Common and low-frequency variants associated with genome-wide recombination rate

• Published in: Nature genetics Vol. 46; no. 1; pp. 11 - 16
• Main Authors: Kong, Augustine, Thorleifsson, Gudmar, Frigge, Michael L, Masson, Gisli, Gudbjartsson, Daniel F, Villemoes, Rasmus, Magnusdottir, Erna, Olafsdottir, Stefania B, Thorsteinsdottir, Unnur, Stefansson, Kari
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2014; Nature Publishing Group
• Subjects: 45/43; 631/208/205/2138; 631/208/457; Agriculture; Animal Genetics and Genomics; Biomedicine; Cancer Research; Chromosome Inversion; Chromosomes; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 4; Fathers; Female; Gene Frequency; Gene Function; Genetic aspects; Genetic diversity; Genetic recombination; Genetic Variation; Genome, Human; Genomics; Histone-Lysine N-Methyltransferase - genetics; Human Genetics; Humans; Iceland; Male; Meiosis; Offspring; Physiological aspects; Polymorphism, Single Nucleotide; Recombination, Genetic; Telomere - genetics; Iceland
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.2833

Augustine Kong, Kari Stefansson and colleagues report the discovery of common and low-frequency variants associated with genome-wide recombination rates. Most of the newly discovered variants exhibit differential effects on male and female recombination rates, and several map to genes with known roles in recombination, including RAD21L and MSH4 . Meiotic recombination contributes to genetic diversity by yielding new combinations of alleles. Individuals vary with respect to the genome-wide recombination counts in their gametes. Exploiting data resources in Iceland, we compiled a data set consisting of 35,927 distinct parents and 71,929 parent-offspring pairs. Within this data set, we called over 2.2 million recombination events and imputed variants with sequence-level resolution from 2,261 whole genome–sequenced individuals into the parents to search for variants influencing recombination rate. We identified 13 variants in 8 regions that are associated with genome-wide recombination rate, 8 of which were previously unknown. Three of these variants associate with male recombination rate only, seven variants associate with female recombination rate only and three variants affect both. Two are low-frequency variants with large effects, one of which is estimated to increase the male and female genetic maps by 111 and 416 cM, respectively. This variant, located in an intron, would not be found by exome sequencing.