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

PLoS Genet. 2015 Nov 5;11(11):e1005387. doi: 10.1371/journal.pgen.1005387. eCollection 2015 Nov.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle / genetics*
  • Chromosome Mapping
  • Female
  • Male
  • Pedigree*
  • Recombination, Genetic*

Grant support

The Ministero delle Politiche Agricole Alimentari e Forestali (MIPAAF, Rome, Italy) funded the HD genotypes contributed by the Innovagen project (DM 10750-7303-2011), and Defra (London, UK) funded the HD genotypes contributed by the United Kingdom as part of the Ruminant Genetic Improvement Network. This research was supported by appropriated project 1265-31000-096-00, "Improving Genetic Predictions in Dairy Animals Using Phenotypic and Genomic Information," of the Agricultural Research Service of the United States Department of Agriculture. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture. The USDA is an equal opportunity provider and employer.