Genomic Footprints Of Selection After 50 Years Of Dairy Cattle Breeding

We have developed and implemented a new sequence-based strategy for identifying chromosome segments under selection, and have shown the approach to be powerful for revealing candidate genes and polymorphisms for selected traits.  Using a combination of whole-genome resequencing and high-density genotyping arrays, genome-wide haplotypes were reconstructed for Pawnee Arlinda Chief (“Chief”) and his son Walkway Chief Mark (“Mark”), two of the most important bulls in the history of the dairy cattle industry.  These bulls each account each for ~7% of all current genomes in the Holstein population. The genome-wide haplotypes inherited by Mark from Chief were reconstructed using ~1 million informative high-quality SNPs. The accuracy of the sequence-based haplotype reconstruction was found to be ~97% by comparing more than 15,000 SNPs that overlapped with SNPs on the BovineSNP50 array. To then track Chief’s haplotypes in the current population, BovineSNP50 genotypes were determined in 1,149 of his descendants and his haplotypes were reconstructed in each individual.  We identified 49 chromosomal segments in which Chief alleles showed strong evidence of selection. Candidate polymorphisms for traits that have been under selection in the dairy cattle population were then identified by referencing Chief’s DNA sequence within these selected chromosome blocks. Eleven candidate genes were identified with functions related to milk production, fertility and disease resistance traits. We also identified a mutation responsible for more than 500,000 spontaneous abortions world-wide.  These data demonstrate that haplotype reconstruction of an ancestral proband by whole-genome resequencing in combination with high density SNP genotyping of descendants can be used for rapid, genome-wide identification of the ancestor’s alleles that have been subjected to artificial selection, and also for the identification of rare mutations affecting quantitative traits.