Parental germline mosaicism in genome-wide phased de novo variants: Recurrence risk assessment and implications for precision genetic counselling.

ABSTRACT: De novo mutations (DNMs) have a significant impact on human health, notably through their contribution to developmental disorders. DNMs occur in both paternal and maternal germlines via diverse mechanisms, including parental early embryonic mosaicism, at high recurrence risk for subsequent pregnancies through germline mosaicism. This phenomenon has been studied mostly on isolated pathogenic variants, but its contribution to genome-wide phased variants in individual genomes is underexplored. We aimed to categorize DNMs and their recurrence risk by detecting and phasing a large set of DNMs via short- and long-read genome sequencing followed by systematic deep sequencing of parental blood and sperm DNA. We detected an average of 85.6 DNM per trio (n=5 trios), with an expected paternal bias of

SUBMITTER: Lecoquierre F 

PROVIDER: S-EPMC11990764 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature