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A characterization of postzygotic mutations identified in monozygotic twins
Author(s) -
Ouwens Klaasjan G.,
Jansen Rick,
Tolhuis Bas,
Slagboom P. Eline,
Penninx Brenda W.J.H.,
Boomsma Dorret I.
Publication year - 2018
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23586
Subject(s) - biology , genetics , gene , monozygotic twin , genome , dna sequencing , mutation , allele
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.