It is now well-established that our genomes mutate at a slow but constant rate of 30-100 new point mutations per generation. Although most de novo mutations (>80%) originate from the father and increase in frequency at the rate 1-2 mutation/paternal year, very little is known about the cellular mechanisms that allow the adult testis to reconcile the contradictory demands for abundant sperm production - that takes place over many decades - and the need to maintain genome integrity (i.e. low mutation rate) across generations.
In this presentation I will discuss how the study of de novo mutations associated with rare human disorders (so-called “Paternal Age Effect disorders”) provides an entry point to discover fundamental mechanisms operating in the testes and the importance of the regulation of spermatogenesis for human disease, genome diversity and evolution.
mutations; selfish selection; oncogenic; clonal expansion