Methylation of cytosines in CpG dinucleotides of DNA is a fundamental, and long-lasting, epigenetic modification that is associated with gene regulation and has been linked to human disease. Gunasekara et al. have published the first survey of human DNA methylation variation across individuals and tissues. This study conducted whole-genome bisulfite sequencing on thyroid, heart, and brain tissue collected from 10 human cadavers. These tissues were selected for study because they are derived from distinct germ layers of the embryo and therefore diverge very early in development. Computational analyses of this bisulfide sequencing found found nearly 10,000 regions that showed significant variation across samples. These variable region comprise about 0.1% of the genome and show association with transposable elements, subtelomeric regions and genes that have been implicated in a variety of human diseases. This “atlas” may serve an important reference as we begin unravelling the relationship between DNA and chromatin modifications to specific disease states.

You can read the Baylor University press release or an overview from ScienceDaily, both of which provide an easy to read, full-page summary of the study. The abstract and link to the original article is listed below.

Background

DNA methylation is thought to be an important determinant of human phenotypic variation, but its inherent cell type specificity has impeded progress on this question. At exceptional genomic regions, interindividual variation in DNA methylation occurs systemically. Like genetic variants, systemic interindividual epigenetic variants are stable, can influence phenotype, and can be assessed in any easily biopsiable DNA sample. We describe an unbiased screen for human genomic regions at which interindividual variation in DNA methylation is not tissue-specific.

Results

For each of 10 donors from the NIH Genotype-Tissue Expression (GTEx) program, CpG methylation is measured by deep whole-genome bisulfite sequencing of genomic DNA from tissues representing the three germ layer lineages: thyroid (endoderm), heart (mesoderm), and brain (ectoderm). We develop a computational algorithm to identify genomic regions at which interindividual variation in DNA methylation is consistent across all three lineages. This approach identifies 9926 correlated regions of systemic interindividual variation (CoRSIVs). These regions, comprising just 0.1% of the human genome, are inter-correlated over long genomic distances, associated with transposable elements and subtelomeric regions, conserved across diverse human ethnic groups, sensitive to periconceptional environment, and associated with genes implicated in a broad range of human disorders and phenotypes. CoRSIV methylation in one tissue can predict expression of associated genes in other tissues.

Conclusions

In addition to charting a previously unexplored molecular level of human individuality, this atlas of human CoRSIVs provides a resource for future population-based investigations into how interindividual epigenetic variation modulates risk of disease.

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