Androgen Insensitivity Syndrome


Sex determination in mammals is dependent on sex chromosome composition, with XX animals being female and XY animals being male. In the absence of the Y-chromosome male determining gene SRY, no androgen is produced in the developing gonad, and the embryo develops as a female. In the presence of the Y-chromosome male determining gene SRY, the developing gonad produces androgen, and the embryo develops as a male. Male development requires a functional androgen receptor on the surface of embryonic cells. Mutations that affect the function of the Androgen Receptor (AR) impair the ability of embryonic cells to initiate male development, transforming chromosomal males (XY) into sterile phenotypic females.

Sterile phenotypic females are obviously unsuitable for breeding, but are otherwise healthy.

Date of Last Update: 04/02/2016


Understanding the Results

Results of the genetic test for Androgen Insensitivity Syndrome are presented as shown below.

Androgen Insensitivity Syndrome
N/N Clear This horse tested negative for AR-M1V.
N/Ar Carrier Both the normal and mutant alleles are present. This horse is positive for the AR-M1V mutation but will not develop symptoms.
Ar/Ar Affected This horse carries two copies of the AR-M1V mutation. Genetic males (XY) will be transformed into sterile phenotypic females. Genetic females (XX) will not be affected.


Disease Name and Genes

Androgen Insensitivity Syndrome is the cause of a Disorder of Sexual Development (DSD) in 64, XY, SRY-positive phenotypic females. Androgen Insensitivity Syndrome is associated with an A to G substitution in the Androgen Receptor (AR) gene that causes a Methionine (M) to Valine (V) substitution in the first codon of the gene (AR-M1V). The substitution of the GTG (V) codon for the ATG (M) codon eliminates the normal start codon for this gene, resulting in a lower level of expression of the Androgen Receptor protein.


Androgen Insensitivity Syndrome is inherited as a recessive disorder. It is caused by a recessive variant of the androgen receptor gene (AR-M1V). The recessive allele is abbreviated here as Ar, with the dominant wild-type allele abbreviated as N.


Carriers of the recessive allele (N/Ar) have no symptoms of the disease. If two carriers are bred, each foal has a 25% chance of having two copies of the normal allele (N/N), a 50% chance of being a carrier (N/Ar), and a 25% chance of potentially being affected (Ar/Ar). Only males are affected: although XY, they will appear as 64, XY, SRY-positive phenotypic females that are sterile.


If a carrier of the recessive allele (N/Ar) is bred to a normal horse (N/N), each foal has a 50% chance of having two copies of the normal allele (N/N) and a 50% chance of being a carrier (N/Ar).