Etalon Equine Genetics Discovers Three New White Marking Variants in a New Gene

Menlo Park, CA - Etalon Equine Genetics has made another landmark discovery in the field of equine genetics. For the first time in 10 years, a new genetic region for color has been found.¹ In the released publication, the researchers detail their findings on three HPS5 mutations that result in white markings within diverse horse breed populations.

Depigmentation - or white markings - is a common phenotype in horses, and the genetics behind them are quite complicated. Over 50 known variants cause white spotting on the skin and coat. The HPS5 gene, which influences melanocyte proliferation, has been implicated in depigmentation in humans, mice, and zebrafish.² ³ ⁴ ⁵ However, its role in horses remained a mystery until now.

The researchers proposed the nomenclature "Eden White (EDXW)" for HPS5 mutations, as a tribute to this pioneering discovery. This designation is a fusion of "Etalon" and the distinguished research collaborator Aiden McFadden's given name, serving as a fitting commemoration of their collective efforts.

The three identified mutations, named Eden White 1 (EDXW1), Eden White 2 (EDXW2), and Eden White 3 (EDXW3), are associated with significant increases in white markings depending on the specific mutation. EDXW1 (S1013C) and EDXW2 (L560F) are both missense mutations causing a change in the structure of the protein and decreasing its functionality. EDXW3 is a donor splice site mutation causing the protein to include some extra sequence causing it to have reduced functionality.

In addition, EDXW1 and EDXW3 showed a rare interaction with MC1R, the gene controlling black vs. red coat color in horses. The dominant E variant, responsible for black pigment, was associated with higher levels of white markings compared to the recessive chestnut genotype. In simple terms: black or bay horses will likely have more or larger white markings than chestnut horses.

In the study, the three identified mutations were found in many horse breeds. Notably, these variants were most frequently observed in stock-type (Paint and Quarter Horses) and heavy horse breeds (Shire and Gypsy) as well as Lusitanos, Miniature Horses, Paso Finos, and much more. While both EDXW1 and EDXW3 were found in nine major breed groups, EDXW2 was absent in thoroughbred horses. This distribution suggests a broad impact of these mutations on depigmentation across many equine lineages.

This study opens new avenues for understanding and managing depigmentation in horses, providing invaluable insights for breeders, veterinarians, and horse enthusiasts worldwide.

A PDF copy of this press release and images are available upon request. For further information or inquiries, please contact Etalon Equine Genetics at [email protected] or 650.380.2995

References

McFadden, A., Martin, K., Vierra, M., Robilliard, H., Lundquist, E. W., Everts, R. E., Brooks, S. A., & Lafayette, C. (2024). Three HPS5 mutations associated with depigmentation in diverse horse breeds. Livestock Science, 282, 105454. https://doi.org/10.1016/j.livsci.2024.105454

¹ Bellone, R. R., Holl, H., Setaluri, V., Devi, S., Maddodi, N., Archer, S., Sandmeyer, L., Ludwig, A., Foerster, D., Pruvost, M., Reissmann, M., Bortfeldt, R., Adelson, D. L., Lim, S. L., Nelson, J., Haase, B., Engensteiner, M., Leeb, T., Forsyth, G., Mienaltowski, M. J., … Brooks, S. A. (2013). Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse. PloS one, 8(10), e78280. https://doi.org/10.1371/journal.pone.0078280

² Di Pietro, S. M., Falcón-Pérez, J. M., & Dell'Angelica, E. C. (2004). Characterization of BLOC-2, a complex containing the Hermansky-Pudlak syndrome proteins HPS3, HPS5 and HPS6. Traffic (Copenhagen, Denmark), 5(4), 276–283. https://doi.org/10.1111/j.1600-0854.2004.0171.x

³ Huizing, M., Hess, R., Dorward, H., Claassen, D. A., Helip-Wooley, A., Kleta, R., Kaiser-Kupfer, M. I., White, J. G., & Gahl, W. A. (2004). Cellular, molecular and clinical characterization of patients with Hermansky-Pudlak syndrome type 5. Traffic (Copenhagen, Denmark), 5(9), 711–722. https://doi.org/10.1111/j.1600-0854.2004.00208.x

⁴ Hirobe, T., Wakamatsu, K., & Ito, S. (2012). A new mutation of mouse ruby-eye 2, ru2(d)/Hps5(ru2-d) inhibits eumelanin synthesis but stimulates pheomelanin synthesis in melanocytes. Zoological science, 29(10), 652–661. https://doi.org/10.2108/zsj.29.652

⁵ Daly, C. M., Willer, J., Gregg, R., & Gross, J. M. (2013). snow white, a zebrafish model of Hermansky-Pudlak Syndrome type 5. Genetics, 195(2), 481–494. https://doi.org/10.1534/genetics.113.154898