Gene or region: ASIP
Reference allele: GAAAAGAAGCA (A)
Mutant allele: -11bp deletion (a)
Affected Breeds: many
Research Confidence: High confidence, findings reproduced in multiple studies
The agouti signaling protein gene (often shortened to agouti or ASIP) controls where black pigment is produced on the horse. In the bay variant (A), black is restricted to the “points,” such as the legs, mane, tail, and ear tips, whereas the rest of the coat produces red/bay pigment. The black allele (E) is restricted or "recessive" to bay (A), and thus a black-based horse needs to inherit two "negative" copies (a/a) of Bay/Agouti to have a uniformly black coat color.
However, bay and black coat colors are a great example of the genetic concept of “epistasis” – that the effect of one gene is dependent on the effect of an independent gene. In this case, since agouti only controls the production of black pigment, it has no visible effect on a horse without black pigment. As a result, red-based horses (chestnut or sorrel and their derivatives) “mask” the presence of agouti. Either knowledge of the parents’ agouti genotypes or genetic testing is necessary to know if a “red” horse can produce black foals.
There are two additional forms of agouti that are thought to exist in horses, though no formal genetic study is available at this time. The first, wild-bay (A+), further restricts black pigment production, limiting black on the legs to around fetlock height. The second, seal brown (At), allows for more black pigment than bay, resulting in a dark brown or black horse with red or tan hairs mostly limited to the muzzle and flanks. Since the genetics are not currently understood, wild bay and seal brown horses genotype A/A or A/a for agouti.
Genotype and Phenotype (Color Names)
Bay (E/_ A/_)
Black (E/_ a/a)
Chestnut (e/e A/_)
Chestnut (e/e a/a)
* Other dilutions, modifiers, and spotting genes can further alter the color of a horse – for simplicity, we have not named all possible combinations!
ASIP acts as an antagonist of the melanocortin-1 receptor (MC1R) by nullifying the actions of melanocyte-stimulating hormone (a-MSH). In horses, the effect of agouti is mainly to change the regional distribution of black pigment, whereas in other species it also controls the temporal production (resulting in individual hairs with alternating bands of black and red pigments). Loss of function mutations result in “self” (entirely black or melanistic) coat colors in a variety of species. The a allele deletion removes a portion of the encoded amino acids, likely resulting in a non-functional protein.
Rieder S et al., “Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus).” (2001) Mamm Genome. 12: 450-5.
More about Agouti