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.
Sartelet, A., Druet, T., Michaux, C., Fasquelle, C., Géron, S., Tamma, N., … Charlier, C. (2012). A splice site variant in the bovine rnf11 gene compromises growth and regulation of the inflammatory response. PLoS Genetics, 8(3). https://doi.org/10.1371/journal.pgen.1002581