In other species: cattle , horse , domestic cat , sheep , pig , golden hamster , North American deer mouse , goat , American mink , rabbit , Mongolian gerbil

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 612271 , 203290

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2002

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the gene corresponding to the brown locus in mice), Schmutz et al. (2002) were the first to sequence the TYRP1 gene in dogs. They identified three likely causal variants, namely "a premature stop codon in exon 5 (Q331ter) [named allele b^s], . . .a [deletion of a] proline residue in exon 5 (345delP) [named allele b^d] . . . [and] A third variant in exon 2 (S41C) [named allele b^c). . . . All 43 of the brown group carried two or more of these sequence variants likely to interfere with TYRP1 function, whereas 0 of 34 in the black group carried two or more of these variants (10 carried one variant)". The authors concluded that "all three [mutations] affect eumelanin production and alter black pigmentation to brown".

Gerding et al. (2011) showed that the typical "grey" coat colour in Weimaraners is due to homozygosity for a non-functional allele (or heterozygosity for different non-functional alleles) at the TYRP1 locus; and that the "blue" coat colour in the same breed is due to the presence of one or two functional alleles at this locus. Thus, "blue" is dominant to "grey". By studying haplotypes, they were also able to show that the funcational allele is not a "reversion" from within the breed.

Letko and Drögemüller (2017) identified alleles b^c and b^d in Leonberger dogs.

Hrckova Turnova et al. (2017) reported a new allele (c.555T>G; p.Tyr185*) in a single pedigree of Australian Shepherd dogs.

Jancuskova et al. (2018) reported the same c.555T>G allele as being more widespread in the Australian Shepherd breed and "also its close relative Miniature American Shepherd".

Breeds: Australian Shepherd, German Shepherd Dog, Leonberger, Miniature American Shepherd.

Associated gene: