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

Abstract

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.

LanguageEnglish
Pages1393-1401
Number of pages9
JournalHuman Mutation
Volume39
Issue number10
DOIs
StatePublished - Oct 2018

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Monozygotic Twins
Mutation
Mosaicism
Genome
Recombinant DNA
Zygote
GTP Phosphohydrolases
DNA
Genes
Research

Cite this

Ouwens, K. G., Jansen, R., Tolhuis, B., Slagboom, P. E., Penninx, B. W. J. H., & Boomsma, D. I. (2018). A characterization of post-zygotic mutations identified in monozygotic twins. Human Mutation, 39(10), 1393-1401. DOI: 10.1002/humu.23586
Ouwens, Klaasjan G ; Jansen, Rick ; Tolhuis, Bas ; Slagboom, P Eline ; Penninx, Brenda W J H ; Boomsma, Dorret I. / A characterization of post-zygotic mutations identified in monozygotic twins. In: Human Mutation. 2018 ; Vol. 39, No. 10. pp. 1393-1401
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Ouwens, KG, Jansen, R, Tolhuis, B, Slagboom, PE, Penninx, BWJH & Boomsma, DI 2018, 'A characterization of post-zygotic mutations identified in monozygotic twins' Human Mutation, vol. 39, no. 10, pp. 1393-1401. DOI: 10.1002/humu.23586

A characterization of post-zygotic mutations identified in monozygotic twins. / Ouwens, Klaasjan G; Jansen, Rick; Tolhuis, Bas; Slagboom, P Eline; Penninx, Brenda W J H; Boomsma, Dorret I.

In: Human Mutation, Vol. 39, No. 10, 10.2018, p. 1393-1401.

Research output: Contribution to JournalArticleAcademicpeer-review

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Ouwens KG, Jansen R, Tolhuis B, Slagboom PE, Penninx BWJH, Boomsma DI. A characterization of post-zygotic mutations identified in monozygotic twins. Human Mutation. 2018 Oct;39(10):1393-1401. Available from, DOI: 10.1002/humu.23586