DNA damage and parental age

Abstract

Mutation Mutations in the sperm and eggs of humans have been attributed to errors in DNA replication. More than 75% of human germline mutations are paternal in origin. This is thought to be a result of male gametes undergoing more rounds of cell division than female gametes and thus having a greater probability of replication error. Gao et al. examined datasets of de novo mutations in the human germline and found that the mutation bias is not driven by spermatogenesis. They observed a surprising degree of C-to-G transversions and CpG transitions, indicative of DNA damage. The authors deduced that most mutations in early embryos are more likely to result from factors associated with maternal age at conception and accumulated damage in oocytes and embryos than from replication error. Proc. Natl. Acad. Sci. U.S.A. 116 , 9491 (2019).