Genetic Analysis of Variation in Human Meiotic Recombination

• Type of Material: Article
• Authors: Reshmi Chowdhury, University of Pennsylvania; Philippe R. J. Bois, The Scripps Research Institute; Eleanor Feingold, University of Pittsburgh; Stephanie Sherman, Emory University; Vivian G. Cheung, University of Pennsylvania
• Language: English
• Date: 2009
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2009 Chowdhury et al.
• Final Published Version (URL): http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000648
• Title of Journal or Parent Work: PLoS Genetics
• ISSN: 1553-7390
• Volume: 5
• Issue: 9
• Start Page: e1000648
• End Page: e1000648
• Grant/Funding Information: The Framingham Heart Study and the Framingham SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University.; This work is supported by grants from the National Institutes of Health (HD057029 to EF and SLS, HG01880 to VGC), the State of Florida to Scripps Florida (PRJB), and the Howard Hughes Medical Institute (VGC).
• Research Categories: Biology, Genetics; Biology, Biostatistics

Abstract

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.