Splashed White (SW)

Horses are unique in the wide range of variable coat color phenotypes they exhibit. Among domesticated animals, they hold the record for the number of identified SW alleles (alleles causing the splashed white phenotype). White markings of varying extent can be seen in many horse breeds. A total of 10 mutations have been identified in the MITF and PAX3 genes: SW1, SW2, SW3, SW4, SW5, SW6, SW7, SW8, SW9 and SW10, which are associated with varying degrees of phenotypic expression of splashed white. It is expected that the number of detected variants is not final and that further research will identify additional mutations responsible for the development of splashed white (SW). The variable distribution of white markings suggests that other, as yet unidentified genes must also influence the expression of splashed white. White markings may be present to a minor extent or may even be so extensive that the horse is completely white. They may be distributed horizontally, vertically, symmetrically or asymmetrically. Horses often have a wide blaze extending to the lateral parts of the head. In chestnut horses, the blaze is usually larger than in bay horses with the same genotype. The legs and parts of the abdomen may also be white. The iris may be blue in one or both eyes, or heterochromatic.

White markings develop during embryonic development. Melanoblasts are derived from neural crest cells and subsequently differentiate into mature pigment cells, melanocytes. Abnormalities in melanocyte development lead to the formation of white markings. There may be two types of causes of the splashed white phenotype. Melanocytes may have a problem producing pigment, or partial or complete loss of melanocyte precursor cells may occur during their migration in embryonic development. In addition to changes in phenotype and heterochromatic irises, splashed white is also associated with a risk of sensorineural deafness and skeletal dysmorphology. The risk of deafness increases in horses carrying combinations of mutant PAX3 alleles with other alleles for white spotting in other genes.

SW1: The SW1 allele is found in the following breeds: American Miniature Horse, American Paint Horse, Appaloosa, Icelandic Horse, Morgan, Quarter Horse, Shetland Pony, Tori Horse, Trakehner. Since all of the breeds mentioned share the same mutation, it is assumed that the origin of the SW1 allele dates back several hundred years, to a time when modern horse breeds had not yet been developed. The SW1 variant (g.21579201delinsATAATAACCTA) in the MITF gene is inherited in an autosomal dominant manner with variable expressivity. A horse homozygous for SW1/SW1 has more pronounced/extensive white markings than a heterozygous N/SW1 horse.

SW2: The SW2 allele is found in American Paint Horse, Quarter Horse, Lipizzan Horse and Norik. The SW2 variant (g.11199026C>T) in the PAX3 gene is inherited in an autosomal dominant manner with variable expressivity. A horse homozygous for SW2/SW2 has more pronounced/extensive white markings than a heterozygous N/SW2 horse. The presence of the SW2 allele together with the SW1 allele leads to a more pronounced expression of the splashed white phenotype. The SW2 allele arose relatively recently. Its origin has been traced back to the late 1980s.

SW3: The SW3 allele is found in American Paint Horse and Quarter Horse. The SW3 variant in the MITF gene (g.21567245_21567249del) is inherited in an autosomal dominant manner. Since no SW3/SW3 homozygote has been identified to date, this genotype is considered embryonically lethal. Breeders should avoid mating horses that both carry the heterozygous N/SW3 genotype.

SW4: The SW4 allele is very rare and is found only in the Appaloosa breed. The SW4 variant (g.11199140G>C) in the PAX3 gene is inherited in an autosomal dominant manner. In the study by Hauswirth et al. 2013, in which the SW4 allele was discovered, only individuals with heterozygous genotypes (N/SW4) were identified. It is likely that the SW4/SW4 genotype may be embryonically lethal. In this respect, the SW4 allele requires further detailed analysis to confirm this assumption of lethality. Due to the potential risk, breeders should avoid mating horses that both carry the heterozygous N/SW4 genotype.
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Resulting genotypes:

N/N – the horse does not carry any of the tested SW1, SW2, SW3 or SW4 variants.
The horse does not have the splashed white phenotype. If the splashed white phenotype is present, it must be caused by a variant not included in the test or by a variant that has not yet been detected.

N/SW1; N/SW2; N/SW3; N/SW4 – the horse carries the splashed white phenotype and can pass it on to its offspring, and itself has variable white markings distributed over the body to a lesser extent.

SW1/SW1; SW2/SW2 – the horse has the splashed white phenotype, with white markings variably distributed over a greater extent than in heterozygotes. The phenotype is also passed on to its offspring.

SW3/SW3; SW4/SW4 – probably embryonically lethal.

When multiple genotypes responsible for the splashed white phenotype are combined, the effect is intensified and the splashed white phenotype becomes more pronounced and/or extensive. White markings may also be more extensive due to combinations with certain tobiano, sabino and overo genotypes and dominant white, which also lead to the formation of white markings.

Genomia laboratory currently does not offer testing for variants SW5, SW6, SW7, SW8, SW9 and SW10.

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References:

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. Animal Genetics 2018, 49 (3), 249–253. https://doi.org/10.1111/age.12657.

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. T.; Rieder, S.; Leeb, T. Mutations in MITF and PAX3 Cause “Splashed White” and Other White Spotting Phenotypes in Horses. PLoS Genetics 2012, 8 (4), e1002653. https://doi.org/10.1371/journal.pgen.1002653.

Hauswirth, R.; Jude, R.; Haase, B.; Bellone, R. R.; Archer, S.; Holl, H.; Brooks, S. A.; Tozaki, T.; Penedo, M. C. T.; Rieder, S.; Leeb, T. Novel Variants in the KIT and PAX3 Genes in Horses with White‐spotted Coat Colour Phenotypes. Animal Genetics 2013, 44 (6), 763–765. https://doi.org/10.1111/age.12057.

Henkel, J.; Lafayette, C.; Brooks, S. A.; Martin, K.; Patterson‐Rosa, L.; Cook, D.; Jagannathan, V.; Leeb, T. Whole‐genome Sequencing Reveals a Large Deletion in the MITF Gene in Horses with White Spotted Coat Colour and Increased Risk of Deafness. Animal Genetics 2019, 50 (2), 172–174. https://doi.org/10.1111/age.12762.