Mutation saturation for fitness effects at human CpG sites.

ABSTRACT: Whole exome sequences have now been collected for millions of humans, with the related goals of identifying pathogenic mutations in patients and establishing reference repositories of data from unaffected individuals. As a result, we are approaching an important limit, in which datasets are large enough that, in the absence of natural selection, every highly mutable site will have experienced at least one mutation in the genealogical history of the sample. Here, we focus on CpG sites that are methylated in the germline and experience mutations to T at an elevated rate of ~10^-7 per site per generation; considering synonymous mutations in a sample of 390,000 individuals, ~ 99 % of such CpG sites harbor a C/T polymorphism. Methylated CpG sites provide a natural mutation saturation

SUBMITTER: Agarwal I 

PROVIDER: S-EPMC8683084 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature