A characterization of post-zygotic mutations identified in monozygotic twins

Klaasjan G Ouwens, Rick Jansen, Bas Tolhuis, P Eline Slagboom, Brenda W J H Penninx, Dorret I Boomsma

Research output: Contribution to JournalArticleAcademicpeer-review


Post-zygotic mutations are DNA changes acquired from the zygote stage onwards throughout the lifespan. These changes lead to differences in DNA sequence among cells of an individual, potentially contributing to the etiology of complex disorders. Here we compared whole genome DNA sequence data of two monozygotic twin pairs, 40 and 100 years old, to detect somatic mosaicism. DNA samples were sequenced twice on two Illumina platforms (13X and 40X read depth) for increased specificity. Using differences in allelic ratios resulted in sets of 1720 and 1739 putative post-zygotic mutations in the 40-year-old twin pair and 100-year-old twin pair, respectively, for subsequent enrichment analysis. This set of putative mutations was strongly (p < 4.37e-91) enriched in both twin pairs for regulatory elements. The corresponding genes were significantly enriched for genes that are alternatively spliced, and for genes involved in GTPase activity. This research shows that somatic mosaicism can be detected in monozygotic twin pairs by using allelic ratios calculated from DNA sequence data and that the mutations which are found by this approach are not randomly distributed throughout the genome. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)1393-1401
Number of pages9
JournalHuman Mutation
Issue number10
Publication statusPublished - Oct 2018


Klaasjan Ouwens is financially supported by the EMGO Institute for Health and Care Research (EMGO+). We acknowledge BBRMI-NL (NWO 184.021.007).

FundersFunder number
EMGO Institute for health and care research

    Cohort Studies

    • Netherlands Twin Register (NTR)


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