Influence of Dominance and Drift on Lethal Mutations in Human Populations.

ABSTRACT: We consider disease-causing mutations that are lethal when homozygous. Lethality involves the very strongest form of negative selection, with the selection coefficient against the disease-carrying homozygote having its maximum value of unity. We determine results for the behavior of the frequency of a lethal allele in an effectively infinite population. This includes an estimate of the time it takes to achieve equilibrium, and a description of transient behavior associated with a sudden change in the fitness of the heterozygote. We determine analogous results for a finite population, showing that a lethal disease-causing allele needs to be described by a modified Wright-Fisher model, which deviates from the standard model, where selection coefficients are assumed small compared with 1. We

SUBMITTER: Waxman D 

PROVIDER: S-EPMC7142268 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature