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

Abstract

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.

Keywords: Cattle; Copy number variation; Genetic diversity; Next-generation sequencing.

Fig. 1

The graphical representation of the number of duplications (a) and deletions (b) per bull and the length of duplications (c) and deletions (d) observed in the whole validated data set

Fig. 2

The percent of duplications falling into non-genic and gene regions. BSW represents Brown Swiss, FLV Fleckvieh, GUE Guernsey, RED Norwegian Red and SIM Simmental breed

Fig. 3

The percent of deletions falling into non-genic and gene regions. BSW represents Brown Swiss, FLV Fleckvieh, GUE Guernsey, RED Norwegian Red and SIM Simmental breed

Fig. 4

The percent of breed specific deletions/duplications (detected in at least two bulls belonging to the same breed). BSW represents Brown Swiss, FLV Fleckvieh, GUE Guernsey, RED Norwegian Red and SIM Simmental breed

Fig. 5

The workflow including CNV detection and annotation pipeline used in this study. White boxes represent particular processes names, while blue boxes represent software. Consensus CNV set constructing and statistical analysis were implemented in self-written scripts

Fig. 6

The average genome coverage per individual. Bulls excluded from further analysis are below the red horizontal line. BSW represents Brown Swiss, FLV Fleckvieh, GUE Guernsey, RED Norwegian Red and SIM Simmental breed. The “other” category contains individuals belonging to breeds such as Parda de la Montaña (4 bulls), Pezzata Rossa Italiana (3), Avileña (2), Bruna Italiana (1), Albera (1), Rubia Gallega (1), Toro de Lidia (1) and Pirenaica (1)