Landscape of copy number variations in Bos taurus: individual - and inter-breed variability

Background: The number of studies of Copy Number Variation in cattle has increased in recent years. This has been prompted by the increased availability of data on polymorphisms and their relationship with phenotypes. In addition, livestock species are good models for some human phenotypes. In the present study, we described the landscape of CNV driven genetic variation in a large population of 146 individuals representing 13 cattle breeds, using whole genome DNA sequence. Results: A highly significant variation among all individuals and within each breed was observed in the number of duplications (P < 10⁻¹⁵) and in the number of deletions (P < 10⁻¹⁵). We also observed significant differences between breeds for duplication (P = 0.01932) and deletion (P = 0.01006) counts. The same variation CNV length - inter-individual and inter-breed differences were significant for duplications (P < 10⁻¹⁵) and deletions (P < 10⁻¹⁵). Moreover, breed-specific variants were identified, with the largest proportion of breed-specific duplications (9.57%) found for Fleckvieh and breed-specific deletions found for Brown Swiss (5.00%). Such breed-specific CNVs were predominantly located in intragenic regions, however in Simmental, one deletion present in five individuals was found in the coding sequence of a novel gene ENSBTAG00000000688 on chromosome 18. In Brown Swiss, Norwegian Red and Simmental breed-specific deletions were located within KIT and MC1R genes, which are responsible for a coat colour. The functional annotation of coding regions underlying the breed-specific CNVs showed that in Norwegian Red, Guernsey, and Simmental significantly under- and overrepresented GO terms were related to chemical stimulus involved in sensory perception of smell and the KEGG pathways for olfactory transduction. In addition, specifically for the Norwegian Red breed, the dopaminergic synapse KEGG pathway was significantly enriched within deleted parts of the genome. Conclusions: The CNV landscape in Bos taurus genome revealed by this study was highly complex, with inter-breed differences, but also a significant variation within breeds. The former, may explain some of the phenotypic differences among analysed breeds, and the latter contributes to within-breed variation available for selection.M. Mielczarek, M. Frąszczak, E. Nicolazzi, J.L. Williams and J. Szyd