Applicability of the Mutation-Selection Balance Model to Population Genetics of Heterozygous Protein-Truncating Variants in Humans.

ABSTRACT: The fate of alleles in the human population is believed to be highly affected by the stochastic force of genetic drift. Estimation of the strength of natural selection in humans generally necessitates a careful modeling of drift including complex effects of the population history and structure. Protein-truncating variants (PTVs) are expected to evolve under strong purifying selection and to have a relatively high per-gene mutation rate. Thus, it is appealing to model the population genetics of PTVs under a simple deterministic mutation-selection balance, as has been proposed earlier (Cassa et al. 2017). Here, we investigated the limits of this approximation using both computer simulations and data-driven approaches. Our simulations rely on a model of demographic history estimated from 33,3

SUBMITTER: Weghorn D 

PROVIDER: S-EPMC6738481 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature