dc.contributor.author | Marzi, SJ | |
dc.contributor.author | Meaburn, EL | |
dc.contributor.author | Dempster, EL | |
dc.contributor.author | Lunnon, K | |
dc.contributor.author | Paya-Cano, JL | |
dc.contributor.author | Smith, RG | |
dc.contributor.author | Volta, M | |
dc.contributor.author | Troakes, C | |
dc.contributor.author | Schalkwyk, LC | |
dc.contributor.author | Mill, J | |
dc.date.accessioned | 2016-03-23T10:06:10Z | |
dc.date.issued | 2016-01-19 | |
dc.description.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 . | en_GB |
dc.description.sponsorship | This work was supported by grants from the UK Medical Research Council (MRC) (grant
number MR/K013807/1) and US National Institutes of Health (grant number AG036039) to
JM. SJM is funded through the Marie Curie Initial Training Network “EpiTrain” (EC FP7). | en_GB |
dc.identifier.citation | Volume 11, pp. 24 - 35 | en_GB |
dc.identifier.doi | 10.1080/15592294.2015.1127479 | |
dc.identifier.uri | http://hdl.handle.net/10871/20815 | |
dc.language.iso | en | en_GB |
dc.publisher | Taylor & Francis | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/26786711 | en_GB |
dc.subject | Allele-specific DNA methylation | en_GB |
dc.subject | SNP | en_GB |
dc.subject | blood | en_GB |
dc.subject | brain | en_GB |
dc.subject | cerebellum | en_GB |
dc.subject | cortex | en_GB |
dc.subject | epigenetics | en_GB |
dc.subject | genomic imprinting | en_GB |
dc.title | Tissue-specific patterns of allelically-skewed DNA methylation | en_GB |
dc.type | Article | en_GB |
dc.identifier.issn | 1559-2294 | |
dc.description | This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record. | en_GB |
dc.description | This is an open access article. | |
dc.identifier.journal | Epigenetics | en_GB |
dc.identifier.pmid | 26786711 | |