Negative linkage disequilibrium between amino acid changing variants reveals interference among deleterious mutations in the human genome.

ABSTRACT: Evolutionary forces like Hill-Robertson interference and negative epistasis can lead to deleterious mutations being found on distinct haplotypes. However, the extent to which these forces depend on the selection and dominance coefficients of deleterious mutations and shape genome-wide patterns of linkage disequilibrium (LD) in natural populations with complex demographic histories has not been tested. In this study, we first used forward-in-time simulations to predict how negative selection impacts LD. Under models where deleterious mutations have additive effects on fitness, deleterious variants less than 10 kb apart tend to be carried on different haplotypes relative to pairs of synonymous SNPs. In contrast, for recessive mutations, there is no consistent ordering of how selection coeffi

SUBMITTER: Garcia JA 

PROVIDER: S-EPMC8351996 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature