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Epigenetics. 2016;11(1):24-35. doi: 10.1080/15592294.2015.1127479. Epub 2016 Jan 19.

Tissue-specific patterns of allelically-skewed DNA methylation.

Author information

1
a Institute of Psychiatry, Psychology and Neuroscience, King's College London , London , UK.
2
b Department of Psychological Sciences , Birkbeck, University of London , London , UK.
3
c University of Exeter Medical School, University of Exeter , Exeter , UK.
4
d School of Biological Sciences, University of Essex , Colchester , UK.

Abstract

While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with > 4% of the ∼220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are tissue-specific. These findings contribute to our understanding of the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood.

KEYWORDS:

Allele-specific DNA methylation; SNP; blood; brain; cerebellum; cortex; epigenetics; genomic imprinting

PMID:
26786711
PMCID:
PMC4846124
DOI:
10.1080/15592294.2015.1127479
[Indexed for MEDLINE]
Free PMC Article

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