The rate of meiotic gene conversion varies by sex and age

• Published in: Nature genetics Vol. 48; no. 11; pp. 1377 - 1384
• Main Authors: Halldorsson, Bjarni V, Hardarson, Marteinn T, Kehr, Birte, Styrkarsdottir, Unnur, Gylfason, Arnaldur, Thorleifsson, Gudmar, Zink, Florian, Jonasdottir, Adalbjorg, Jonasdottir, Aslaug, Sulem, Patrick, Masson, Gisli, Thorsteinsdottir, Unnur, Helgason, Agnar, Kong, Augustine, Gudbjartsson, Daniel F, Stefansson, Kari
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2016; Nature Publishing Group
• Subjects: 45/23; 45/61; 631/208; 631/208/212; Adult; Agriculture; Animal Genetics and Genomics; Base Composition; Biomedicine; Cancer Research; Child; Chromosomes; Datasets; Female; Gene Conversion; Gene Function; Genes; Genetic aspects; Genetic diversity; Genetic recombination; Growth; Human Genetics; Humans; Identification and classification; Male; Maternal Age; Meiosis; Mutation; Oocytes; Polymorphism, Single Nucleotide; Sex Characteristics; Single nucleotide polymorphisms
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.3669

Bjarni Halldorsson, Kari Stefansson and colleagues use SNP array and whole-genome sequencing data to estimate the meiotic gene conversion rate ( G ) in humans. They find that G for SNPs is 7.0 conversions/Mb per generation, is 2.17 greater in mothers than in fathers, and increases with maternal age. Meiotic recombination involves a combination of gene conversion and crossover events that, along with mutations, produce germline genetic diversity. Here we report the discovery of 3,176 SNP and 61 indel gene conversions. Our estimate of the non-crossover (NCO) gene conversion rate ( G ) is 7.0 for SNPs and 5.8 for indels per megabase per generation, and the GC bias is 67.6%. For indels, we demonstrate a 65.6% preference for the shorter allele. NCO gene conversions from mothers are longer than those from fathers, and G is 2.17 times greater in mothers. Notably, G increases with the age of mothers, but not the age of fathers. A disproportionate number of NCO gene conversions in older mothers occur outside double-strand break (DSB) regions and in regions with relatively low GC content. This points to age-related changes in the mechanisms of meiotic gene conversion in oocytes.