The number of recombination events per meiosis varies extensively among individuals. This recombination phenotype differs between female and male, and also among individuals of each gender. In this study, we used high-density SNP genotypes of over 2,300 individuals and their offspring in two datasets to characterize recombination landscape and to map the genetic variants that contribute to variation in recombination phenotypes. We found six genetic loci that are associated with recombination phenotypes. Two of these (RNF212 and an inversion on chromosome 17q21.31) were previously reported in the Icelandic population, and this is the first replication in any other population. Of the four newly identified loci (KIAA1462, PDZK1, UGCG, NUB1), results from expression studies provide support for their roles in meiosis. Each of the variants that we identified explains only a small fraction of the individual variation in recombination. Notably, we found different sequence variants associated with female and male recombination phenotypes, suggesting that they are regulated by different genes. Characterization of genetic variants that influence natural variation in meiotic recombination will lead to a better understanding of normal meiotic events as well as of non-disjunction, the primary cause of pregnancy loss.
Meiotic recombination is essential for the formation of human gametes and is a key process that generates genetic diversity. Given its importance, we would expect the number and location of exchanges to be tightly regulated. However, studies show significant gender and inter-individual variation in genome-wide recombination rates. The genetic basis for this variation is poorly understood. In this study, we used genotypes from high-density single nucleotide polymorphism (SNP) markers of 2,315 individuals and their children from two Caucasian samples in a genome-wide association study to identify genetic variants that influence the number of meiotic recombination events per gamete. We found three loci that influence female recombination and three different loci that influence male recombination. Our results suggest that gender differences in recombination result from differences in the genetic regulation of female and male meiosis. Also, each identified locus only explains a small proportion of variance; together, each set of loci explains about 10% of the variation in the gender-specific recombination phenotype. This suggests a mechanism for variability in recombination that is essential for genetic diversity while maintaining the number of recombinations within a range to ensure proper chromosome segregation.