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Inter-individual variability contrasts with regional homogeneity in the human brain DNA methylome.

TitleInter-individual variability contrasts with regional homogeneity in the human brain DNA methylome.
Publication TypeJournal Article
Year of Publication2015
AuthorsIllingworth R, Gruenewald-Schneider U, De Sousa D, Webb S, Merusi C, Kerr ARW, James KD, Smith C, Walker R, Andrews R, Bird AP
JournalNucleic Acids Res
Volume43
Issue2
Pagination732-44
Date Published2015 Jan
ISSN1362-4962
KeywordsBase Sequence, Brain, Cerebellum, CpG Islands, DNA, DNA Methylation, Humans
Abstract

The possibility that alterations in DNA methylation are mechanistic drivers of development, aging and susceptibility to disease is widely acknowledged, but evidence remains patchy or inconclusive. Of particular interest in this regard is the brain, where it has been reported that DNA methylation impacts on neuronal activity, learning and memory, drug addiction and neurodegeneration. Until recently, however, little was known about the 'landscape' of the human brain methylome. Here we assay 1.9 million CpGs in each of 43 brain samples representing different individuals and brain regions. The cerebellum was a consistent outlier compared to all other regions, and showed over 16 000 differentially methylated regions (DMRs). Unexpectedly, the sequence characteristics of hypo- and hypermethylated domains in cerebellum were distinct. In contrast, very few DMRs distinguished regions of the cortex, limbic system and brain stem. Inter-individual DMRs were readily detectable in these regions. These results lead to the surprising conclusion that, with the exception of cerebellum, DNA methylation patterns are more homogeneous between different brain regions from the same individual, than they are for a single brain region between different individuals. This finding suggests that DNA sequence composition, not developmental status, is the principal determinant of the human brain DNA methylome.

DOI10.1093/nar/gku1305
Alternate JournalNucleic Acids Res.
PubMed ID25572316
PubMed Central IDPMC4333374
Grant List077224 / / Wellcome Trust / United Kingdom
G0800026 / / Medical Research Council / United Kingdom
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