🧬We are born with hundreds of de novo DNA mutations that were not present in genomes of our parents. But why do some people have more of them than others? In a new preprint the authors analyzed 28,985 sibling pairs and identified more than 800,000 de novo mutations. The main factor is parental age especially paternal age with about 1.5 extra mutations per year of the father’s age and 0.4 per year of the mother’s age The authors did not find convincing evidence that the total number of de novo mutations is associated with genetic ancestry or parental smoking The most interesting part is rare variants in DNA repair and replication genes. Disruptive variants in REV1 were associated with about a 16% increase in the total mutation rate while variants in LIG1 were linked to a 24 to 26% increase in CpG to TpG mutations A key feature of the study was the analysis of IBD-segments in siblings genomic regions that both children inherited from the same parental chromosomes. Differences within these regions can point to new mutations. biorxiv.org/content/10.64898… #deNovo #mutations #reparation #inheritance #siblings