Description: Brown or chocolate coat color in many mammalian species is frequently due to variants at the B locus or TYRP1 gene. In dogs, five different TYRP1 loss-of-function alleles have been described, which explain the vast majority of brown coat color of dogs. Recently, had been identified mutation caused brown color in French Bulldogs that did not carry any of the known mutant TYRP1 alleles. The revealed mutation is a nonsense variant in HPS3 gene, c.2420G>A, or p.(Trp807). The brown dog was homozygous for the mutant allele at this variant.
The HPS3 gene encodes a protein required for the correct biogenesis of lysosome-related organelles, including melanosomes. 373 French Bulldogs have been genotyped and a strong association of the homozygous mutant HPS3 genotype with the brown coat color has been found. The genotype-phenotype association and the comprehensive knowledge on HPS3 function from other species strongly suggest that HPS3:c.2420G>A is the causative variant for the observed brown coat color in French Bulldogs. In order to clearly distinguish HPS3-related from the TYRP1-related brown coat color, and in line with the murine nomenclature, it has been proposed to designate this dog phenotype as “cocoa”, and the mutant allele as HPS3co.
Inheritance: autosomal recessive
Mutation: c.2420G>A (p.Trp807) in HPS3 gene
Sample: EDTA whole blood (1.0 ml) or 2 buccal brushes
The analysis is suitable for the following breeds: French Bulldog
Notes: There may be other mutations causing this trait. A negative result for this mutation does not rule out the possibility that another, as yet unidentified, mutation or mutations in the genome may lead to similar traits.