OMIA 001688-9796 : Coat colour, white spotting, PAX3-related in Equus caballus

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 193500 , 148820

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Semi-Dominant

Considered a defect: unknown

Key variant known: yes

Year key variant first reported: 2012

Cross-species summary: Variable degree of white spotting ranging from tiny white spots up to completely white animals. The absence of pigment is caused by the absence of skin melanocytes ("leucism"), not by failure in the biochemical reactions required for pigment synthesis.

Species-specific name: splashed white

Species-specific description: Currently (in 2016), the horse is among domesticated animals the species with the highest number of known genetic variants that lead to white spotting phenotypes. Related coat colour phenotypes are caused by variants in the EDNRB, KIT, MITF, PAX3 and TRPM1 genes. Combinations of multiple variants in these gene can lead to more pronounced coat colour phenotypes. The splashed white phenotype may be caused by variants in the PAX3 gene as outlined below. However, by far the most common causative varaint for the splashed white phenotype is a non-coding regulatory promoter variant in the MITF gene.

History: Hauswirth et al. (2012) reported the first functional variant in the equine PAX3 gene.

Inheritance: The mode of inheritance depends on the specific variant and there are interactions with other genes. Animals with the typical splashed white phenotype normally have only one copy of the mutant allele(s). Homozygosity for the mutant alleles results in either embryonic lethality or more pronounced depigmentation phenotypes.

Molecular basis: Hauswirth et al. (2012) reported three independent mutations causing the splashed white phenotype, two of them in the MITF gene and one in the PAX3 gene: A missense mutation in the PAX3 gene (c.209G>A; p.C70Y; "SW2"), which arose in the year 1987 in a Quarter Horse mare. It has only been encountered in Quarter Horses and American Paint Horses, which descend from this founder mare.

Hauswirth et al. (2013) reported a second missense variant in the PAX3 gene in an Appaloosa family segregating for a splashed white phenotype (c.95C>G; p:Pro32Arg).

Table S1 of Dürig et al. (2017) provides details of all PAX3 alleles (plus alleles at EDNRB, KIT, MITF) known in July 2016.

Clinical features: Magdesian et al. 2009 demonstrated an increased risk for deafness in horses with the splashed white and/or frame overo spotting phenotype. Hauswirth et al. 2012 reported that "Some, but not all, splashed white horses are deaf."

Prevalence: Druml et al. (2018) reported that "besides Quarter Horses, the PAX3^C70Y [SW2] allele is also present in Noriker (seven out of 189) and Lipizzan (three out of 329) horses" and that of "10 heterozygous PAX3^C70Y-carrier horses, two had nearly a splashed white phenotype".

Genetic testing: Genetic testing is offered by the Veterinary Genetics Laboratory of UC Davis.

Breeds: American Paint Horse, Appaloosa, Quarter Horse.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
PAX3 paired box 3 Equus caballus 6 NC_009149.3 (11200892..11108461) PAX3 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
Lipizzan Noriker Quarter Horse Splashed white PAX3 SW2 missense EquCab2 6 g.11429753G>A c.209G>A p.C70Y 2012 22511888 Variant coordinates gleaned from or confirmed by Table S1 of Durig et al. (2017) Anim Genet 48:123-124
Appaloosa Splashed white PAX3 missense EquCab2.0 6 g.11429867G>C c.95C>G p.Pro32Arg 2013 23659293

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.
2018 Druml, T., Grilz-Seger, G., Neuditschko, M., Horna, M., Ricard, A., Pausch, H., Brem, G. :
Novel insights into Sabino1 and splashed white coat color patterns in horses. Anim Genet 49:249-253, 2018. Pubmed reference: 29635692. DOI: 10.1111/age.12657.
2017 Dürig, N., Jude, R., Jagannathan, V., Leeb, T. :
A novel MITF variant in a white American Standardbred foal. Anim Genet 48:123-124, 2017. Pubmed reference: 27592871. DOI: 10.1111/age.12484.
Negro, S., Imsland, F., Valera, M., Molina, A., Solé, M., Andersson, L. :
Association analysis of KIT, MITF, and PAX3 variants with white markings in Spanish horses. Anim Genet 48:349-352, 2017. Pubmed reference: 28084638. DOI: 10.1111/age.12528.
2013 Hauswirth, R., Jude, R., Haase, B., Bellone, R.R., Archer, S., Holl, H., Brooks, S.A., Tozaki, T., Penedo, M.C., Rieder, S., Leeb, T. :
Novel variants in the KIT and PAX3 genes in horses with white-spotted coat colour phenotypes. Anim Genet 44:763-5, 2013. Pubmed reference: 23659293. DOI: 10.1111/age.12057.
2012 Hauswirth, R., Haase, B., Blatter, M., Brooks, S.A., Burger, D., Drögemüller, C., Gerber, V., Henke, D., Janda, J., Jude, R., Magdesian, K.G., Matthews, J.M., Poncet, P.A., Svansson, V., Tozaki, T., Wilkinson-White, L., Penedo, M.C., Rieder, S., Leeb, T. :
Mutations in MITF and PAX3 cause "splashed white" and other white spotting phenotypes in horses. PLoS Genet 8(4):e1002653, 2012. Pubmed reference: 22511888. DOI: 10.1371/journal.pgen.1002653.
2009 Magdesian, KG., Williams, DC., Aleman, M., LeCouteur, RA., Madigan, JE. :
Evaluation of deafness in American Paint Horses by phenotype, brainstem auditory-evoked responses, and endothelin receptor B genotype. J Am Vet Med Assoc 235:1204-11, 2009. Pubmed reference: 19912043. DOI: 10.2460/javma.235.10.1204.

Edit History


  • Created by Frank Nicholas on 19 Apr 2012
  • Changed by Frank Nicholas on 03 Jun 2013
  • Changed by Tosso Leeb on 02 Nov 2016
  • Changed by Tosso Leeb on 03 Nov 2016
  • Changed by Frank Nicholas on 02 Mar 2017
  • Changed by Frank Nicholas on 19 Apr 2018