                  67777952 
                 ALDH3B1 
               
               
                   
                   
                 CAGCTCAGCAACTCCGGGTTACAGGCA 
                   
                   
                   
               
               
                   
                   
                 GCCCAGG[CG]GGCCTAGCCACCGGCA 
                   
                   
                   
               
               
                   
                   
                 GCTGCACTCAGAGGCCACTGTGTCCTG 
                   
                   
                   
               
               
                   
                   
                 GCTGAGCTCATCTGCCT 
                   
                   
                   
               
               
                   
               
               
                 243 
                 cg07770222 
                 CTCTCTTCCTATTTTGTGATTAGGATGC 
                  8 
                 144120106 
                 C8orf31 
               
               
                   
                   
                 TCCATCAGTTTCTGCCACCAGCTTGCTG 
                   
                   
                   
               
               
                   
                   
                 GAGA[CG]CTGCGTGTCCCTGACTCCTC 
                   
                   
                   
               
               
                   
                   
                 TCAAAGGGTGAAAAGCTCAGTCGCACC 
                   
                   
                   
               
               
                   
                   
                 CGAGACCTGCTCC 
                   
                   
                   
               
               
                   
               
               
                 244 
                 cg07849904 
                 AGCAGCAACAAGTTTTGCATTTCAGCA 
                 22 
                  28197796 
                 MN1 
               
               
                   
                   
                 ATCAATTTCAGCCATTACATTTGCACC 
                   
                   
                   
               
               
                   
                   
                 AATCAG[CG]CCGCCCAAGTTCCGGGCT 
                   
                   
                   
               
               
                   
                   
                 CGGGGCGGGGCTCGCTCTTAAGGTGGT 
                   
                   
                   
               
               
                   
                   
                 CCGGGGTCCTGGCTG 
                   
                   
                   
               
               
                   
               
               
                 245 
                 cg08186124 
                 GCTAACGGAAACCGAGGCACGTGGAC 
                  3 
                  45883676 
                 LZTFL1 
               
               
                   
                   
                 TGCAATTATGCATTTTCATTGGTCCTCA 
                   
                   
                   
               
               
                   
                   
                 GGATCA[CG]CGACAGGAAGTATTGCGT 
                   
                   
                   
               
               
                   
                   
                 AACCGGTTGACTGCCACATGCGCATTG 
                   
                   
                   
               
               
                   
                   
                 GCTTCCAGGGCCGGA 
                   
                   
                   
               
               
                   
               
               
                 246 
                 cg08331960 
                 TCGGGGTCCCTTGGCCTGGAGACCCTT 
                 16 
                   2076597 
                 SLC9A3R2 
               
               
                   
                   
                 TGTCCAACCCGTCGCCCACCTCAAGAC 
                   
                   
                   
               
               
                   
                   
                 CTGCCT[CG]ATGCTGCGCATACAGTAG 
                   
                   
                   
               
               
                   
                   
                 GTATCCAATAAATGTTCCTGGGATAGA 
                   
                   
                   
               
               
                   
                   
                 AGGCAAAGGCGCTGG 
                   
                   
                   
               
               
                   
               
               
                 247 
                 cg09133026 
                 TCACTAACATCGCGCTCCAGGGCCAGC 
                 14 
                  75388105 
                 RPS6KL1 
               
               
                   
                   
                 CGGATCTGCGTGGCCGCATCCACCAGA 
                   
                   
                   
               
               
                   
                   
                 TAGTCA[CG]TTTTGTCATGTCAGGCAC 
                   
                   
                   
               
               
                   
                   
                 TCCCAGAGCCACCCTGTTGCGAATCTG 
                   
                   
                   
               
               
                   
                   
                 CTCCAGGTACACGTG 
                   
                   
                   
               
               
                   
               
               
                 248 
                 cg09441152 
                 GCAGAAACGCGGGGCGGCCTCTCCCCA 
                 18 
                  77712293 
                 PQLC1 
               
               
                   
                   
                 TCCCCGTGTAGTTCTCCGGGCTGAACC 
                   
                   
                   
               
               
                   
                   
                 GTTGGG[CG]CCTATTTGCAGAAAAGGC 
                   
                   
                   
               
               
                   
                   
                 AGCTCCTGAGCCTCAAGACAGACTCGG 
                   
                   
                   
               
               
                   
                   
                 GGGCCAGGCGTGCGT 
                   
                   
                   
               
               
                   
               
               
                 249 
                 cg09646392 
                 TCACTATTCTTAGTCCACAGGGGAGTA 
                 13 
                 108921052 
                 TNFSF13B 
               
               
                   
                   
                 GTGACTACCCAGGGCTTGGTAAGTGCT 
                   
                   
                   
               
               
                   
                   
                 CAGTAA[CG]TTTGTTGAAAGATGAATC 
                   
                   
                   
               
               
                   
                   
                 AATATTTCAATGCTGGGGCAAAGCAGT 
                   
                   
                   
               
               
                   
                   
                 GAAAAACTGGGGAAT 
                   
                   
                   
               
               
                   
               
               
                 250 
                 cg09722397 
                 TCGGGGTATTTTTAGGCCGGCGATAAA 
                 17 
                  72855943 
                 GRIN2C 
               
               
                   
                   
                 TAATTCATAGGGAACGTGGCATCAGGC 
                   
                   
                   
               
               
                   
                   
                 TCCCCC[CG]CGGGAGGAGGGGGCGCG 
                   
                   
                   
               
               
                   
                   
                 AGCAGCGAGAGCCACCGTCACCCGCG 
                   
                   
                   
               
               
                   
                   
                 GCTCAAGGACACTCGCG 
                   
                   
                   
               
               
                   
               
               
                 251 
                 cg09722555 
                 ATCAGCATTAGGGGTTGGGACTGAGGT 
                  9 
                  34662282 
                 CCL27 
               
               
                   
                   
                 CAGAGTCAGGGGTATCAGGGGTGGGA 
                   
                   
                   
               
               
                   
                   
                 GCTCACA[CG]AAAGCCTGGAGGTGAC 
                   
                   
                   
               
               
                   
                   
                 AGTCCCCGTCAGCCTCCTGCAGTTCCA 
                   
                   
                   
               
               
                   
                   
                 CCTGGATGACCTTCCTC 
                   
                   
                   
               
               
                   
               
               
                 252 
                 cg09809672 
                 CCCCAGAGAGCTTTCATCTAGAAGGTT 
                  1 
                 236557682 
                 EDARAD 
               
               
                   
                   
                 TGACTCTGGCCAGACAACCAGCGAGCA 
                   
                   
                 D 
               
               
                   
                   
                 TCTTCT[CG]CAATCTGTTGCTTCTTCCA 
                   
                   
                   
               
               
                   
                   
                 TGGCAAACTCCAGAGAATTAAGAAGC 
                   
                   
                   
               
               
                   
                   
                 CAAACTCAACATCGC 
                   
                   
                   
               
               
                   
               
               
                 253 
                 cg10045881 
                 TCACAAGTCTGCCAGGGGAAGTCCCTG 
                  1 
                 111770291 
                 CHI3L2 
               
               
                   
                   
                 GACTTCTTGCTTCTTTCGTGTAGGACAG 
                   
                   
                   
               
               
                   
                   
                 GCTGT[CG]AAACCTCAGTGGATAAAAG 
                   
                   
                   
               
               
                   
                   
                 ACCTAGAGAATGTGTATCCCAGAAGAA 
                   
                   
                   
               
               
                   
                   
                 GCTGGCCAAGGATA 
                   
                   
                   
               
               
                   
               
               
                 254 
                 cg10266490 
                 TGGGGGTGCCTGGAGTTTGGCTGGGGC 
                  1 
                  55013709 
                 ACOT11 
               
               
                   
                   
                 TGGGTGCCCAGTGGGCGGGCACAGGC 
                   
                   
                   
               
               
                   
                   
                 CCCTTGA[CG]TGGCTGTGGCCTAGCTG 
                   
                   
                   
               
               
                   
                   
                 GCAGCCTCGTCCTTCCTCTCCGCTAGG 
                   
                   
                   
               
               
                   
                   
                 CGGGCACTGGAGCTTT 
                   
                   
                   
               
               
                   
               
               
                 255 
                 cg10345936 
                 AACGGGGAAGAGGCTGAGATTGTATG 
                  5 
                 150727812 
                 SLC36A2 
               
               
                   
                   
                 ACTCCCAGCCACAGTTTGCTGGGCAAG 
                   
                   
                   
               
               
                   
                   
                 ATACTGG[CG]CCAGGAGGTGGTGAGAT 
                   
                   
                   
               
               
                   
                   
                 TTGTCTAAGGTCACACATGAAATCCAG 
                   
                   
                   
               
               
                   
                   
                 GATAGAACTCTGCAGC 
                   
                   
                   
               
               
                   
               
               
                 256 
                 cg10865119 
                 ACTCTGGGGCTCGAGCTTAGGATAACT 
                  6 
                 170190112 
                 C6orf122; 
               
               
                   
                   
                 TCAGGTTCAGCTGAGGCCTCTGAACTG 
                   
                   
                 C6orf208 
               
               
                   
                   
                 TGACTC[CG]CCCCGTGGCCGCATGCGT 
                   
                   
                   
               
               
                   
                   
                 CGGAACTCCTACCTGCCCTTTGCCCTTC 
                   
                   
                   
               
               
                   
                   
                 TCGAGGCCGGTGCT 
                   
                   
                   
               
               
                   
               
               
                 257 
                 cg10940099 
                 TCTTGCCCTCAGATTACCAGACACGAC 
                  6 
                 109703938 
                 CD164 
               
               
                   
                   
                 GCAGCTGGACTTGTCTCATGCCTGCGA 
                   
                   
                   
               
               
                   
                   
                 TAGGGA[CG]GCCCCCACCCTGACTTGC 
                   
                   
                   
               
               
                   
                   
                 ATGGAACAGTCGACATAATGTGGCCTA 
                   
                   
                   
               
               
                   
                   
                 CTGCTTCCACCTGAG 
                   
                   
                   
               
               
                   
               
               
                 258 
                 cg11025793 
                 TGGTCTCCCCTGGAGGGTGGGCGGGTT 
                 19 
                  13262015 
                 IER2; 
               
               
                   
                   
                 ATCTGAGGGAGTCCTCGGAGGGTCGCC 
                   
                   
                 STX10 
               
               
                   
                   
                 CCCTTG[CG]CGTCAGAGTTGCTGCGTG 
                   
                   
                   
               
               
                   
                   
                 GGGTCTCAGAGATAGCGCCTGGGCTGG 
                   
                   
                   
               
               
                   
                   
                 GGAAATCATTGTGGG 
                   
                   
                   
               
               
                   
               
               
                 259 
                 cg11299964 
                 TGTTAGGCTTCTCCATCGAATCTTCTTT 
                  9 
                 128469783 
                 MAPKAP1 
               
               
                   
                   
                 CTCCCCATTTCCACGGAGAAAAGCCCT 
                   
                   
                   
               
               
                   
                   
                 TAGTT[CG]TCCAGAAATGAGTGATGAG 
                   
                   
                   
               
               
                   
                   
                 GCAGCTCAGCCTCTCTGAGAAAGACCT 
                   
                   
                   
               
               
                   
                   
                 GGGTTCAAATGCCA 
                   
                   
                   
               
               
                   
               
               
                 260 
                 cg11314684 
                 AAATGCTCAAAATCAAGAATTACAAA 
                  1 
                 244006288 
                 AKT3 
               
               
                   
                   
                 AAAATCCCTTAATAACAAGCAAATTCC 
                   
                   
                   
               
               
                   
                   
                 TAACACA[CG]TTAAATATATCATTTCT 
                   
                   
                   
               
               
                   
                   
                 CTCTTACTAGACATAGCATGACACAGT 
                   
                   
                   
               
               
                   
                   
                 TTAACAGTATCAGAAA 
                   
                   
                   
               
               
                   
               
               
                 261 
                 cg11388238 
                 GGTCTTGTGTGTTCAGAGGCTGGTTTTA 
                  2 
                 201375098 
                 KCTD18 
               
               
                   
                   
                 CAGGTGAAGAGAAGAAACAGCCGCAG 
                   
                   
                   
               
               
                   
                   
                 AAGTTG[CG]ATTGTCCAAGGTCACTTA 
                   
                   
                   
               
               
                   
                   
                 ATAAGTGGCAAGAATTAGGATGTTAAG 
                   
                   
                   
               
               
                   
                   
                 TGTTCTCACCCCCAG 
                   
                   
                   
               
               
                   
               
               
                 262 
                 cg11653266 
                 ACCCCTGGACGCTGCGTCCTGATTTCC 
                 17 
                  73901339 
                 MRPL38 
               
               
                   
                   
                 CCAGGGACGCAGGCCTGGTTGGGAGA 
                   
                   
                   
               
               
                   
                   
                 AGGGGTG[CG]AGCTCCGATTCCGGACT 
                   
                   
                   
               
               
                   
                   
                 CTGCTTGGGTTTAAAACCCAGATTGAG 
                   
                   
                   
               
               
                   
                   
                 GGCTGGGCGCGGTGGC 
                   
                   
                   
               
               
                   
               
               
                 263 
                 cg12413566 
                 ACCAGGGGGTGATGCCAGACATTGCTC 
                  3 
                  39235366 
                 XIRP1 
               
               
                   
                   
                 ACTTTTTCCATGTAGTCAATGTCAGTCC 
                   
                   
                   
               
               
                   
                   
                 TGCAG[CG]TCAGCTGGGATGGGGGTAA 
                   
                   
                   
               
               
                   
                   
                 GGACATCTGGGAACCCCCTCTTCCTGG 
                   
                   
                   
               
               
                   
                   
                 TCTCCCTCCCTCTT 
                   
                   
                   
               
               
                   
               
               
                 264 
                 cg12616277 
                 GGGCCCCGAGCTGCGCCTGTCCAGCCA 
                  3 
                 138153763 
                 ESYT3 
               
               
                   
                   
                 GCTGCTGCCCGAGCTCTGTACCTTCGT 
                   
                   
                   
               
               
                   
                   
                 GGTGCG[CG]TGCTGTTCTACCTGGGGC 
                   
                   
                   
               
               
                   
                   
                 CTGTCTACCTAGCTGGCTACCTGGGGC 
                   
                   
                   
               
               
                   
                   
                 TCAGCATAACCTGGT 
                   
                   
                   
               
               
                   
               
               
                 265 
                 cg12941369 
                 TCACATGTTTCGTTTCTAGTCCTGAAAC 
                  3 
                  33839389 
                 PDCD6IP 
               
               
                   
                   
                 ATGGTTAAGTGCTTGCCTCCTAGGGCC 
                   
                   
                   
               
               
                   
                   
                 TCTGC[CG]CAGGCTTTTGGTTTGGAGG 
                   
                   
                   
               
               
                   
                   
                 CTCTCCTTTGCCACTCCACCCCTCTCCA 
                   
                   
                   
               
               
                   
                   
                 CTCTTCTCCTCTT 
                   
                   
                   
               
               
                   
               
               
                 266 
                 cg12985418 
                 ATTCACATTTAGTTCGCCTAGGAAAAC 
                 18 
                  19320538 
                 MIB1 
               
               
                   
                   
                 TAGCAGTTAGTGAAAAACTGGCCACAT 
                   
                   
                   
               
               
                   
                   
                 CACAGC[CG]CACAGCTCCAGCAGCCCG 
                   
                   
                   
               
               
                   
                   
                 GGTAGCTTCCCCACCCTCACTTTCTCCA 
                   
                   
                   
               
               
                   
                   
                 GCCCCGCCTCCAGG 
                   
                   
                   
               
               
                   
               
               
                 267 
                 cg13129046 
                 CTACTCAAGGGGCATCCACGGAGCTGG 
                 10 
                  71389696 
                 C10orf35 
               
               
                   
                   
                 GTCAGCAAACATAACACTGGTCATCTG 
                   
                   
                   
               
               
                   
                   
                 AGCCTG[CG]CCCGCCCTTCCTCCCAGG 
                   
                   
                   
               
               
                   
                   
                 CCAGGGCGCCCCCACCCCCTGGGTTTT 
                   
                   
                   
               
               
                   
                   
                 TCCTCCGTGGACGCC 
                   
                   
                   
               
               
                   
               
               
                 268 
                 cg13269407 
                 CAGACACCGAGCCGCGGCCACAGGGC 
                 22 
                  46450107 
                 C22orf26; 
               
               
                   
                   
                 CAGCCGCACAGTCGGAGGAAGGGCCG 
                   
                   
                 LOC15038 
               
               
                   
                   
                 GAGCGAGG[CG]GGGCCCGGGGCTGTC 
                   
                   
                 1 
               
               
                   
                   
                 AAGGAGAAAAACATCCCAAGGCCTGC 
                   
                   
                   
               
               
                   
                   
                 AAATTGCTGCTCTCAGCTT 
                   
                   
                   
               
               
                   
               
               
                 269 
                 cg13302154 
                 AAGGGTTCATCAGGATGGAGATATCCG 
                 12 
                  15039432 
                 MGP 
               
               
                   
                   
                 GTGCACCATGAGTTCTGTTTCCTTAATC 
                   
                   
                   
               
               
                   
                   
                 AACAC[CG]TTGTAACTTGCCCATCCAG 
                   
                   
                   
               
               
                   
                   
                 TTTTGTGACATTAATTCAAACCTGTGCC 
                   
                   
                   
               
               
                   
                   
                 CTAGTCCTCTTTT 
                   
                   
                   
               
               
                   
               
               
                 270 
                 cg13547237 
                 GCAGTGCATCGAGCTGGAGCAGCAGTT 
                 11 
                  65687877 
                 C11orf68; 
               
               
                   
                   
                 TGACTTCTTGAAGGACCTGGTGGCATC 
                   
                   
                 DRAP1 
               
               
                   
                   
                 TGTTCC[CG]ACATGCAGGGGGACGGGG 
                   
                   
                   
               
               
                   
                   
                 AAGACAACCACATGGATGGGGACAAG 
                   
                   
                   
               
               
                   
                   
                 GGCGCCCGCAGGTGGG 
                   
                   
                   
               
               
                   
               
               
                 271 
                 cg13828047 
                 TCAACATACTACATGATTTGCTTACAA 
                 15 
                  75182130 
                 MPI 
               
               
                   
                   
                 TACTTGTCTGTCTTGCCTTCACCAGAAT 
                   
                   
                   
               
               
                   
                   
                 GTAAG[CG]CTCTACAAAGGCAGAGGG 
                   
                   
                   
               
               
                   
                   
                 AAGGCTATCTTGCTCTCTGATGTATCCT 
                   
                   
                   
               
               
                   
                   
                 CCAGCCCTTAGAAC 
                   
                   
                   
               
               
                   
               
               
                 272 
                 cg13931228 
                 GGTGTGAATCACACTGCCCGGTCGGGC 
                  7 
                  24612418 
                 MPP6 
               
               
                   
                   
                 CTTTGGGAAAAAATTAATGAAGGACAC 
                   
                   
                   
               
               
                   
                   
                 AGTCAG[CG]CCGTAGAACCTGCCAAAT 
                   
                   
                   
               
               
                   
                   
                 ACACATCAGATCCAGTGGAGTCTGTGA 
                   
                   
                   
               
               
                   
                   
                 AGGGGGAGGGGGAGA 
                   
                   
                   
               
               
                   
               
               
                 273 
                 cg14060828 
                 GCCTTTCTCGGGATCTATCTTTCTGTGT 
                 19 
                  49926276 
                 PTH2 
               
               
                   
                   
                 CTCTTTCCCTTGCTGATTTTCTGTCCAT 
                   
                   
                   
               
               
                   
                   
                 TTCC[CG]CACCACCACTACCACCAAAC 
                   
                   
                   
               
               
                   
                   
                 CCTCCTCCCGCCTTCCCCCACCCCTAGT 
                   
                   
                   
               
               
                   
                   
                 CTCTGTCTTCTC 
                   
                   
                   
               
               
                   
               
               
                 274 
                 cg14163776 
                 ACTTTGCTCCTGGTGGTTTTCACTGTTC 
                  3 
                 195164580 
                 ACAP2 
               
               
                   
                   
                 TGCCATGGTGGGGTTCTGAAGACCAGG 
                   
                   
                   
               
               
                   
                   
                 CTCAT[CG]TACTCACCTTGCAACACCT 
                   
                   
                   
               
               
                   
                   
                 GCCCCTCTAATCCACACTTTTTCTAGAA 
                   
                   
                   
               
               
                   
                   
                 GCACTTTAAGATA 
                   
                   
                   
               
               
                   
               
               
                 275 
                 cg14175438 
                 CGCACAAAATCCCAGCCTCAAGGGCA 
                  7 
                 121036729 
                 FAM3C 
               
               
                   
                   
                 GAACATTTTAAATGACCCACCCATCCT 
                   
                   
                   
               
               
                   
                   
                 AGAGATG[CG]CCAGTTAGGTCATCTTA 
                   
                   
                   
               
               
                   
                   
                 TATATCTTGAGATAGCTGAGATGGTCA 
                   
                   
                   
               
               
                   
                   
                 GATCAACCAAGGACCT 
                   
                   
                   
               
               
                   
               
               
                 276 
                 cg14408969 
                 ACTGACAATGCTATAGCATCCTGGCCA 
                  8 
                  42396118 
                 C8orf40; 
               
               
                   
                   
                 TATCCAGTTTTGAAAACACTACGGTGT 
                   
                   
                 SLC20A2 
               
               
                   
                   
                 CAGCCA[CG]CACCATTTAGGACGGGGA 
                   
                   
                   
               
               
                   
                   
                 GAATGGAAAGCCAGTTTGGAGAACAG 
                   
                   
                   
               
               
                   
                   
                 ACGCTTTCTTAAGAGT 
                   
                   
                   
               
               
                   
               
               
                 277 
                 cg14409958 
                 TCCCTAGTATCACATTCTCAGCTACTTC 
                  8 
                 120651652 
                 ENPP2 
               
               
                   
                   
                 TGCCTCCTTGAAAGTTTCTCATGATGA 
                   
                   
                   
               
               
                   
                   
                 AATTT[CG]CAAAATTGTAACTAACATA 
                   
                   
                   
               
               
                   
                   
                 AAAGATAACATTATTTTCCCCATGCTG 
                   
                   
                   
               
               
                   
                   
                 TGGTTCAAGTTTAG 
                   
                   
                   
               
               
                   
               
               
                 278 
                 cg14423778 
                 GTCAGTGTTCTTTTAGTTTGCTTAAACT 
                  3 
                 151985433 
                 MBNL1; 
               
               
                   
                   
                 GTGTGGGTACTTGAGTCCTTTTAAACG 
                   
                   
                 LOC40109 
               
               
                   
                   
                 ATTAA[CG]CTGGGAAGAGGCACCATTT 
                   
                   
                 3 
               
               
                   
                   
                 AATTAATTAATTTGTTCTGGAAGGGAT 
                   
                   
                   
               
               
                   
                   
                 CAGTGTACAATTTT 
                   
                   
                   
               
               
                   
               
               
                 279 
                 cg14597908 
                 GGAGACAGAACTTTCCCCTTTTTTCCC 
                 20 
                  57414960 
                 GNASAS; 
               
               
                   
                   
                 ATCCCTTCTTCTTGCTCAGAGAGGCAA 
                   
                   
                 GNAS 
               
               
                   
                   
                 GCAAGG[CG]CGGAGCTTTAGAAAGTTC 
                   
                   
                   
               
               
                   
                   
                 TTAAGTGGTCAGGAAGGTAGGTGCTTC 
                   
                   
                   
               
               
                   
                   
                 CCTTTTTCTCCTCAC 
                   
                   
                   
               
               
                   
               
               
                 280 
                 cg14654875 
                 TGTCCTTTGTGTCTTGAGCGGATGGTG 
                 16 
                   3493997 
                 NAT15; 
               
               
                   
                   
                 GGGCCGTGGAACATGAAGGAGTATCTT 
                   
                   
                 ZNF597 
               
               
                   
                   
                 TGTGTA[CG]TTCACAACGTTCACATCG 
                   
                   
                   
               
               
                   
                   
                 GTGTAGGCCAGGTTGCTGGACTCTGAC 
                   
                   
                   
               
               
                   
                   
                 TCAAAGTGTTATAGA 
                   
                   
                   
               
               
                   
               
               
                 281 
                 cg14727952 
                 CCAACTTCGAGACTTGCAGTCAAAGCG 
                 11 
                 102218358 
                 BIRC2 
               
               
                   
                   
                 ATTTTTAAAATGACTTGTTTTCAAGCCT 
                   
                   
                   
               
               
                   
                   
                 CTGGC[CG]CCGCCCACTCTTCTGGCCC 
                   
                   
                   
               
               
                   
                   
                 TTGGACTTTGACCAAGATGTTTTCTCGC 
                   
                   
                   
               
               
                   
                   
                 AGTTTTTGCAAGG 
                   
                   
                   
               
               
                   
               
               
                 282 
                 cg15185286 
                 CCCCCTCGCCCGGCCCGGCGCCCACTA 
                  6 
                 143381675 
                 AIG1 
               
               
                   
                   
                 GCCACAGGGCCCGCTTCCCCCTGGAGA 
                   
                   
                   
               
               
                   
                   
                 TCAGCG[CG]CACTTCCCGAGCCCTCGT 
                   
                   
                   
               
               
                   
                   
                 AGCACTCAGAGGTCGCATCCACACCTG 
                   
                   
                   
               
               
                   
                   
                 GGATGCCTAGGGGGC 
                   
                   
                   
               
               
                   
               
               
                 283 
                 cg15262928 
                 GGAGTCCTGGCTCCCATTGGCTGCAGC 
                  1 
                 201924572 
                 TIMM17A 
               
               
                   
                   
                 GGGAAATGGTGAACCAATGCTCATAG 
                   
                   
                   
               
               
                   
                   
                 ACCTTAA[CG]CCCTCCTCTCGGGATCA 
                   
                   
                   
               
               
                   
                   
                 CTTCCGCCTCTGGGGTCAGGCTCCGCC 
                   
                   
                   
               
               
                   
                   
                 CAGCTTGCCCGGCATC 
                   
                   
                   
               
               
                   
               
               
                 284 
                 cg15703512 
                 CCAGAAATTGGGCGGCAGTGAGGTCG 
                 16 
                  22012565 
                 C16orf65 
               
               
                   
                   
                 CCGCAAGGCTTCCCGTGGACCCTGCAA 
                   
                   
                   
               
               
                   
                   
                 AACGTGG[CG]TGGGCATTGCACACCAT 
                   
                   
                   
               
               
                   
                   
                 TGTACTGTATGGAAACTTCTGCAGAGG 
                   
                   
                   
               
               
                   
                   
                 TTAGCACCGTGCCTGA 
                   
                   
                   
               
               
                   
               
               
                 285 
                 cg15804973 
                 GGCTAAATTGATCAGGTTCTCCCATGT 
                  6 
                 137114513 
                 MAP3K5 
               
               
                   
                   
                 ACTTTTCCTTTTAAAATTTCCAGTGGCT 
                   
                   
                   
               
               
                   
                   
                 CATTC[CG]TTATCAGTAATGAGTAATT 
                   
                   
                   
               
               
                   
                   
                 GATTAGTGCCAACTGCCGAAGGACTTA 
                   
                   
                   
               
               
                   
                   
                 GTATTCTCATTTAG 
                   
                   
                   
               
               
                   
               
               
                 286 
                 cg16034652 
                 GTTGAAAAAGCTAAGTAATTCTGTAAA 
                 14 
                  93798309 
                 BTBD7; 
               
               
                   
                   
                 AATGTCTACTTTCTCATTACAGTAAGA 
                   
                   
                 KIAA1409 
               
               
                   
                   
                 TGTTTT[CG]CAGAGTTAACAGTGCTCT 
                   
                   
                   
               
               
                   
                   
                 GGTGTAGATAACCAAGACTGCTTCTGT 
                   
                   
                   
               
               
                   
                   
                 AAATTAGGCCTACTC 
                   
                   
                   
               
               
                   
               
               
                 287 
                 cg16168311 
                 CCTCAGCCAGGAGGAGGCCCAGGCCG 
                  1 
                 156561947 
                 APOA1BP 
               
               
                   
                   
                 TGGACCAGGAGCTATTTAACGAATACC 
                   
                   
                   
               
               
                   
                   
                 AGTTCAG[CG]TGGACCAACTTATGGAA 
                   
                   
                   
               
               
                   
                   
                 CTGGCCGGGCTGAGCTGTGCTACAGCC 
                   
                   
                   
               
               
                   
                   
                 ATCGCCAAGGTCAGTG 
                   
                   
                   
               
               
                   
               
               
                 288 
                 cg16358826 
                 CCGCACTCTAGTCCCAGTATTTGCTAA 
                  4 
                  46996264 
                 GABRA4 
               
               
                   
                   
                 GCTATTGCTTTAAAGACACCCCATTTCT 
                   
                   
                   
               
               
                   
                   
                 TTACC[CG]CCTCCACCAGACACGCGCA 
                   
                   
                   
               
               
                   
                   
                 CACCCTCCGCTTTGCTGCTCCATCCTTT 
                   
                   
                   
               
               
                   
                   
                 TCTGGAGAGGAGG 
                   
                   
                   
               
               
                   
               
               
                 289 
                 cg16408394 
                 TTATCCCCAAAGCAGCCCACGCCCGGG 
                  9 
                 137219075 
                 RXRA 
               
               
                   
                   
                 TGGGCAGGGTCCCCCGGGGCTGTATGA 
                   
                   
                   
               
               
                   
                   
                 ACAGAA[CG]TCAGACCTGGGAAGGCC 
                   
                   
                   
               
               
                   
                   
                 CCATTCCAGAAATGGGGCCCCTCACTC 
                   
                   
                   
               
               
                   
                   
                 TGGCACCCCCGGGTGT 
                   
                   
                   
               
               
                   
               
               
                 290 
                 cg16419345 
                 CCCGCAACCTGGCAGTTACTAGAGGTC 
                 17 
                  73976089 
                 ACOX1; 
               
               
                   
                   
                 TTGGAATCCAGACTTCTTTGCTTTCGCC 
                   
                   
                 C17orf106 
               
               
                   
                   
                 ATCAC[CG]TCATCAAAGTGGGAAATGC 
                   
                   
                   
               
               
                   
                   
                 ACACTTACTGTTAAAACCTAGTGTAGG 
                   
                   
                   
               
               
                   
                   
                 GCCGGGCGCGGTGG 
                   
                   
                   
               
               
                   
               
               
                 291 
                 cg16744741 
                 CAGCTGGATGCACTTGTTCTGGAGCTC 
                  4 
                  82126025 
                 PRKG2 
               
               
                   
                   
                 CTCTGTGAGTTCAGCAATGGCCACAGT 
                   
                   
                   
               
               
                   
                   
                 CTGCTT[CG]ACAGCTGCTCCCGCAGCT 
                   
                   
                   
               
               
                   
                   
                 CCTTCAAATGGTACTCCCGCTCCTGGA 
                   
                   
                   
               
               
                   
                   
                 TCTCAGCATCCTTCC 
                   
                   
                   
               
               
                   
               
               
                 292 
                 cg16899442 
                 CGGTGCTGCCTCCACGCCCGGCTTCCC 
                 16 
                    776458 
                 CCDC78; 
               
               
                   
                   
                 CATGGCTGCTGCTGCCACTGGCACTGC 
                   
                   
                 HAGHL 
               
               
                   
                   
                 TAAGTG[CG]TTGCCAAGGCCTCTGTTG 
                   
                   
                   
               
               
                   
                   
                 GTCCCAGGTGACTCCCAGGGCACCGCC 
                   
                   
                   
               
               
                   
                   
                 CACAGGGGCCGGCCA 
                   
                   
                   
               
               
                   
               
               
                 293 
                 cg16984944 
                 TTTCTTCAAATTAAATTGCTACAGCAG 
                  3 
                  99979425 
                 TBC1D23 
               
               
                   
                   
                 GAAATTACTGAACTGTGGCTCTTCTCC 
                   
                   
                   
               
               
                   
                   
                 TACGTC[CG]CCTTCCCTATGTCAATTCC 
                   
                   
                   
               
               
                   
                   
                 CATTTCCCTTGCTTTCTCCAATAGTTAG 
                   
                   
                   
               
               
                   
                   
                 GACTGTAAATTCT 
                   
                   
                   
               
               
                   
               
               
                 294 
                 cg17274064 
                 AAAATAATAATTAAAACTCCCTCAACT 
                 21 
                  40033892 
                 ERG; ERG 
               
               
                   
                   
                 TTTAAGGCCGAGCAACATAATCTATTA 
                   
                   
                   
               
               
                   
                   
                 ATTGGT[CG]CTATTAACATGCAGTTTTA 
                   
                   
                   
               
               
                   
                   
                 TTGACCATAGCACACAGAAGTCTGATT 
                   
                   
                   
               
               
                   
                   
                 GTGAGGGAGGAGTG 
                   
                   
                   
               
               
                   
               
               
                 295 
                 cg17324128 
                 CCCTCCCCCGCCAGCCTGGCGCATTGC 
                 10 
                  45455500 
                 RASSF4 
               
               
                   
                   
                 GGGCCTCGGGCTCATTGCTGAGAGGGG 
                   
                   
                   
               
               
                   
                   
                 GCACTG[CG]CCTGGCACCTCTGTTAAG 
                   
                   
                   
               
               
                   
                   
                 CAATTTAGGGGCTACAACCTGAGCAAG 
                   
                   
                   
               
               
                   
                   
                 ACAGATGAGCCCGGC 
                   
                   
                   
               
               
                   
               
               
                 296 
                 cg17338403 
                 TGGAAGGTGCTGTTTCCTGGTACCTGT 
                 15 
                  92395836 
                 SLCO3A1 
               
               
                   
                   
                 CCAGCCCTCTGAGCTTTTCTCTCAGCTT 
                   
                   
                   
               
               
                   
                   
                 CCAAA[CG]CTGCAGTTGAGAACTAGCA 
                   
                   
                   
               
               
                   
                   
                 GATCCTATTGGTAGTGCCCTGTGGCCC 
                   
                   
                   
               
               
                   
                   
                 ACACTCCTTGGTAA 
                   
                   
                   
               
               
                   
               
               
                 297 
                 cg17589341 
                 CCAGGGGACCAGTTCCTTGGTGTTGCT 
                 18 
                  43304079 
                 SLC14A1 
               
               
                   
                   
                 TTGGCATTGATGCCTGAAGTGGGAGGA 
                   
                   
                   
               
               
                   
                   
                 GAAAGC[CG]AGCCCACAAACACACAG 
                   
                   
                   
               
               
                   
                   
                 AGCAGAGTGGGGCTCTGAGTATATAAC 
                   
                   
                   
               
               
                   
                   
                 TGTTAGGTGCCTCCCT 
                   
                   
                   
               
               
                   
               
               
                 298 
                 cg17686885 
                 TCTGAGGTTTGTGTTATTAACCCCCTAT 
                 17 
                  52977769 
                 TOM1L1 
               
               
                   
                   
                 TATCTTTGGTCTACCCAGGGCAGCCAA 
                   
                   
                   
               
               
                   
                   
                 AGAGG[CG]CAGAGAAGAATGACAAGG 
                   
                   
                   
               
               
                   
                   
                 TGCCCAGCAAGCGGCAGGATCAAAGC 
                   
                   
                   
               
               
                   
                   
                 CTGGGTCTCTAATTCC 
                   
                   
                   
               
               
                   
               
               
                 299 
                 cg18031008 
                 GGCGATTCCGTAATTTCCGCTTCCGGT 
                  1 
                 150266311 
                 MRPS21 
               
               
                   
                   
                 AGTGAGAACCCTTCCGGTGGGCTAGGT 
                   
                   
                   
               
               
                   
                   
                 ACTGAG[CG]CGCGAGGTGAGGAGTTGT 
                   
                   
                   
               
               
                   
                   
                 GCAGGGTTTGGGGAAAGGAAGGCTGG 
                   
                   
                   
               
               
                   
                   
                 CTTGGCGAGAGGGCAG 
                   
                   
                   
               
               
                   
               
               
                 300 
                 cg18139769 
                 GCAGAGCAGGCTGCCTGCCTACTTGTG 
                  7 
                  94286955 
                 SGCE; 
               
               
                   
                   
                 CTTGATTGAAGTGGCGGTGTAGTTGTG 
                   
                   
                 PEG10 
               
               
                   
                   
                 GTGGCG[CG]AATCAGCGTCCAGCAACA 
                   
                   
                   
               
               
                   
                   
                 GTTTGTGGAAACTGTGGGTTTGCTGAG 
                   
                   
                   
               
               
                   
                   
                 TATGGCGGGGGAATT 
                   
                   
                   
               
               
                   
               
               
                 301 
                 cg18328933 
                 CCAGTAGAGCGGGTCAGATGTTGCCAA 
                  3 
                  52008538 
                 ABHD14B 
               
               
                   
                   
                 CCTCTGCAGAGTAGCAATAAGCAGTAA 
                   
                   
                   
               
               
                   
                   
                 ACGCCA[CG]CTCTGCACAGCCTCCCAG 
                   
                   
                   
               
               
                   
                   
                 TGCTGGGCCTGGTCGCCACGCGGAGCC 
                   
                   
                   
               
               
                   
                   
                 TTGGGCTGGGACAGG 
                   
                   
                   
               
               
                   
               
               
                 302 
                 cg18956095 
                 ACTGCTGGATCGTGAGAGGTAAGCATG 
                  8 
                 124287111 
                 ZHX1 
               
               
                   
                   
                 CTGGCTTCTACTGAAACGCCCCTTGTC 
                   
                   
                   
               
               
                   
                   
                 ATCACA[CG]CCCATCCCCTGGGGCGAC 
                   
                   
                   
               
               
                   
                   
                 ACGACCCAGGCCCCGCCCCTCGGGGGG 
                   
                   
                   
               
               
                   
                   
                 CTGCTGCGAGTCCGG 
                   
                   
                   
               
               
                   
               
               
                 303 
                 cg19044674 
                 CTCGACCTCGGCTTGGGAGGCAGCGGC 
                  1 
                  43232628 
                 LEPRE1; 
               
               
                   
                   
                 CACGACAGCCAGCAGTGTGGTCAGCA 
                   
                   
                 C1orf50 
               
               
                   
                   
                 GCTTCAA[CG]CGCGTACCGCCATCGCT 
                   
                   
                   
               
               
                   
                   
                 CCCTCAGACCTAACGGAACCGCCAGCC 
                   
                   
                   
               
               
                   
                   
                 ACCCGCCACCAAGGCC 
                   
                   
                   
               
               
                   
               
               
                 304 
                 cg19046959 
                 CAGTAGCAGCAGCAGCAGCGAAGACA 
                  1 
                  36565856 
                 COL8A2 
               
               
                   
                   
                 GGGGTGTCAGAGTCCCCAGCATGGCGT 
                   
                   
                   
               
               
                   
                   
                 CCGTGGA[CG]TGCTGCAAAGAAGAAC 
                   
                   
                   
               
               
                   
                   
                 AGAGAAAGTCATCAAGCCAGCCCTGG 
                   
                   
                   
               
               
                   
                   
                 GTGGTTTGGCACTAGGCC 
                   
                   
                   
               
               
                   
               
               
                 305 
                 cg19420968 
                 CGATTATCTGTACCCAAAACAGTATGA 
                  1 
                  32084964 
                 HCRTR1 
               
               
                   
                   
                 GTGGGTCCTCATCGCAGCCTATGTGGC 
                   
                   
                   
               
               
                   
                   
                 TGTGTT[CG]TCGTGGCCCTGGTGGGCA 
                   
                   
                   
               
               
                   
                   
                 ACACGCTGGGTAGGTCCAGGGCTTGCC 
                   
                   
                   
               
               
                   
                   
                 CGGCAGTGCTGCCGG 
                   
                   
                   
               
               
                   
               
               
                 306 
                 cg19569684 
                 GGGCCCTCCATGCCATCGGAGCTGGCA 
                  5 
                 138726419 
                 MGC2950 
               
               
                   
                   
                 TCTCCAGCTAGAAAATGGCCAGTTGTT 
                   
                   
                 6 
               
               
                   
                   
                 CTGATT[CG]TAGCTCTCCTAGTCAGCTT 
                   
                   
                   
               
               
                   
                   
                 CCAGTCCAGGGCAGAGGGCAGGGACT 
                   
                   
                   
               
               
                   
                   
                 GCTAGGGACCTGGGC 
                   
                   
                   
               
               
                   
               
               
                 307 
                 cg19706682 
                 ATAACAATAATAATAATGGTAGCAAGC 
                 16 
                  84179331 
                 LRRC50; 
               
               
                   
                   
                 AACGCTCTGCAGTAGGGGCTTCTCTCG 
                   
                   
                 HSDL1 
               
               
                   
                   
                 CCATTT[CG]TACTGAGGAGGAAACATA 
                   
                   
                   
               
               
                   
                   
                 CTTAAGAGGTTACAAAACTTGCACCAA 
                   
                   
                   
               
               
                   
                   
                 ACAGATAACCCTCGG 
                   
                   
                   
               
               
                   
               
               
                 308 
                 cg19722847 
                 TCTGCTTACAGCTGCTTCCAAATTAAG 
                 12 
                  30849114 
                 IPO8 
               
               
                   
                   
                 CATATCTGGATGGTGTGACACTTTTTGT 
                   
                   
                   
               
               
                   
                   
                 TAGTC[CG]AGAACTGTATGGGCATCGC 
                   
                   
                   
               
               
                   
                   
                 AACTGGGCCTGTTCCAAGATAGACTTG 
                   
                   
                   
               
               
                   
                   
                 TTGGGACCTTCAAA 
                   
                   
                   
               
               
                   
               
               
                 309 
                 cg19724470 
                 CATTCTTATGCGACTGTGTGTTCAGAA 
                  9 
                   5450936 
                 CD274 
               
               
                   
                   
                 TATAGCTCTGATGCTAGGCTGGAGGTC 
                   
                   
                   
               
               
                   
                   
                 TGGACA[CG]GGTCCAAGTCCACCGCCA 
                   
                   
                   
               
               
                   
                   
                 GCTGCTTGCTAGTAACATGACTTGTGT 
                   
                   
                   
               
               
                   
                   
                 AAGTTATCCCAGCTG 
                   
                   
                   
               
               
                   
               
               
                 310 
                 cg19761273 
                 GGACAAAGCCACCACCTTTCACAAAAT 
                 17 
                  80232096 
                 CSNK1D 
               
               
                   
                   
                 GAGGCCAGACCACCTGCCTCCCTCCAG 
                   
                   
                   
               
               
                   
                   
                 TCCCTG[CG]GCCTGGAGACGGAGTCAA 
                   
                   
                   
               
               
                   
                   
                 CATTCTTATCTGTGTTGGATCTGAATGT 
                   
                   
                   
               
               
                   
                   
                 TCCTCCTTGCAAAG 
                   
                   
                   
               
               
                   
               
               
                 311 
                 cg19853760 
                 AAAAGGGTGGGAGCGTCCGGGGGCCC 
                 22 
                  38071677 
                 LGALS1 
               
               
                   
                   
                 ATCTCTCTCGGGTGGAGTCTTCTGACA 
                   
                   
                   
               
               
                   
                   
                 GCTGGTG[CG]CCTGCCCGGGAACATCC 
                   
                   
                   
               
               
                   
                   
                 TCCTGGACTCAATCATGGCTTGTGTGA 
                   
                   
                   
               
               
                   
                   
                 GTGTGGGGACCCCCCC 
                   
                   
                   
               
               
                   
               
               
                 312 
                 cg20100381 
                 GACTAGCATTTTATTTCCATTGGACAG 
                 16 
                  66864408 
                 NAE1 
               
               
                   
                   
                 CGCTGGCTGAGAACAAAACCTAACCCT 
                   
                   
                   
               
               
                   
                   
                 CTGTGC[CG]CCCTCGCGGCCGGGATGC 
                   
                   
                   
               
               
                   
                   
                 GGTGCGCCCCGGGCCTCCCCATTCGGA 
                   
                   
                   
               
               
                   
                   
                 AAACGAGGAGCCTGG 
                   
                   
                   
               
               
                   
               
               
                 313 
                 cg20240860 
                 ACTGCGATGAAAGGCCATAAGGATGCT 
                 11 
                  44087423 
                 ACCS 
               
               
                   
                   
                 CACACCCGAATCTAAAAAGCCCTTTGT 
                   
                   
                   
               
               
                   
                   
                 GTGGGC[CG]CAGCCAAGCATACTTTGG 
                   
                   
                   
               
               
                   
                   
                 CAAGAAATTTCTGTGGCTCTAACCTCC 
                   
                   
                   
               
               
                   
                   
                 TTTGAAAACTGGAGA 
                   
                   
                   
               
               
                   
               
               
                 314 
                 cg21211748 
                 GACGGAGACAGAGGGTGGTTCCGGGA 
                  1 
                  23858035 
                 E2F2 
               
               
                   
                   
                 TTCACAGTGCAGAGGCGGCCAGAGCA 
                   
                   
                   
               
               
                   
                   
                 GTGCACAG[CG]CCCCGAGAAATGGGC 
                   
                   
                   
               
               
                   
                   
                 CCGGATTCCCTGGGATTGAAGGGAAAC 
                   
                   
                   
               
               
                   
                   
                 ATTTTGGCGCGGGGTCCC 
                   
                   
                   
               
               
                   
               
               
                 315 
                 cg21305265 
                 GTAGTCCCCGAGGTCACAAGGCAGTGG 
                  8 
                  25316571 
                 KCTD9; 
               
               
                   
                   
                 CAGGTGTCTGTAGTCCTCGGGTTGACT 
                   
                   
                 CDCA2 
               
               
                   
                   
                 GCAGCT[CG]CGGTGGTCCCTCTCCGAG 
                   
                   
                   
               
               
                   
                   
                 CCCAGGAAGCCACTCCAGTGCCGAGG 
                   
                   
                   
               
               
                   
                   
                 GAGAGGCCTGGGAGCG 
                   
                   
                   
               
               
                   
               
               
                 316 
                 cg21370143 
                 AGACCCAACCCCAGTCCTAAAGCTACC 
                 11 
                  47374208 
                 MYBPC3 
               
               
                   
                   
                 TGGCTTCTTCCCCGGCTCAGGCATCCT 
                   
                   
                   
               
               
                   
                   
                 GAGAGA[CG]TCACACCAGGCACGAAG 
                   
                   
                   
               
               
                   
                   
                 CAGGCACAGGTCACCCAAAGAGGGAC 
                   
                   
                   
               
               
                   
                   
                 TGAGTGGGGTCCTGTCC 
                   
                   
                   
               
               
                   
               
               
                 317 
                 cg21395782 
                 GGCCTGCGCAACACCCCAGAGGCAAG 
                 19 
                  19626814 
                 NDUFA13; 
               
               
                   
                   
                 GTGAACGCGAGGGCCTATAATGCAAG 
                   
                   
                 TSSK6 
               
               
                   
                   
                 AACCAAGG[CG]AGTCACGCCCTGTCTG 
                   
                   
                   
               
               
                   
                   
                 GGCAAAAGAGGAGTAAAGACCCCTCA 
                   
                   
                   
               
               
                   
                   
                 GCTGCAGCCCGGCAGCGC 
                   
                   
                   
               
               
                   
               
               
                 318 
                 cg21950518 
                 GTCGGCCTGGCAGGCGCGGCCCCCGGT 
                  5 
                  55290746 
                 IL6ST 
               
               
                   
                   
                 TCAGCTGCGCCGGGGCGGCCCAGCGCG 
                   
                   
                   
               
               
                   
                   
                 ACTCCG[CG]GGCCTTTTGGCTGCTCGC 
                   
                   
                   
               
               
                   
                   
                 CCCGGCTCCGGAACACTGTCAGATCCT 
                   
                   
                   
               
               
                   
                   
                 TCTCCGCAGAGGTAG 
                   
                   
                   
               
               
                   
               
               
                 319 
                 cg22171829 
                 CTGTGTCCCCTCTCACCAAAGTCCAGT 
                  7 
                  95225520 
                 PDK4 
               
               
                   
                   
                 AGCTGCTTCATGGACAGCGGGGACGG 
                   
                   
                   
               
               
                   
                   
                 GCTGTAG[CG]CGAGAAATGCTCCACCT 
                   
                   
                   
               
               
                   
                   
                 CTCGGGGCACCAGGCCGGCGCCGTTGA 
                   
                   
                   
               
               
                   
                   
                 GCGAGCCAGCGCTGCG 
                   
                   
                   
               
               
                   
               
               
                 320 
                 cg22190114 
                 TTTTATTGTTTTATGTCTCTGCAGGTCT 
                 19 
                  56459234 
                 NLRP8 
               
               
                   
                   
                 CGTGTTTCTCTCTTCCAATCGGTTGTCT 
                   
                   
                   
               
               
                   
                   
                 TTAT[CG]TGGACACTGAGGTGTTCTCT 
                   
                   
                   
               
               
                   
                   
                 GCCTTGACTAAAGATGAGTGACGTGAA 
                   
                   
                   
               
               
                   
                   
                 TCCACCCTCTGAC 
                   
                   
                   
               
               
                   
               
               
                 321 
                 cg22197830 
                 GAAGGCTCCTGGGCCTTTCTGGCTCTG 
                  5 
                 134209784 
                 TXNDC15 
               
               
                   
                   
                 GGAATGAAGCGTGGAAAACCCTCCTTA 
                   
                   
                   
               
               
                   
                   
                 GGCGGG[CG]CAGTGCTTCAAGTAGCCA 
                   
                   
                   
               
               
                   
                   
                 AGCTCTGACTTCCGAGGGAAGAAAGG 
                   
                   
                   
               
               
                   
                   
                 AGGCCATGGGCCTCTG 
                   
                   
                   
               
               
                   
               
               
                 322 
                 cg22568540 
                 GACCACGAGCATGGACATGATGGTCGC 
                 19 
                  58864846 
                 NCRNA00 
               
               
                   
                   
                 GCTCACTCCGGTGCAGTGAGTGTCTGG 
                   
                   
                 181; A1BG 
               
               
                   
                   
                 GGTGAG[CG]TCTGCAGCAATGAGGCCC 
                   
                   
                   
               
               
                   
                   
                 CAAGGGAGGGCGGTGGGGTGGCTCGG 
                   
                   
                   
               
               
                   
                   
                 GCACTGACCTCTTCCC 
                   
                   
                   
               
               
                   
               
               
                 323 
                 cg22613010 
                 ATTAGGGTAGGCCCCTGGTCCTCGCGC 
                  3 
                 184079172 
                 CLCN2 
               
               
                   
                   
                 TTCCCAGGGTAACCTGGAGCAGGGGTC 
                   
                   
                   
               
               
                   
                   
                 CCGGAG[CG]CACTCCTGGGGCTCAGCT 
                   
                   
                   
               
               
                   
                   
                 CAGCTTCACTTACCAGGGTCTGCTCGT 
                   
                   
                   
               
               
                   
                   
                 ACTGCAGCGCCCGTG 
                   
                   
                   
               
               
                   
               
               
                 324 
                 cg22637507 
                 GCCTGTGATTGGGAGTTGCTGGAGTCG 
                 11 
                  43902407 
                 ALKBH3 
               
               
                   
                   
                 GTGCTTCACTCTTAAGGTTCCGATCAC 
                   
                   
                   
               
               
                   
                   
                 AGACTG[CG]GAGTGGGTCAGGGGCTG 
                   
                   
                   
               
               
                   
                   
                 CGAGGGCTGCCCCAAGTCCTACCGGGT 
                   
                   
                   
               
               
                   
                   
                 TTGCACGGGCGCGCCC 
                   
                   
                   
               
               
                   
               
               
                 325 
                 cg22947000 
                 TAGCTATGACACATGGCTTGGAAATTA 
                 16 
                  81272281 
                 BCMO1 
               
               
                   
                   
                 ACCTTTAACCAAACATCTTATAAGTAA 
                   
                   
                   
               
               
                   
                   
                 CGCCAG[CG]CAGCTTCCCTTGTGAATG 
                   
                   
                   
               
               
                   
                   
                 TAAAGAGATCCAGGGCTCTTGGAGAG 
                   
                   
                   
               
               
                   
                   
                 GGACAAGTGAGAGCCA 
                   
                   
                   
               
               
                   
               
               
                 326 
                 cg23092072 
                 CAAAAAAGGCGGGCTGTTTTGTAAATA 
                  4 
                  87927706 
                 AFF1 
               
               
                   
                   
                 TTTGTCTCTATGTAAGGAAATCAAAAC 
                   
                   
                   
               
               
                   
                   
                 TGAAAG[CG]GAGTAACACCAAGTATG 
                   
                   
                   
               
               
                   
                   
                 CCCGTTTCTTGAGCTCAAGCACTGGAA 
                   
                   
                   
               
               
                   
                   
                 GGATCAAAAGTAGCGA 
                   
                   
                   
               
               
                   
               
               
                 327 
                 cg23124451 
                 TCAGTCTCCCCATATTTACAATAAAAG 
                 22 
                  39548131 
                 CBX7 
               
               
                   
                   
                 GGGAGCGAGGTGGGATGGCGCTGAGG 
                   
                   
                   
               
               
                   
                   
                 ATCCCTA[CG]TCCGATCCTAATCTCCA 
                   
                   
                   
               
               
                   
                   
                 GCTCAGGCAGGCTCGGCCGCCACTAGC 
                   
                   
                   
               
               
                   
                   
                 ATCCTGGAGCGACAAC 
                   
                   
                   
               
               
                   
               
               
                 328 
                 cg23180365 
                 AACCCCGGCATGACCACCAGCCTCCCG 
                  3 
                  33138627 
                 GLB1; 
               
               
                   
                   
                 GCTCTGCAGTCGGCGCCCAGGCCGGCC 
                   
                   
                 TMPPE 
               
               
                   
                   
                 GCTTCG[CG]TCACTTGACTAAGGACCC 
                   
                   
                   
               
               
                   
                   
                 ACGGCCTGGCACCGCCCCTCGTCGGCC 
                   
                   
                   
               
               
                   
                   
                 CAGCAGCCAGCCCTC 
                   
                   
                   
               
               
                   
               
               
                 329 
                 cg23786576 
                 AGAGACTCCCAGCTCTGACACCAATTA 
                  1 
                  47133596 
                 ATPAF1 
               
               
                   
                   
                 GCTGTGTGATCTTGGGCAAGTGACCTA 
                   
                   
                   
               
               
                   
                   
                 GCCTCG[CG]GAGCCTGGCTACATCATC 
                   
                   
                   
               
               
                   
                   
                 TGAAGAGCTGGGACAGTACTAGTGCCC 
                   
                   
                   
               
               
                   
                   
                 ACCTCACAGGGCTGT 
                   
                   
                   
               
               
                   
               
               
                 330 
                 cg24058132 
                 GGGCCATGAGTGGCCCTACCATGGCTC 
                 14 
                  88459866 
                 GALC 
               
               
                   
                   
                 TTCCCCAGCATCTCAGGGAGTATCTAC 
                   
                   
                   
               
               
                   
                   
                 CTCGTG[CG]AGGACCAGGCTTGGACAC 
                   
                   
                   
               
               
                   
                   
                 CAGGTCCCGATTCCATTGTCATCTTGGT 
                   
                   
                   
               
               
                   
                   
                 GGAATCACTTTGCT 
                   
                   
                   
               
               
                   
               
               
                 331 
                 cg24081819 
                 CGCGCTGGGCTTGCAGCCCAGCTTTCA 
                  8 
                  27348940 
                 EPHX2 
               
               
                   
                   
                 GATTGCTCCTGTGCCGGAGCCCTGCGA 
                   
                   
                   
               
               
                   
                   
                 ATCATG[CG]AATCATGAAACTGAAGAC 
                   
                   
                   
               
               
                   
                   
                 CTGGCCCTGAAGTCCCAGTGCATATGA 
                   
                   
                   
               
               
                   
                   
                 GGAGATCCGTTGTCT 
                   
                   
                   
               
               
                   
               
               
                 332 
                 cg24471894 
                 TTTTTCTTGTGCTGTCTTTGTACTCTTTC 
                  9 
                   2838508 
                 KIAA0020 
               
               
                   
                   
                 CTGTGAATTGCTTTTTCCCTTTAACTTC 
                   
                   
                   
               
               
                   
                   
                 CAT[CG]TAGCAACTCTGGAAAACCAAA 
                   
                   
                   
               
               
                   
                   
                 ACCAAAACCAAAAACAATCACTGCAG 
                   
                   
                   
               
               
                   
                   
                 TTCTCTTCATCAA 
                   
                   
                   
               
               
                   
               
               
                 333 
                 cg24888049 
                 AGCATTGCTGGTTCTATTTAATGGACA 
                 15 
                  91426667 
                 FES; 
               
               
                   
                   
                 TGAGATAATGTTAGAGGTTTTAAAGTG 
                   
                   
                 FURIN 
               
               
                   
                   
                 ATTAAA[CG]TGCAGACTATGCAAACCA 
                   
                   
                   
               
               
                   
                   
                 GGCCCAGTCTCCAGTGTGGTACCGTTG 
                   
                   
                   
               
               
                   
                   
                 CTCCTGCATCGCAGC 
                   
                   
                   
               
               
                   
               
               
                 334 
                 cg24899750 
                 GGAGGAACTGGCTATCCTAAAGGTGAT 
                 20 
                  16710314 
                 SNRPB2 
               
               
                   
                   
                 TTTAAACCGGGGTAGCTAGAGCCCAAA 
                   
                   
                   
               
               
                   
                   
                 GAAGGG[CG]AAACCAGGACTAACTGC 
                   
                   
                   
               
               
                   
                   
                 CCCATAGCATGAGGGGCAGCGCCTGTA 
                   
                   
                   
               
               
                   
                   
                 AAATTACATAGGATTT 
                   
                   
                   
               
               
                   
               
               
                 335 
                 cg25101936 
                 CTGGCCCACCCGTGAGTCACGGACAGA 
                 11 
                 113929164 
                 ZBTB16 
               
               
                   
                   
                 ACATGCAGACTCAGGCCTTGGTGACAT 
                   
                   
                   
               
               
                   
                   
                 AAGCTC[CG]CATTGCTAAAACCGCGTG 
                   
                   
                   
               
               
                   
                   
                 ACCTCGAGGGCTGACTGGCCTGAGAAC 
                   
                   
                   
               
               
                   
                   
                 CCTGGATGGCGCTCT 
                   
                   
                   
               
               
                   
               
               
                 336 
                 cg25159610 
                 GCCATCTTGTGGAATGTTCCGGAATGC 
                  5 
                  57756802 
                 PLK2 
               
               
                   
                   
                 CGTTAGGTGTCGAAGTGGGCAGCGGTT 
                   
                   
                   
               
               
                   
                   
                 GACAAC[CG]TGGGCCTTTGACAGTTAC 
                   
                   
                   
               
               
                   
                   
                 TAGTACTAAACATCGATGCCGATTGTG 
                   
                   
                   
               
               
                   
                   
                 AGTTTCCAATCAGAG 
                   
                   
                   
               
               
                   
               
               
                 337 
                 cg25166896 
                 CGTGGTCCCTGCAGGGTGTGTGGGCTG 
                 22 
                  20009063 
                 C22orf25 
               
               
                   
                   
                 CTCGGCCTTGGCCAGCATCAGGGACAG 
                   
                   
                   
               
               
                   
                   
                 CTCTGG[CG]CCCGGTCACTCTGCCCCC 
                   
                   
                   
               
               
                   
                   
                 TACCCGCGGCCTGCTGCGGGCCAGCAG 
                   
                   
                   
               
               
                   
                   
                 GGTGACAGCTAATGT 
                   
                   
                   
               
               
                   
               
               
                 338 
                 cg25411725 
                 TCTACCTGTCTCATTTGAGTTGAGTGTG 
                  3 
                  38306672 
                 SLC22A13 
               
               
                   
                   
                 AATTGTTTAGGATATTGCAATTAGAGG 
                   
                   
                   
               
               
                   
                   
                 TGGTG[CG]GGCTGGCTGGTTGCTATAA 
                   
                   
                   
               
               
                   
                   
                 GCCATCTTAACATTTGGCTAAGCTCAC 
                   
                   
                   
               
               
                   
                   
                 TCCTGTGTGCTGGG 
                   
                   
                   
               
               
                   
               
               
                 339 
                 cg25564800 
                 GATGGAATGAATGATGGAATGATTGAA 
                  3 
                 122234134 
                 KPNA1 
               
               
                   
                   
                 GGCTGAGGGAGTATTACAAAATTAGTA 
                   
                   
                   
               
               
                   
                   
                 GGTCAG[CG]CCTCGTGTCTAAAGGGCT 
                   
                   
                   
               
               
                   
                   
                 CACATGCAGCATGAATGCAGGAAGCTT 
                   
                   
                   
               
               
                   
                   
                 CTGGACATTCCTTTT 
                   
                   
                   
               
               
                   
               
               
                 340 
                 cg25657834 
                 CGAGCTGCCTGGTTAGTGAGCACCTCC 
                  2 
                  11810365 
                 NTSR2 
               
               
                   
                   
                 TCTTCTCTGGGAACCTCTAGAACTGGG 
                   
                   
                   
               
               
                   
                   
                 AGGACA[CG]CCCCCGAAAGGGTGTCCC 
                   
                   
                   
               
               
                   
                   
                 TGAGCCAACGTGGGACCGCGAGTGCC 
                   
                   
                   
               
               
                   
                   
                 AGCCCGTTAGCGTCGG 
                   
                   
                   
               
               
                   
               
               
                 341 
                 cg25809905 
                 ACTTGATTCTGGTTGGGGGCTTTGCCT 
                 17 
                  42467728 
                 ITGA2B 
               
               
                   
                   
                 AGGGGAGCCTTCCCTGACTCCTCAGGC 
                   
                   
                   
               
               
                   
                   
                 TGGCCG[CG]TGGGCTAACACACGTAGG 
                   
                   
                   
               
               
                   
                   
                 CACAGCATTGAGCACACTGTTTACTCT 
                   
                   
                   
               
               
                   
                   
                 TGGTCCGTTCACAGG 
                   
                   
                   
               
               
                   
               
               
                 342 
                 cg25928579 
                 AATGAGTTGTTTCATATTTTGCACTGTC 
                 17 
                  46692534 
                 HOXB8 
               
               
                   
                   
                 TTTTCATGATCATTTGCATCCATTAGAG 
                   
                   
                   
               
               
                   
                   
                 ACCC[CG]CATCCTATTGGCTTCTTCGTA 
                   
                   
                   
               
               
                   
                   
                 CTCCTCCCGGACAGAACGCAGAGCGA 
                   
                   
                   
               
               
                   
                   
                 GGGTGAGAGCGAG 
                   
                   
                   
               
               
                   
               
               
                 343 
                 cg26043391 
                 AACTCCTGCCTCCCTCTCCCCCCGGCC 
                  1 
                 224302174 
                 FBXO28 
               
               
                   
                   
                 GAGGTCTGGGAGATGAGAAGGGAGCG 
                   
                   
                   
               
               
                   
                   
                 CGTTCCC[CG]GGAAGGGAGCCCCCCGC 
                   
                   
                   
               
               
                   
                   
                 GAGCCCCAGCCGGCTACAGATCTGGGA 
                   
                   
                   
               
               
                   
                   
                 GGGAGCCGCTCCCGTC 
                   
                   
                   
               
               
                   
               
               
                 344 
                 cg26162695 
                 AAGCGCCCACATGCGCCCGTCTCCACC 
                 17 
                  12921313 
                 ELAC2 
               
               
                   
                   
                 AAAACTGAGAAAGCCGCCGGTCACCT 
                   
                   
                   
               
               
                   
                   
                 ACGCCCG[CG]TTTCCCGTGCACCACCT 
                   
                   
                   
               
               
                   
                   
                 AGCCGCTCCGCATGGCGGATCCAGCCA 
                   
                   
                   
               
               
                   
                   
                 ATCAGCGCGCCGTGCA 
                   
                   
                   
               
               
                   
               
               
                 345 
                 cg26394940 
                 TAAATAAATAAGGGCTTTTGTTTGTTTG 
                 22 
                  46449461 
                 C22orf26; 
               
               
                   
                   
                 CCGGCTCCTGCACATGGCTGCTGGGAC 
                   
                   
                 LOC15038 
               
               
                   
                   
                 TCAAG[CG]CTCGTGTTGTCTGCGCCTCT 
                   
                   
                 1 
               
               
                   
                   
                 GTGGGACTCTGGGGACGGGAGGCAGG 
                   
                   
                   
               
               
                   
                   
                 GGAGGCCCCCGCAG 
                   
                   
                   
               
               
                   
               
               
                 346 
                 cg26456957 
                 CCGGGTAAAGGGGATGAATAGCAGAC 
                 19 
                  55629363 
                 PPP1R12C 
               
               
                   
                   
                 TGCCCCGGGGCAGTTAGGAATTCGACT 
                   
                   
                   
               
               
                   
                   
                 GGACAGC[CG]CGTGGGAGGGAGTGCG 
                   
                   
                   
               
               
                   
                   
                 GGGAGAGGCAGAGTTGTTTTGTTATTG 
                   
                   
                   
               
               
                   
                   
                 TTGTTTTATTTTGTTTT 
                   
                   
                   
               
               
                   
               
               
                 347 
                 cg26614073 
                 CTTGGGCAACGTAGGAGACCTCCGTCT 
                  3 
                  47517819 
                 SCAP 
               
               
                   
                   
                 CCACAAGTAAAATTAATTAGCCGGCTG 
                   
                   
                   
               
               
                   
                   
                 TGGTGG[CG]CGCACCTGTGGTCCCAGC 
                   
                   
                   
               
               
                   
                   
                 TACTCAGGAGGCTGAGGTAGGAGGAT 
                   
                   
                   
               
               
                   
                   
                 CACCTGAGCCCGGGAG 
                   
                   
                   
               
               
                   
               
               
                 348 
                 cg26723847 
                 AGCCTGCAGGTGGGTTTGTTAGGGGGA 
                 11 
                 134095652 
                 VPS26B; 
               
               
                   
                   
                 GACCGCTCTGCCAATACTGGCTTTCCC 
                   
                   
                 NCAPD3 
               
               
                   
                   
                 ATCGCC[CG]GCCATCTGCAACTGCCAG 
                   
                   
                   
               
               
                   
                   
                 ACGCAAAGTGAGGCTCGTCCACCGAGC 
                   
                   
                   
               
               
                   
                   
                 CCCACTTCCCAGAGC 
                   
                   
                   
               
               
                   
               
               
                 349 
                 cg26824091 
                 GGACTGGTACAGGACAGGCATCTTTGA 
                  6 
                  38670437 
                 GLO1 
               
               
                   
                   
                 ACCTATTTCTGGGAGTTCTGAAACTAC 
                   
                   
                   
               
               
                   
                   
                 TGTTCT[CG]TGGGCCTTGGCGACTGAT 
                   
                   
                   
               
               
                   
                   
                 TTGGGAAAGCTGACCCTGGGTTGGCCT 
                   
                   
                   
               
               
                   
                   
                 GGCTTCCAGCCACCG 
                   
                   
                   
               
               
                   
               
               
                 350 
                 cg27015931 
                 TGTTTTTGTGGGAGGCCTTCTGCATGGT 
                 16 
                  22012404 
                 C16orf65 
               
               
                   
                   
                 CCCGGGAGGTCAGGCAGCCCGGGAGG 
                   
                   
                   
               
               
                   
                   
                 GCCTCC[CG]GAGCAGAGGCTGGAGTCA 
                   
                   
                   
               
               
                   
                   
                 GTCCCAATGCCAACAGTTTCGAACCTT 
                   
                   
                   
               
               
                   
                   
                 GCCCGCGGGCACTGC 
                   
                   
                   
               
               
                   
               
               
                 351 
                 cg27016307 
                 TCTCTCCCTGGCCAGGAGACGGTGGCC 
                 19 
                  49658913 
                 HRC 
               
               
                   
                   
                 AAGGGACTTGACTTTGAACTACCAACA 
                   
                   
                   
               
               
                   
                   
                 AGCTCA[CG]TTTGGCAGCTGCAAAGAC 
                   
                   
                   
               
               
                   
                   
                 AAAGGCTAGACTTTTAGCAGGTTTTTG 
                   
                   
                   
               
               
                   
                   
                 GGGGAGCCTGGGGCA 
                   
                   
                   
               
               
                   
               
               
                 352 
                 cg27202708 
                 CGGGCAAGGTCTGAAGACTGCGAGGA 
                  1 
                 223566709 
                 C1orf65 
               
               
                   
                   
                 CCCAGCTGCCAGGCGCATTGTGAAGTG 
                   
                   
                   
               
               
                   
                   
                 GCCCGAG[CG]TCACAGGCGACCCGGA 
                   
                   
                   
               
               
                   
                   
                 CCTCGGGACCGGGGGGCAGGGCGGGT 
                   
                   
                   
               
               
                   
                   
                 GTCTGCAGCGTCCTCGGG 
                   
                   
                   
               
               
                   
               
               
                 353 
                 cg27544190 
                 GAACCCTCGACTGGGGGCAGCCGCACC 
                 21 
                  33785434 
                 C21orf63 
               
               
                   
                   
                 AGTGGACACGGCGGGGTAGGATTAAA 
                   
                   
                   
               
               
                   
                   
                 GTTGAGG[CG]TGCTCACAGACACTTGT 
                   
                   
                   
               
               
                   
                   
                 CTGGTGTGAGCCCTTGGCATATAGATG 
                   
                   
                   
               
               
                   
                   
                 GCTGCGAGTGAAGTGG 
                   
                   
                   
               
               
                   
               
               
                 354 
                 cg21296230 
                 GGTGCGTTGTTCGCGGGGGTGAATTGT 
                 15 
                  33010536 
                 GREM1 
               
               
                   
                   
                 GAAGAACCATCGCGGGGTCCTTCCTGC 
                   
                   
                   
               
               
                   
                   
                 TGAGGC[CG]CGGACACCGTGACCTCGC 
                   
                   
                   
               
               
                   
                   
                 TGCTCTGGGTCTGCAGGGAAACGTAGG 
                   
                   
                   
               
               
                   
                   
                 AAAAAAAGTTGTCAG 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Listing of 110 CpGs Subset 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Sequence with the CpG  
                 Chromo- 
                   
                   
               
               
                 Probe 
                 site marked with [ ] 
                 some 
                 Position 
                 Gene 
               
               
                   
               
               
                 cg00075967 
                 GGTGTGGCCAGGAGCCACCCCCACCCC 
                 15 
                  74495354 
                 STRA6 
               
               
                   
                 CGCACCTGACTTCACACACATACCTGC 
                   
                   
                   
               
               
                   
                 CTTCAG[CG]CCTGCCCCAGAGCTCCCA 
                   
                   
                   
               
               
                   
                 AGCCCCTGCCCGCCACATCTGCAGTGC 
                   
                   
                   
               
               
                   
                 CGCACACAGACAGGA 
                   
                   
                   
               
               
                   
               
               
                 cg01511567 
                 GTAGTTTTATTGTATCAGACTTAGTACA 
                 11 
                  57103631 
                 SSRP1 
               
               
                   
                 GGGGTGGGGTGGGGGTGTGTATTGGAA 
                   
                   
                   
               
               
                   
                 TGATG[CG]TGCCCGTTTCTCTGCAAAA 
                   
                   
                   
               
               
                   
                 TAGTTTCTATGTCATGGAAAGGAGTCG 
                   
                   
                   
               
               
                   
                 ATGGGACAAGAAGA 
                   
                   
                   
               
               
                   
               
               
                 cg27544190 
                 GAACCCTCGACTGGGGGCAGCCGCACC 
                 21 
                  33785434 
                 C21orf63 
               
               
                   
                 AGTGGACACGGCGGGGTAGGATTAAA 
                   
                   
                   
               
               
                   
                 GTTGAGG[CG]TGCTCACAGACACTTGT 
                   
                   
                   
               
               
                   
                 CTGGTGTGAGCCCTTGGCATATAGATG 
                   
                   
                   
               
               
                   
                 GCTGCGAGTGAAGTGG 
                   
                   
                   
               
               
                   
               
               
                 cg19761273 
                 GGACAAAGCCACCACCTTTCACAAAAT 
                 17 
                  80232096 
                 CSNK1D 
               
               
                   
                 GAGGCCAGACCACCTGCCTCCCTCCAG 
                   
                   
                   
               
               
                   
                 TCCCTG[CG]GCCTGGAGACGGAGTCAA 
                   
                   
                   
               
               
                   
                 CATTCTTATCTGTGTTGGATCTGAATGT 
                   
                   
                   
               
               
                   
                 TCCTCCTTGCAAAG 
                   
                   
                   
               
               
                   
               
               
                 cg17324128 
                 CCCTCCCCCGCCAGCCTGGCGCATTGC 
                 10 
                  45455500 
                 RASSF4 
               
               
                   
                 GGGCCTCGGGCTCATTGCTGAGAGGGG 
                   
                   
                   
               
               
                   
                 GCACTG[CG]CCTGGCACCTCTGTTAAG 
                   
                   
                   
               
               
                   
                 CAATTTAGGGGCTACAACCTGAGCAAG 
                   
                   
                   
               
               
                   
                 ACAGATGAGCCCGGC 
                   
                   
                   
               
               
                   
               
               
                 cg27015931 
                 TGTTTTTGTGGGAGGCCTTCTGCATGGT 
                 16 
                  22012404 
                 C16orf65 
               
               
                   
                 CCCGGGAGGTCAGGCAGCCCGGGAGG 
                   
                   
                   
               
               
                   
                 GCCTCC[CG]GAGCAGAGGCTGGAGTCA 
                   
                   
                   
               
               
                   
                 GTCCCAATGCCAACAGTTTCGAACCTT 
                   
                   
                   
               
               
                   
                 GCCCGCGGGCACTGC 
                   
                   
                   
               
               
                   
               
               
                 cg26614073 
                 CTTGGGCAACGTAGGAGACCTCCGTCT 
                  3 
                  47517819 
                 SCAP 
               
               
                   
                 CCACAAGTAAAATTAATTAGCCGGCTG 
                   
                   
                   
               
               
                   
                 TGGTGG[CG]CGCACCTGTGGTCCCAGC 
                   
                   
                   
               
               
                   
                 TACTCAGGAGGCTGAGGTAGGAGGAT 
                   
                   
                   
               
               
                   
                 CACCTGAGCCCGGGAG 
                   
                   
                   
               
               
                   
               
               
                 cg02275294 
                 GTTTGAATGTTGCTGAAGGACGCTGGT 
                  1 
                 179262462 
                 SOAT1 
               
               
                   
                 TTTCAAACGGTAAGGAATCTCCTGATA 
                   
                   
                   
               
               
                   
                 AAGGCA[CG]AATCTTGGTGTGCAGATA 
                   
                   
                   
               
               
                   
                 AGCCAGCGATTCTTGCTTCTGGCTAGT 
                   
                   
                   
               
               
                   
                 TCTACGTTGTTCCTG 
                   
                   
                   
               
               
                   
               
               
                 cg19722847 
                 TCTGCTTACAGCTGCTTCCAAATTAAG 
                 12 
                  30849114 
                 IPO8 
               
               
                   
                 CATATCTGGATGGTGTGACACTTTTTGT 
                   
                   
                   
               
               
                   
                 TAGTC[CG]AGAACTGTATGGGCATCGC 
                   
                   
                   
               
               
                   
                 AACTGGGCCTGTTCCAAGATAGACTTG 
                   
                   
                   
               
               
                   
                 TTGGGACCTTCAAA 
                   
                   
                   
               
               
                   
               
               
                 cg19167673 
                 TTTTCTCTTTGCAGCGAGGCTGGAGGG 
                 22 
                  39640835 
                 PDGFB 
               
               
                   
                 TGGGCTTTTTTTTTTTTTTTTCCTTTTTG 
                   
                   
                   
               
               
                   
                 CGCG[CG]TATGTATGTGTGTGCGCGCA 
                   
                   
                   
               
               
                   
                 AAGTATCTCTATCTAGGGAATGAAAAA 
                   
                   
                   
               
               
                   
                 TGGGCGCTGGCGG 
                   
                   
                   
               
               
                   
               
               
                 cg07388493 
                 GGGAGCCAGTGTTCTTTCTCTCCTGTG 
                  1 
                  39491459 
                 NDUFS5 
               
               
                   
                 ACTTTGGTGAAGTCTCTCACCACTCAG 
                   
                   
                   
               
               
                   
                 TGTTGT[CG]TGAGCATGCTAGGCAGAG 
                   
                   
                   
               
               
                   
                 TGCAAGAAAGGAGCAAGAACTCACTA 
                   
                   
                   
               
               
                   
                 ATGGCTAGGCCTTCCC 
                   
                   
                   
               
               
                   
               
               
                 cg08331960 
                 TCGGGGTCCCTTGGCCTGGAGACCCTT 
                 16 
                   2076597 
                 SLC9A3R2 
               
               
                   
                 TGTCCAACCCGTCGCCCACCTCAAGAC 
                   
                   
                   
               
               
                   
                 CTGCCT[CG]ATGCTGCGCATACAGTAG 
                   
                   
                   
               
               
                   
                 GTATCCAATAAATGTTCCTGGGATAGA 
                   
                   
                   
               
               
                   
                 AGGCAAAGGCGCTGG 
                   
                   
                   
               
               
                   
               
               
                 cg05442902 
                 GCCAGGTCACCCTCTCACTCTGTGCCT 
                 22 
                  21369010 
                 MGC1670 
               
               
                   
                 CTTAGTTATCTTGCATGCTCTGGTCTTT 
                   
                   
                 3; P2RX6 
               
               
                   
                 GCATA[CG]CTGCTCCCTGCACCAGGAA 
                   
                   
                   
               
               
                   
                 CCTCCATCCCCATCTTTGTCTGCTTGTC 
                   
                   
                   
               
               
                   
                 GAACTTCAGAAAT 
                   
                   
                   
               
               
                   
               
               
                 cg01459453 
                 GCAAGTTTAAAAGTACTCACAAAATCT 
                  1 
                 169599212 
                 SELP 
               
               
                   
                 AATAGGCAATTCAACATAAAACTCCAT 
                   
                   
                   
               
               
                   
                 GGCTA[CG]TCTGTTCCTCACTTTCTGAA 
                   
                   
                   
               
               
                   
                 CCTTTACCTGCCTGACTTTACTCCATAC 
                   
                   
                   
               
               
                   
                 CACTCCAACTCAC 
                   
                   
                   
               
               
                   
               
               
                 cg03286783 
                 TTTCCCCGCCTCCCAACCGTGAGGTGT 
                 15 
                  44580973 
                 CASC4 
               
               
                   
                 TGGGTTTGGGGGACGCTGGCAGCTGGG 
                   
                   
                   
               
               
                   
                 TTCTCC[CG]GTTCCCTTGGGCAGGTGC 
                   
                   
                   
               
               
                   
                 AGGGTCGGGTTCAAAGCCTCCGGAACG 
                   
                   
                   
               
               
                   
                 CGTTTTGGCCTGATT 
                   
                   
                   
               
               
                   
               
               
                 cg03019000 
                 TGAGCATAGTTGTCACCTTCCCCACCT 
                  3 
                  51704351 
                 TEX264 
               
               
                   
                 CCCACCAAAAGTCCGGGATTTTCACGA 
                   
                   
                   
               
               
                   
                 GGGGAG[CG]TTTTATCTTTGGGCCCCT 
                   
                   
                   
               
               
                   
                 AGAAGAGTGCTTTGTAGTTTGTAGGTC 
                   
                   
                   
               
               
                   
                 CTCAGAAATTTGAGG 
                   
                   
                   
               
               
                   
               
               
                 cg16744741 
                 CAGCTGGATGCACTTGTTCTGGAGCTC 
                  4 
                  82126025 
                 PRKG2 
               
               
                   
                 CTCTGTGAGTTCAGCAATGGCCACAGT 
                   
                   
                   
               
               
                   
                 CTGCTT[CG]ACAGCTGCTCCCGCAGCT 
                   
                   
                   
               
               
                   
                 CCTTCAAATGGTACTCCCGCTCCTGGA 
                   
                   
                   
               
               
                   
                 TCTCAGCATCCTTCC 
                   
                   
                   
               
               
                   
               
               
                 cg07158339 
                 TACAGGGCTTAACTCATTTTATCCTTAC 
                  9 
                  71650237 
                 FXN 
               
               
                   
                 CACAATCCTATGAAGTAGGAACTTTTA 
                   
                   
                   
               
               
                   
                 TAAAA[CG]CATTTTATAAACAAGGCAC 
                   
                   
                   
               
               
                   
                 AGAGAGGTTAATTAACTTGCCCTCTGG 
                   
                   
                   
               
               
                   
                 TCACACAGCTAGGA 
                   
                   
                   
               
               
                   
               
               
                 cg11388238 
                 GGTCTTGTGTGTTCAGAGGCTGGTTTTA 
                  2 
                 201375098 
                 KCTD18 
               
               
                   
                 CAGGTGAAGAGAAGAAACAGCCGCAG 
                   
                   
                   
               
               
                   
                 AAGTTG[CG]ATTGTCCAAGGTCACTTA 
                   
                   
                   
               
               
                   
                 ATAAGTGGCAAGAATTAGGATGTTAAG 
                   
                   
                   
               
               
                   
                 TGTTCTCACCCCCAG 
                   
                   
                   
               
               
                   
               
               
                 cg25070637 
                 TGCCAATCGGCGTGTAATCCTGTAGGA 
                  8 
                  97505868 
                 SDC2 
               
               
                   
                 ATTTCTCCCGGGTTTATCTGGGAGTCA 
                   
                   
                   
               
               
                   
                 CACTGC[CG]CCTCCTCTCCCCAGTCGC 
                   
                   
                   
               
               
                   
                 CCAGGGGAGCCCGGAGAAGCAGGCTC 
                   
                   
                   
               
               
                   
                 AGGAGGGAGGGAGCCA 
                   
                   
                   
               
               
                   
               
               
                 cg13547237 
                 GCAGTGCATCGAGCTGGAGCAGCAGTT 
                 11 
                  65687877 
                 C11orf68; 
               
               
                   
                 TGACTTCTTGAAGGACCTGGTGGCATC 
                   
                   
                 DRAP1 
               
               
                   
                 TGTTCC[CG]ACATGCAGGGGGACGGGG 
                   
                   
                   
               
               
                   
                 AAGACAACCACATGGATGGGGACAAG 
                   
                   
                   
               
               
                   
                 GGCGCCCGCAGGTGGG 
                   
                   
                   
               
               
                   
               
               
                 cg13931228 
                 GGTGTGAATCACACTGCCCGGTCGGGC 
                  7 
                  24612418 
                 MPP6 
               
               
                   
                 CTTTGGGAAAAAATTAATGAAGGACAC 
                   
                   
                   
               
               
                   
                 AGTCAG[CG]CCGTAGAACCTGCCAAAT 
                   
                   
                   
               
               
                   
                 ACACATCAGATCCAGTGGAGTCTGTGA 
                   
                   
                   
               
               
                   
                 AGGGGGAGGGGGAGA 
                   
                   
                   
               
               
                   
               
               
                 cg22947000 
                 TAGCTATGACACATGGCTTGGAAATTA 
                 16 
                  81272281 
                 BCMO1 
               
               
                   
                 ACCTTTAACCAAACATCTTATAAGTAA 
                   
                   
                   
               
               
                   
                 CGCCAG[CG]CAGCTTCCCTTGTGAATG 
                   
                   
                   
               
               
                   
                 TAAAGAGATCCAGGGCTCTTGGAGAG 
                   
                   
                   
               
               
                   
                 GGACAAGTGAGAGCCA 
                   
                   
                   
               
               
                   
               
               
                 cg00431549 
                 TAACTGCTGGACCTGACTGTGTTACAC 
                 12 
                  15039025 
                 MGP 
               
               
                   
                 AGGATGCTGCTCTGGTGCAGAAGTTTT 
                   
                   
                   
               
               
                   
                 GGCCAT[CG]TATGCTTGGGGACAGACC 
                   
                   
                   
               
               
                   
                 TGGGCAAAAGCCCACAGAGGAAGTTG 
                   
                   
                   
               
               
                   
                 CCACAAACACATGATC 
                   
                   
                   
               
               
                   
               
               
                 cg25809905 
                 ACTTGATTCTGGTTGGGGGCTTTGCCT 
                 17 
                  42467728 
                 ITGA2B 
               
               
                   
                 AGGGGAGCCTTCCCTGACTCCTCAGGC 
                   
                   
                   
               
               
                   
                 TGGCCG[CG]TGGGCTAACACACGTAGG 
                   
                   
                   
               
               
                   
                 CACAGCATTGAGCACACTGTTTACTCT 
                   
                   
                   
               
               
                   
                 TGGTCCGTTCACAGG 
                   
                   
                   
               
               
                   
               
               
                 cg26394940 
                 TAAATAAATAAGGGCTTTTGTTTGTTTG 
                 22 
                  46449461 
                 C22orf26; L 
               
               
                   
                 CCGGCTCCTGCACATGGCTGCTGGGAC 
                   
                   
                 OC150381 
               
               
                   
                 TCAAG[CG]CTCGTGTTGTCTGCGCCTCT 
                   
                   
                   
               
               
                   
                 GTGGGACTCTGGGGACGGGAGGCAGG 
                   
                   
                   
               
               
                   
                 GGAGGCCCCCGCAG 
                   
                   
                   
               
               
                   
               
               
                 cg08090772 
                 TCTTACTCCGTGGGAAAATGGCCCTGA 
                  8 
                  67344640 
                 ADHFE1 
               
               
                   
                 GCCCGACTGGCTTGAGGCTTAGACAGG 
                   
                   
                   
               
               
                   
                 TGACCC[CG]CGAAGCGGGTGGGCAGG 
                   
                   
                   
               
               
                   
                 CGCGGCCGAGGGGCGGGAGGCGGGCA 
                   
                   
                   
               
               
                   
                 GCCTCCGTGATTGGCCG 
                   
                   
                   
               
               
                   
               
               
                 cg01027805 
                 CGGTTTGGAGACGGGGGGCGCTGTCGG 
                 14 
                  21566863 
                 ZNF219; C 
               
               
                   
                 AGGGAGGGAGGAAGGGAGGGAGCGG 
                   
                   
                 14orf176 
               
               
                   
                 GGGTGGGG[CG]CACAGAGGATTCCAA 
                   
                   
                   
               
               
                   
                 CAGGAGACTGGAAGAGATTTTGAAAG 
                   
                   
                   
               
               
                   
                 GTCATCTCGTCCTTCCCCC 
                   
                   
                   
               
               
                   
               
               
                 cg04474832 
                 CCAGCCAAGTGGCCTTGATCGTTTTCC 
                  3 
                  52008487 
                 ABHD14B 
               
               
                   
                 CAATGCCCCCGAGCCTGTTTCCTGCCA 
                   
                   
                   
               
               
                   
                 GTAGAG[CG]GGTCAGATGTTGCCAACC 
                   
                   
                   
               
               
                   
                 TCTGCAGAGTAGCAATAAGCAGTAAAC 
                   
                   
                   
               
               
                   
                 GCCACGCTCTGCACA 
                   
                   
                   
               
               
                   
               
               
                 cg24899750 
                 GGAGGAACTGGCTATCCTAAAGGTGAT 
                 20 
                  16710314 
                 SNRPB2 
               
               
                   
                 TTTAAACCGGGGTAGCTAGAGCCCAAA 
                   
                   
                   
               
               
                   
                 GAAGGG[CG]AAACCAGGACTAACTGC 
                   
                   
                   
               
               
                   
                 CCCATAGCATGAGGGGCAGCGCCTGTA 
                   
                   
                   
               
               
                   
                 AAATTACATAGGATTT 
                   
                   
                   
               
               
                   
               
               
                 cg04268405 
                 TGACGTTACGTACTGGAAGTCCCAGGA 
                 10 
                  73723221 
                 CHST3 
               
               
                   
                 GGAATGCCCAGCAAGTGGAATCCAAG 
                   
                   
                   
               
               
                   
                 ACGTTCT[CG]CCTTCTCGGGGACAGGG 
                   
                   
                   
               
               
                   
                 CCATCACCAGGATTCGGAAAGGAACA 
                   
                   
                   
               
               
                   
                 GGGAGGTTCGGTTTGTG 
                   
                   
                   
               
               
                   
               
               
                 cg12413566 
                 ACCAGGGGGTGATGCCAGACATTGCTC 
                  3 
                  39235366 
                 XIRP1 
               
               
                   
                 ACTTTTTCCATGTAGTCAATGTCAGTCC 
                   
                   
                   
               
               
                   
                 TGCAG[CG]TCAGCTGGGATGGGGGTAA 
                   
                   
                   
               
               
                   
                 GGACATCTGGGAACCCCCTCTTCCTGG 
                   
                   
                   
               
               
                   
                 TCTCCCTCCCTCTT 
                   
                   
                   
               
               
                   
               
               
                 cg01820374 
                 GGGAGGCTCAGTTCCTGGGCTTGCTGT 
                 12 
                   6882083 
                 LAG3 
               
               
                   
                 TTCTGCAGCCGCTTTGGGTGGCTCCAG 
                   
                   
                   
               
               
                   
                 GTAAAA[CG]GGGATGGCGGGAGGGTT 
                   
                   
                   
               
               
                   
                 GACCTCCAGCCCCACAGGAGGGGACC 
                   
                   
                   
               
               
                   
                 AGCAGGGATCTCTGTGG 
                   
                   
                   
               
               
                   
               
               
                 cg06557358 
                 AGCATCGAGACAGCGGGCGAACGGGC 
                 17 
                  32907002 
                 TMEM132 
               
               
                   
                 GTCCGGGGACAGGGTGGGGGCGGCGG 
                   
                   
                 E; C17orf10 
               
               
                   
                 GGAGGAGG[CG]TCGGAGACTCTGAAC 
                   
                   
                 2 
               
               
                   
                 CCCAGAAAAGTTCAAGGTTTGTGCAGG 
                   
                   
                   
               
               
                   
                 TTCCCCCAGGGAAGGCGA 
                   
                   
                   
               
               
                   
               
               
                 cg09809672 
                 CCCCAGAGAGCTTTCATCTAGAAGGTT 
                  1 
                 236557682 
                 EDARAD 
               
               
                   
                 TGACTCTGGCCAGACAACCAGCGAGCA 
                   
                   
                 D 
               
               
                   
                 TCTTCT[CG]CAATCTGTTGCTTCTTCCA 
                   
                   
                   
               
               
                   
                 TGGCAAACTCCAGAGAATTAAGAAGC 
                   
                   
                   
               
               
                   
                 CAAACTCAACATCGC 
                   
                   
                   
               
               
                   
               
               
                 cg18328933 
                 CCAGTAGAGCGGGTCAGATGTTGCCAA 
                  3 
                  52008538 
                 ABHD14B 
               
               
                   
                 CCTCTGCAGAGTAGCAATAAGCAGTAA 
                   
                   
                   
               
               
                   
                 ACGCCA[CG]CTCTGCACAGCCTCCCAG 
                   
                   
                   
               
               
                   
                 TGCTGGGCCTGGTCGCCACGCGGAGCC 
                   
                   
                   
               
               
                   
                 TTGGGCTGGGACAGG 
                   
                   
                   
               
               
                   
               
               
                 cg22197830 
                 GAAGGCTCCTGGGCCTTTCTGGCTCTG 
                  5 
                 134209784 
                 TXNDC15 
               
               
                   
                 GGAATGAAGCGTGGAAAACCCTCCTTA 
                   
                   
                   
               
               
                   
                 GGCGGG[CG]CAGTGCTTCAAGTAGCCA 
                   
                   
                   
               
               
                   
                 AGCTCTGACTTCCGAGGGAAGAAAGG 
                   
                   
                   
               
               
                   
                 AGGCCATGGGCCTCTG 
                   
                   
                   
               
               
                   
               
               
                 cg13828047 
                 TCAACATACTACATGATTTGCTTACAA 
                 15 
                  75182130 
                 MPI 
               
               
                   
                 TACTTGTCTGTCTTGCCTTCACCAGAAT 
                   
                   
                   
               
               
                   
                 GTAA[CG]GCTCTACAAAGGCAGAGGG 
                   
                   
                   
               
               
                   
                 AAGGCTATCTTGCTCTCTGATGTATCCT 
                   
                   
                   
               
               
                   
                 CCAGCCCTTAGAAC 
                   
                   
                   
               
               
                   
               
               
                 cg19724470 
                 CATTCTTATGCGACTGTGTGTTCAGAA 
                  9 
                   5450936 
                 CD274 
               
               
                   
                 TATAGCTCTGATGCTAGGCTGGAGGTC 
                   
                   
                   
               
               
                   
                 TGGACA[CG]GGTCCAAGTCCACCGCCA 
                   
                   
                   
               
               
                   
                 GCTGCTTGCTAGTAACATGACTTGTGT 
                   
                   
                   
               
               
                   
                 AAGTTATCCCAGCTG 
                   
                   
                   
               
               
                   
               
               
                 cg01407797 
                 TGATTATATGTACTATTATTATCTCATT 
                 22 
                  29168514 
                 CCDC117 
               
               
                   
                 TTACTACTGTGGAAACTGAGATACGAA 
                   
                   
                   
               
               
                   
                 ACTTG[CG]GAGTGAGGATTTGAACCTA 
                   
                   
                   
               
               
                   
                 GGTCATACTCTTGGCCAGCCAGAGACA 
                   
                   
                   
               
               
                   
                 CCCTAAGCCCCAGC 
                   
                   
                   
               
               
                   
               
               
                 cg07408456 
                 GGCCTGGAGACCAGGTGGTTCAGACTC 
                 19 
                  15590532 
                 PGLYRP2 
               
               
                   
                 CATAAACTCTGCCCATTCTCCAGTGAG 
                   
                   
                   
               
               
                   
                 GTGGAC[CG]AGGCAACCCCTCAAGTCC 
                   
                   
                   
               
               
                   
                 TGTCCCTCCCCATAGTGACGGCTCTGT 
                   
                   
                   
               
               
                   
                 AGCCGCTGCTGGCCA 
                   
                   
                   
               
               
                   
               
               
                 cg27202708 
                 CGGGCAAGGTCTGAAGACTGCGAGGA 
                  1 
                 223566709 
                 C1orf65 
               
               
                   
                 CCCAGCTGCCAGGCGCATTGTGAAGTG 
                   
                   
                   
               
               
                   
                 GCCCGAG[CG]TCACAGGCGACCCGGA 
                   
                   
                   
               
               
                   
                 CCTCGGGACCGGGGGGCAGGGCGGGT 
                   
                   
                   
               
               
                   
                 GTCTGCAGCGTCCTCGGG 
                   
                   
                   
               
               
                   
               
               
                 cg01570885 
                 GGAGGAGGGTTGGAGAGCAGGGCCGT 
                  6 
                   3849272 
                 FAM50B 
               
               
                   
                 GTTGCAAGGCTCTCTGGGTGGCCACAG 
                   
                   
                   
               
               
                   
                 CAGCTTG[CG]CTGCGCCCACATTGCTT 
                   
                   
                   
               
               
                   
                 CTGCGTGTTTACAGTTGGGCACGAGAA 
                   
                   
                   
               
               
                   
                 GGCTCAGCACGCACGC 
                   
                   
                   
               
               
                   
               
               
                 cg24058132 
                 GGGCCATGAGTGGCCCTACCATGGCTC 
                 14 
                  88459866 
                 GALC 
               
               
                   
                 TTCCCCAGCATCTCAGGGAGTATCTAC 
                   
                   
                   
               
               
                   
                 CTCGTG[CG]AGGACCAGGCTTGGACAC 
                   
                   
                   
               
               
                   
                 CAGGTCCCGATTCCATTGTCATCTTGGT 
                   
                   
                   
               
               
                   
                 GGAATCACTTTGCT 
                   
                   
                   
               
               
                   
               
               
                 cg11025793 
                 TGGTCTCCCCTGGAGGGTGGGCGGGTT 
                 19 
                  13262015 
                 IER2; STX 
               
               
                   
                 ATCTGAGGGAGTCCTCGGAGGGTCGCC 
                   
                   
                 10 
               
               
                   
                 CCCTTG[CG]CGTCAGAGTTGCTGCGTG 
                   
                   
                   
               
               
                   
                 GGGTCTCAGAGATAGCGCCTGGGCTGG 
                   
                   
                   
               
               
                   
                 GGAAATCATTGTGGG 
                   
                   
                   
               
               
                   
               
               
                 cg19853760 
                 AAAAGGGTGGGAGCGTCCGGGGGCCC 
                 22 
                  38071677 
                 LGALS1 
               
               
                   
                 ATCTCTCTCGGGTGGAGTCTTCTGACA 
                   
                   
                   
               
               
                   
                 GCTGGTG[CG]CCTGCCCGGGAACATCC 
                   
                   
                   
               
               
                   
                 TCCTGGACTCAATCATGGCTTGTGTGA 
                   
                   
                   
               
               
                   
                 GTGTGGGGACCCCCCC 
                   
                   
                   
               
               
                   
               
               
                 cg02217159 
                 TATTTCCGATGACCTACATCTCAGGGA 
                  6 
                  62996697 
                 KHDRBS2 
               
               
                   
                 CGCAGTAGGATGTTCATTGATAAACAA 
                   
                   
                   
               
               
                   
                 ATAAAG[CG]GCTCGAAGAAATATTGTG 
                   
                   
                   
               
               
                   
                 CAGAGACATGATTGAGGTGTACAATCA 
                   
                   
                   
               
               
                   
                 TTAGGATATTGAATT 
                   
                   
                   
               
               
                   
               
               
                 cg27319898 
                 GGAATTCCTGATTCCCTGGTGGACCCT 
                  7 
                  88389003 
                 ZNF804B 
               
               
                   
                 GGAAGTTGTCCTTAAATAAATATATCG 
                   
                   
                   
               
               
                   
                 CTGGCC[CG]CGGTTGAGCAGCCACCTC 
                   
                   
                   
               
               
                   
                 GTCAGAGCAGCATGTGGACTGGCTCGC 
                   
                   
                   
               
               
                   
                 CGGGTCCCCTCCGTG 
                   
                   
                   
               
               
                   
               
               
                 cg13269407 
                 CAGACACCGAGCCGCGGCCACAGGGC 
                 22 
                  46450107 
                 C22orf26; L 
               
               
                   
                 CAGCCGCACAGTCGGAGGAAGGGCCG 
                   
                   
                 OC150381 
               
               
                   
                 GAGCGAGG[CG]GGGCCCGGGGCTGTC 
                   
                   
                   
               
               
                   
                 AAGGAGAAAAACATCCCAAGGCCTGC 
                   
                   
                   
               
               
                   
                 AAATTGCTGCTCTCAGCTT 
                   
                   
                   
               
               
                   
               
               
                 cg14654875 
                 TGTCCTTTGTGTCTTGAGCGGATGGTG 
                 16 
                   3493997 
                 NAT15; ZN 
               
               
                   
                 GGGCCGTGGAACATGAAGGAGTATCTT 
                   
                   
                 F597 
               
               
                   
                 TGTGTA[CG]TTCACAACGTTCACATCG 
                   
                   
                   
               
               
                   
                 GTGTAGGCCAGGTTGCTGGACTCTGAC 
                   
                   
                   
               
               
                   
                 TCAAAGTGTTATAGA 
                   
                   
                   
               
               
                   
               
               
                 cg13129046 
                 CTACTCAAGGGGCATCCACGGAGCTGG 
                 10 
                  71389696 
                 C10orf35 
               
               
                   
                 GTCAGCAAACATAACACTGGTCATCTG 
                   
                   
                   
               
               
                   
                 AGCCTG[CG]CCCGCCCTTCCTCCCAGG 
                   
                   
                   
               
               
                   
                 CCAGGGCGCCCCCACCCCCTGGGTTTT 
                   
                   
                   
               
               
                   
                 TCCTCCGTGGACGCC 
                   
                   
                   
               
               
                   
               
               
                 cg12941369 
                 TCACATGTTTCGTTTCTAGTCCTGAAAC 
                  3 
                  33839389 
                 PDCD6IP 
               
               
                   
                 ATGGTTAAGTGCTTGCCTCCTAGGGCC 
                   
                   
                   
               
               
                   
                 TCTGC[CG]CAGGCTTTTGGTTTGGAGG 
                   
                   
                   
               
               
                   
                 CTCTCCTTTGCCACTCCACCCCTCTCCA 
                   
                   
                   
               
               
                   
                 CTCTTCTCCTCTT 
                   
                   
                   
               
               
                   
               
               
                 cg09191327 
                 GCTCCGTGCTCCCGGCTGAGGCCCTGG 
                  9 
                 133540108 
                 PRDM12 
               
               
                   
                 TGCTCAAGACCGGGCTGAAGGCGCCG 
                   
                   
                   
               
               
                   
                 GGACTGG[CG]CTGGCCGAGGTTATCAC 
                   
                   
                   
               
               
                   
                 CTCCGACATCCTGCACAGCTTCCTGTA 
                   
                   
                   
               
               
                   
                 CGGCCGCTGGCGCAAC 
                   
                   
                   
               
               
                   
               
               
                 cg22171829 
                 CTGTGTCCCCTCTCACCAAAGTCCAGT 
                  7 
                  95225520 
                 PDK4 
               
               
                   
                 AGCTGCTTCATGGACAGCGGGGACGG 
                   
                   
                   
               
               
                   
                 GCTGTAG[CG]CGAGAAATGCTCCACCT 
                   
                   
                   
               
               
                   
                 CTCGGGGCACCAGGCCGGCGCCGTTGA 
                   
                   
                   
               
               
                   
                 GCGAGCCAGCGCTGCG 
                   
                   
                   
               
               
                   
               
               
                 cg17338403 
                 TGGAAGGTGCTGTTTCCTGGTACCTGT 
                 15 
                  92395836 
                 SLCO3A1 
               
               
                   
                 CCAGCCCTCTGAGCTTTTCTCTCAGCTT 
                   
                   
                   
               
               
                   
                 CCAAA[CG]CTGCAGTTGAGAACTAGCA 
                   
                   
                   
               
               
                   
                 GATCCTATTGGTAGTGCCCTGTGGCCC 
                   
                   
                   
               
               
                   
                 ACACTCCTTGGTAA 
                   
                   
                   
               
               
                   
               
               
                 cg09722397 
                 TCGGGGTATTTTTAGGCCGGCGATAAA 
                 17 
                  72855943 
                 GRIN2C 
               
               
                   
                 TAATTCATAGGGAACGTGGCATCAGGC 
                   
                   
                   
               
               
                   
                 TCCCCC[CG]CGGGAGGAGGGGGCGCG 
                   
                   
                   
               
               
                   
                 AGCAGCGAGAGCCACCGTCACCCGCG 
                   
                   
                   
               
               
                   
                 GCTCAAGGACACTCGCG 
                   
                   
                   
               
               
                   
               
               
                 cg02489552 
                 CTCCTCCCCCCACCTCTGGAATTCCACC 
                 19 
                  15121531 
                 CCDC105 
               
               
                   
                 TCCCTTGTTGCGCCCATCGCTATGGTG 
                   
                   
                   
               
               
                   
                 ACGGG[CG]CTCTCAGTACACTGTCTCT 
                   
                   
                   
               
               
                   
                 ACAGGCCAGGAAAGAGTTGTGTGTCTT 
                   
                   
                   
               
               
                   
                 TGGGGTCCCTTCCG 
                   
                   
                   
               
               
                   
               
               
                 cg15661409 
                 TTGTTAATCTTTAATTTAATTAAAGAAT 
                 14 
                  57960976 
                 C14orf105 
               
               
                   
                 TTATCCCCCAAATAGGAAAGAAAGCA 
                   
                   
                   
               
               
                   
                 GCGGAG[CG]GCTAAAGCGTCATTTGAT 
                   
                   
                   
               
               
                   
                 TTTTCTGTCGATGACTTGAGTTGCCTTT 
                   
                   
                   
               
               
                   
                 GAAGGGGGTGAATA 
                   
                   
                   
               
               
                   
               
               
                 cg06810647 
                 TGCCGCGGGGGAGAGGAACCCCTCGC 
                 16 
                   1665094 
                 CRAMP1L 
               
               
                   
                 CCCAGCCGGGCTCCACCCTAGCTCACC 
                   
                   
                   
               
               
                   
                 CATCCCG[CG]GCCTACACTGAGGCTCT 
                   
                   
                   
               
               
                   
                 CAATTTGGGTGGCACTTATGGGGCATG 
                   
                   
                   
               
               
                   
                 TGTCCCCTCTCTCCTT 
                   
                   
                   
               
               
                   
               
               
                 cg02388150 
                 AACCTATGAAAATAAACAAAAGCTGCT 
                  8  
                  41165699 
                 SFRP1 
               
               
                   
                 CCAAGCATTCTCTCGGCCTTTCTGAACT 
                   
                   
                   
               
               
                   
                 TTCTA[CG]CTTTGGGTTTTTGTTTTTTCC 
                   
                   
                   
               
               
                   
                 TCCCGTCTCAGAGGTTAAAAACTTCGA 
                   
                   
                   
               
               
                   
                 TAGGGACTCGGA 
                   
                   
                   
               
               
                   
               
               
                 cg18983672 
                 GGCAGCCAGAAAGGCAGCTCCAAGTT 
                  1 
                  47881256 
                 FOXE3 
               
               
                   
                 GTGGATTTCCTGGGGGCTCTTCATTTA 
                   
                   
                   
               
               
                   
                 AAGCGGC[CG]CACCACTTTCCACAATT 
                   
                   
                   
               
               
                   
                 CTGTTTTTTCAGAGAATGCTCTCAAGG 
                   
                   
                   
               
               
                   
                 CCTGGAGGGAGGGCAT 
                   
                   
                   
               
               
                   
               
               
                 cg06993413 
                 GAGGCGCGGGGTGGAGACTGGGCCGA 
                 15 
                  65810204 
                 DPP8 
               
               
                   
                 GCAGGGGATAGAGATGAACTCCAGAA 
                   
                   
                   
               
               
                   
                 AGGAACAG[CG]ACTTGCTGAAAGTCAC 
                   
                   
                   
               
               
                   
                 AGGGCAAAATGTGGCGCGTCTGTAGTC 
                   
                   
                   
               
               
                   
                 AATAAATAATATATATT 
                   
                   
                   
               
               
                   
               
               
                 cg26842024 
                 CGACGACGACCTCAACAGCGTGCTGGA 
                 19 
                  16436122 
                 KLF2 
               
               
                   
                 CTTCATCCTGTCCATGGGGCTGGATGG 
                   
                   
                   
               
               
                   
                 CCTGGG[CG]CCGAGGCCGCCCCGGAGC 
                   
                   
                   
               
               
                   
                 CGCCGCCGCCGCCCCCGCCGCCTGCGT 
                   
                   
                   
               
               
                   
                 TCTATTACCCCGAAC 
                   
                   
                   
               
               
                   
               
               
                 cg21870884 
                 GGGCCCGCGGCGGCTGGTGGATACCTT 
                  1 
                 200842429 
                 GPR25 
               
               
                   
                 CGTGCTGCACCTGGCGGCAGCTGACCT 
                   
                   
                   
               
               
                   
                 GGGCTT[CG]TGCTCACGCTGCCGCTGT 
                   
                   
                   
               
               
                   
                 GGGCCGCGGCGGCGGCGCTAGGCGGC 
                   
                   
                   
               
               
                   
                 CGCTGGCCGTTCGGCG 
                   
                   
                   
               
               
                   
               
               
                 cg18984151 
                 TCCCTTGGCCTCGCTCTCTGCCCAGCCC 
                  3 
                  47555476 
                 C3orf75 
               
               
                   
                 CGGGCTCCTTTTCTCCACACGTGGCTGT 
                   
                   
                   
               
               
                   
                 CAAG[CG]CCTTCTGTATGCCCCACACT 
                   
                   
                   
               
               
                   
                 CCTGGGAGCTTGGGCTACATCGATGAA 
                   
                   
                   
               
               
                   
                 CAAAAACAAAGGA 
                   
                   
                   
               
               
                   
               
               
                 cg18180783 
                 AGCCAGGATCTGCCTTTTAACCTCCAT 
                 10 
                  75402320 
                 MYOZ1 
               
               
                   
                 TTGCTGTTGAGATGCTCAGTTCAACCT 
                   
                   
                   
               
               
                   
                 GCTGTG[CG]GGATAGACATCGATGTCT 
                   
                   
                   
               
               
                   
                 CCCTGAGAAGCACATATAGGCTCTCTG 
                   
                   
                   
               
               
                   
                 AGGTTTCTTTTCTTC 
                   
                   
                   
               
               
                   
               
               
                 cg16547529 
                 CACTGGCTTGTTAACTCTTCAAGGGCA 
                 11 
                  75140681 
                 KLHL35 
               
               
                   
                 GAATTATGGGCACCGAGCCTCTAAAAT 
                   
                   
                   
               
               
                   
                 GTTGAA[CG]AATGACTGAATATCATCA 
                   
                   
                   
               
               
                   
                 AGAGGCAGTACTAAAAGATGATGAAA 
                   
                   
                   
               
               
                   
                 GAATGAATGAGCGGTG 
                   
                   
                   
               
               
                   
               
               
                 cg22901840 
                 GTGCAGGGAAAGCACACCGTGGCTGC 
                  1 
                  68512777 
                 DIRAS3 
               
               
                   
                 AGCCCAGCAACTGGCAGTAGGTATTTT 
                   
                   
                   
               
               
                   
                 CAATGGT[CG]GCAGGTACTCATGACGG 
                   
                   
                   
               
               
                   
                 AAGTTGCCGCTCGCCCACTTGTGCAGC 
                   
                   
                   
               
               
                   
                 AGCGTACTTTTCCCCA 
                   
                   
                   
               
               
                   
               
               
                 cg02332492 
                 CGGGGCAGCTGTCAGTGAAGCTCTACG 
                  9 
                 139840678 
                 C8G 
               
               
                   
                 GTATGTGGGGGCCAGCCTCTGTGACCA 
                   
                   
                   
               
               
                   
                 GGCAGG[CG]CTCAAGCTCTGCACACTC 
                   
                   
                   
               
               
                   
                 ACTGGGCCACCCCGAGGGGCTGGGTG 
                   
                   
                   
               
               
                   
                 AGCCCATGGGGACACA 
                   
                   
                   
               
               
                   
               
               
                 cg24262469 
                 CTCTGCAAGCTCCATGAGGACAGGCGT 
                  3 
                 156391694 
                 TIPARP; L 
               
               
                   
                 GAAGTTCAGGCTACATGCCTGGTACGT 
                   
                   
                 OC100287 
               
               
                   
                 AATAGA[CG]CTCTGACAGACATTTGCT 
                   
                   
                 227 
               
               
                   
                 GAATGAATAAGTTAGTCACTACGGCGT 
                   
                   
                   
               
               
                   
                 TTGTGGGCTTTAAAA 
                   
                   
                   
               
               
                   
               
               
                 cg15547534 
                 CTCCTCCTCTTGAAAACTCTGCTATGGC 
                  7 
                 100034410 
                 C7orf47 
               
               
                   
                 TGAGTTACCCAGAGGAATCTTAGTCCT 
                   
                   
                   
               
               
                   
                 GCTAG[CG]CTGCGATGCCCATTGCCCA 
                   
                   
                   
               
               
                   
                 GTGTGTCAGTCCTCATTCTGGGGCGCC 
                   
                   
                   
               
               
                   
                 AAATGGGGCAGCAT 
                   
                   
                   
               
               
                   
               
               
                 cg20828084 
                 GACTCCATATGCCCTAGGGATGTGTTG 
                 15 
                  81070851 
                 KIAA1199 
               
               
                   
                 TGATGAACTTTTCCTACTGGTACTGTTT 
                   
                   
                   
               
               
                   
                 CCTCC[CG]CGAGGGAATGTCTAGACCA 
                   
                   
                   
               
               
                   
                 GCCGCACCTTCTTGCTTTGACCCTTCAG 
                   
                   
                   
               
               
                   
                 AACTTTGGCCTGT 
                   
                   
                   
               
               
                   
               
               
                 cg02580606 
                 AACCTAAATTTTGGGAGCACCTACTCT 
                 17 
                  39526726 
                 KRT33B 
               
               
                   
                 GCATGAAGCACTGTGCTCCATGCCTGT 
                   
                   
                   
               
               
                   
                 GCACAG[CG]TGACTCTGTCATTGGTGA 
                   
                   
                   
               
               
                   
                 TGGGTCCTGCTTGCTGAGCCTCCACTG 
                   
                   
                   
               
               
                   
                 TGCACCAGGCACAGT 
                   
                   
                   
               
               
                   
               
               
                 cg05675373 
                 AAGGAGGAGATGGCCAAGGGCGAGGC 
                  1 
                 110754257 
                 KCNC4 
               
               
                   
                 GTCGGAGAAGATCATCATCAACGTGGG 
                   
                   
                   
               
               
                   
                 CGGCACG[CG]ACATGAGACCTACCGCA 
                   
                   
                   
               
               
                   
                 GCACCCTGCGCACCCTACCGGGAACCC 
                   
                   
                   
               
               
                   
                 GCCTCGCCTGGCTGGC 
                   
                   
                   
               
               
                   
               
               
                 cg26453588 
                 GGCTGCCCACCCGCCCACCCCGCCTGG 
                 22 
                  43506021 
                 BIK 
               
               
                   
                 AAGCTTTCTGATTTCTCTGTTCGCCCCG 
                   
                   
                   
               
               
                   
                 CCAGG[CG]CTGTGGGGTCCGTCTCACC 
                   
                   
                   
               
               
                   
                 AGGTCTGCACGTGAGCCCCCTGCCCCC 
                   
                   
                   
               
               
                   
                 AATCCCTCCCAGTC 
                   
                   
                   
               
               
                   
               
               
                 cg13682722 
                 AGTGGTTGGGACCCTGTGAGAACCGGA 
                 14 
                  90798568 
                 C14orf102 
               
               
                   
                 ACTGCGAAAACCGGAGAAGGGAATTG 
                   
                   
                   
               
               
                   
                 TTGACCG[CG]AAAGGGACTAAGGAAA 
                   
                   
                   
               
               
                   
                 TTGGGATTCCAGTTCGACCCCTAAATT 
                   
                   
                   
               
               
                   
                 CACACCATCCTTGCTAA 
                   
                   
                   
               
               
                   
               
               
                 cg01353448 
                 GCCCAGCCTCGGTGAGCACACACGCCC 
                  7 
                  31726912 
                 C7orf16 
               
               
                   
                 TCCCTGTCTCTCGCCTTCGCTTCCCTGC 
                   
                   
                   
               
               
                   
                 ATCTG[CG]CTGATTGGTAAGTGCTTCA 
                   
                   
                   
               
               
                   
                 GATTTTTACTCCAAGAACTTTTGTGGTG 
                   
                   
                   
               
               
                   
                 AGAAAAGCAAGTT 
                   
                   
                   
               
               
                   
               
               
                 cg24580001 
                 TCTTCTGAAGGATTTGATGCTGGTGCTT 
                 11 
                  64106532 
                 CCDC88B 
               
               
                   
                 TTCAGGTGTGGGTCCTGACAGTGATGT 
                   
                   
                   
               
               
                   
                 TGGGA[CG]GCAGCTAGCCAGACAGCA 
                   
                   
                   
               
               
                   
                 ACTGTACCATGTAAACTCACTTCAGAG 
                   
                   
                   
               
               
                   
                 GTGTAGAATGGGGGC 
                   
                   
                   
               
               
                   
               
               
                 cg18440048 
                 GTAGCCCTGTTCCTGTCTGCCCTCCCCG 
                 22 
                  24093826 
                 ZNF70 
               
               
                   
                 CCCCCACAGAAATAGAGATGAGAAGG 
                   
                   
                   
               
               
                   
                 GGCAGG[CG]AAGAACTAGGAGTGTCT 
                   
                   
                   
               
               
                   
                 GCGAGACCATCCCAGGACCCTGAGCCC 
                   
                   
                   
               
               
                   
                 CCCAACTCTCTGCATC 
                   
                   
                   
               
               
                   
               
               
                 cg13460409 
                 ATCTCTCACCTTGCTACTTTCTCGGTAG 
                 21 
                  38379570 
                 DSCR6 
               
               
                   
                 CCGTTTCTGTTGTCCCTGGATTGGGGG 
                   
                   
                   
               
               
                   
                 CTCGG[CG]TTCGCTGTCCCTGGGCACC 
                   
                   
                   
               
               
                   
                 AACCCTTTTAAAGACAGTAACGTTGTA 
                   
                   
                   
               
               
                   
                 GGAAATCAAATTAG 
                   
                   
                   
               
               
                   
               
               
                 cg01968178 
                 CTGCAGCGGCCCCGTTTGCAGGGCAGG 
                  2 
                  86565038 
                 REEP1 
               
               
                   
                 GACCCGGGTGCTGCCCCACCCTCAGCG 
                   
                   
                   
               
               
                   
                 TTCCAG[CG]GAGAAACTGAAGTCCGAA 
                   
                   
                   
               
               
                   
                 CCTGAACCTCGGGAATCTGTCTGCACC 
                   
                   
                   
               
               
                   
                 TGTCTAGGTGGGATG 
                   
                   
                   
               
               
                   
               
               
                 cg13038560 
                 GACCTCAAGTGATCCACCGACCTGGGC 
                  2 
                 200819113 
                 C2orf60; C 
               
               
                   
                 CTCCCAAAATGTTAGGATTACTGGCAT 
                   
                   
                 2orf47 
               
               
                   
                 GAACCA[CG]GCGCCCAGCCCATCCGAC 
                   
                   
                   
               
               
                   
                 TTTTGTAACACTCAGAATTGTAGTTTTG 
                   
                   
                   
               
               
                   
                 TTTGTTTGTTTGAG 
                   
                   
                   
               
               
                   
               
               
                 cg23517605 
                 CTCCAGTGCCGGCAGGTGGGAGGGCTG 
                  6 
                   3228365 
                 TUBB2B 
               
               
                   
                 AGGTGGCACAGGCTGCTCCGCCACCTC 
                   
                   
                   
               
               
                   
                 GGACTG[CG]GCTCCTACTCGGCCACTG 
                   
                   
                   
               
               
                   
                 GCCAGAGTCCCTCCAGCCAACTGCCCC 
                   
                   
                   
               
               
                   
                 TGGTGAGACCACCGT 
                   
                   
                   
               
               
                   
               
               
                 cg13975369 
                 CCATTTGAGGGCAAGGGCTGTGTCTTT 
                  7 
                 130080553 
                 TSGA14 
               
               
                   
                 GGGTACTTCGCTCCTCGCAGTCACAAG 
                   
                   
                   
               
               
                   
                 TACTGG[CG]TGCGTACGCGGGGAGAG 
                   
                   
                   
               
               
                   
                 ATCGCTCCTCAAAACGGGGTCCTGAAC 
                   
                   
                   
               
               
                   
                 GCTGCCCCGCGGCCCC 
                   
                   
                   
               
               
                   
               
               
                 cg19008809 
                 GCGCGCGTGCCGCCGCCGCGGGCACTG 
                  3 
                  53080682 
                 SFMBT1 
               
               
                   
                 CGCCCGTTTGCCTGCCCCTCGTCGGGG 
                   
                   
                   
               
               
                   
                 ATCGGG[CG]CTCCCTCTGAGACCTGAA 
                   
                   
                   
               
               
                   
                 AGGGCACCCAAGTGCCCCCTGTCTGCG 
                   
                   
                   
               
               
                   
                 AAGTCCGGCGCGGGC 
                   
                   
                   
               
               
                   
               
               
                 cg12830694 
                 CCACTGGCCCGGTTCAACGAATATCTA 
                 19 
                  38747796 
                 PPP1R14A 
               
               
                   
                 TTAAGTATCCACTCTATACCAGACACT 
                   
                   
                   
               
               
                   
                 GCTTTA[CG]CTCCAGGGATAGAGCAGG 
                   
                   
                   
               
               
                   
                 GAACAAAACAGACAAAACCAGTCCCA 
                   
                   
                   
               
               
                   
                 CGCAGTTGACAGTTGT 
                   
                   
                   
               
               
                   
               
               
                 cg23662675 
                 TGGCTGCCCCGGCAAATCGGAGTGTAA 
                 20 
                  45985596 
                 ZMYND8 
               
               
                   
                 AGCCGCCCCGGATTGGCTGAAACACTT 
                   
                   
                   
               
               
                   
                 CCTGAG[CG]ATTATCTTTGTGAGGCTC 
                   
                   
                   
               
               
                   
                 GGGTGAGCAAGAGCCATCCTGTGCATA 
                   
                   
                   
               
               
                   
                 GAAAAAGACAGGCTA 
                   
                   
                   
               
               
                   
               
               
                 cg02331561 
                 CAGCGGCGGTAGCCGAGCGAGGGCGC 
                 16 
                   2391081 
                 ABCA17P; 
               
               
                   
                 GGTGGCCTCTGACAGGAATGACTCTGC 
                   
                   
                 ABCA3 
               
               
                   
                 GCACGTG[CG]TTTCGCAGCAGTGGAAG 
                   
                   
                   
               
               
                   
                 TCTTCACACCCGGAAACTCGACTTTGG 
                   
                   
                   
               
               
                   
                 CCGTTTCTCCATTTCT 
                   
                   
                   
               
               
                   
               
               
                 cg10523019 
                 CTCGCTGCTTCTCCCCTAGTCTTCGGGT 
                  2 
                 227700458 
                 RHBDD1 
               
               
                   
                 CCCTTGAACGCAGGTCGCTTGTTTGCC 
                   
                   
                   
               
               
                   
                 TTACG[CG]TAGTCAGCGGCCAGTGGCT 
                   
                   
                   
               
               
                   
                 ATTTATGGCAGTAAGGAATATTATCCA 
                   
                   
                   
               
               
                   
                 CATTTCACATGGAG 
                   
                   
                   
               
               
                   
               
               
                 cg27377450 
                 CTACACAAAGGCGCTCACACTTTATCC 
                 19 
                   7446301 
                   
               
               
                   
                 GAAACAGCAGTGGGGCTTGGGTGCGG 
                   
                   
                   
               
               
                   
                 TGGCTCA[CG]CCTATAATCCCAGCACT 
                   
                   
                   
               
               
                   
                 TTGGGAGGCCGAGGAGGGTGGATCAT 
                   
                   
                   
               
               
                   
                 CTGAGGTCAGGAGTTCA 
                   
                   
                   
               
               
                   
               
               
                 cg06144905 
                 CTGACCTCACCACCCACCAGGGAGGTG 
                 17 
                  27369780 
                 PIPOX 
               
               
                   
                 GGTCTTATTCTGGGCATCGTGCCAAGT 
                   
                   
                   
               
               
                   
                 TCTTAG[CG]GGGCCCTCTAGAATCTCT 
                   
                   
                   
               
               
                   
                 AAAGCAAATCAGGCTGAAGAGGGGAA 
                   
                   
                   
               
               
                   
                 AACCAGCAGGGGGAGG 
                   
                   
                   
               
               
                   
               
               
                 cg26845300 
                 CGCAACACCCCAGGCGTGGGGCAAAG 
                  6 
                 158243833 
                 SNX9 
               
               
                   
                 ACAGCGGGGTTGCGGGGCTCCTGTCTG 
                   
                   
                   
               
               
                   
                 CCCGGGG[CG]TCGAGAGTTCCTGCCGC 
                   
                   
                   
               
               
                   
                 CCCCTCCCGCCTCATGCACGGAAAGCG 
                   
                   
                   
               
               
                   
                 CCGAGCCACGGCGTGC 
                   
                   
                   
               
               
                   
               
               
                 cg25771195 
                 GATAAGCGCCTAATATACATCCCTGCC 
                 16 
                  58163814 
                 C16orf80 
               
               
                   
                 TGTCATTATTCACATTGTGGCATGCAG 
                   
                   
                   
               
               
                   
                 TCAAAG[CG]ACACTCTGAGGAAAATGT 
                   
                   
                   
               
               
                   
                 ATCGCCTTAAATACATTGATTAGAAAA 
                   
                   
                   
               
               
                   
                 TAAGAAAGCCCGAAC 
                   
                   
                   
               
               
                   
               
               
                 cg12946225 
                 CCGGCGGGCGGCAAGGCTCCGGGCCA 
                 19 
                   3573751 
                 HMG20B 
               
               
                   
                 GCATGGGGGCTTCGTGGTGACTGTCAA 
                   
                   
                   
               
               
                   
                 GCAAGAG[CG]CGGCGAGGGTCCACGC 
                   
                   
                   
               
               
                   
                 GCGGGCGAGAAGGGGTCCCACGAGGA 
                   
                   
                   
               
               
                   
                 GGAGGTGAGAGTCCCTGC 
                   
                   
                   
               
               
                   
               
               
                 cg26005082 
                 AGCTCTCCACCGACCGAAGGAGGAGA 
                 19 
                   4769660 
                 MIR7- 
               
               
                   
                 ATGCTATTTATTTCAGCACCAAATATC 
                   
                   
                 3; C19orf30 
               
               
                   
                 CGGACAG[CG]CCTCTCGGGAGGTCCGA 
                   
                   
                   
               
               
                   
                 GAAGAGAACCGCGATCTGTTTCAGCAC 
                   
                   
                   
               
               
                   
                 CGGGGCTCAGGACAGT 
                   
                   
                   
               
               
                   
               
               
                 cg21378206 
                 AAATAGGGGAGTCTACACCCTGTGGAG 
                  2 
                 113817043 
                 IL1F5 
               
               
                   
                 CTCAAGATGGTCCTGAGTGGGGCGCTG 
                   
                   
                   
               
               
                   
                 TGCTTC[CG]GTGAGTGTATGAGGCCCT 
                   
                   
                   
               
               
                   
                 GGTTTGGTGGTGTCCTCCGGAGGAAGT 
                   
                   
                   
               
               
                   
                 GAGTTCTGGATAGAC 
                   
                   
                   
               
               
                   
               
               
                 cg10281002 
                 TTGGGATGCGATAACTCAGTGCCCTCT 
                 12 
                 114846399 
                 TBX5 
               
               
                   
                 TGCAGACTTGCATAGAAATAATTACTG 
                   
                   
                   
               
               
                   
                 GGTTGT[CG]TGGAGGGGACACGAGAC 
                   
                   
                   
               
               
                   
                 AGAGGGAGTTCTCCGTAATGTGCCTTG 
                   
                   
                   
               
               
                   
                 CGGAGAGAAAGGTCCA 
                   
                   
                   
               
               
                   
               
               
                 cg22920873 
                 CGAAGATCCGGCCAATTTGCCCAGCGC 
                  7 
                 139025153 
                 C7orf55 
               
               
                   
                 GCTGTGCTCCGCGACGGCGCATGCCCG 
                   
                   
                   
               
               
                   
                 CTTTTG[CG]CAGGCGCGGGGACTACGG 
                   
                   
                   
               
               
                   
                 CGCAGGCGCGGAGACTATTGCGCAGG 
                   
                   
                   
               
               
                   
                 CAAGCGCGTACGCAGA 
                   
                   
                   
               
               
                   
               
               
                 cg19945840 
                 GCGCGCCCTGGAGCGGGAGCAGGCGC 
                  1 
                   1168036 
                 SDF4; B3G 
               
               
                   
                 GGCACGGGGACCTGCTGCTGCTGCCCG 
                   
                   
                 ALT6 
               
               
                   
                 CGCTGCG[CG]ACGCCTACGAAAACCTC 
                   
                   
                   
               
               
                   
                 ACGGCCAAGGTGCTGGCCATGCTGGCC 
                   
                   
                   
               
               
                   
                 TGGCTGGACGAGCACG 
                   
                   
                   
               
               
                   
               
               
                 cg04084157 
                 AGGGTGCCTGCCTCTCCCGGCCTGCGC 
                  7 
                 100809049 
                 VGF 
               
               
                   
                 CTGCGCGCTGGGGCCTTCGGCTGAAGG 
                   
                   
                   
               
               
                   
                 GGTGTG[CG]CTAGCGGAGCTCCGGGAA 
                   
                   
                   
               
               
                   
                 ATGAATGAATGAATGAATGAATGAAAT 
                   
                   
                   
               
               
                   
                 GCTGAAGCGGGCAGG 
                   
                   
                   
               
               
                   
               
               
                 cg20692569 
                 CGACCCGGAGCGCGGGCGCGGGGCTG 
                  7 
                  72848481 
                 FZD9 
               
               
                   
                 CGCCGTGCCAGGCGGTGGAGATCCCCA 
                   
                   
                   
               
               
                   
                 TGTGCCG[CG]GCATCGGCTACAACCTG 
                   
                   
                   
               
               
                   
                 ACCCGCATGCCCAACCTGCTGGGCCAC 
                   
                   
                   
               
               
                   
                 ACGTCGCAGGGCGAGG 
                   
                   
                   
               
               
                   
               
               
                 cg26297688 
                 ATAAGCCACGTCTCTCCTCACCCCTAG 
                 12 
                 107349093 
                 C12orf23 
               
               
                   
                 CACTTAATCACAAAGGCCTGTAGAGAG 
                   
                   
                   
               
               
                   
                 TCCCGA[CG]AGAACTTCTGAGCAGGCC 
                   
                   
                   
               
               
                   
                 CCGCTGTCAGTCCCTGAGGACAGCATG 
                   
                   
                   
               
               
                   
                 CAAGGGAGGTTGACG 
                   
                   
                   
               
               
                   
               
               
                 cg04528819 
                 GCAGCCCGGGAAGGGGCATTGGTGGC 
                  7 
                 130418315 
                 KLF14 
               
               
                   
                 GCTTGGCAGCAGGTGTGACAGACCTCC 
                   
                   
                   
               
               
                   
                 TCCGGGG[CG]CCTGATCCGCGGCGGGG 
                   
                   
                   
               
               
                   
                 GCGGGGCCTGCCCCTAGGGCCCCTCCA 
                   
                   
                   
               
               
                   
                 GAGAACCCACCAGAGG 
                   
                   
                   
               
               
                   
               
               
                 cg06493994 
                 GGAGAGCAAGTCAAGAAATACGGTGA 
                  6 
                  25652602 
                 SCGN 
               
               
                   
                 AGGAGTCCTTCCCAAAGTTGTCTAGGT 
                   
                   
                   
               
               
                   
                 CCTTCCG[CG]CCGGTGCCTGGTCTTCGT 
                   
                   
                   
               
               
                   
                 CGTCAACACCATGGACAGCTCCCGGGA 
                   
                   
                   
               
               
                   
                 ACCGACTCTGGGGCG 
                   
                   
                   
               
               
                   
               
               
                 cg25505610 
                 GAGGCGCCAGCGGGAGGCAACATCAA 
                 11 
                  32605184 
                 EIF3M 
               
               
                   
                 TGCAGTTAGCTACACGGGCCTGAAAAC 
                   
                   
                   
               
               
                   
                 TGGAGGC[CG]CGACAAGCGTCGCTGA 
                   
                   
                   
               
               
                   
                 GTGGAGGCCCAGTAAGTCCCACCCACT 
                   
                   
                   
               
               
                   
                 AGGCCAGCCCGAGCGCG 
                   
                   
                   
               
               
                   
               
               
                 cg00864867 
                 AGTACAAGACCGTATTATTTGAGAGAA 
                 12 
                  80085268 
                 PAWR 
               
               
                   
                 AGTCTCGAACGCTGCTGGCTAAGGGGA 
                   
                   
                   
               
               
                   
                 AAAGTG[CG]ATAACTTGTGATGATTCA 
                   
                   
                   
               
               
                   
                 GGGAATGACTAGACAGGATGGGAAAA 
                   
                   
                   
               
               
                   
                 TACCCACGTGTCTCTT 
                   
                   
                   
               
               
                   
               
               
                 cg02479575 
                 GAGGGACAGCTCTCCACCGACCGAAG 
                 19 
                   4769653 
                 MIR7- 
               
               
                   
                 GAGGAGAATGCTATTTATTTCAGCACC 
                   
                   
                 3; C19orf30 
               
               
                   
                 AAATATC[CG]GACAGCGCCTCTCGGGA 
                   
                   
                   
               
               
                   
                 GGTCCGAGAAGAGAACCGCGATCTGTT 
                   
                   
                   
               
               
                   
                 TCAGCACCGGGGCTCA 
                   
                   
                   
               
               
                   
               
               
                 cg22736354 
                 TGCGCCAGGGCGGCCACGCAGGCCAG 
                  6 
                  18122719 
                 NHLRC1 
               
               
                   
                 GCAGACCACGTGGCCGCAGGACAGGT 
                   
                   
                   
               
               
                   
                 TGCGCGGG[CG]CCGCTGCTGCCGGTGG 
                   
                   
                   
               
               
                   
                 CCAAACTTCTCAAAGCACACCTTGCAC 
                   
                   
                   
               
               
                   
                 TCGAGCAGGCTGATCTC 
                   
                   
                   
               
               
                   
               
               
                 cg14424579 
                 TAAGCGATAAGGAGTTTCACACGATGT 
                  2 
                  27274309 
                 AGBL5 
               
               
                   
                 CTTTTTATTTCGCAGTTGAGTCCCAGTT 
                   
                   
                   
               
               
                   
                 TCTGC[CG]CTTTATCTTTCCCGCCTCCC 
                   
                   
                   
               
               
                   
                 GGCAGGCAGGCCGTTAACCGTCTTCCG 
                   
                   
                   
               
               
                   
                 GAAGACGCTGCTA 
                   
                   
                   
               
               
                   
               
               
                 cg16241714 
                 GGCACAGCTCCAGGGTGGGCACGGCG 
                  8 
                  48650511 
                 CEBPD 
               
               
                   
                 GCCATGGAGTCGATGTAGGCGCTGAAG 
                   
                   
                   
               
               
                   
                 TCGATGG[CG]CTCTCGTCGTCGTACAT 
                   
                   
                   
               
               
                   
                 GGCGGGGGCGGCGGCGCCTGGCTCGC 
                   
                   
                   
               
               
                   
                 CTAGGGCCCCTGGCTCG 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Listing of 38 CpGs Subset 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Sequence with the CpG 
                 Chromo- 
                   
                   
               
               
                 Probe 
                 site marked with [ ] 
                 some 
                 Position 
                 Gene 
               
               
                   
               
               
                 cg00431549 
                 TAACTGCTGGACCTGACTGTGTTACAC 
                 12 
                  15039025 
                 MGP 
               
               
                   
                 AGGATGCTGCTCTGGTGCAGAAGTTTT 
                   
                   
                   
               
               
                   
                 GGCCAT[CG]TATGCTTGGGGACAGACC 
                   
                   
                   
               
               
                   
                 TGGGCAAAAGCCCACAGAGGAAGTTG 
                   
                   
                   
               
               
                   
                 CCACAAACACATGATC 
                   
                   
                   
               
               
                   
               
               
                 cg00864867 
                 AGTACAAGACCGTATTATTTGAGAGAA 
                 12 
                  80085268 
                 PAWR 
               
               
                   
                 AGTCTCGAACGCTGCTGGCTAAGGGGA 
                   
                   
                   
               
               
                   
                 AAAGTG[CG]ATAACTTGTGATGATTCA 
                   
                   
                   
               
               
                   
                 GGGAATGACTAGACAGGATGGGAAAA 
                   
                   
                   
               
               
                   
                 TACCCACGTGTCTCTT 
                   
                   
                   
               
               
                   
               
               
                 cg01353448 
                 GCCCAGCCTCGGTGAGCACACACGCCC 
                  7 
                  31726912 
                 C7orf16 
               
               
                   
                 TCCCTGTCTCTCGCCTTCGCTTCCCTGC 
                   
                   
                   
               
               
                   
                 ATCTG[CG]CTGATTGGTAAGTGCTTCA 
                   
                   
                   
               
               
                   
                 GATTTTTACTCCAAGAACTTTTGTGGTG 
                   
                   
                   
               
               
                   
                 AGAAAAGCAAGTT 
                   
                   
                   
               
               
                   
               
               
                 cg01459453 
                 GCAAGTTTAAAAGTACTCACAAAATCT 
                  1 
                 169599212 
                 SELP 
               
               
                   
                 AATAGGCAATTCAACATAAAACTCCAT 
                   
                   
                   
               
               
                   
                 GGCTAT[CG]CTGTTCCTCACTTTCTGAA 
                   
                   
                   
               
               
                   
                 CCTTTACCTGCCTGACTTTACTCCATAC 
                   
                   
                   
               
               
                   
                 CACTCCAACTCAC 
                   
                   
                   
               
               
                   
               
               
                 cg01511567 
                 GTAGTTTTATTGTATCAGACTTAGTACA 
                 11 
                  57103631 
                 SSRP1 
               
               
                   
                 GGGGTGGGGTGGGGGTGTGTATTGGAA 
                   
                   
                   
               
               
                   
                 TGATG[CG]TGCCCGTTTCTCTGCAAAA 
                   
                   
                   
               
               
                   
                 TAGTTTCTATGTCATGGAAAGGAGTCG 
                   
                   
                   
               
               
                   
                 ATGGGACAAGAAGA 
                   
                   
                   
               
               
                   
               
               
                 cg02275294 
                 GTTTGAATGTTGCTGAAGGACGCTGGT 
                  1 
                 179262462 
                 SOAT1 
               
               
                   
                 TTTCAAACGGTAAGGAATCTCCTGATA 
                   
                   
                   
               
               
                   
                 AAGGCA[CG]AATCTTGGTGTGCAGATA 
                   
                   
                   
               
               
                   
                 AGCCAGCGATTCTTGCTTCTGGCTAGT 
                   
                   
                   
               
               
                   
                 TCTACGTTGTTCCTG 
                   
                   
                   
               
               
                   
               
               
                 cg02479575 
                 GAGGGACAGCTCTCCACCGACCGAAG 
                 19 
                   4769653 
                 MIR7- 
               
               
                   
                 GAGGAGAATGCTATTTATTTCAGCACC 
                   
                   
                 3; C19orf30 
               
               
                   
                 AAATATC[CG]GACAGCGCCTCTCGGGA 
                   
                   
                   
               
               
                   
                 GGTCCGAGAAGAGAACCGCGATCTGTT 
                   
                   
                   
               
               
                   
                 TCAGCACCGGGGCTCA 
                   
                   
                   
               
               
                   
               
               
                 cg04084157 
                 AGGGTGCCTGCCTCTCCCGGCCTGCGC 
                  7 
                 100809049 
                 VGF 
               
               
                   
                 CTGCGCGCTGGGGCCTTCGGCTGAAGG 
                   
                   
                   
               
               
                   
                 GGTGTG[CG]CTAGCGGAGCTCCGGGAA 
                   
                   
                   
               
               
                   
                 ATGAATGAATGAATGAATGAATGAAAT 
                   
                   
                   
               
               
                   
                 GCTGAAGCGGGCAGG 
                   
                   
                   
               
               
                   
               
               
                 cg04528819 
                 GCAGCCCGGGAAGGGGCATTGGTGGC 
                  7 
                 130418315 
                 KLF14 
               
               
                   
                 GCTTGGCAGCAGGTGTGACAGACCTCC 
                   
                   
                   
               
               
                   
                 TCCGGGG[CG]CCTGATCCGCGGCGGGG 
                   
                   
                   
               
               
                   
                 GCGGGGCCTGCCCCTAGGGCCCCTCCA 
                   
                   
                   
               
               
                   
                 GAGAACCCACCAGAGG 
                   
                   
                   
               
               
                   
               
               
                 cg05442902 
                 GCCAGGTCACCCTCTCACTCTGTGCCT 
                 22 
                  21369010 
                 MGC1670 
               
               
                   
                 CTTAGTTATCTTGCATGCTCTGGTCTTT 
                   
                   
                 3; P2RX6 
               
               
                   
                 GCATA[CG]CTGCTCCCTGCACCAGGAA 
                   
                   
                   
               
               
                   
                 CCTCCATCCCCATCTTTGTCTGCTTGTC 
                   
                   
                   
               
               
                   
                 GAACTTCAGAAAT 
                   
                   
                   
               
               
                   
               
               
                 cg06117855 
                 TGGGGAGGGTTTCCTGGACAGAGGTCC 
                  3 
                  45067788 
                 CLEC3B 
               
               
                   
                 TTTGGCTGCTGCCTTAAGACGTGCAGC 
                   
                   
                   
               
               
                   
                 CTGGGC[CG]TGGCTGTCACTGCGTTCG 
                   
                   
                   
               
               
                   
                 GACCCAGACCCGCTGCAGGCAGCAGC 
                   
                   
                   
               
               
                   
                 AGCCCCCGCCCGCGCA 
                   
                   
                   
               
               
                   
               
               
                 cg06493994 
                 GGAGAGCAAGTCAAGAAATACGGTGA 
                  6 
                  25652602 
                 SCGN 
               
               
                   
                 AGGAGTCCTTCCCAAAGTTGTCTAGGT 
                   
                   
                   
               
               
                   
                 CCTTCCG[CG]CCGGTGCCTGGTCTTCGT 
                   
                   
                   
               
               
                   
                 CGTCAACACCATGGACAGCTCCCGGGA 
                   
                   
                   
               
               
                   
                 ACCGACTCTGGGGCG 
                   
                   
                   
               
               
                   
               
               
                 cg07158339 
                 TACAGGGCTTAACTCATTTTATCCTTAC 
                  9 
                  71650237 
                 FXN 
               
               
                   
                 CACAATCCTATGAAGTAGGAACTTTTA 
                   
                   
                   
               
               
                   
                 TAAAA[CG]CATTTTATAAACAAGGCAC 
                   
                   
                   
               
               
                   
                 AGAGAGGTTAATTAACTTGCCCTCTGG 
                   
                   
                   
               
               
                   
                 TCACACAGCTAGGA 
                   
                   
                   
               
               
                   
               
               
                 cg07388493 
                 GGGAGCCAGTGTTCTTTCTCTCCTGTG 
                  1 
                  39491459 
                 NDUFS5 
               
               
                   
                 ACTTTGGTGAAGTCTCTCACCACTCAG 
                   
                   
                   
               
               
                   
                 TGTTGT[CG]TGAGCATGCTAGGCAGAG 
                   
                   
                   
               
               
                   
                 TGCAAGAAAGGAGCAAGAACTCACTA 
                   
                   
                   
               
               
                   
                 ATGGCTAGGCCTTCCC 
                   
                   
                   
               
               
                   
               
               
                 cg08331960 
                 TCGGGGTCCCTTGGCCTGGAGACCCTT 
                 16 
                   2076597 
                 SLC9A3R2 
               
               
                   
                 TGTCCAACCCGTCGCCCACCTCAAGAC 
                   
                   
                   
               
               
                   
                 CTGCCT[CG]ATGCTGCGCATACAGTAG 
                   
                   
                   
               
               
                   
                 GTATCCAATAAATGTTCCTGGGATAGA 
                   
                   
                   
               
               
                   
                 AGGCAAAGGCGCTGG 
                   
                   
                   
               
               
                   
               
               
                 cg10281002 
                 TTGGGATGCGATAACTCAGTGCCCTCT 
                 12 
                 114846399 
                 TBX5 
               
               
                   
                 TGCAGACTTGCATAGAAATAATTACTG 
                   
                   
                   
               
               
                   
                 GGTTGT[CG]TGGAGGGGACACGAGAC 
                   
                   
                   
               
               
                   
                 AGAGGGAGTTCTCCGTAATGTGCCTTG 
                   
                   
                   
               
               
                   
                 CGGAGAGAAAGGTCCA 
                   
                   
                   
               
               
                   
               
               
                 cg10523019 
                 CTCGCTGCTTCTCCCCTAGTCTTCGGGT 
                  2 
                 227700458 
                 RHBDD1 
               
               
                   
                 CCCTTGAACGCAGGTCGCTTGTTTGCC 
                   
                   
                   
               
               
                   
                 TTACG[CG]TAGTCAGCGGCCAGTGGCT 
                   
                   
                   
               
               
                   
                 ATTTATGGCAGTAAGGAATATTATCCA 
                   
                   
                   
               
               
                   
                 CATTTCACATGGAG 
                   
                   
                   
               
               
                   
               
               
                 cg13547237 
                 GCAGTGCATCGAGCTGGAGCAGCAGTT 
                 11 
                  65687877 
                 C11orf68; 
               
               
                   
                 TGACTTCTTGAAGGACCTGGTGGCATC 
                   
                   
                 DRAP1 
               
               
                   
                 TGTTCC[CG]ACATGCAGGGGGACGGGG 
                   
                   
                   
               
               
                   
                 AAGACAACCACATGGATGGGGACAAG 
                   
                   
                   
               
               
                   
                 GGCGCCCGCAGGTGGG 
                   
                   
                   
               
               
                   
               
               
                 cg14424579 
                 TAAGCGATAAGGAGTTTCACACGATGT 
                  2 
                  27274309 
                 AGBL5 
               
               
                   
                 CTTTTTATTTCGCAGTTGAGTCCCAGTT 
                   
                   
                   
               
               
                   
                 TCTGC[CG]CTTTATCTTTCCCGCCTCCC 
                   
                   
                   
               
               
                   
                 GGCAGGCAGGCCGTTAACCGTCTTCCG 
                   
                   
                   
               
               
                   
                 GAAGACGCTGCTA 
                   
                   
                   
               
               
                   
               
               
                 cg16744741 
                 CAGCTGGATGCACTTGTTCTGGAGCTC 
                  4 
                  82126025 
                 PRKG2 
               
               
                   
                 CTCTGTGAGTTCAGCAATGGCCACAGT 
                   
                   
                   
               
               
                   
                 CTGCTT[CG]ACAGCTGCTCCCGCAGCT 
                   
                   
                   
               
               
                   
                 CCTTCAAATGGTACTCCCGCTCCTGGA 
                   
                   
                   
               
               
                   
                 TCTCAGCATCCTTCC 
                   
                   
                   
               
               
                   
               
               
                 cg17324128 
                 CCCTCCCCCGCCAGCCTGGCGCATTGC 
                 10 
                  45455500 
                 RASSF4 
               
               
                   
                 GGGCCTCGGGCTCATTGCTGAGAGGGG 
                   
                   
                   
               
               
                   
                 GCACTG[CG]CCTGGCACCTCTGTTAAG 
                   
                   
                   
               
               
                   
                 CAATTTAGGGGCTACAACCTGAGCAAG 
                   
                   
                   
               
               
                   
                 ACAGATGAGCCCGGC 
                   
                   
                   
               
               
                   
               
               
                 cg19722847 
                 TCTGCTTACAGCTGCTTCCAAATTAAG 
                 12 
                  30849114 
                 IPO8 
               
               
                   
                 CATATCTGGATGGTGTGACACTTTTTGT 
                   
                   
                   
               
               
                   
                 TAGTC[CG]AGAACTGTATGGGCATCGC 
                   
                   
                   
               
               
                   
                 AACTGGGCCTGTTCCAAGATAGACTTG 
                   
                   
                   
               
               
                   
                 TTGGGACCTTCAAA 
                   
                   
                   
               
               
                   
               
               
                 cg19724470 
                 CATTCTTATGCGACTGTGTGTTCAGAA 
                  9 
                   5450936 
                 CD274 
               
               
                   
                 TATAGCTCTGATGCTAGGCTGGAGGTC 
                   
                   
                   
               
               
                   
                 TGGACA[CG]GGTCCAAGTCCACCGCCA 
                   
                   
                   
               
               
                   
                 GCTGCTTGCTAGTAACATGACTTGTGT 
                   
                   
                   
               
               
                   
                 AAGTTATCCCAGCTG 
                   
                   
                   
               
               
                   
               
               
                 cg19761273 
                 GGACAAAGCCACCACCTTTCACAAAAT 
                 17 
                  80232096 
                 CSNK1D 
               
               
                   
                 GAGGCCAGACCACCTGCCTCCCTCCAG 
                   
                   
                   
               
               
                   
                 TCCCTG[CG]GCCTGGAGACGGAGTCAA 
                   
                   
                   
               
               
                   
                 CATTCTTATCTGTGTTGGATCTGAATGT 
                   
                   
                   
               
               
                   
                 TCCTCCTTGCAAAG 
                   
                   
                   
               
               
                   
               
               
                 cg19945840 
                 GCGCGCCCTGGAGCGGGAGCAGGCGC 
                  1 
                   1168036 
                 SDF4; B3G 
               
               
                   
                 GGCACGGGGACCTGCTGCTGCTGCCCG 
                   
                   
                 ALT6 
               
               
                   
                 CGCTGCG[CG]ACGCCTACGAAAACCTC 
                   
                   
                   
               
               
                   
                 ACGGCCAAGGTGCTGGCCATGCTGGCC 
                   
                   
                   
               
               
                   
                 TGGCTGGACGAGCACG 
                   
                   
                   
               
               
                   
               
               
                 cg20692569 
                 CGACCCGGAGCGCGGGCGCGGGGCTG 
                  7 
                  72848481 
                 FZD9 
               
               
                   
                 CGCCGTGCCAGGCGGTGGAGATCCCCA 
                   
                   
                   
               
               
                   
                 TGTGCCG[CG]GCATCGGCTACAACCTG 
                   
                   
                   
               
               
                   
                 ACCCGCATGCCCAACCTGCTGGGCCAC 
                   
                   
                   
               
               
                   
                 ACGTCGCAGGGCGAGG 
                   
                   
                   
               
               
                   
               
               
                 cg21801378 
                 CCACGAAGAGCTTGATGGCGTCGTGGT 
                 15 
                  72612125 
                 BRUNOL6 
               
               
                   
                 CCTTCATGGGTACGGCGGGACCGGGGT 
                   
                   
                   
               
               
                   
                 TTAGCC[CG]CTCATGCCGACGCCGCTG 
                   
                   
                   
               
               
                   
                 TCCGCGGTGCTGAAACCCAGGCGCGGG 
                   
                   
                   
               
               
                   
                 CCGGGGCCAGCGGGC 
                   
                   
                   
               
               
                   
               
               
                 cg22736354 
                 TGCGCCAGGGCGGCCACGCAGGCCAG 
                  6 
                  18122719 
                 NHLRC1 
               
               
                   
                 GCAGACCACGTGGCCGCAGGACAGGT 
                   
                   
                   
               
               
                   
                 TGCGCGGG[CG]CCGCTGCTGCCGGTGG 
                   
                   
                   
               
               
                   
                 CCAAACTTCTCAAAGCACACCTTGCAC 
                   
                   
                   
               
               
                   
                 TCGAGCAGGCTGATCTC 
                   
                   
                   
               
               
                   
               
               
                 cg22947000 
                 TAGCTATGACACATGGCTTGGAAATTA 
                 16 
                  81272281 
                 BCMO1 
               
               
                   
                 ACCTTTAACCAAACATCTTATAAGTAA 
                   
                   
                   
               
               
                   
                 CGCCAG[CG]CAGCTTCCCTTGTGAATG 
                   
                   
                   
               
               
                   
                 TAAAGAGATCCAGGGCTCTTGGAGAG 
                   
                   
                   
               
               
                   
                 GGACAAGTGAGAGCCA 
                   
                   
                   
               
               
                   
               
               
                 cg23517605 
                 CTCCAGTGCCGGCAGGTGGGAGGGCTG 
                  6 
                   3228365 
                 TUBB2B 
               
               
                   
                 AGGTGGCACAGGCTGCTCCGCCACCTC 
                   
                   
                   
               
               
                   
                 GGACTG[CG]GCTCCTACTCGGCCACTG 
                   
                   
                   
               
               
                   
                 GCCAGAGTCCCTCCAGCCAACTGCCCC 
                   
                   
                   
               
               
                   
                 TGGTGAGACCACCGT 
                   
                   
                   
               
               
                   
               
               
                 cg24899750 
                 GGAGGAACTGGCTATCCTAAAGGTGAT 
                 20 
                  16710314 
                 SNRPB2 
               
               
                   
                 TTTAAACCGGGGTAGCTAGAGCCCAAA 
                   
                   
                   
               
               
                   
                 GAAGGG[CG]AAACCAGGACTAACTGC 
                   
                   
                   
               
               
                   
                 CCCATAGCATGAGGGGCAGCGCCTGTA 
                   
                   
                   
               
               
                   
                 AAATTACATAGGATTT 
                   
                   
                   
               
               
                   
               
               
                 cg25771195 
                 GATAAGCGCCTAATATACATCCCTGCC 
                 16 
                  58163814 
                 C16orf80 
               
               
                   
                 TGTCATTATTCACATTGTGGCATGCAG 
                   
                   
                   
               
               
                   
                 TCAAAG[CG]ACACTCTGAGGAAAATGT 
                   
                   
                   
               
               
                   
                 ATCGCCTTAAATACATTGATTAGAAAA 
                   
                   
                   
               
               
                   
                 TAAGAAAGCCCGAAC 
                   
                   
                   
               
               
                   
               
               
                 cg25809905 
                 ACTTGATTCTGGTTGGGGGCTTTGCCT 
                 17 
                  42467728 
                 ITGA2B 
               
               
                   
                 AGGGGAGCCTTCCCTGACTCCTCAGGC 
                   
                   
                   
               
               
                   
                 TGGCCG[CG]TGGGCTAACACACGTAGG 
                   
                   
                   
               
               
                   
                 CACAGCATTGAGCACACTGTTTACTCT 
                   
                   
                   
               
               
                   
                 TGGTCCGTTCACAGG 
                   
                   
                   
               
               
                   
               
               
                 cg26005082 
                 AGCTCTCCACCGACCGAAGGAGGAGA 
                 19 
                   4769660 
                 MIR7- 
               
               
                   
                 ATGCTATTTATTTCAGCACCAAATATC 
                   
                   
                 3; C19orf30 
               
               
                   
                 CGGACAG[CG]CCTCTCGGGAGGTCCGA 
                   
                   
                   
               
               
                   
                 GAAGAGAACCGCGATCTGTTTCAGCAC 
                   
                   
                   
               
               
                   
                 CGGGGCTCAGGACAGT 
                   
                   
                   
               
               
                   
               
               
                 cg26394940 
                 TAAATAAATAAGGGCTTTTGTTTGTTTG 
                 22 
                  46449461 
                 C22orf26; L 
               
               
                   
                 CCGGCTCCTGCACATGGCTGCTGGGAC 
                   
                   
                 OC150381 
               
               
                   
                 TCAAG[CG]CTCGTGTTGTCTGCGCCTCT 
                   
                   
                   
               
               
                   
                 GTGGGACTCTGGGGACGGGAGGCAGG 
                   
                   
                   
               
               
                   
                 GGAGGCCCCCGCAG 
                   
                   
                   
               
               
                   
               
               
                 cg26453588 
                 GGCTGCCCACCCGCCCACCCCGCCTGG 
                 22 
                  43506021 
                 BIK 
               
               
                   
                 AAGCTTTCTGATTTCTCTGTTCGCCCCG 
                   
                   
                   
               
               
                   
                 CCAGG[CG]CTGTGGGGTCCGTCTCACC 
                   
                   
                   
               
               
                   
                 AGGTCTGCACGTGAGCCCCCTGCCCCC 
                   
                   
                   
               
               
                   
                 AATCCCTCCCAGTC 
                   
                   
                   
               
               
                   
               
               
                 cg26614073 
                 CTTGGGCAACGTAGGAGACCTCCGTCT 
                  3 
                  47517819 
                 SCAP 
               
               
                   
                 CCACAAGTAAAATTAATTAGCCGGCTG 
                   
                   
                   
               
               
                   
                 TGGTGG[CG]CGCACCTGTGGTCCCAGC 
                   
                   
                   
               
               
                   
                 TACTCAGGAGGCTGAGGTAGGAGGAT 
                   
                   
                   
               
               
                   
                 CACCTGAGCCCGGGAG 
                   
                   
                   
               
               
                   
               
               
                 cg27015931 
                 TGTTTTTGTGGGAGGCCTTCTGCATGGT 
                 16 
                  22012404 
                 C16orf65 
               
               
                   
                 CCCGGGAGGTCAGGCAGCCCGGGAGG 
                   
                   
                   
               
               
                   
                 GCCTCC[CG]GAGCAGAGGCTGGAGTCA 
                   
                   
                   
               
               
                   
                 GTCCCAATGCCAACAGTTTCGAACCTT 
                   
                   
                   
               
               
                   
                 GCCCGCGGGCACTGC 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Listing of 17 CpGs Subset 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Sequence with the CpG 
                 Chromo- 
                   
                   
               
               
                 Probe 
                 site marked with [ ] 
                 some 
                 Position 
                 Gene 
               
               
                   
               
               
                 cg00431549 
                 TAACTGCTGGACCTGACTGTGTTACAC 
                 12 
                  15039025 
                 MGP 
               
               
                   
                 AGGATGCTGCTCTGGTGCAGAAGTTTT 
                   
                   
                   
               
               
                   
                 GGCCAT[CG]TATGCTTGGGGACAGACC 
                   
                   
                   
               
               
                   
                 TGGGCAAAAGCCCACAGAGGAAGTTG 
                   
                   
                   
               
               
                   
                 CCACAAACACATGATC 
                   
                   
                   
               
               
                   
               
               
                 cg01459453 
                 GCAAGTTTAAAAGTACTCACAAAATCT 
                  1 
                 169599212 
                 SELP 
               
               
                   
                 AATAGGCAATTCAACATAAAACTCCAT 
                   
                   
                   
               
               
                   
                 GGCTAT[CG]CTGTTCCTCACTTTCTGAA 
                   
                   
                   
               
               
                   
                 CCTTTACCTGCCTGACTTTACTCCATAC 
                   
                   
                   
               
               
                   
                 CACTCCAACTCAC 
                   
                   
                   
               
               
                   
               
               
                 cg01511567 
                 GTAGTTTTATTGTATCAGACTTAGTACA 
                 11 
                  57103631 
                 SSRP1 
               
               
                   
                 GGGGTGGGGTGGGGGTGTGTATTGGAA 
                   
                   
                   
               
               
                   
                 TGATG[CG]TGCCCGTTTCTCTGCAAAA 
                   
                   
                   
               
               
                   
                 TAGTTTCTATGTCATGGAAAGGAGTCG 
                   
                   
                   
               
               
                   
                 ATGGGACAAGAAGA 
                   
                   
                   
               
               
                   
               
               
                 cg02275294 
                 GTTTGAATGTTGCTGAAGGACGCTGGT 
                  1 
                 179262462 
                 SOAT1 
               
               
                   
                 TTTCAAACGGTAAGGAATCTCCTGATA 
                   
                   
                   
               
               
                   
                 AAGGCA[CG]AATCTTGGTGTGCAGATA 
                   
                   
                   
               
               
                   
                 AGCCAGCGATTCTTGCTTCTGGCTAGT 
                   
                   
                   
               
               
                   
                 TCTACGTTGTTCCTG 
                   
                   
                   
               
               
                   
               
               
                 cg04528819 
                 GCAGCCCGGGAAGGGGCATTGGTGGC 
                  7 
                 130418315 
                 KLF14 
               
               
                   
                 GCTTGGCAGCAGGTGTGACAGACCTCC 
                   
                   
                   
               
               
                   
                 TCCGGGG[CG]CCTGATCCGCGGCGGGG 
                   
                   
                   
               
               
                   
                 GCGGGGCCTGCCCCTAGGGCCCCTCCA 
                   
                   
                   
               
               
                   
                 GAGAACCCACCAGAGG 
                   
                   
                   
               
               
                   
               
               
                 cg06117855 
                 TGGGGAGGGTTTCCTGGACAGAGGTCC 
                  3 
                  45067788 
                 CLEC3B 
               
               
                   
                 TTTGGCTGCTGCCTTAAGACGTGCAGC 
                   
                   
                   
               
               
                   
                 CTGGGC[CG]TGGCTGTCACTGCGTTCG 
                   
                   
                   
               
               
                   
                 GACCCAGACCCGCTGCAGGCAGCAGC 
                   
                   
                   
               
               
                   
                 AGCCCCCGCCCGCGCA 
                   
                   
                   
               
               
                   
               
               
                 cg06493994 
                 GGAGAGCAAGTCAAGAAATACGGTGA 
                  6 
                  25652602 
                 SCGN 
               
               
                   
                 AGGAGTCCTTCCCAAAGTTGTCTAGGT 
                   
                   
                   
               
               
                   
                 CCTTCCG[CG]CCGGTGCCTGGTCTTCGT 
                   
                   
                   
               
               
                   
                 CGTCAACACCATGGACAGCTCCCGGGA 
                   
                   
                   
               
               
                   
                 ACCGACTCTGGGGCG 
                   
                   
                   
               
               
                   
               
               
                 cg07158339 
                 TACAGGGCTTAACTCATTTTATCCTTAC 
                  9 
                  71650237 
                 FXN 
               
               
                   
                 CACAATCCTATGAAGTAGGAACTTTTA 
                   
                   
                   
               
               
                   
                 TAAAA[CG]CATTTTATAAACAAGGCAC 
                   
                   
                   
               
               
                   
                 AGAGAGGTTAATTAACTTGCCCTCTGG 
                   
                   
                   
               
               
                   
                 TCACACAGCTAGGA 
                   
                   
                   
               
               
                   
               
               
                 cg07388493 
                 GGGAGCCAGTGTTCTTTCTCTCCTGTG 
                  1 
                  39491459 
                 NDUFS5 
               
               
                   
                 ACTTTGGTGAAGTCTCTCACCACTCAG 
                   
                   
                   
               
               
                   
                 TGTTGT[CG]TGAGCATGCTAGGCAGAG 
                   
                   
                   
               
               
                   
                 TGCAAGAAAGGAGCAAGAACTCACTA 
                   
                   
                   
               
               
                   
                 ATGGCTAGGCCTTCCC 
                   
                   
                   
               
               
                   
               
               
                 cg10523019 
                 CTCGCTGCTTCTCCCCTAGTCTTCGGGT 
                  2 
                 227700458 
                 RHBDD1 
               
               
                   
                 CCCTTGAACGCAGGTCGCTTGTTTGCC 
                   
                   
                   
               
               
                   
                 TTACG[CG]TAGTCAGCGGCCAGTGGCT 
                   
                   
                   
               
               
                   
                 ATTTATGGCAGTAAGGAATATTATCCA 
                   
                   
                   
               
               
                   
                 CATTTCACATGGAG 
                   
                   
                   
               
               
                   
               
               
                 cg17324128 
                 CCCTCCCCCGCCAGCCTGGCGCATTGC 
                 10 
                  45455500 
                 RASSF4 
               
               
                   
                 GGGCCTCGGGCTCATTGCTGAGAGGGG 
                   
                   
                   
               
               
                   
                 GCACTG[CG]CCTGGCACCTCTGTTAAG 
                   
                   
                   
               
               
                   
                 CAATTTAGGGGCTACAACCTGAGCAAG 
                   
                   
                   
               
               
                   
                 ACAGATGAGCCCGGC 
                   
                   
                   
               
               
                   
               
               
                 cg19722847 
                 TCTGCTTACAGCTGCTTCCAAATTAAG 
                 12 
                  30849114 
                 IPO8 
               
               
                   
                 CATATCTGGATGGTGTGACACTTTTTGT 
                   
                   
                   
               
               
                   
                 TAGTC[CG]AGAACTGTATGGGCATCGC 
                   
                   
                   
               
               
                   
                 AACTGGGCCTGTTCCAAGATAGACTTG 
                   
                   
                   
               
               
                   
                 TTGGGACCTTCAAA 
                   
                   
                   
               
               
                   
               
               
                 cg22736354 
                 TGCGCCAGGGCGGCCACGCAGGCCAG 
                  6 
                  18122719 
                 NHLRC1 
               
               
                   
                 GCAGACCACGTGGCCGCAGGACAGGT 
                   
                   
                   
               
               
                   
                 TGCGCGGG[CG]CCGCTGCTGCCGGTGG 
                   
                   
                   
               
               
                   
                 CCAAACTTCTCAAAGCACACCTTGCAC 
                   
                   
                   
               
               
                   
                 TCGAGCAGGCTGATCTC 
                   
                   
                   
               
               
                   
               
               
                 cg25809905 
                 ACTTGATTCTGGTTGGGGGCTTTGCCT 
                 17 
                  42467728 
                 ITGA2B 
               
               
                   
                 AGGGGAGCCTTCCCTGACTCCTCAGGC 
                   
                   
                   
               
               
                   
                 TGGCCG[CG]TGGGCTAACACACGTAGG 
                   
                   
                   
               
               
                   
                 CACAGCATTGAGCACACTGTTTACTCT 
                   
                   
                   
               
               
                   
                 TGGTCCGTTCACAGG 
                   
                   
                   
               
               
                   
               
               
                 cg26394940 
                 TAAATAAATAAGGGCTTTTGTTTGTTTG 
                 22 
                  46449461 
                 C22orf26; L 
               
               
                   
                 CCGGCTCCTGCACATGGCTGCTGGGAC 
                   
                   
                 OC150381 
               
               
                   
                 TCAAG[CG]CTCGTGTTGTCTGCGCCTCT 
                   
                   
                   
               
               
                   
                 GTGGGACTCTGGGGACGGGAGGCAGG 
                   
                   
                   
               
               
                   
                 GGAGGCCCCCGCAG 
                   
                   
                   
               
               
                   
               
               
                 cg26614073 
                 CTTGGGCAACGTAGGAGACCTCCGTCT 
                  3 
                  47517819 
                 SCAP 
               
               
                   
                 CCACAAGTAAAATTAATTAGCCGGCTG 
                   
                   
                   
               
               
                   
                 TGGTGG[CG]CGCACCTGTGGTCCCAGC 
                   
                   
                   
               
               
                   
                 TACTCAGGAGGCTGAGGTAGGAGGAT 
                   
                   
                   
               
               
                   
                 CACCTGAGCCCGGGAG 
                   
                   
                   
               
               
                   
               
               
                 cg27015931 
                 TGTTTTTGTGGGAGGCCTTCTGCATGGT 
                 16 
                  22012404 
                 C16orf65 
               
               
                   
                 CCCGGGAGGTCAGGCAGCCCGGGAGG 
                   
                   
                   
               
               
                   
                 GCCTCC[CG]GAGCAGAGGCTGGAGTCA 
                   
                   
                   
               
               
                   
                 GTCCCAATGCCAACAGTTTCGAACCTT 
                   
                   
                   
               
               
                   
                 GCCCGCGGGCACTGC 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Listing of 6 CpGs Subset 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Sequence with the CpG 
                 Chromo- 
                   
                   
               
               
                 Probe 
                 site marked with [ ] 
                 some 
                 Position 
                 Gene 
               
               
                   
               
               
                 cg01511567 
                 GTAGTTTTATTGTATCAGACTTAGTACA 
                 11 
                 57103631 
                 SSRP1 
               
               
                   
                 GGGGTGGGGTGGGGGTGTGTATTGGAA 
                   
                   
                   
               
               
                   
                 TGATG[CG]TGCCCGTTTCTCTGCAAAA 
                   
                   
                   
               
               
                   
                 TAGTTTCTATGTCATGGAAAGGAGTCG 
                   
                   
                   
               
               
                   
                 ATGGGACAAGAAGA 
                   
                   
                   
               
               
                   
               
               
                 cg07388493 
                 GGGAGCCAGTGTTCTTTCTCTCCTGTG 
                  1 
                 39491459 
                 NDUFS5 
               
               
                   
                 ACTTTGGTGAAGTCTCTCACCACTCAG 
                   
                   
                   
               
               
                   
                 TGTTGT[CG]TGAGCATGCTAGGCAGAG 
                   
                   
                   
               
               
                   
                 TGCAAGAAAGGAGCAAGAACTCACTA 
                   
                   
                   
               
               
                   
                 ATGGCTAGGCCTTCCC 
                   
                   
                   
               
               
                   
               
               
                 cg19722847 
                 TCTGCTTACAGCTGCTTCCAAATTAAG 
                 12 
                 30849114 
                 IPO8 
               
               
                   
                 CATATCTGGATGGTGTGACACTTTTTGT 
                   
                   
                   
               
               
                   
                 TAGTC[CG]AGAACTGTATGGGCATCGC 
                   
                   
                   
               
               
                   
                 AACTGGGCCTGTTCCAAGATAGACTTG 
                   
                   
                   
               
               
                   
                 TTGGGACCTTCAAA 
                   
                   
                   
               
               
                   
               
               
                 cg22736354 
                 TGCGCCAGGGCGGCCACGCAGGCCAG 
                  6 
                 18122719 
                 NHLRC1 
               
               
                   
                 GCAGACCACGTGGCCGCAGGACAGGT 
                   
                   
                   
               
               
                   
                 TGCGCGGG[CG]CCGCTGCTGCCGGTGG 
                   
                   
                   
               
               
                   
                 CCAAACTTCTCAAAGCACACCTTGCAC 
                   
                   
                   
               
               
                   
                 TCGAGCAGGCTGATCTC 
                   
                   
                   
               
               
                   
               
               
                 cg26394940 
                 TAAATAAATAAGGGCTTTTGTTTGTTTG 
                 22 
                 46449461 
                 C22orf26; L 
               
               
                   
                 CCGGCTCCTGCACATGGCTGCTGGGAC 
                   
                   
                 OC150381 
               
               
                   
                 TCAAG[CG]CTCGTGTTGTCTGCGCCTCT 
                   
                   
                   
               
               
                   
                 GTGGGACTCTGGGGACGGGAGGCAGG 
                   
                   
                   
               
               
                   
                 GGAGGCCCCCGCAG 
                   
                   
                   
               
               
                   
               
               
                 cg26614073 
                 CTTGGGCAACGTAGGAGACCTCCGTCT 
                  3 
                 47517819 
                 SCAP 
               
               
                   
                 CCACAAGTAAAATTAATTAGCCGGCTG 
                   
                   
                   
               
               
                   
                 TGGTGG[CG]CGCACCTGTGGTCCCAGC 
                   
                   
                   
               
               
                   
                 TACTCAGGAGGCTGAGGTAGGAGGAT 
                   
                   
                   
               
               
                   
                 CACCTGAGCCCGGGAG 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
            
               
                 Edaradd (NCBI Reference Sequence: NM_080738.3): 
                   
               
               
                 (SEQ ID NO: 355) 
                   
               
               
                 TTGTATGGGAACTCTGGTGAATGCGAATCATTTTTAAATTACTTTTTTTGTAAAGTGCAAAACAACAATAG 
                   
               
               
                   
               
               
                 CACCCATTTGCGTCATACTTTATAGTTCGCAAAGCACATGGGAAAAATAAAGGTAATGATGGGGATCGTTG 
               
               
                   
               
               
                 CAATTCATAGGAAAGGAGGCACGAGGAAATGAAAATGAAAGGGAGTAATAACTACGTAACTAGTCAATCTT 
               
               
                   
               
               
                 CCTTAAAAAAAAAAACCCTTAAAATATACCACCATCTTCTATTTGATATAATGCAGAATGGGAATGATAAA 
               
               
                   
               
               
                 AACATGAATTACATTTCAGAGTTTCAAAAAGCAAACCAGCTTTATAGCAATGCTTGAGGTTGGGCTGCTAA 
               
               
                   
               
               
                 CAAGCTCACTCAACTAGTGTTTCCTGACGGCCAACGTCAGAATAATTCCATCTCCATGAGAAGTACAGAAA 
               
               
                   
               
               
                 GAACCACAAACCAAACCTCCAAATTGATTCTAAGATAAAATACCCTTAAAAAAAATTTCCCTTCCTATCCG 
               
               
                   
               
               
                 GGCGGCAGACCAAGAGGAAGTTTATCCTCCCACCTACAAATTCCCCAGAGAGCTTTCATCTAGAAGGTTTG 
               
               
                   
               
               
                 ACTCTGGCCAGACAACCAGCGAGCATCTTCT CG CAATCTGTTGCTTCTTCCATGGCAAACTCCAGAGAATT 
               
               
                   
               
               
                 AAGAAGCCAAACTCAACATCGCCATGGGCCTCAGGACGACTAAACAGATGGGGAGAGGCACTGGCAGACCA 
               
               
                   
               
               
                 AGAGGAAGTTTATCCTCCCACCTACAAATTCCCCAGAGAGCTTTCATCTAGAAGGTTTGACTCTGGCCAGA 
               
               
                   
               
               
                 CAACCAGCGAGCATCTTCTCGCAATCTGTTGCTTCTTCCATGGCAAACTCCAGAGAATTAAGAAGCCAAAC 
               
               
                   
               
               
                 TCAACATCGCCATGGGCCTCAGGACGACTAAACAGATGGGGAGAGGCACTAAAGCTCCTGGTCACCAAGAG 
               
               
                   
               
               
                 GGTATGTAGGCATTTGCTGTCTTCCTGGATTTCTCAGAGCTGAGTTTTTAGCCAGAGGTTGCTTATTTACG 
               
               
                   
               
               
                 ATAATTCTTGGATATATTATACACTAAATACTATTATTATCTTTTTCGACCCGACTTTTATCTTTCTGTTC 
               
               
                   
               
               
                 TTATGTGTGAAGGCAGAGAAAGATTATTTAGAGCTCTTCAAAGATTCCTATTTAATTTAAAATGCCTGTCG 
               
               
                   
               
               
                 CCTTCCTATAATAGGCTTATGATGGATGATAGCTTTAGTTAAAATGTAGCAATCTTAAATATATT 
               
               
                   
               
               
                 GREM1 NCBI REFERENCE SEQUENCE: XM_006725542.1 
               
               
                 (SEQ ID NO: 356) 
                   
               
               
                 ATTTAAACGGGAGACGGCGCGATGCCTGGCACTCGGTGCGCCTTCCGCGGACCGGGCGAC 
                   
               
               
                   
               
               
                 CCAGTGCACGGCCGCCGCGTCACTCTCGGTCCCGCTGACCCCGCGCCGAGCCCCGGCGGC 
               
               
                   
               
               
                 TCTGGCCGCGGCCGCACTCAGCGCCACGCGTCGAAAGCGCAGGCCCCGAGGACCCGCCGC 
               
               
                   
               
               
                 ACTGACAGTATGAGCCGCACAGCCTACACGGTGGGAGCCCTGCTTCTCCTCTTGGGGACC 
               
               
                   
               
               
                 CTGCTGCCGGCTGCTGAAGGGAAAAAGAAAGGGTCCCAAGGTGCCATCCCCCCGCCAGAC 
               
               
                   
               
               
                 AAGGCCCAGCACAATGACTCAGAGCAGACTCAGTCGCCCCAGCAGCCTGGCTCCAGGAAC 
               
               
                   
               
               
                 CGGGGGCGGGGCCAAGGGCGGGGCACTGCCATGCCCGGGGAGGAGGTGCTGGAGTCCAGC 
               
               
                   
               
               
                 CAAGAGGCCCTGCATGTGACGGAGCGCAAATACCTGAAGCGAGACTGGTGCAAAACCCAG 
               
               
                   
               
               
                 CCGCTTAAGCAGACCATCCACGAGGAAGGCTGCAACAGTCGCACCATCATCAACCGCTTC 
               
               
                   
               
               
                 TGTTACGGCCAGTGCAACTCTTTCTACATCCCCAGGCACATCCGGAAGGAGGAAGGTTCC 
               
               
                   
               
               
                 TTTCAGTCCTGCTCCTTCTGCAAGCCCAAGAAATTCACTACCATGATGGTCACACTCAAC 
               
               
                   
               
               
                 TGCCCTGAACTACAGCCACCTACCAAGAAGAAGAGAGTCACACGTGTGAAGCAGTGTCGT 
               
               
                   
               
               
                 TGCATATCCATCGATTTGGATTAAGCCAAATCCAGGTGCACCCAGCATGTCCTAGGAATG 
               
               
                   
               
               
                 CAGCCCCAGGAAGTCCCAGACCTAAAACAACCAGATTCTTACTTGGCTTAAACCTAGAGG 
               
               
                   
               
               
                 CCAGAAGAACCCCCAGCTGCCTCCTGGCAGGAGCCTGCTTGTGCGTAGTTCGTGTGCATG 
               
               
                   
               
               
                 AGTGTGGATGGGTGCCTGTGGGTGTTTTTAGACACCAGAGAAAACACAGTCTCTGCTAGA 
               
               
                   
               
               
                 GAGCACTCCCTATTTTGTAAACATATCTGCTTTAATGGGGATGTACCAGAAACCCACCTC 
               
               
                   
               
               
                 ACCCCGGCTCACATCTAAAGGGGCGGGGCCGTGGTCTGGTTCTGACTTTGTGTTTTTGTG 
               
               
                   
               
               
                 CCCTCCTGGGGACCAGAATCTCCTTTCGGAATGAATGTTCATGGAAGAGGCTCCTCTGAG 
               
               
                   
               
               
                 GGCAAGAGACCTGTTTTAGTGCTGCATTCGACATGGAAAAGTCCTTTTAACCTGTGCTTG 
               
               
                   
               
               
                 CATCCTCCTTTCCTCCTCCTCCTCACAATCCATCTCTTCTTAAGTTGATAGTGACTATGT 
               
               
                   
               
               
                 CAGTCTAATCTCTTGTTTGCCAAGGTTCCTAAATTAATTCACTTAACCATGATGCAAATG 
               
               
                   
               
               
                 TTTTTCATTTTGTGAAGACCCTCCAGACTCTGGGAGAGGCTGGTGTGGGCAAGGACAAGC 
               
               
                   
               
               
                 AGGATAGTGGAGTGAGAAAGGGAGGGTGGAGGGTGAGGCCAAATCAGGTCCAGCAAAAGT 
               
               
                   
               
               
                 CAGTAGGGACATTGCAGAAGCTTGAAAGGCCAATACCAGAACACAGGCTGATGCTTCTGA 
               
               
                   
               
               
                 GAAAGTCTTTTCCTAGTATTTAACAGAACCCAAGTGAACAGAGGAGAAATGAGATTGCCA 
               
               
                   
               
               
                 GAAAGTGATTAACTTTGGCCGTTGCAATCTGCTCAAACCTAACACCAAACTGAAAACATA 
               
               
                   
               
               
                 AATACTGACCACTCCTATGTTCGGACCCAAGCAAGTTAGCTAAACCAAACCAACTCCTCT 
               
               
                   
               
               
                 GCTTTGTCCCTCAGGTGGAAAAGAGAGGTAGTTTAGAACTCTCTGCATAGGGGTGGGAAT 
               
               
                   
               
               
                 TAATCAAAAACCGCAGAGGCTGAAATTCCTAATACCTTTCCTTTATCGTGGTTATAGTCA 
               
               
                   
               
               
                 GCTCATTTCCATTCCACTATTTCCCATAATGCTTCTGAGAGCCACTAACTTGATTGATAA 
               
               
                   
               
               
                 AGATCCTGCCTCTGCTGAGTGTACCTGACAGTAGTCTAAGATGAGAGAGTTTAGGGACTA 
               
               
                   
               
               
                 CTCTGTTTTAGCAAGAGATATTTTGGGGGTCTTTTTGTTTTAACTATTGTCAGGAGATTG 
               
               
                   
               
               
                 GGCTAAAGAGAAGACGACGAGAGTAAGGAAATAAAGGGAATTGCCTCTGGCTAGAGAGTA 
               
               
                   
               
               
                 GTTAGGTGTTAATACCTGGTAGAGATGTAAGGGATATGACCTCCCTTTCTTTATGTGCTC 
               
               
                   
               
               
                 ACTGAGGATCTGAGGGGACCCTGTTAGGAGAGCATAGCATCATGATGTATTAGCTGTTCA 
               
               
                   
               
               
                 TCTGCTACTGGTTGGATGGACATAACTATTGTAACTATTCAGTATTTACTGGTAGGCACT 
               
               
                   
               
               
                 GTCCTCTGATTAAACTTGGCCTACTGGCAATGGCTACTTAGGATTGATCTAAGGGCCAAA 
               
               
                   
               
               
                 GTGCAGGGTGGGTGAACTTTATTGTACTTTGGATTTGGTTAACCTGTTTTCTTCAAGCCT 
               
               
                   
               
               
                 GAGGTTTTATATACAAACTCCCTGAATACTCTTTTTGCCTTGTATCTTCTCAGCCTCCTA 
               
               
                   
               
               
                 GCCAAGTCCTATGTAATATGGAAAACAAACACTGCAGACTTGAGATTCAGTTGCCGATCA 
               
               
                   
               
               
                 AGGCTCTGGCATTCAGAGAACCCTTGCAACTCGAGAAGCTGTTTTTATTTCGTTTTTGTT 
               
               
                   
               
               
                 TTGATCCAGTGCTCTCCCATCTAACAACTAAACAGGAGCCATTTCAAGGCGGGAGATATT 
               
               
                   
               
               
                 TTAAACACCCAAAATGTTGGGTCTGATTTTCAAACTTTTAAACTCACTACTGATGATTCT 
               
               
                   
               
               
                 CACGCTAGGCGAATTTGTCCAAACACATAGTGTGTGTGTTTTGTATACACTGTATGACCC 
               
               
                   
               
               
                 CACCCCAAATCTTTGTATTGTCCACATTCTCCAACAATAAAGCACAGAGTGGATTTAATT 
               
               
                   
               
               
                 AAGCACACAAATGCTAAGGCAGAATTTTGAGGGTGGGAGAGAAGAAAAGGGAAAGAAGCT 
               
               
                   
               
               
                 GAAAATGTAAAACCACACCAGGGAGGAAAAATGACATTCAGAACCAGCAAACACTGAATT 
               
               
                   
               
               
                 TCTCTTGTTGTTTTAACTCTGCCACAAGAATGCAATTTCGTTAACGGAGATGACTTAAGT 
               
               
                   
               
               
                 TGGCAGCAGTAATCTTCTTTTAGGAGCTTGTACCACAGTCTTGCACATAAGTGCAGATTT 
               
               
                   
               
               
                 GGCTCAAGTAAAGAGAATTTCCTCAACACTAACTTCACTGGGATAATCAGCAGCGTAACT 
               
               
                   
               
               
                 ACCCTAAAAGCATATCACTAGCCAAAGAGGGAAATATCTGTTCTTCTTACTGTGCCTATA 
               
               
                   
               
               
                 TTAAGACTAGTACAAATGTGGTGTGTCTTCCAACTTTCATTGAAAATGCCATATCTATAC 
               
               
                   
               
               
                 CATATTTTATTCGAGTCACTGATGATGTAATGATATATTTTTTCATTATTATAGTAGAAT 
               
               
                   
               
               
                 ATTTTTATGGCAAGATATTTGTGGTCTTGATCATACCTATTAAAATAATGCCAAACACCA 
               
               
                   
               
               
                 AATATGAATTTTATGATGTACACTTTGTGCTTGGCATTAAAAGAAAAAAACACACATCCT 
               
               
                   
               
               
                 GGAAGTCTGTAAGTTGTTTTTTGTTACTGTAGGTCTTCAAAGTTAAGAGTGTAAGTGAAA 
               
               
                   
               
               
                 AATCTGGAGGAGAGGATAATTTCCACTGTGTGGAATGTGAATAGTTAAATGAAAAGTTAT 
               
               
                   
               
               
                 GGTTATTTAATGTAATTATTACTTCAAATCCTTTGGTCACTGTGATTTCAAGCATGTTTT 
               
               
                   
               
               
                 CTTTTTCTCCTTTATATGACTTTCTCTGAGTTGGGCAAAGAAGAAGCTGACACACCGTAT 
               
               
                   
               
               
                 GTTGTTAGAGTCTTTTATCTGGTCAGGGGAAACAAAATCTTGACCCAGCTGAACATGTCT 
               
               
                   
               
               
                 TCCTGAGTCAGTGCCTGAATCTTTATTTTTTAAATTGAATGTTCCTTAAAGGTTAACATT 
               
               
                   
               
               
                 TCTAAAGCAATATTAAGAAAGACTTTAAATGTTATTTTGGAAGACTTACGATGCATGTAT 
               
               
                   
               
               
                 ACAAACGAATAGCAGATAATGATGACTAGTTCACACATAAAGTCCTTTTAAGGAGAAAAT 
               
               
                   
               
               
                 CTAAAATGAAAAGTGGATAAACAGAACATTTATAAGTGATCAGTTAATGCCTAAGAGTGA 
               
               
                   
               
               
                 AAGTAGTTCTATTGACATTCCTCAAGATATTTAATATCAACTGCATTATGTATTATGTCT 
               
               
                   
               
               
                 GCTTAAATCATTTAAAAACGGCAAAGAATTATATAGACTATGAGGTACCTTGCTGTGTAG 
               
               
                   
               
               
                 GAGGATGAAAGGGGAGTTGATAGTCTCATAAAACTAATTTGGCTTCAAGTTTCATGAATC 
               
               
                   
               
               
                 TGTAACTAGAATTTAATTTTCACCCCAATAATGTTCTATATAGCCTTTGCTAAAGAGCAA 
               
               
                   
               
               
                 CTAATAAATTAAACCTATTCTTTC 
               
               
                   
               
               
                 NHLRC NCBI Reference Sequence: NM_198586.2 
               
               
                 (SEQ ID NO: 357) 
                   
               
               
                 GCACAGGACGCGCCATGGCGGCCGAAGCCTCGGAGAGCGGGCCAGCGCTGCATGAGCTCA 
                   
               
               
                   
               
               
                 TGCGCGAGGCGGAGATCAGCCTGCTCGAGTGCAAGGTGTGCTTTGAGAAGTTTGGCCACC 
               
               
                   
               
               
                 GGCAGCAGCGGCGCCCGCGCAACCTGTCCTGCGGCCACGTGGTCTGCCTGGCCTGCGTGG 
               
               
                   
               
               
                 CCGCCCTGGCGCACCCGCGCACTCTGGCCCTCGAGTGCCCATTCTGCAGGCGAGCTTGCC 
               
               
                   
               
               
                 GGGGCTGCGACACCAGCGACTGCCTGCCGGTGCTGCACCTCATAGAGCTCCTGGGCTCAG 
               
               
                   
               
               
                 CGCTTCGCCAGTCCCCGGCCGCCCATCGCGCCGCCCCCAGCGCCCCCGGAGCCCTCACCT 
               
               
                   
               
               
                 GCCACCACACCTTCGGCGGCTGGGGGACCCTGGTCAACCCCACCGGACTGGCGCTTTGTC 
               
               
                   
               
               
                 CCAAGACGGGGCGTGTCGTGGTGGTGCACGACGGCAGGAGGCGTGTCAAGATTTTTGACT 
               
               
                   
               
               
                 CAGGGGGAGGATGCGCGCATCAGTTTGGAGAGAAGGGGGACGCTGCCCAAGACATTAGGT 
               
               
                   
               
               
                 ACCCTGTGGATGTCACCATCACCAACGACTGCCATGTGGTTGTCACTGACGCCGGCGATC 
               
               
                   
               
               
                 GCTCCATCAAAGTGTTTGATTTTTTTGGCCAGATCAAGCTTGTCATTGGAGGCCAATTCT 
               
               
                   
               
               
                 CCTTACCTTGGGGTGTGGAGACCACCCCTCAGAATGGGATTGTGGTAACTGATGCGGAGG 
               
               
                   
               
               
                 CAGGGTCCCTGCACCTCCTGGACGTCGACTTCGCGGAAGGGGTCCTTCGGAGAACTGAAA 
               
               
                   
               
               
                 GGTTGCAAGCTCATCTGTGCAATCCCCGAGGGGTGGCAGTGTCTTGGCTCACCGGGGCCA 
               
               
                   
               
               
                 TTGCGGTCCTGGAGCACCCCCTGGCCCTGGGGACTGGGGTTTGCAGCACCAGGGTGAAAG 
               
               
                   
               
               
                 TGTTTAGCTCAAGTATGCAGCTTGTCGGCCAAGTGGATACCTTTGGGCTGAGCCTCTACT 
               
               
                   
               
               
                 TTCCCTCCAAAATAACTGCCTCCGCTGTGACCTTTGATCACCAGGGAAATGTGATTGTTG 
               
               
                   
               
               
                 CAGATACATCTGGTCCAGCTATCCTTTGCTTAGGAAAACCTGAGGAGTTTCCAGTACCGA 
               
               
                   
               
               
                 AGCCCATGGTCACTCATGGTCTTTCGCATCCTGTGGCTCTTACCTTCACCAAGGAGAATT 
               
               
                   
               
               
                 CTCTTCTTGTGCTGGACACAGCATCTCATTCTATAAAAGTCTATAAAGTTGACTGGGGGT 
               
               
                   
               
               
                 GATGGGCTGGGGTGGGTCCCTGGAATCAGAAGCACTAGTGCTGCCATTAATGAATTGTTT 
               
               
                   
               
               
                 AACCCTGGATAAGTCACTTAAACTCATCTATCCAGGCAGGGATAATTAAAACCATCTGGC 
               
               
                   
               
               
                 AGACTTACAAAGCTTGGGACAGTTATTGGAGATTAATCTACCATTTATTGAATGCATACT 
               
               
                   
               
               
                 CTGTGCAAGGAAATTTGCAAATATTAGCTTATTTAATCTGTACTATCCAGTGAGGTAATT 
               
               
                   
               
               
                 TCTTCCCCCCCAAGATAGAGTCAAGCTCTGTCACCCAGGCTGGAGTGCAGAAGCATGATC 
               
               
                   
               
               
                 ACAGCTCACTACAGTTTCAACGTCCCCCGCTCAGGTGGTCCTTCCACCTCAGCCTCCCAA 
               
               
                   
               
               
                 GTAGCTGGGACCACAAGTGTGCATTACCACACTCAGCTAATTTTTGTATTTTGGCAGAGA 
               
               
                   
               
               
                 TGGGGTTTCACCATGTTGCCCAGGCTGGTCTCAAACTCCTGAGTTCAAGCAATCCACCTT 
               
               
                   
               
               
                 CCTCGGCCTCCCAAAGTACTAGGAGTACAGGCATAGCCACTTGCTCAGCCATAATTTTTA 
               
               
                   
               
               
                 TTATTAATCTCATTGTACAAGTGAGAAAACTGAGACCCAGAGAGCTTAAGTGACTTCCTC 
               
               
                   
               
               
                 GAGGTCATAGTTACTTACTGCCTTAGTCCCAATTTGAATTCAATTCTGATTCCAAATAAG 
               
               
                   
               
               
                 TTGCGCTTAAATAAGACAACAGATGTGGGAAAAATATGTGAATGTGTAGTGTTGCTATGT 
               
               
                   
               
               
                 GTACTGTCTTTACAAGTAGCTAATTATTTTAGCACAAAGATGTGCAAAGAAAGGAGACTT 
               
               
                   
               
               
                 TATGGAGAGTTCAGGAGAAAAAGGATTTTGTGGTGGCCATCACTTTCATTCAATTTGCGA 
               
               
                   
               
               
                 CTGCTCTGATGGCACATTAGATGAAGTTACTGTTGATCCTGAGTTACGTGAATAAGAAAA 
               
               
                   
               
               
                 ACAATTGAACTGCTTATTAAAAAAGTAAACATGT 
               
               
                   
               
               
                 SCGN NCBI Reference Sequence: NM_006998.3 
               
               
                 (SEQ ID NO: 358) 
                   
               
               
                 CAGCCGCTGGTTTTGCTGAGGGCTGAGGGACGGCTCAGCGACGCCACGGCCAGCAGCGCT 
                   
               
               
                   
               
               
                 CGCGTCCTCCCCAGCAACAGTTACTCAAAGCTAATCAGATAGCGAAAGAAGCAGGAGAGC 
               
               
                   
               
               
                 AAGTCAAGAAATACGGTGAAGGAGTCCTTCCCAAAGTTGTCTAGGTCCTTCCGCGCCGGT 
               
               
                   
               
               
                 GCCTGGTCTTCGTCGTCAACACCATGGACAGCTCCCGGGAACCGACTCTGGGGCGCTTGG 
               
               
                   
               
               
                 ACGCCGCTGGCTTCTGGCAGGTCTGGCAGCGCTTTGATGCGGATGAAAAAGGTTACATAG 
               
               
                   
               
               
                 AAGAGAAGGAACTCGATGCTTTCTTTCTCCACATGTTGATGAAACTGGGTACTGATGACA 
               
               
                   
               
               
                 CGGTCATGAAAGCAAATTTGCACAAGGTGAAACAGCAGTTTATGACTACCCAAGATGCCT 
               
               
                   
               
               
                 CTAAAGATGGTCGCATTCGGATGAAAGAGCTTGCTGGTATGTTCTTATCTGAGGATGAAA 
               
               
                   
               
               
                 ACTTTCTTCTGCTCTTTCGCCGGGAAAACCCACTGGACAGCAGCGTGGAGTTTATGCAGA 
               
               
                   
               
               
                 TTTGGCGCAAATATGACGCTGACAGCAGTGGCTTTATATCAGCTGCTGAGCTCCGCAACT 
               
               
                   
               
               
                 TCCTCCGAGACCTCTTTCTTCACCACAAAAAGGCCATTTCTGAGGCTAAACTGGAAGAAT 
               
               
                   
               
               
                 ACACTGGCACCATGATGAAGATTTTTGACAGAAATAAAGATGGTCGGTTGGATCTAAATG 
               
               
                   
               
               
                 ACTTAGCAAGGATTCTGGCTCTTCAGGAAAACTTCCTTCTCCAATTTAAAATGGATGCTT 
               
               
                   
               
               
                 GTTCTACTGAAGAAAGGAAAAGGGACTTTGAGAAAATCTTTGCCTACTATGATGTTAGTA 
               
               
                   
               
               
                 AAACAGGAGCCCTGGAAGGCCCAGAAGTGGATGGGTTTGTCAAAGACATGATGGAGCTTG 
               
               
                   
               
               
                 TCCAGCCCAGCATCAGCGGGGTGGACCTTGATAAGTTCCGCGAGATTCTCCTGCGTCACT 
               
               
                   
               
               
                 GCGACGTGAACAAGGATGGAAAAATTCAGAAGTCTGAGCTGGCTTTGTGTCTTGGGCTGA 
               
               
                   
               
               
                 AAATCAACCCATAATCCCAGACTGCTTTGCCTTTTGCTCTTACTATGTTTCTGTGATCTT 
               
               
                   
               
               
                 GCTGGTAGAATTGTATCTGTGCATTGATGTTGGGAACACAGTGGGCAAACTCACAAATGG 
               
               
                   
               
               
                 TGTGCTATTCTTGGGCAAGAACAGGGACGCTAGGGCCTTCCTTCCACCGGCGTGATCTAT 
               
               
                   
               
               
                 CCCTGTCTCACTGAAAGCCCCTGTGTAGTGTCTGTGTTGTTTTCCCTTGACCCTGGGCTT 
               
               
                   
               
               
                 TCCTATCCTCCCAAAGACTCAGCTCCCCTGTTAGATGGCTCTGCCTGTCCTTCCCCAGTC 
               
               
                   
               
               
                 ACCAGGGTGGGGGGGACAGGGGCAGCTGAGTGCATTCATTTTGTGCTTTTCTTGTGGGCT 
               
               
                   
               
               
                 TTCTGCTTAGTCTGAAAGGTGTGTGGCATTCATGGCAATCCTGTAACTTCAACATAGATT 
               
               
                   
               
               
                 TTTTTGTGTGTGTGGAAATAAATCTGCAATTGGAAACAAAAAAAAAAAAAAA