There are several known variants that result in the brown phenotype in dogs. All are in tyrosinase related protein 1 (TYRP1). However, these known variants do not account for all brown phenotypes in dogs. The cocoa variant is in another gene and is therefore not another allele of TYRP1. This has important implications for breeding as in some instances the alleles at both genes would need to be considered during mate selection. Specifically, in French Bulldogs, a variant associated with a visually distinct chocolate phenotype was identified in the Hermansky-Pudlak syndrome 3 (HPS3) gene. Dogs with the HPS3 gene variant are visibly darker brown than the phenotypes associated with the previously described TYRP1 brown allele (b).
The canine cocoa variant is a single base change in the HPS3 gene. The single nucleotide change (c.2420G>A) causes a premature protein stop codon in the gene product (p.Trp807*). This results in a loss of nearly 19% of the end of the protein. In humans and mice, changes within this gene have pleiotropic effects, meaning additional effects of the variant are observed beyond a hair/skin pigmentation difference. In humans and mice, additional symptoms include: vision impairment, nystagmus (uncontrolled eye movement), abnormal eye pigmentation, and bleeding due to platelet dysfunction. These additional effects have not been reported in dogs homozygous for the cocoa variant. Therefore, it is unknown if the cocoa variant (co) has pleiotropic effects in dogs.
The variant associated with the cocoa phenotype is inherited in an autosomal recessive fashion. Thus, two copies must be present for the phenotype to be observed and both sexes are affected equally. Data suggest one copy of cocoa (carrier) and one copy of any of the previously described gene variant (carrier) for brown will not result in a brown phenotype. Dogs with two copies of the cocoa variant may be cocoa, however the final phenotype of the dog is dependent on the alleles at other coat color loci.
At this time the interaction of cocoa and the other brown allele is not understood. Therefore, it is not yet possible to predict the phenotype of a dog with two copies of cocoa (co) and two copies of the TYRP1 brown (b).
At this time, it is also unknown if the cocoa variant is found in other dog breeds.
Note: This test is specific for the autosomal recessive variant causing cocoa in French Bulldogs and is distinct from the other known variants resulting in a brown phenotype.