Whole-Genome Sequencing Reveals the Diversity and Population-Genetic Properties of Cattle CNVs

Structural and functional impacts of copy number variations (CNVs) on livestock genomes are not yet well understood. We identified 1853 CNV regions using population-scale sequencing data generated from 75 cattle representing 8 breeds (Holstein, Angus, Jersey, Limousin, Romagnola, Brahman, Gir and Nelore). Individual genome sequence coverage ranged from 4 to 30 fold, with a mean of 11.8 fold. A total of 3.1% (87.5 Mb) of the cattle genome is predicted to be copy number variable, representing a substantial increase over previous estimates (~2%). This dataset was highly correlated with array comparative genomic hybridization (CGH) data (r² = 0.761) and was validated to be accurate with an estimated 12% false positive rate and a 19% false negative rate based upon qPCR and array CGH, respectively. Hundreds of CNVs were found to be either breed specific or differentially variable across breeds, including the RICTOR gene in dairy breeds and the PNPLA3 gene in beef breeds. In contrast, clusters of the PRP and PAG genes were found to be duplicated in all sequenced animals, implicating that subfunctionalization, neofunctionalization or overdominance play roles in diversifying these fertility related genes. Further population-genetic analyses based on CNVs revealed the population structures of these taurine and indicine breeds and uncovered hundreds of positively selected CNV candidates near important functional genes, such as AOX1, ASZ1, GAT, GLYAT, and KRTAP9-1. These CNV results provide a new glimpse into the diverse selection histories of cattle breeds during speciation, domestication, breed formation, and more recently, genetic improvement.