A premature stop codon in the TYRP 1 gene is associated with brown coat colour in the European rabbit ( Oryctolagus cuniculus )

Summary Classical genetic studies in E uropean rabbits ( O ryctolagus cuniculus ) suggested the presence of two alleles at the brown coat colour locus: a wild‐type B allele that gives dense black pigment throughout the coat and a recessive b allele that in the homozygous condition ( b / b genotype) produces brown rabbits that are unable to develop black pigmentation. In several other species, this locus is determined by mutations in the tyrosinase‐related protein 1 ( TYRP 1 ) gene, encoding a melanocyte enzyme needed for the production of dark eumelanin. In this study, we investigated the rabbit TYRP 1 gene as a strong candidate for the rabbit brown coat colour locus. A total of 3846 bp of the TYRP 1 gene were sequenced in eight rabbits of different breeds and identified 23 single nucleotide polymorphisms ( SNP s; 12 in intronic regions, five in exons and six in the 3′‐untranslated region) and an insertion/deletion of 13 bp, in the 3′‐untranslated region, organised in a few haplotypes. A mutation in exon 2 (g.41360196G>A) leads to a premature stop codon at position 190 of the deduced amino acid sequence (p.Trp190ter). Therefore, translation predicts a truncated TYRP 1 protein lacking almost completely the tyrosinase domain. Genotyping 203 rabbits of 32 different breeds identified this mutation only in brown Havana rabbits. Its potential functional relevance in disrupting the TYRP 1 protein and its presence only in brown animals strongly argue for this non‐sense mutation being a causative mutation for the recessive b allele at the brown locus in O ryctolagus cuniculus .