a splice site variant in the bovine rnf11 gene compromises growth and regulation of the inflammatory response拼接网站牛rnf11基因变体妥协增长和调节炎症反应.pdfVIP

A Splice Site Variant in the Bovine RNF11 Gene Compromises Growth and Regulation of the Inflammatory Response 1 1 2 1 ´ 1 1 Arnaud Sartelet , Tom Druet , Charles Michaux , Corinne Fasquelle , Sarah Geron , Nico Tamma , 1 1 1 1 Zhiyan Zhang , Wouter Coppieters , Michel Georges , Carole Charlier * ` ` 1 Unit of Animal Genomics, GIGA-R and Department of Animal Sciences, Faculty of Veterinary Medicine, University of Liege, Liege, Belgium, 2 Unit of Bioinformatics, ` ` Department of Animal Sciences, Faculty of Veterinary Medicine, University of Liege, Liege, Belgium Abstract We report association mapping of a locus on bovine chromosome 3 that underlies a Mendelian form of stunted growth in Belgian Blue Cattle (BBC). By resequencing positional candidates, we identify the causative c124-2A.G splice variant in intron 1 of the RNF11 gene, for which all affected animals are homozygous. We make the remarkable observation that 26% of healthy Belgian Blue animals carry the corresponding variant. We demonstrate in a prospective study design that approximately one third of homozygous mutants die prematurely with major inflammatory lesions, hence explaining the rarity of growth-stunted animals despite the high frequency of carriers. We provide preliminary evidence that heterozygous advantage for an as of yet unidentified phenotype may have caused a selective sweep accounting for the high frequency of