Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide analysis of autosomal sex differences in human DNA methylome

ABSTRACT: Sex difference had been implicated in pathophysiology and prognosis of common diseases, such as acute lymphoblastic leukemia and coronary heart disease. It is well known that the disease phenotype is shaped by the interaction between the environment, genome, and epigenome. The environmental and the genetic components were extensively studied in the past. Unlike the formers, the role of epigenetics has only been recently investigated. To date, little has been known about differences in epigenetic makeup between the two sexes. Here we present a genome-wide study of sex-specific differences in DNA methylation in healthy individuals. We compared the methylation status of ~26,000 CpGs in the promoter of ~14,000 genes between age-matched males (n=12) and females (n=12). We identified 19 CpGs in 18 genes to have significant sex-specific methylation differences. Our finding was validated by a recent publication of Liu et al. 2010 where they found similar results (ie. 11 of their 12 CpGs overlapped with ours) using the same microarray platform. However, with further investigation we showed that the probes with sex-specific methylation differences displayed cross-reactive targets on the sex chromosomes. This data indicates that autosomal sex-specific methylation detected in this study and by Lui et al, 2010 using the Illumina array platform, is the result of technical artifacts or non-specificity of those microarray probes. Overall, our findings suggest that there is no sex-specific DNA methylation difference in human beyond the sex chromosomes using the Illumina Methylation 27 microarray. Genome-wide DNA methylation data of sodium-bisulfite converted-genomic DNA obtained from whole blood lymphocytes of 12 healthy males compared to that of 12 age-matched healthy females

ORGANISM(S): Homo sapiens

SUBMITTER: Rosanna Weksberg

PROVIDER: E-GEOD-23638 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Sequence overlap between autosomal and sex-linked probes on the Illumina HumanMethylation27 microarray.

Chen Yi-an YA Choufani Sanaa S Ferreira Jose Carlos JC Grafodatskaya Daria D Butcher Darci T DT Weksberg Rosanna R

Genomics 20110104 4

The Illumina Infinium HumanMethylation27 BeadChip (Illumina 27k) microarray is a high-throughput platform capable of interrogating the human DNA methylome. In a search for autosomal sex-specific DNA methylation using this microarray, we discovered autosomal CpG loci showing significant methylation differences between the sexes. However, we found that the majority of these probes cross-reacted with sequences from sex chromosomes. Moreover, we determined that 6-10% of the microarray probes are non ...[more]

PMID: 21211562

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Project description:Age-related changes in DNA methylation occurring in blood leukocytes during early childhood may reflect epigenetic maturation. We hypothesized that some of these changes involve gene networks of critical relevance in leukocyte biology and conducted a prospective study to elucidate the dynamics of DNA methylation. Serial blood samples were collected at 3, 6, 12, 24, 36, 48 and 60 months after birth in 10 healthy girls born in Finland and participating in the Type 1 Diabetes Prediction and Prevention Study. DNA methylation was measured using the HumanMethylation450 BeadChip. After filtering for the presence of polymorphisms and cell-lineage-specific signatures, 794 CpGs showed significant DNA methylation differences as a function of age in all children (41.5% age-methylated and 58.4% age-demethylated, bonferroni corrected p-value <0.001). Age-methylated CpGs were more frequently located in gene bodies and within +5 to +50 kilobases (kb) of transcription start sites (TSS), and enriched in developmental, neuronal and plasma membrane genes. Age-demethylated CpGs were associated to promoters and DNAse-I hypersensitivity sites, located within -5 to +5 kb of the nearest TSS, and enriched in genes related to immunity, antigen presentation, the polycomb-group protein complex and cytoplasm. This study reveals that susceptibility loci for complex inflammatory diseases (e.g. IRF5, NOD2, PTGER4) and genes encoding histone modifiers and chromatin remodeling factors (e.g. HDAC4, KDM2A, KDM2B, JARID2, ARID3A, SMARCD3) undergo DNA methylation changes in leukocytes during early childhood. These results open new perspectives to understand leukocyte maturation and provide a catalog of CpGs that may need to be corrected for age effects when performing DNA methylation studies in children. We analysed the longitudinal changes in DNA methylation in a total of 60 samples at 3, 6, 12, 24, 36, 48, and 60 months after birth, using serial DNA samples extracted from peripheral blood leukocytes of 10 healthy girls of the Diabetes Prediction and Prevention Study (DIPP).

Project description:Background: Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intrauterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. In a unique cohort of 17 monozygotic (MZ) monochorionic female twins very discordant for birth weight (relative differences ranging from 21.3-35.7%), we examined if adverse prenatal growth conditions experienced by the smaller co-twins lead to systemic long-lasting DNA methylation changes. Genome-wide DNA methylation profiles were acquired from saliva DNA using the Infinium HumanMethylation450 BeadChip, targeting ~2% of all CpGs in the genome. Results: Overall, co-twins showed very similar genome-wide DNA methylation profiles. Since observed differences were almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3153 were differentially methylated between the heavy and light co-twins at nominal significance (p<0.01), of which 45 showed absolute mean β-value differences >0.05 (max=0.08). Deep bisulfite sequencing of eight such loci revealed that differences remained in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicated no significant intra-pair differences. Conclusions: Severe intrauterine growth differences observed within these MZ twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies. DNA methylation profiles of saliva from 17 Adult Female MZ MC Twins discordant for birth weight.

Dataset Information

Genome-wide analysis of autosomal sex differences in human DNA methylome

Publications

Sequence overlap between autosomal and sex-linked probes on the Illumina HumanMethylation27 microarray.

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