Copy number variation in the bovine genome

Abstract

Background: Copy number variations (CNVs), which represent a significant source of genetic diversity in mammals, have been shown to be associated with phenotypes of clinical relevance and to be causative of disease. Notwithstanding, little is known about the extent to which CNV contributes to genetic variation in cattle.

Results: We designed and 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 median probe spacing of 301 bp. 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. The CNVRs identified covered 0.68% (22 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 co-localized with segmental duplications, while 30% encompass genes, of which the majority is involved in environmental response. About 10% of the human orthologous of these genes are associated with human disease susceptibility and, hence, may have important phenotypic consequences.

Conclusions: Together, this analysis provides a useful resource for assessment of the impact of CNVs regarding variation in bovine health and production traits.

Figure 1

Example of an identification procedure for CNV gain or loss status. Y axis represents log2ratios and X axis represents genomic positions along chromosome 7. (A) animals 2 vs. 19; (B) 19 vs. 6 (gain in 19 or loss in 6); (C) 6 vs. 20 (loss in 6 or gain in 20) and (D) 20 vs. 17. The only plots that show a CNV are B and C, and since the only animal common to those hybridizations is animal 6, we classify this CNV as a deletion in animal 6.

Figure 2

CNV calling pipeline (details in Methods section). Data analysis procedure to discover copy number variations in array CGH data.

Figure 3

Bovine karyotype, with CNVR distribution. Green arrows correspond to gains and red arrows correspond to losses.

Figure 4

Size range distribution of the CNVRs detected.