Pembrey, Golding and Connelly recently proposed the 'Meiotic Mismatch Methylation' (3M) hypothesis [1], in which mothers who are heterozygous for a deletion experience silencing of the non-deleted allele via methylation of the mismatched sequence. Because allele silencing occurs in the maternal germline, maternal biology is not effected by 3M. However, all children will inherit either a deleted or a silenced allele from their mother, either of which may influence the risk of developing disease.

In this project we will directly test the Meiotic Mismatch Methylation hypothesis using complementary methylation and genetic data from families in the ALSPAC cohort. The 3M hypothesis has the potential to significantly progress our understanding of complex disease heritability.

[1] Pembrey M, Golding J, Connelly J. ZNF277 microdeletions, specific language impairment and the meiotic mismatch methylation (3M) hypothesis. Eur J Hum Genet. 2015 Sep;23(9):1113