OMIA 000991-9796 : Androgen insensitivity syndrome (AIS) in Equus caballus

In other species: domestic cat , cattle , dog , pig

Possibly relevant human trait(s) and/or gene(s) (MIM number): 300068

Mendelian trait/disorder: yes

Mode of inheritance: X-linked recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

Cross-species summary: Previously known as Testicular Feminisation Syndrome. Following the recommendations on nomenclature for disorders of sexual development (DSD) proposed by Lee et al. (Pediatrics 2006;118;e488; DOI: 10.1542/peds.2006-0738), this disorder is now classified as a type of XY DSD. This is an abnormality of sexual development in which affected individuals have an XY chromosomal constitution, undescended testes and female secondary sexual characteristics (including female external genitalia). Also, instead of normally developed Mullerian duct derivatives (Fallopian tubes, uterus, cervix, and upper protion of the vagina), they have under-developed Wolffian duct derivatives (epididymis, vas deferens, and seminal vesicle). In all species so far investigated, the inheritance is X-linked recessive. In humans and mice, this disorder is known to be due to a deficiency of an androgen receptor encoded by a gene on the X chromosome. The presence of a Y chromosome induces the undifferentiated embryonic gonads to develop as testes, but, in the absence of androgen receptor, the androgens produced by the testes cannot exert any effect. The result is that the embryo follows the "default" path of development, which is female.

Species-specific symbol: AIS

Molecular basis: Révay et al. (2012) reported that this disorder in a family of American Quarter Horses is due to "a transition in the first nucleotide of the [androgen receptor] AR start codon (c.1A>G)", with the result that "a reduced amount of the functional AR is expressed during androgen-critical periods of development in the XY genetic male embryo, which alters its gonadal development and results in the observed phenotype". This is the first report of a mutation in the AR gene in domestic animals.

In a "Warmblood horse pedigree segregating AIS", Welsford et al. (2017) "provided evidences that a 25-bp deletion of the DNA-binding domain [of the AR gene] is causative" in this breed.

Breeds: American Quarter Horse, Warmblood.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
AR androgen receptor Equus caballus X NC_009175.3 (52728703..52884282) AR Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Warmblood Androgen insensitivity syndrome AR deletion, gross (>20) "a 25-bp deletion of the DNA-binding domain [of the AR gene]" 2017 28192783
Quarter Horse Androgen insensitivity syndrome (AIS) AR regulatory c.1A>G mutation in start codon 2012 22095250
Thoroughbred Androgen insensitivity syndrome AR missense c.2042G>C 2016 27073903

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2017 Welsford, G.E., Munk, R., Villagómez, D.A., Hyttel, P., King, W.A., Revay, T. :
Androgen Insensitivity Syndrome in a Family of Warmblood Horses Caused by a 25-bp Deletion of the DNA-Binding Domain of the Androgen Receptor Gene. Sex Dev 11:40-45, 2017. Pubmed reference: 28192783. DOI: 10.1159/000455114.
2016 Bolzon, C., Joonè, C.J., Schulman, M.L., Harper, C.K., Villagómez, D.A., King, W.A., Révay, T. :
Missense Mutation in the Ligand-Binding Domain of the Horse Androgen Receptor Gene in a Thoroughbred Family with Inherited 64,XY (SRY+) Disorder of Sex Development. Sex Dev 10:37-44, 2016. Pubmed reference: 27073903. DOI: 10.1159/000444991.
2012 Pujar, S., Meyers-Wallen, V. :
Sequence Variations in Equine Candidate Genes For XX and XY Inherited Disorders of Sexual Development. Reprod Domest Anim :, 2012. Pubmed reference: 22239239. DOI: 10.1111/j.1439-0531.2011.01976.x.
Révay, T., Villagómez, D.A., Brewer, D., Chenier, T., King, W.A. :
GTG mutation in the start codon of the androgen receptor gene in a family of horses with 64,XY disorder of sex development. Sex Dev 6:108-16, 2012. Pubmed reference: 22095250. DOI: 10.1159/000334049.
2011 Villagómez, D.A., Lear, T.L., Chenier, T., Lee, S., McGee, R.B., Cahill, J., Foster, R.A., Reyes, E., St John, E., King, W.A. :
Equine disorders of sexual development in 17 mares including XX, SRY-negative, XY, SRY-negative and XY, SRY-positive genotypes. Sex Dev 5:16-25, 2011. Pubmed reference: 21196712. DOI: 10.1159/000322811.
2005 Switonski, M., Chmurzynska, A., Szczerbal, I., Lipczynski, A., Yang, F., Nowicka-Posluszna, A. :
Sex reversal syndrome (64,XY; SRY-positive) in a mare demonstrating masculine behaviour. J Anim Breed Genet 122 Suppl 1:60-3, 2005. Pubmed reference: 16130458.
2004 Howden, K.J. :
Androgen insensitivity syndrome in a thoroughbred mare (64, XY--testicular feminization). Can Vet J 45:501-3, 2004. Pubmed reference: 15283519.
1992 Crabbe, B.G., Freeman, D.A., Grant, B.D., Kennedy, P., Whitlatch, L., Macrae, K. :
Testicular Feminization Syndrome in a Mare Journal of the American Veterinary Medical Association 200:1689-1691, 1992. Pubmed reference: 1624347.
1986 Enbergs, H., Schulte-Beckhausen, W. :
[Sex chromosome anomalies in mares and cytogenetic investigations on mares with severe fertility disturbances] Zuchthygiene 21:105-114, 1986.
1976 Kieffer, N.M. :
Male pseudohermaphroditism of the testicular feminizing type in a horse. Equine Vet J 8:38-41, 1976. Pubmed reference: 943286.

Edit History


  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 04 Jul 2012
  • Changed by Frank Nicholas on 06 Aug 2017