title: A splice site variant in the bovine RNF11 gene compromises growth and regulation of the inflammatory response.
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 the RNF11 c124-2A>G mutation in Belgian Blue Cattle.
authors.affiliation: Unit of Animal Genomics, GIGA-R, Department of Animal Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Sartelet
authors.forename: Tom
authors.initials: T
authors.lastname: Druet
authors.forename: Charles
authors.initials: C
authors.lastname: Michaux
authors.forename: Corinne
authors.initials: C
authors.lastname: Fasquelle
authors.forename: Sarah
authors.initials: S
authors.lastname: Géron
authors.forename: Nico
authors.initials: N
authors.lastname: Tamma
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wouter
authors.initials: W
authors.lastname: Coppieters
authors.forename: Michel
authors.initials: M
authors.lastname: Georges
authors.forename: Carole
authors.initials: C
authors.lastname: Charlier
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002417:Cattle; D004268:DNA-Binding Proteins; D056726:Genetic Association Studies; D006128:Growth / Q000235:genetics / Q000502:physiology; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; C404508:RNF11 protein, human