%0 Journal Article
%T Population-specificity of human DNA methylation
%A Hunter B Fraser
%A Lucia L Lam
%A Sarah M Neumann
%A Michael S Kobor
%J Genome Biology
%D 2012
%I BioMed Central
%R 10.1186/gb-2012-13-2-r8
%X Here we measure DNA methylation near the transcription start sites of over 14, 000 genes in 180 cell lines derived from one African and one European population. We find population-specific patterns of DNA methylation at over a third of all genes. Furthermore, although the methylation at over a thousand CpG sites is heritable, these heritabilities also differ between populations, suggesting extensive divergence in the genetic control of DNA methylation. In support of this, genetic mapping of DNA methylation reveals that most of the population specificity can be explained by divergence in allele frequencies between populations, and that there is little overlap in genetic associations between populations. These population-specific genetic associations are supported by the patterns of DNA methylation in several hundred brain samples, suggesting that they hold in vivo and across tissues.These results suggest that DNA methylation is highly divergent between populations, and that this divergence may be due in large part to a combination of differences in allele frequencies and complex epistasis or gene กม environment interactions.In multicellular organisms, the great diversity of cell types is maintained by mitotically heritable differences in gene expression, which are in part regulated by epigenetic mechanisms [1]. These include histone modifications, histone variants, RNA-based mechanisms, and DNA methylation [2]. The latter is perhaps the best understood component of the epigenetic machinery [3] and in somatic cells occurs almost exclusively on cytosine residues in the context of CpG dinucleotides [4]. While CpGs are underrepresented across the human genome, they are enriched at the majority of gene promoters, forming regions known as CpG islands that can regulate the expression of neighboring genes [4]. DNA methylation is not only closely linked to tissue-specific gene expression, but also to a number of intriguing biological phenomena such as X-chromosome inactivation
%U http://genomebiology.com/2012/13/2/R8