Tissue-specific patterns of allelically-skewed DNA methylation

Sarah J. Marzi (1), Emma L. Meaburn (2), Emma L. Dempster (3), Katie Lunnon (3), Jose L. Paya-Cano (1), Rebecca G. Smith (3), Manuela Volta (1), Claire Troakes (1), Leonard C. Schalkwyk (4), Jonathan Mill (1,3)

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

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 often located in an extended genomic context of intermediate DNA methylation. Interestingly, we detect cases of genotype-driven ASM, which are also tissue-specific. These findings contribute to our understanding about the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. A searchable web-resource of allele-specific methylation signals of ~220,000 loci across the human genome covering multiple tissues is available, see below:

Visualize the data:

Enter an Affymetrix 6.0 Human SNP array probe to get a plot for it

UCSC Genome Browser track:

Displays informative sites for the MSNP protocol and their absolute ASM scores for each sample.