Identical twins carry a persistent epigenetic signature of early genome programming.
Monozygotic (MZ) twins and higher-order multiples arise when a zygote splits during pre-implantation stages of development. The mechanisms underpinning this event have remained a mystery. Because MZ twinning rarely runs in families, the leading hypothesis is that it occurs at random. Here, we show that MZ twinning is strongly associated with a stable DNA methylation signature in adult somatic tissues. This signature spans regions near telomeres and centromeres, Polycomb-repressed regions and heterochromatin, genes involved in cell-adhesion, WNT signaling, cell fate, and putative human metastable epialleles. Our study also demonstrates a never-anticipated corollary: because identical twins keep a lifelong molecular signature, we can retrospectively diagnose if a person was conceived as monozygotic twin.
van Dongen, J; Gordon, SD; McRae, AF; Odintsova, VV; Mbarek, H; Breeze, CE; Sugden, K; Lundgren, S; Castillo-Fernandez, JE; Hannon, E; Moffitt, TE; Hagenbeek, FA; van Beijsterveldt, CEM; Jan Hottenga, J; Tsai, P-C; BIOS Consortium, ; Genetics of DNA Methylation Consortium, ; Min, JL; Hemani, G; Ehli, EA; Paul, F; Stern, CD; Heijmans, BT; Slagboom, PE; Daxinger, L; van der Maarel, SM; de Geus, EJC; Willemsen, G; Montgomery, GW; Reversade, B; Ollikainen, M; Kaprio, J; Spector, TD; Bell, JT; Mill, J; Caspi, A; Martin, NG; Boomsma, DI
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