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Similarities and differences in patterns of germline mutation between mice and humans
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Similarities and differences in patterns of germline mutation between mice and humans
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Journal Article
Similarities and differences in patterns of germline mutation between mice and humans
2019
Overview
Whole genome sequencing (WGS) studies have estimated the human germline mutation rate per basepair per generation (~1.2 × 10
−8
) to be higher than in mice (3.5–5.4 × 10
−9
). In humans, most germline mutations are paternal in origin and numbers of mutations per offspring increase with paternal and maternal age. Here we estimate germline mutation rates and spectra in six multi-sibling mouse pedigrees and compare to three multi-sibling human pedigrees. In both species we observe a paternal mutation bias, a parental age effect, and a highly mutagenic first cell division contributing to the embryo. We also observe differences between species in mutation spectra, in mutation rates per cell division, and in the parental bias of mutations in early embryogenesis. These differences between species likely result from both species-specific differences in cellular genealogies of the germline, as well as biological differences within the same stage of embryogenesis or gametogenesis.
Estimates of mutation rates differ between species. Here, Lindsay et al. perform side-by-side analyses of germline mutation rates using multi-sibling mouse and human pedigrees and find different mutation rates between species, also stratified by sex and temporal stage of mutation acquisition.
