Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes.

ABSTRACT: Mosaic mutations present in the germline have important implications for reproductive risk and disease transmission. We previously demonstrated a phenomenon occurring in the male germline, whereby specific mutations arising spontaneously in stem cells (spermatogonia) lead to clonal expansion, resulting in elevated mutation levels in sperm over time. This process, termed "selfish spermatogonial selection," explains the high spontaneous birth prevalence and strong paternal age-effect of disorders such as achondroplasia and Apert, Noonan and Costello syndromes, with direct experimental evidence currently available for specific positions of six genes (FGFR2, FGFR3, RET, PTPN11, HRAS, and KRAS). We present a discovery screen to identify novel mutations

SUBMITTER: Maher GJ 

PROVIDER: S-EPMC6280762 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature