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Title:   Author  item
                                            Cole, Johnitem
                                            Hutchison, Janaitem
                                            Null, Danielitem
                                            Vanraden, Paulitem
                                            Liu, Ge

                                                         - *George*item
                                            Schroeder, Steven

                                                         - *Steve*item
                                            Sonstegard, Taditem
                                            Van Tassell, Curtis

                                                         - *Curt*item
                                            Bickhart, Derek
  Submitted to: Plant and Animal Genome Conference Proceedings
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 1/10/2014
                                    Publication  Date: 1/10/2014
                                    Citation: Cole, J.B., Hutchison, J.L., Null, D.J., Van Raden, P.M., Liu, G., Schroeder, S.G., Sonstegard, T.S., Van Tassell, C.P., Bickhart, D.M. 2014. Candidate causative mutation on BTA18 associated with calving and conformation traits in Holstein bulls. Plant and Animal Genome Conference Proceedings. Plant Animal Genome XXII, San Diego, CA, Jan. 11–15, P1097.Interpretive Summary:
                                Technical Abstract: Complementing quantitative methods with sequence data analysis is a major goal of the post-genome era of biology. In this study, we analyzed Illumina HiSeq sequence data derived from 11 US Holstein bulls in order to identify putative causal mutations associated with calving and conformation traits. Originally, SNP marker ARS-BFGL-NGS-109285 at 57,589,121 (UMD3.1 assembly) on BTA18 was identified with large predicted effects on 4 measures of body shape and size, 2 measures of dystocia, longevity, and lifetime economic merit using a genomic scan of 38,416 SNP scored in 5,360 Holstein bulls. This region of the bovine genome shares significant sequence similarity with the human Sialic acid Ig-like Lectin 6 (Siglec-6) gene. Using a pedigree-based sample selection method, we sequenced a homozygote for the allele, 4 carriers, and 3 non-carrier bulls from the same family. We sequenced 3 additional, unrelated, carrier bulls to provide confirmation for any putative causal variant outside of the initially selected family. All bulls were sequenced to 20X coverage on the Illumina HiSeq2000. Tandem duplications, insertions and deletions were detected using custom analysis software that makes use of paired-end read alignments and split-read mapping. One duplication CNV and two different tandem duplication events were detected within the gene. Predicted tandem duplications present in the carrier animals suggest that the portions of two exons and a connecting intron within the Ig-like protein domains of the Siglec-6 gene may have been duplicated. This study demonstrates that sequence data analysis can be used to generate novel hypotheses from quantitative studies.


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