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Title:   Author  item
                                            HOU, YALI - University Of Marylanditem
                                            Liu, Ge

                                                         - *George*item
                                            Bickhart, Derekitem
                                            CARDONE, MARIA - University Of Bariitem
                                            WANG, KAI - Children'S Hospital - Philadelphia, Pennsylvaniaitem
                                            Kim, Eui-Sooitem
                                            MATUKUMALLI, LAKSHMI - George Mason Universityitem
                                            VENTURA, MARIO - University Of Bariitem
                                            SONG, JIUZHOU - University Of Marylanditem
                                            Vanraden, Paulitem
                                            Sonstegard, Taditem
                                            Van Tassell, Curtis

                                                         - *Curt*
  Submitted to: BMC Genomics
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 2/23/2011
                                    Publication  Date: 2/23/2011
                                    Citation: Hou, Y., Liu, G., Bickhart, D.M., Cardone, M.F., Wang, K., Kim, E., Matukumalli, L., Ventura, M., Song, J., Van Raden, P.M., Sonstegard, T.S., Van Tassell, C.P. 2011. Genomic characteristics of cattle copy number variations. Biomed Central (BMC) Genomics. 12:127.Interpretive Summary: In this study, we performed a systematic analysis of cattle copy number variations (CNVs) using the Bovine HapMap SNP genotyping data, including over 500 animals of 21 modern cattle breeds and 6 outgroups. After optimizing the program settings, we identified 682 candidate CNV regions (CNVRs), which cover 139.8 megabases (~4.60%) of the genome. Selected CNVs were further validated by FISH or qPCR, and we found that duplication CNVs are predominantly tandem clustered repeats. Gene content analysis confirmed our earlier observation that CNV associated cattle genes are significantly enriched for immunity, lactation, reproduction and rumination. We compared our dataset with other published CNVRs datasets, highlighting the novelties and commonalities between studies. Phylogenetic analysis based on CNV indicated that Taurine, Indicine and African breeds were clearly separated, supporting three domesticated origins in Fertile Crescent, Indus Valley and Africa, respectively. The distribution of Taurine breeds also reflected their known historical and geographical origins. In conclusion, we presented a comprehensive genomic and evolutionary analysis of cattle CNVs by SNP arrays. Compared to SNPs, gene-containing CNVRs may help identify genes undergoing artificial selection (such as for milk and meat production) in domesticated animals.
                                Technical Abstract: We performed a systematic analysis of cattle copy number variations (CNVs) using the Bovine HapMap SNP genotyping data, including 539 animals of 21 modern cattle breeds and 6 outgroups. After correcting genomic waves and considering the trio information, we identified 682 candidate CNV regions (CNVRs), which cover 139.8 megabases (~4.60%) of the genome. Selected CNVs were further validated by FISH or qPCR, and we found that duplication CNVs are predominantly tandem clustered repeats rather than interspersed duplications. Approximately 56% of the CNVRs overlap with 1,263 cattle genes, which are significantly enriched for immunity, lactation, reproduction and rumination. We compared this dataset with other published CNVRs datasets and the overlap was usually <40%; while considering large CNVRs with frequency>5%, the overlap increased to 90%, highlighting the differences and commonalities between technical platforms. A cluster analysis based on the copy number distributions of 3,456 polymorphic SNPs from 15 representative breeds indicated that Taurine, Indicine and African breeds were clearly separated, supporting three domesticated origins in Fertile Crescent, Indus Valley and Africa, respectively. The distribution of Taurine breeds also reflected their known historical and geographical origins. In conclusion, we presented a comprehensive genomic and evolutionary analysis of cattle CNVs by SNP arrays.


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