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Title:   Author  item
                                            Bickhart, Derekitem
                                            HOU, YALI - University Of Marylanditem
                                            Schroeder, Steven

                                                         - *Steve*item
                                            ALKAN, CAN - University Of Washington Medical Schoolitem
                                            CARDONE, MARIA FRANCESCA - University Of Bariitem
                                            MATUKUMALLI, LAKSHMI - Sao Paulo State University (UNESP)item
                                            SONG, JIUZHOU - University Of Marylanditem
                                            SCHNABEL, ROBERT - University Of Missouriitem
                                            VENTURA, MARIO - University Of Bariitem
                                            TAYLOR, JEREMY - University Of Missouriitem
                                            GARCIA, JOSE FERNANDO - Sao Paulo State University (UNESP)item
                                            Van Tassell, Curtis

                                                         - *Curt*item
                                            Sonstegard, Taditem
                                            EICHLER, EVAN - University Of Washington Medical Schoolitem
                                            Liu, Ge

                                                         - *George*
  Submitted to: Plant and Animal Genome Conference
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 11/2/2011
                                    Publication  Date: 1/14/2012
                                    Citation: Bickhart, D.M., Hou, Y., Schroeder, S.G., Alkan, C., Cardone, M., Matukumalli, L.K., Song, J., Schnabel, R.D., Ventura, M., Taylor, J.F., Garcia, J., Van Tassell, C.P., Sonstegard, T.S., Eichler, E.E., Liu, G. 2012. Copy number variation of individual cattle genomes using next-generation sequencing. Plant and Animal Genome Conference. p. 549.Interpretive Summary:
                                Technical Abstract: Copy number variations (CNVs) affect a wide range of phenotypic traits; however, CNVs in or near segmental duplication regions are often intractable. Using a read depth approach based on next-generation sequencing, we examined genome-wide copy number differences among five taurine (three Angus, one Holstein and one Hereford) and one indicine (Nelore) cattle. Within mapped chromosomal sequence, we identified 1,265 CNVRs comprising ~55.6 Mbp sequence—476 of which (~38%) have not previously been reported. We validated this sequence-based CNV call set with aCGH, qPCR and FISH, achieving a validation rate of 82% and a false positive rate of 8%. We further estimated absolute copy numbers for genomic segments and annotated genes in each individual. Surveys of the top 25 most variable genes revealed that the Nelore individual had the lowest copy numbers in 13 cases (~52%, chi squared test; p value <0.05). In contrast, genes related to pathogen- and parasite-resistance such as CATHL4 and ULBP17, were highly duplicated in the Nelore individual relative to the taurine cattle, while genes involved in lipid transport and metabolism, including APOL3 and FABP2, were highly duplicated in the beef breeds. These CNVRs also harbor genes like BSP30A and WC1, suggesting that some CNVs may be associated with breed-specific differences in adaptation, health, and production traits. By providing the first individualized cattle CNV and segmental duplication maps and genome-wide gene copy number estimates, we enable future CNV studies into highly duplicated regions in the cattle genome.


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