Copy number variation in the bovine genome

Copy number variations (CNVs), which represent a significant source of genetic diversity in mammals, are currently being associated with phenotypes of clinical relevance, mostly in humans and mice. Notwithstanding, little is known about the extent of CNV that contributes to genetic variation in cattle. This study reports the highest resolution map of copy number variation in the cattle genome, with 304 CNV regions (CNVRs) being identified among the genomes of 20 bovine samples from 4 dairy and beef breeds. We used a set of NimbleGen CGH arrays that tile across the assayable portion of the cattle genome with approximately 6.3 million probes, at a 301 bp median probe spacing. These CNVRs covered 0.68% (23 Mb) of the genome, and ranged in size from 1.7 to 2,031 kb (median size 16.7 kb). About 20% of the CNVs colocalized with segmental duplications while 30% encompassed genes, mostly related with environmental response. About 10% of the orthologous CNV cow-human genes are related with human disease susceptibility and, hence, may have important phenotypic consequences. Together, this analysis provides a useful resource to assist with the assessment of CNVs in the contexts of bovine variation, health and productive efficiency. 20 samples were analyzed in a dye-swap loop design. In order to cover the latest bovine genome assembly (bt4) with high density, custom Nimblegen HD2 CGH arrays were planned in 3 designs. Each design covered a specific set of chromosomes with 2.1M probes, which yielded 420 bp of average probe spacing (301 bp median probe spacing).