UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory
Splashed White Mutations – SW1, SW2, SW3, SW4, and SW5

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Quick Summary

Splashed white is a variable white spotting pattern characterized by a broad blaze, extended white markings on the legs, variable white spotting on the belly, and often blue eyes. Five mutations in two different genes have been shown to cause the splashed white pattern.

Phenotype: Splashed white is a variable white spotting pattern characterized often by a large broad blaze, extended white markings on the legs, variable white spotting on the belly, and blue eyes.

Mode of Inheritance: Autosomal dominant

Alleles: N = Normal/Unaffected, SW1/SW2/SW3/SW4/SW5 = Splashed white 1/2/3/4/5

Breeds appropriate for testing: Appaloosa, Icelandic Horse, Miniature Horse, Morgan Horse, Paint Horse, Quarter Horse, Shetland Pony, Thoroughbred, Trakehner, Pony of the Americas

Explanation of Results:

  • Horses with N/N genotype do not have the splashed white pattern caused by SW1, SW2, SW3, SW4, or SW5. If this horse has a white spotting pattern, it is caused by some other genetic mutation.
  • Horses with N/SW1, N/SW2, N/SW3, N/SW4, or N/SW5 genotype will have splashed white patterning. They may transmit a splashed white variant to 50% of their offspring. Matings with N/N genotype will result in a 50% chance of producing a foal with splashed white patterning.
  • Horses with two splashed white variants, which can be SW1/SW1, SW2/SW2, SW1/SW3, SW1/SW5*SW3/SW5*, or SW2/SW4, will have splashed white patterning and will transmit a splashed white variant to all of their offspring. Matings with any genotype are predicted to produce all splashed white offspring.

*Horses homozygous for the SW3, SW4, and SW5 variants (SW3/SW3, SW4/SW4 SW5/SW5 genotypes) have not been detected and may be embryonic lethal. In addition the VGL has not identified any SW1/SW5 or SW3/SW5 compound heterozygotes. It is unknown at this time if these combinations are non-viable or just not yet detected because of the low frequency of SW5.

Additional Details

Splashed white is a variable white spotting pattern characterized primarily by a large, broad blaze, extensive white markings on legs, variable white spotting on the belly, and often blue eyes. Some, but not all, splashed white horses are also deaf. Five mutations have been identified and have been named in the order they were discovered: SW1, SW2, SW3, SW4, and SW5. All of these mutations cause a similar splashed white phenotype in horses although the amount of white patterning is variable and thought to be controlled by several genes. Some are known, but mostly these additional genes, contributing to the variation in splash white phenotype, are yet to be identified.

MITF - SW1, SW3, and SW5

SW1, SW3, and SW5 are mutations in the MITF (microphthalmia associated transcription factor) gene. MITF is an important protein for normal pigment cell function. It is a transcription factor that activates other genes in the pigment process including those known to regulate melanocyte proliferation and migration.

SW1 is found in several breeds – Quarter Horse, Appaloosa, Paint Horse, Morgan Horse, Trakehner, Miniature Horse, Shetland Pony and Icelandic Horse – and may be present in other breeds as well. The SW1 mutation is a 10 bp insertion in the MITF promotor (chr16:g.20,117,302Tdelins11). The promoter is the region of the gene that regulates gene expression. The SW1 mutation is thought to disrupt the normal gene production thus impacting pigment cell division. Horses homozygous for SW1 (SW1/SW1) have been identified, which suggests that this mutation is not homozygous lethal.

SW3 occurs exclusively in certain lines of Quarter Horses and Paint Horses and is caused by a frameshift mutation in MITF (p.C280Sfs*20). SW3 is thought to be lethal in the homozygous state (SW3/SW3) as no individuals with this genotype have yet been identified. The current recommendation is that mating of two horses that carry SW3 should be avoided.

SW5 is a large deletion of 63 thousand nucleotides in the MITF gene (chr16:21,503,211–21,566,617). This mutation deletes several important regions of the gene and likely causes the protein to have a reduced or complete loss of function. This mutation was identified in an American Paint Horse family. Subsequent research at the VGL, suggest the frequency of this mutation is low in the Paint Horse breed. It is unknown if SW5 is homozygous lethal, and no homozygotes have been reported.

PAX3 - SW2 and SW4

SW2 and SW4 are mutations in the PAX3 (paired box gene 3) gene. SW2 is found in certain lines of Quarter Horses and Paint Horses and is caused by a missense mutation in PAX3 (p.Cys70Tyr). PAX3 is essential for proper development of some nerve tissue and pigment cells. Based on testing results from the VGL, SW2 is currently considered not homozygous lethal, though horses that have SW2 may be deaf. The rare SW4 mutation has been identified in a family of Appaloosa horses and may cause a splashed white pattern or a broad blaze. SW4 is caused by a missense mutation in PAX3 (p.Pro32Arg), and is also thought to be lethal in the homozygous state, though this remains to be determined.

Splashed white mutations are inherited as dominant traits with variable expression, which means that one copy of a SW mutation will produce a white spotting phenotype with a variable amount of white. Horses that carry combinations of the splashed white mutations, tobiano, or lethal white overo can display extensive white patterning or their coats may be entirely white.

Testing for the splashed white pattern allows breeders to identify which splashed white mutation is present in their horse and can aid in breeding decisions and clinical decisions if deafness is suspected.

Splashed White results reported as:

Test Result

Interpretation

Splashed White (SW1, SW3, SW5)

N/N

No copies of SW1, SW3, or SW5 Splashed White mutations detected.

N/SW1

One copy of SW1 detected.

SW1/SW1

Two copies of SW1 detected.

N/SW3

One copy of SW3 detected.

SW3/SW3

Two copies of SW3 detected.*

N/SW5

One copy of SW5 detected.

SW5/SW5

Two copies of SW5 detected.*

SW1/SW3

One copy of SW1 and one copy of SW3 detected.

SW1/SW5

One copy of SW1 and one copy of SW5 detected.#

SW3/SW5

One copy of SW3 and one copy of SW5 detected.#

Splashed White (SW2, SW4)

N/N

No copies of SW2 or SW4 detected.

N/SW2

One copy of SW2 detected.

SW2/SW2

Two copies of SW2 detected.

N/SW4

One copy of SW4 detected.

SW4/SW4

Two copies of SW4 detected.*

SW2/SW4

One copy of SW2 and one copy of SW4 detected.

*Homozygous genotypes for the SW3, SW4, and SW5 mutations (SW3/SW3, SW4/SW4, and SW5/SW5) may be embryonic lethal.
# These combinations of splashed white have not been observed, either due to low frequency of the SW5 allele or embryonic lethality.

References

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. (2012). Mutations in MITF and PAX3 cause "Splashed White" and other white spotting phenotypes in horses. Plos Genetics, 8(4): e1002653. doi: 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., Rieder, S., & Leeb, T. (2013). Novel variants in the KIT and PAX3 genes in horses with white-spotted coat colour phenotypes. Animal Genetics, 44(6), 763-765. doi: 10.1111/age.12057

Henkel, J., Lafayette, C., Brooks, S.A., Martin, K., Patterson-Rosa, L., Cook, D., Jagannathan, V., & Leeb, T. (2019). 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, 50(2), 172-174. doi: 10.1111/age.12762

 
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