Human de novo mutation rates from a four-generation pedigree reference.

ABSTRACT: Understanding the human de novo mutation (DNM) rate requires complete sequence information¹. Here using five complementary short-read and long-read sequencing technologies, we phased and assembled more than 95% of each diploid human genome in a four-generation, twenty-eight-member family (CEPH 1463). We estimate 98-206 DNMs per transmission, including 74.5 de novo single-nucleotide variants, 7.4 non-tandem repeat indels, 65.3 de novo indels or structural variants originating from tandem repeats, and 4.4 centromeric DNMs. Among male individuals, we find 12.4 de novo Y chromosome events per generation. Short tandem repeats and variable-number tandem repeats are the most mutable, with 32 loci exhibiting recurrent mutation through the generations. We accurately assemble 288 centrome

SUBMITTER: Porubsky D 

PROVIDER: S-EPMC12240836 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature