Cattle Sex-Specific Recombinations and Their Genetic Control from a Large Pedigree Analysis

Meiotic recombination is an essential biological process that ensures proper segregation of chromosomes during meiosis and generates novel genetic variants. 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 linkage maps for <60K autosomal SNPs that spanned 25.75 and 23.39 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 (R = 0.71). We identified 1,447 and 1,439 recombination hotspots for males and females respectively, with 547 of them shared between sexes. The strongest hotspots happened to be clustered around SHOX that encompasses the top recombination hotspot in humans. Strikingly, during the past forty years, both sexes showed a decreasing trend in recombination rate that coincided with the period of steady selection response to artificial selection for milk production. Using sex-specific GWAS analyses, we confirmed three genetic loci, PRDM9, CPLX1, REC114, and identified a novel gene, NEK9, associated with genome-wide recombination rate in both sexes. Three genes, MSH4, SMC3 and CEP55, were associated with recombination rate in females only. In addition to PRDM9, we identified a novel gene, CAMK4, to be associated with recombination hotspot usage in both sexes. Concomitantly, disruption of CAMK4 resulted in defective spermiogenesis and sterility in mice in previous studies. Given the largest sample size ever reported for such studies, our results contribute large sample evidence to the understanding of mammalian recombination.