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Title:   Author  item
                                            HOU, YALI - University Of Marylanditem
                                            Liu, Ge

                                                         - *George*item
                                            Bickhart, Derekitem
                                            MATUKUMALLI, LAKSHMI - George Mason Universityitem
                                            Li, Congjun

                                                         - *Cj*item
                                            SONG, JIUZHOU - University Of Marylanditem
                                            Gasbarre, Louisitem
                                            Van Tassell, Curtis

                                                         - *Curt*item
                                            Sonstegard, Tad
  Submitted to: Functional and Integrative Genomics
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 8/17/2011
                                    Publication  Date: 9/18/2011
                                    Citation: Hou, Y., Liu, G., Bickhart, D.M., Matukumalli, L.K., Li, C., Song, J., Gasbarre, L.C., Van Tassell, C.P., Sonstegard, T.S. 2011. Genomic regions showing copy number variations associate with resistance or susceptibility to gastrointestinal nematodes in Angus Cattle. Functional and Integrative Genomics. 12(1):81-92.Interpretive Summary: 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 intestinal nematodes. In this study, we performed a large scale analysis of CNVs using SNP genotyping data from 472 animals of the same population. We identified and validated multiple CNVs in cattle with extreme resistant and susceptible phenotypes. We then used pathway analyses to further shed light into the underlined mechanisms. Some of the CNVs are likely to contribute to the detected variations in gene expression and thus differences in host parasite resistance. The knowledge created in these studies could potentially enhance genetic improvement of agricultural livestock and could help us to face challenges in this "green" era by enhancing food safety through genomic selection of parasite-resistant animals.
                                Technical Abstract: 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 intestinal 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 two groups of 100 individual animals with extremely low or high estimated breeding values (EBVs) of eggs per gram of feces (EPG), 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 (qPCR). 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. Pathway 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 genes which are overrepresented in environmental interactions. Pathway analyses indicated that the PS specific genes are particularly enriched for inflammatory response, immune cell trafficking, metabolic disease, cell cycle, and cellular organization and movement. These results provide valuable information for the future study of cattle CNVs underling economically important health and production traits.


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