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

Abstract

Meiotic recombination is an essential biological process that generates genetic diversity and ensures proper segregation of chromosomes during meiosis. From a large USDA dairy cattle pedigree with over half a million genotyped animals, we extracted 186,927 three-generation families, identified over 8.5 million maternal and paternal recombination events, and constructed sex-specific recombination maps for 59,309 autosomal SNPs. The recombination map spans for 25.5 Morgans in males and 23.2 Morgans in females, for a total studied region of 2,516 Mb (986 kb/cM in males and 1,085 kb/cM in females). The male map is 10% longer than the female map and the sex difference is most pronounced in the subtelomeric regions. We identified 1,792 male and 1,885 female putative recombination hotspots, with 720 hotspots shared between sexes. These hotspots encompass 3% of the genome but account for 25% of the genome-wide recombination events in both sexes. During the past forty years, males showed a decreasing trend in recombination rate that coincided with the artificial selection for milk production. Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes. Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only. Among the multiple PRDM9 paralogues on the bovine genome, our GWAS of recombination hotspot usage together with linkage analysis identified the PRDM9 paralogue on chromosome 1 to be associated in the U.S. Holstein data. Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination.

Author Summary

Previous studies on cattle recombination largely focused on males. Using a large Holstein sample from the USDA national database, we studied both male and female recombination by assembling paternal and maternal recombination events in at least three generations. This unique data set provides unprecedented statistical power to study cattle genome recombination in the two sexes: (1) We report for the first time that bulls have more recombination than cows, contrary to the common perception that females have more recombination than males as observed in many mammalian species including humans and mice, and that the sex difference in recombination primarily occurs near the subtelomeric regions of all bovine autosomes; (2) We identify several genes associated with cattle recombination in both females and males, and genes affecting female recombination only; (3) We define putative recombination hotspots and find the cattle PRDM9 gene to be associated with recombination hotspot usage. These results provide new insights for understanding cattle and mammalian genome recombination.