New insights into the (epi)genetics of twinning

Abstract

Spontaneous dizygotic (DZ) twins, i.e. twins conceived without the use of ARTs, run in familiesãnd their prevalence varies widelyãround the globe. In contrast, monozygotic (MZ) twins occurãtã constant rateãcross timeãnd geographical regionsãnd, with some rare exceptions, do not cluster in families. The leading hypothesis for MZ twins, whichãrise whenã zygote splits during preimplantation stages of development, is random occurrence. We have found the first series of genes underlying the liability of being the mother of DZ twinsãnd have shown that beingãn MZ twin is stronglyãssociated withã stable DNA methylation signature in childãndãdult somatic tissues. Because identical twins keep this molecular signatureãcross the lifespan, this discovery opens up completely new possibilities for the retrospective diagnosis of whetherã person isãn MZ twin whose co-twin may have vanished in the early stages of pregnancy. Here, we summarize the gene finding results for mothers of DZ twins based on geneticãssociation studies followed by meta-analysis,ãnd further present the striking epigenetic results for MZ twins.