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Title:   Author  item
                                            MA, LI - University Of Marylanditem
                                            O'CONNELL, JEFFREY - University Of Marylanditem
                                            Vanraden, Paulitem
                                            SHEN, BOTONG - University Of Marylanditem
                                            PADHI, ABINASH - University Of Marylanditem
                                            SUN, CHUANYU - National Association Of Animal Breedersitem
                                            Bickhart, Derekitem
                                            Cole, Johnitem
                                            Null, Danielitem
                                            Liu, Ge

                                                         - *George*item
                                            DA, YANG - University Of Minnesotaitem
                                            Wiggans, George
  Submitted to: PLoS Genetics
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/23/2015
                                    Publication  Date: 11/5/2015
                                    Citation: Ma, L., O'Connell, J.R., Van Raden, P.M., Shen, B., Padhi, A., Sun, C., Bickhart, D.M., Cole, J.B., Null, D.J., Liu, G., Da, Y., Wiggans, G.R. 2015. Cattle sex-specific recombination and genetic control from a very large pedigree. PLoS Genetics. 11(11):e1005387.Interpretive Summary: Recombination of chromosomes during meiosis is an essential biological process, providing new combinations of genetic variants that allow efficient selection and faster evolution. Crossovers contribute to genetic diversity by reshuffling maternal and paternal genetic alleles into the next generation. Locations are known to be non-random, and numbers of crossovers vary considerably across the species, gender, and even individuals.  Using over a half million genotyped dairy cattle in a large pedigree, we identified over 8.5 million maternal and paternal crossover events in 186,927 three-generation Holstein families. The estimated male recombination map was 10% longer than the female map and spanned 25.5 and 23.2 Morgans, respectively, using 59,309 autosomal loci. Many hotspots of increased crossover rate and several genes influencing these were identified and compared to other species. Precise cattle linkage maps were constructed for use by researchers instead of the physical maps used currently.
                                Technical Abstract: Meiotic recombination is an essential biological process that generates novel genetic variants and ensures proper segregation of chromosomes during meiosis. From a large USDA dairy cattle pedigree with over half million genotyped animals, we extracted 186,927 three-generation families, identified over 8.5 million maternal and paternal crossover events, and constructed sex-specific recombination maps for 59,309 autosomal SNPs that spanned 25.5 and 23.2 Morgans in males and females respectively. The male map is 10% longer than the female map and the higher male recombination rate is most pronounced in the telomeric regions, although males and females exhibit similar recombination rates at other chromosomal locations. We identified 1,792 and 1,885 recombination hotspots for males and females respectively, with 720 of them shared between sexes. These recombination hotspots encompass about 3% of the genome but account for 25% of the genome-wide recombinations in both sexes. Strikingly, during the past forty years, both sexes showed a decreasing trend in recombination rate that coincided with the artificial selection for milk production in cattle. Using sex-specific GWAS analyses, we confirmed two genes, PRDM9 and CPLX1, and identified novel loci, NEK9 and REC114, to be associated with genome-wide recombination rate in both sexes. Three loci, MSH4, SMC3 and CEP55, were associated with recombination rate only in females. From GWAS of recombination hotspot usage, we clearly confirmed the cattle PRDM9 to be the paralogue on chromosome 1, despite a total of four paralogues in the cattle genome. Given the largest sample size ever reported for such studies, our results contribute large sample evidence to the understanding of mammalian recombination.


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