Hotspots of human mutation point to clonal expansions in spermatogonia.

ABSTRACT: In renewing tissues, mutations conferring selective advantage may result in clonal expansions^1-4. In contrast to somatic tissues, mutations driving clonal expansions in spermatogonia (CES) are also transmitted to the next generation. This results in an effective increase of de novo mutation rate for CES drivers^5-8. CES was originally discovered through extreme recurrence of de novo mutations causing Apert syndrome⁵. Here, we develop a systematic approach to discover CES drivers as hotspots of human de novo mutation. Our analysis of 54,715 trios ascertained for rare conditions^9-13, 6,065 control trios12,14-19, and population variation from 807,162 mostly healthy individuals²⁰ identifies genes manifesting rates of

SUBMITTER: Seplyarskiy V 

PROVIDER: S-EPMC12204251 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature