Genomic regions showing copy number variations associate with resistance or susceptibility to gastrointestinal...

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. We previously reported an initial analysis of copy number variations (CNVs) in Angus cattle selected for resistance or susceptibility to gastrointestinal nematodes. In this study, we performed a large-scale analysis of CNVs using SNP genotyping data from 472 animals of the same population. We detected 811 candidate CNV regions, which represent 141.8 Mb (~4.7%) of the genome. To investigate the functional impacts of CNVs, we created 2 groups of 100 individual animals with extremely low or high estimated breeding values of eggs per gram of feces and referred to these groups as parasite resistant (PR) or parasite susceptible (PS), respectively. We identified 297 (~51 Mb) and 282 (~48 Mb) CNV regions from PR and PS groups, respectively. Approximately 60% of the CNV regions were specific to the PS group or PR group of animals. Selected PR- or PS-specific CNVs were further experimentally validated by quantitative PCR. A total of 297 PR CNV regions overlapped with 437 Ensembl genes enriched in immunity and defense, like WC1 gene which uniquely expresses on gamma/delta T cells in cattle. Network analyses indicated that the PR-specific genes were predominantly involved in gastrointestinal disease, immunological disease, inflammatory response, cell-to-cell signaling and interaction, lymphoid tissue development, and cell death. By contrast, the 282 PS CNV regions contained 473 Ensembl genes which are overrepresented in environmental interactions. Network analyses indicated that the PS-specific genes were particularly enriched for inflammatory response, immune cell trafficking, metabolic disease, cell cycle, and cellular organization and movement.