E Locus - e^A (Ancient Red, Spitz and Scent Hound Type)

Testing Summary

The e^A Locus (Ancient Red) coat color test reliably determines if a dog has one of the following genotypes:

Detailed Summary

The two major pigments that impact canine coat color are eumelanin (black pigment) and pheomelanin (yellow/red pigment). These pigments are produced within specialized cells called melanocytes located in the canine epidermis and hair follicles. The MC1R gene, also known as the extension E Locus, controls the production of eumelanin in the melanocytes. The dominant wild-type form of the MC1R gene (E) allows for normal production of eumelanin in the melanocytes. However, DNA variants in the MC1R gene can prevent production of eumelanin in the melanocytes leaving only the production of pheomelanin. Variants of MC1R follow the following order of dominance: E^m (melanistic mask) > E^g (grizzle/domino) > E (wild-type) > e^A (ancient red) > e^1-3 (recessive apricot/yellow/red, cream, white). Paw Print Genetics offers genetic testing for each of these variants and explanations for each are available under their respective tests. The ancient red Allele (e^A) can impact the coat color of dogs in different ways depending on the breed and the K (dominant black) and A (agouti) locus genotypes of the dog.

First, when a dog is k^y/k^y at the K locus (which allows for agouti expression), the ancient red allele can alter the agouti patterning, typically by increasing the amount of pheomelanin (yellow/red pigment) and reducing the amount of eumelanin (black pigment) that is expressed in the coat. Dogs that are k^y/k^y at the K locus and have an ancient red genotype (e^A/e^A or e^A/e) show an increase in agouti expression that varies depending on the breed and the A locus genotype. Dogs that have an ancient red genotype (e^A/e^A or e^A/e) and are also fawn with minimal to no eumelanin expression at the A locus (A^y), have coats that appear similar to recessive apricot/yellow/red, cream, or white (e^1-3/e^1-3). For example, in breeds like the Berger d’Auvergne where A^y typically produces a fawn colored coat with minimal eumelanin, the coat becomes almost cream in dogs with an ancient red genotype. Alternatively, dogs like the Finnish Lapphund that have an ancient red genotype and are also heavily shaded sable/fawn with some eumelanin expression at the A locus (A^y), have coats that appear to have a "domino" pattern with greater pheomelanin expression around the muzzle, eyes, and body. Likewise, dogs that have an ancient red genotype and are wolf sable at the A locus (a^w) can also have a "domino" pattern that is often found in Alaskan Malamutes and Siberian Huskies. Dogs that have an ancient red genotype and are tan pointed at the A locus (a^t) can show an increase in the size of the tan points or have more "tan" (pheomelanin) interspersed with the dark (eumelanin) hairs. This is referred to as "grizzle" in Chihuahuas or "pied" in Beagles. Lastly, dogs that have an ancient red genotype and are recessive black at the A locus (a/a), can express some pheomelanin similar to domino, wolf sable, or tan points depending on the breed.

Second, when a dog is dominant black (K^B/K^B or K^B/k^y) at the K locus (which typically blocks agouti expression), the ancient red allele can bypass the K locus block and allow agouti (A locus) expression (i.e., sable/fawn, wolf sable, or tan points). Thus, dogs with one or two copies of the ancient red allele (e^A/e^A or e^A/e) will show some amount of the agouti patterning (depending on the A locus genotype) even if they are K^B/K^B or K^B/k^y (dominant black) at the K locus. Ancient red may, therefore, account for what is sometimes referred to as a "leaky K allele" when a dog displays some atypical agouti patterning even in the presence of one or two copies of K^B (dominant black).

Testing Tips

The e^A Locus (Ancient Red) coat color test evaluates the MC1R gene to determine the e^A locus genotype for the dog. Because variants of MC1R exhibit the following order of dominance: E^m (melanistic mask) > E^g (grizzle/domino) > E (wild-type) > e^A (ancient red) > e^1-3 (recessive apricot/yellow/red, cream, white), additional testing for other E locus alleles (as well as the K and A loci) may be necessary to determine the final genotype and expected coat color of the dog. The ancient red Mutation highlights the interactions that occur between all of the color loci to influence the final coat color and pattern of a dog. Dogs with coat colors that do not match what is typically expected for the breed with their specific K and A locus genotypes could be checked for ancient red. Normal results do not exclude inherited mutations not tested in these or other genes that may also contribute to coat colors and traits in dogs. Reliable genetic testing is important for determining breeding practices.

There may be other causes of this condition in dogs and a normal result does not exclude a different mutation in this gene or any other gene that may result in a similar genetic disease or trait.

References

• Anderson H, Honkanen L, Ruotanen P, Mathlin J, Donner J. Comprehensive genetic testing combined with citizen science reveals a recently characterized ancient MC1R mutation associated with partial recessive red phenotypes in dog. Canine Med Genet. 2020 Nov 5;7(1):16. [PubMed: 33292722]