genetic analysis of variation in human meiotic recombination在人类减数分裂重组遗传变异分析.pdfVIP

Genetic Analysis of Variation in Human Meiotic Recombination 1 2 3 4 Reshmi Chowdhury , Philippe R. J. Bois , Eleanor Feingold , Stephanie L. Sherman *, Vivian G. Cheung1,5,6* 1 Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2 The Scripps Research Institute, Genome Plasticity Laboratory, La Jolla, California, United States of America, 3 Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 4 Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America, 5 Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 6 Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America 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