Labrador Retriever coat colour genetics

Colour variation within yellow Labradors due to differences in pheomelanin expression.

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.[8]

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.[3] 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,[9] 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,[10] while a mutation in SLC7A11 found to cause pheomelanin dilution in mice was not found in a survey of cream-coloured dogs.[11]

Labradors showing eumelaninistic colour phenotypes: Black (BB,Bb) and chocolate (bb).

The three recognised colours of Labrador Retrievers result from differences in two genetic loci that affect pigment expression. Those affecting the colour of the dark pigment, eumelanin, are referred to as the B (brown) locus. The variation displayed by this locus is observed in many mammals, reflecting a so-called 'dilution', a lightening, of black eumelanin to a brown colour. Initial genetic research excluded a role for the melanocortin 1 receptor and the Agouti locus as being the cause of the black dilution trait in dogs.[12] Instead, TYRP1 (tyrosinase related protein 1) was found to be responsible.[6] This enzyme is localised to melanosomes, the cellular organelles that produce and store pigments, and serves to catalyze oxidation of eumelanin precursors.[3]

In dogs, three mutations in the TYRP1 gene have been identified, one resulting in a truncation of the protein, the other two leading to an amino acid deletion or a single amino acid substitution in the sequence of the protein. All of these mutations are found across the range of dogs, and hence are thought to have preceded the divergence of distinct breeds, and all three are found within Labrador Retrievers.[6] Each of the mutations appears to eliminate or significantly reduce enzymatic activity, and the colouration phenotypes (the visible traits) produced by the three mutations are indistinguishable.[3]

These represent recessive mutations in the TYRP1 gene, and since mammals have two copies of each gene, one from each parent, an animal with at least one copy of the fully functioning TYRP1 protein (represented as 'B') will display the dominant trait, black pigmentation, while to display brown pigmentation, both copies of this gene must be mutant alleles (collectively represented as 'b'). Thus a dog with the genotypes BB or Bb will express black eumelanin, while brown eumelanin will be seen in dogs with the bb genotype.[1]

Yellow Labrador with a Black Labrador. Gain-of-function alleles at various genetic loci will cause either the dominant inheritance of a yellow coat and the dominant inheritance of a black coat.[8][Note 1]

A second gene affects whether these eumelanin pigments will be expressed in the fur or solely in the skin. Called the 'extension' (E) trait, this is directed by the melanocortin 1 receptor (MC1R). This receptor signals the pigment-producing cell in response to melanocortins and results in deposition of eumelanin into the hair. Mutations in this protein have been shown to be involved in pale or red colour phenotypes in a range of species, including humans, horses, pigs, cattle, mice, fur seals, mammoths and the Kermode bear, as well as colouration in whiptail lizards.[13]

In most dogs, activity of MC1R is modulated by two signaling molecules, a repressor that is a product of the Agouti gene (A locus), and an activator, β-Defensin 103 (CBD103), recently named the K locus. In Labradors a highly-active mutated version of the K gene, (K^B) is invariant, producing uniform eumelanin distribution independent of the Agouti genotype and leaving differences in MC1R to mediate the sole variability of this signaling pathway.[14][8][15]

A recessive mutation in this E gene truncates the protein, producing a non-functional receptor incapable of directing eumelanin deposition in the fur.[16] Among dogs, this mutation is unique to yellow Labrador Retrievers and Golden Retrievers and is thought to have arisen in the retriever population before these individual breeds became distinct. The exact mutation has also been found to underlie the colouration of white coyotes found around Newfoundland, having apparently passed into that population through interbreeding with a Golden Retriever.[17]

A variant of the functional MC1R allele that produces a facial 'mask' in other breeds of dogs (E^m) is also present in Labradors, but since the colour of the mask is determined by the B locus, in Labradors the mask this gene produces is indistinguishable from the overall coat colour.[18]

The interplay between these two genes determines the colour of a Labrador Retriever, and is widely used as an example of epistasis. If a dog possesses the dominant phenotype for the extension allele (genotype EE or Ee), then it will display the fur colouration determined by its brown locus genotype, while a dog with the recessive extension trait (ee) will have a yellow coat with either black (BB, Bb) or brown (bb) exposed skin. This results in the three coat colours seen:

Yellow Labradors with black (top) and brown skin colouration, as seen in the exposed areas of the noses, lips and lining of the eyes.

• Black Labradors can have any genotype with at least one dominant allele at both the B and E loci: BBEE, BBEe, BbEE, or BbEe.
• Chocolate Labradors will have a genotype with at least one dominant E allele, but must have only recessive b alleles: bbEE and bbEe.
• Yellow Labradors with black skin pigment will have a dominant B allele but must have recessive e alleles: BBee or Bbee.
• Yellow Labradors with pale or chocolate pigment, or an absence of skin pigment, can have only recessive alleles at both loci: bbee. These dogs are often referred to as Dudleys, and are disqualified in the showring, although are eligible for registration under current standards.[1] Aging-related declines in eumelanin production can cause the exposed skin in a Labrador with black skin pigmentation begin to appear lighter, but Dudley dogs have this colouration throughout their lives.

These genes assort independently, so a single genetic cross involving two black Labradors each with a recessive allele at both the B and the E locus (BbEe) has the potential of producing all of the possible colour combinations, while crosses involving chocolate dogs can never produce black (there being no dominant B allele in either parent) but can give rise to yellow. Yellow Labradors will breed true with regard to fur colour but those with black skin can potentially produce a Dudley. Dudleys breed true for both fur and skin. The ability of the E locus to override the coat colour directed by the B locus is a classical example of epistasis, where multiple genetic loci affect the same observed trait.[2]

In a study of Labrador retrievers in the United Kingdom, it was found that chocolate labradors had a shorter average lifespan than either black or yellow labradors. They were also found to suffer from more skin and ear disorders. It is unknown whether this is a direct consequence of their melanin genotype, or is due to other recessive genes, amplified through the inbreeding used to propagate the chocolate phenotype.[19]