A splice site variant in the bovine rnf11 gene compromises growth and regulation of the inflammatory response

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. © 2012 sartelet et al.