Genome Changes Due to Forty Years of Artificial Selection Associated with Divergent Dairy Production and Reproduction

Artificial selection in dairy cattle since 1964 has achieved steady increase in milk production that was accompanied by unintended declines in fertility. Direct comparison of 45,878 SNPs between a group of Holstein cattle unselected since 1964 and the contemporary Holsteins was conducted to identify genome changes due to selection. About 31% SNPs had allele frequency differences (AFD) in the range 0.10-0.53 and had allele frequency changes in the same direction during the first and second 20 years of selection, indicating that approximately 31% of the Holstein genome was affected by the 40 years of artificial selection. The analysis of AFD, long-range AFD and heterozygosity, and extended haplotype homozygosity (EHH) including haplotype frequency changes identified many specific chromosome regions potentially affected by selection. These regions include the bovine MHC region of chr23, a chr21 region with a large cluster of 90 RNA genes, a chr10 region near PGF, a chr19 region near the telomere, and the TSPAN7-DMD region of the X chromosome. The 20-53Mb region of chr20 that includes GHR and PRLR had the strongest EHH evidence of selection. For the DGAT1 region, selection signal was observed upstream and downstream of DGAT1. Striking long-range AFD between an elite group and the unselected Holsteins were observed on chromosomes 7, 13, 14, 18, and 24 in addition to the aforementioned regions. These results provide a unique understanding of the changing Holstein genome due to selection and provide secondary evidence for QTL mapping.