UC Davis

Key PointsMillions of new genetic variants have been discovered through sequencing studies and deposited in human genomic databases. Many of these, particularly rare variants, have been annotated as deleterious.Recent research has examined whether different human populations have a varying burden of deleterious alleles — a concept referred to as mutation load.Several recent studies have suggested that there is no significant difference among populations in the estimated number of deleterious alleles per individual. However, these analyses are sensitive to annotation prediction algorithms and summary statistics, leading to different, sometimes contradictory, interpretations.These calculations also involved a number of simplifying assumptions, including additive allelic effects, no epistasis and simple distributions of selection coefficients across deleterious variants and across populations.Following classical models of mutation load, we consider genotype frequencies in order to highlight how mutation load can change under different models of dominance.Additionally, genetic drift has shifted the allele frequency spectrum of deleterious variants such that the genomes of individuals in Out-of-Africa populations carry more common deleterious variants.The frequency distribution of deleterious variants has implications for characterizing the genetic architecture of diseases across populations.