Identical twins carry a persistent epigenetic signature of early genome programming

Jenny van Dongen, Scott D. Gordon, Veronika V. Odintsova, Hamdi Mbarek, Fiona A. Hagenbeek, Catharina E.M. van Beijsterveldt, Jouke Jan Hottenga, Eco J.C. de Geus, Gonneke Willemsen, Dorret I. Boomsma, Genetics of DNA Methylation Consortium, BIOS Consortium

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number5618
Pages (from-to)1-14
Number of pages14
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 28 Sept 2021

Bibliographical note

Funding Information:
We acknowledge funding from the Netherlands Organization for Scientific Research (NWO): Biobanking and Biomolecular Research Infrastructure (BBMRI–NL, 184.021.007; 184.033.111), and NWO Large Scale infrastructures, X-Omics (184.034.019). Cohort-specific acknowledgments are provided in Supplementary Note 8. We thank Peter Visscher and Jian Yang for their helpful comments.

Publisher Copyright:
© 2021, The Author(s).

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