Agouti

For a long time this gene was quite a mystery regarding the mechanism and the alleles. The Agouti SIgnal Peptide (ASIP) is an antagonist of the MC1R receptor. This receptor influences the switch in melanocytes from producing eumelanin (black/brown) to pheomelanin (yellow). We already know this receptor from the E-locus.

The expression of this gene (and thus the production of ASIP) is controlled by two promotors. Promotors are areas in the DNA to which the enzymes that transcribe the gene bind and then initiate the production of mRNA. The mRNA will be used to produce the protein.

The alleles for the A locus are caused by several mutations of those two promotors. One promotor influences the switch between yellow and black (or brown) roughly between the belly and the back. This one is called the Ventral Promotor (VP) and there are two variants, VP1 and VP2. VP1 differs from VP2 that it contains a SINE and at a different point some base pairs have been inserted. This results in increased expression levels of ASIP with VP1.

The second promotor influences the switch in time during the life cycle of the hair. This causes a banding pattern on individual hairs and is called the Hair Cycle Promotor (HCP). There are five variants, HCP1, HCP2, HCP3, HCP4 and HCP5. These variants have different (SINE) insertions, deletions and short insertions at various points. The expression levels of ASIP are highest with HCP1 and lowest with HCP3,4,5.

Phenotypes and genotypes

The Ventral Promotor and the Hair Cycle Promotor work rather independently. Together they produce six different phenotypes:

Dominant yellow

VP1-HCP1 (combined with VP1,2-HCP1,3,4,5).
Only pheomelanin is produced and the coat is entirely yellow/red.
Will be reported as ASIP^DY.

Shaded yellow

VP2-HCP1 (combined with VP2-HCP1,3,5).
Tips of individual hairs are dark (eumelanin) and the base is colored by pheomelanin.
Will be reported as ASIP^SY.

Agouti

VP2-HCP2 (combined with VP2-HCP2,3,5).
The individual hairs have bands of eumelanin and pheomelanin.
Will be reported as ASIP^AG.

Black saddle

VP1-HCP4 (combined with VP1,2-HCP3,4).
Head and legs are yellow/red and on the back is a saddle-shaped dark (eumelanin) area.
Will be reported as ASIP^BS.

Black back

VP2-HCP3,4,5 (combined with VP2-HCP3,4,5).
Most of the coat is dark (eumelanin) and there are specific areas with pheomelanin (end of the legs, inside of knees, lower part of head, throat, eye browes)
Will be reported as ASIP^BB1, ASIP^BB2 and ASIP^BB3 (for HPC3, HPC4 and HPC5 respectively)

Recessive black

A single nucleotide modification, mostly seen on a VP2-HPC3 base.
Only eumelanin is produced.
Will be reported as ASIP^a.