Germline Stem Cell Competition, Mutation Hot Spots, Genetic Disorders, and Older Fathers.

ABSTRACT: Some de novo human mutations arise at frequencies far exceeding the genome average mutation rate. Examples include the common mutations at one or a few sites in the genes that cause achondroplasia, Apert syndrome, multiple endocrine neoplasia type 2B, and Noonan syndrome. These mutations are recurrent, provide a gain of function, are paternally derived, and are more likely to be transmitted as the father ages. Recent experiments have tested whether the high mutation frequencies are due to an elevated mutation rate per cell division, as expected, or to an advantage of the mutant spermatogonial stem cells over wild-type stem cells. The evidence, which includes the surprising discovery of testis mutation clusters, rules out the former model but not the latter. We propose how the mutations mig

SUBMITTER: Arnheim N 

PROVIDER: S-EPMC5007215 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature