Discovery of an unusually high number of de novo mutations in sperm of older men using duplex sequencing.

ABSTRACT: De novo mutations (DNMs) are important players in heritable diseases and evolution. Of particular interest are highly recurrent DNMs associated with congenital disorders that have been described as selfish mutations expanding in the male germline, thus becoming more frequent with age. Here, we have adapted duplex sequencing (DS), an ultradeep sequencing method that renders sequence information on both DNA strands; thus, one mutation can be reliably called in millions of sequenced bases. With DS, we examined ∼4.5 kb of the FGFR3 coding region in sperm DNA from older and younger donors. We identified sites with variant allele frequencies (VAFs) of 10^-4 to 10^-5, with an overall mutation frequency of the region of ∼6 × 10^-7 Some of the substitutions are

SUBMITTER: Salazar R 

PROVIDER: S-EPMC8896467 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature