Li Ma1, Jeffrey R. O'Connell2, Paul M. VanRaden3, Botong Shen1, Abinash Padi1, Chuanyu Sun4, Derek M. Bickhart3, John B. Cole3, Daniel J. Null3, George E. Liu3, Yang Da5, and George R. Wiggans3
1Department of Animal and Avian Sciences, University of Maryland, College Park, MD, 20742, USA; 2Department of Medicine, University of Maryland Medical School, Baltimore, Maryland, 21201, USA; 3Animal Genomics and Improvement Laboratory, Agricultural Research Service, USDA, Beltsville, Maryland, 20705, USA; 4National Association of Animal Breeders, Columbia, Missouri, 65205, USA; 5Department of Animal Science, University of Minnesota, St. Paul, Minnesota, 55108, USA
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.