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What is the A locus?

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The “A locus” is the name for the DNA sequence that makes up the agouti-signaling protein (ASIP) gene, which is located on chromosome 24 in the dog genome. This gene contains instructions to make a protein (ASIP) that acts as a molecular switch: when ASIP is present, it tells hair cells to produce the red/yellow...

What is the A Locus

The “A locus” is the name for the DNA sequence that makes up the agouti-signaling protein (ASIP) gene, which is located on chromosome 24 in the dog genome.

This gene contains instructions to make a protein (ASIP) that acts as a molecular switch: when ASIP is present, it tells hair cells to produce the red/yellow pigment pheomelanin. When it is not present, cells instead produce the black or brown pigment eumelanin. The ASIP gene makes the ASIP protein in different parts of a dog’s body at different times in its development, resulting in various patterns of light and dark fur. These include:

  • Clear/fawn sable
  • Tipped/shaded sable
  • Wolf sable (AKA agouti)
  • Tan points
  • Recessive black

Clear/fawn sable

rhodesian ridgeback

Tipped/shaded sable

Wolf sable (AKA agouti)

Tan points

Recessive black

german shepherd dog

What are the different A locus alleles?

Alleles are different versions of the same DNA sequence, which sometimes result in different phenotypes (such as coat pattern).

There are 4 well studied ASIP alleles that Embark and other services test for: aw, ay [1], at [2], and a [3]. The aw allele is the “wild type” allele, and produces the wolf sable coat pattern. The ay allele has the same DNA sequence as the aw allele, except for one single base pair mutation referred to as “A82S”. Dogs with one or two ay alleles usually have either the clear/fawn or tipped sable coat pattern. The at allele has the same DNA sequence as the aw allele, except that it has some additional DNA from a SINE insertion mutation. This allele is responsible for the tan point coat pattern. Finally, the a allele has the same SINE insertion present on the at allele plus an additional single base pair mutation referred to as “R96C”. Dogs with two copies of the a allele generally have the recessive black coat pattern.

Note: the E locus and K locus can “mask” the effects of the A locus. For example, most Labrador Retrievers are genetically black and tan at the A locus, but you rarely see black and tan Labradors because almost all Labs are either ee at the E locus (yellow) or KB- at the K locus (black or chocolate).

Here is a diagram showing which mutations are present on each ASIP allele and where in the ASIP gene sequence they are located relative to each other (not to scale):

Learn about the A Locus

How do we determine a dog’s genotype at the A locus?

To determine what ASIP alleles a dog has, we test for the three variants described above as three different ASIP “subloci”. This table shows the possible genotype results and their meaning for each of the three sublocus tests:

Sublocus Test Chart

 

This means that, although every dog has two ASIP alleles (one from each parent), they get three different genotype calls as well as an overall genotype call for the A locus.

How do we predict a dog’s phenotype from its A locus genotype?

The four ASIP alleles typically behave according to a “dominance hierarchy” [2]: the ay allele is generally dominant to the other three, aw is generally dominant to at and a, and at is dominant to a. We can use this hierarchy to predict a dog’s coat pattern phenotype from its A locus genotype. For instance, a dog that has one aw and one at allele will most likely exhibit the wolf sable coat pattern because aw is dominant to at.

However, this hierarchy doesn’t always accurately predict a dog’s phenotype! Recent studies have shown that there are actually more than four A locus alleles in domestic dogs, many of which are combinations of the four common alleles [4, 5]. These “recombinant” alleles arise during meiosis I, when a dog’s DNA is replicated and “shuffled”, and then split up into cells that will become egg or sperm cells.

Recombination can put mutations that don’t normally occur on the same DNA molecule next to each other, resulting in a new allele. For example, if a dog has one copy of the normal ay allele and one copy of the at allele, each of her egg cells can have one of four possible alleles: the normal ay allele, the normal at allele, or one of two recombinant alleles:

Learn about the A locus

Recombinant Allele 1 contains both the ay A82S mutation and the at SINE insertion, and Recombinant Allele 2 contains neither. Based on what is currently known about recombinant ASIP alleles, it is difficult to predict how they will affect dogs’ coat pattern phenotypes. For example, a dog carrying one copy of Recombinant Allele 1 and one copy of the normal at allele might have the fawn sable phenotype if Recombinant Allele 1 works like a normal ay allele, but it could also have the tan point phenotype if Recombinant Allele 1 works like a normal at allele. Or, Recombinant Allele 1 might behave differently from either the normal ay or at allele [5].

Embark and other canine genetics research groups are working to identify new A locus alleles and understand how they affect dogs’ phenotypes. If you have already tested a dog with us, we encourage you to fill out the surveys located in the Research section of your dog’s profile and upload any veterinary reports, photos, or other documents to the Documents section. This information will greatly aid us in learning more about new A locus alleles.

References

  1. Berryere TG, Kerns JA, Barsh GS, Schmutz SM. Association of an Agouti allele with fawn or sable coat color in domestic dogs. Mamm Genome. 2005 Apr;16(4):262-72. doi: 10.1007/s00335-004-2445-6. PMID: 15965787.
  2. Dreger DL, Schmutz SM. A SINE insertion causes the black-and-tan and saddle tan phenotypes in domestic dogs. J Hered. 2011 Sep-Oct;102 Suppl 1:S11-8. doi: 10.1093/jhered/esr042. PMID: 21846741.
  3. Kerns JA, Newton J, Berryere TG, Rubin EM, Cheng JF, Schmutz SM, Barsh GS. Characterization of the dog Agouti gene and a nonagouti mutation in German Shepherd Dogs. Mamm Genome. 2004 Oct;15(10):798-808. doi: 10.1007/s00335-004-2377-1. PMID: 15520882.
  4. Dreger DL, Hooser BN, Hughes AM, Ganesan B, Donner J, Anderson H, Holtvoigt L, Ekenstedt KJ. True Colors: Commercially-acquired morphological genotypes reveal hidden allele variation among dog breeds, informing both trait ancestry and breed potential. PLoS One. 2019 Oct 28;14(10):e0223995. doi: 10.1371/journal.pone.0223995. PMID: 31658272.
  5. Dreger DL, Anderson H, Donner J, Clark JA, Dykstra A, Hughes AM, Ekenstedt KJ. Atypical Genotypes for Canine Agouti Signaling Protein Suggest Novel Chromosomal Rearrangement. Genes (Basel). 2020 Jul 3;11(7):739. doi: 10.3390/genes11070739. PMID: 32635139.

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