The genetic basis of coat colour in the Labrador Retriever has been found to depend on several distinct genes. The interplay among these genes is used as an example of epistasis.
Background
Labrador Retrievers are a popular dog breed in many countries. There are three recognised colours, black, chocolate, and yellow, that result from the interplay among genes that direct production and expression of two pigments, eumelanin (brown or black pigment) and pheomelanin (yellow to red pigment), in the fur and skin of the dog. The recognized colours are due to two genes, while a third gene affects the range of colouration observed within the yellow Labrador. These individual genes do not act independently of each other, and their interaction in affecting the trait of coat colour is used by biology textbooks to demonstrate the genetic principle of epistasis, where multiple genes react synergistically to affect a single trait.
The genetics of mammalian colouration has been studied in detail, and similar mechanisms have been identified across many species. For this reason, much of the early work on the colouration of dogs in general and Labradors in particular have relied heavily on analogy to the traits characterized in mice and other mammals. Initial genetic studies of coat colour in dogs published in the 1950s concluded that there were two main genes involved, one distinguishing blacks from browns, and the other distinguishing blacks from reds and yellows. A 1977 study using crosses within a population of purebred Labradors showed the involvement of two specific genes in production of the three main coat colours of Labradors and described the underlying genetics of these colour varieties.
Genes for black, chocolate, and yellow colouration
Pheomelanin in yellow Labradors
According to Candille, et al. (2007), dog coat color can largely be explained by three genes: MC1R, Agouti and CBD103. When a dog has wild-type alleles at all three genes, it will have a yellow coat. When the dog has a loss-of-function allele at MC1R, it will have a yellow coat regardless of the genes it carries on the other two genes. Only a dominant black allele at CBD103 will produce a black coat color in dogs possessing wild-type alleles at MC1R and Agouti.
The E locus also determines whether the phenotype due to the third genetic locus affecting coat colour will be evident. This locus is recognised as affecting coat colour through the expression of pheomelanin, the pigment responsible for red and yellow pigmentation. The effects on pheomelanin pigmentation are only seen if there is no eumelanin expressed in the fur, else the dark eumelanin will mask any pheomelanin present. Thus these differences are visible only in yellow Labradors, which as a result range in colour from light cream to copper-red.
It had long been thought that the genetic locus for this trait was the same seen regulating pheomelanin in other mammals, subsequently identified as tyrosinase. This enzyme makes both eumelanin and pheomelanin, and when subject to a knockout mutation results in albinism. A less extreme mutation of the same tyrosinase gene, the so-called Chinchilla trait, produces a dilution that selectively affects pheomelanin alone, similar to the phenotype observed in yellow Labradors. Thus, as with Chinchilla-related pheomelanin dilution in other species, this trait in yellow Labradors has been represented by the letter C. However, genetic analysis of the inheritance of coat colour in yellow Labradors has shown that the locus responsible is entirely distinct from the Chinchilla trait of the tyrosinase gene, and likewise is distinct from SLC45A2, the so-called cream gene responsible for the dilution of pheomelanin in buckskin, palomino and cremello horses and also for the absence of pheomelanin in the white tiger, while a mutation in SLC7A11 found to cause pheomelanin dilution in mice was not found in a survey of cream-coloured dogs.