Selective mutation accumulation: a computational model of the paternal age effect

摘要

Motivation: As the mean age of parenthood grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father, but have a deleterious effect in offspring. In this paper we present a computational technique to model the SSC niche in order to examine the phenomenon and draw conclusions across different genes and disorders.