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Title:   Author  item
                                            Liu, Ge

                                                         - *George*item
                                            Brown, Twainitem
                                            Hebert, Deborah

                                                         - *Van Hook*item
                                            CARDONE, MARIA - University Of Bariitem
                                            HOU, YALI - University Of Marylanditem
                                            CHOUDHARY, RATAN - University Of Marylanditem
                                            Shaffer, Jessicaitem
                                            AMAZU, CHINWENDU - Eleanor Roosevelt High Schoolitem
                                            Connor, Erinitem
                                            VENTURA, MARIO - University Of Bariitem
                                            GASBARRE, LOUIS - Retired ARS Employee
  Submitted to: Mammalian Genome
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 11/11/2010
                                    Publication  Date: 12/3/2010
                                    Citation: Liu, G., Brown, T.E., Hebert, D.A., Cardone, M.F., Hou, Y., Choudhary, R.K., Shaffer, J.F., Amazu, C., Connor, E.E., Ventura, M., Gasbarre, L.C. 2010. Initial analysis of copy number variations in cattle selected for resistance or susceptibility to intestinal nematodes. Mammalian Genome. 22:111-121.Interpretive Summary: In this study, we employed an integrated approach combining array CGH screens, PCR confirmations and FISH verifications to study the CNVs associated with parasite resistance. We describe an initial genome-wide analysis of CNVs in the 2 Angus populations selected for selected for either resistance or susceptibility to intestinal nematodes. We identified 25 CNVRs covering about 3.8 mega bases. Selected CNVs were further validated by independent methods using quantitative PCR and FISH. Pathway analyses indicated that annotated cattle genes within these variable regions are particularly enriched for immune function by regulating receptor activities, signal transduction, and transcription. Analysis of TFBS within the promoter regions of differentially-expressed genes suggested that common transcription factors are probably involved in parasite resistance. Results of this study provide valuable hypotheses for the future study of cattle CNVs underling economically-important health and production traits. This work is an important first step for studying the functional impacts of CNVs. It provides the foundation for correlating structural variation in the genome with the genetic basis of host responses.
                                Technical Abstract: Genomic structural variation is an important and abundant source of genetic and phenotypic variation. We report an initial analysis of copy number variations (CNVs) in cattle selected for resistance or susceptibility to intestinal nematodes. We performed 4 array comparative genomic hybridization (CGH) experiments to compare 6 Angus cattle with extreme phenotypes for fecal egg count and serum pepsinogen level. We identified 25 candidate CNVs in total, of which 13 were within known chromosomes harboring or adjacent to gains or losses. Over 90% of the CNV identified (23/25) overlapped with cattle CNV regions that were reported recently. Selected CNVs were further validated by independent methods using quantitative PCR (qPCR) and FISH. Pathway analysis indicated that annotated cattle genes within these variable regions are particularly enriched for immune function by regulating receptor activities, signal transduction, and transcription. Analysis of TFBS within the promoter regions of differentially-expressed genes suggested that common transcription factors are probably involved in parasite resistance. These results provide valuable hypotheses for the future study of cattle CNVs underling economically-important health and production traits.


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