A characterization of postzygotic mutations identified in monozygotic twins. Issue 10 (18th July 2018)

• Record Type: Journal Article
• Authors: Ouwens, Klaasjan G.; Jansen, Rick; Tolhuis, Bas; Slagboom, P. Eline; Penninx, Brenda W.J.H.; Boomsma, Dorret I.
• Is Part Of: Human mutation. Volume 39:Issue 10(2018)
• Page Start: 1393
• Page End: 1401
• Publication Date: 2018-07-18
• Subjects: genetics -- mutations -- next‐generation sequencing -- postzygotic mutations -- somatic mosaicism; Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.23586
• Languages: English
• ISSNs: 1059-7794

Abstract

Abstract: Postzygotic 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 1, 720 and 1, 739 putative postzygotic 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. Abstract : Whole genome DNA sequence data of monozygotic twin pairs was compared to detect somatic mosaicism. Sets of putative mutations were found to be strongly ( p < 4.37e–91) enriched in both twin pairs for regulatory elements, and corresponding genes were significantly enriched for genes involved in GTPase activity. This research shows that somatic mosaicism can be detected in monozygotic twin pairs by using allelic ratios and that the mutations found by this approach are not randomly distributed throughout the genome.