Uniquely marked horses lead Etalon to a rare human disorder

Looks are important... at least in the horse world, where humans have bred horses for their color and pattern for centuries. Today, so much is known about the genetics of coat color that online simulators can help you figure out the color and pattern of your foal before she’s even born. In a recently published article in the journal Animal Genetics, our team of experts report that there is more to learn about horse coat color and patterns than meets the eye, and our discovery unexpectedly connected us to a rare human disorder.

At Etalon, we were intrigued by a family of Paint horses who were sporting lovely white markings unlike anything we had previously seen, so we set out to discover the genetic cause. We studied a stallion and 8 of his daughters who all had varying patterns of white markings from being speckled to being nearly completely white. Most of these horses had white faces (commonly referred to as a “bald face”) striking blue eyes, and 6 were deaf.

Using cutting-edge genome sequencing technology, we discovered a new deletion in the MITF gene (deletion: a part of the gene sequence is now absent or missing). This gene plays a key role in the development and function of pigment-producing cells, which affect hair and skin color as well as the inner ear where affected cells are also found. All of the horses in our study have the same MITF gene deletion, and all of the deaf horses had additional genetic variants that may have contributed to their hearing loss.

Although the connection between lack of pigmentation and deafness is not new, we don’t fully understand the underlying biology. Previously discovered white spotting patterns or genetic variants in other horse families have also shown correlation with blue eyes and hearing loss. Reports of other animals, such as mice, ferrets, cats and dogs show that the connection between pigmentation and hearing runs deep in the history of mammalian evolution.

In humans, the MITF gene is involved in a rare genetic disorder called [Waardenburg syndrome.]https://ghr.nlm.nih.gov/condition/waardenburg-syndrome) People with Waardenburg syndrome resulting from MITF genetic variants often have a very striking appearance, with piercing blue eyes, a distinctive patch of white or grey hair, and/or patches of skin lighter than their overall skin tone. They also have an increased risk of congenital deafness in one or both ears. Waardenburg syndrome is a rare disorder and there is, currently, no known cure.

The genetic and physical similarities between this family of horses and people with Waardenburg syndrome raises the question of how discoveries in horse genetics may translate to humans. Our study illustrates the potential contribution of genome sequencing in horses for identifying meaningful genetic variants associated with human disease. These discoveries may eventually lead us to genetic targets for drug development and novel therapeutics without the use of laboratory animals (essentially, cruelty-free animal research).

Team Etalon is proud to provide cutting-edge genetic services to professional equestrians and horse enthusiasts as part of a collaboration to accelerate genetic discovery. Our unique, comprehensive genetic testing panels evaluate horse health and disease risk and can be used to gain insights into horse temperament, performance, and abilities. We feel the key to faster discovery lies with the knowledge of those who know the horses best: horse owners and riders! As we are always adding new traits to our panels, we encourage you to collaborate with us and be a part of the research. We invite you and your horse to join us today at Etalon.

We would like to thank the following for their contributions and collaboration:

1. Stef Sanjati - We truly appreciate your willingness to share, educate, and the way you live out loud. Kudos to you!!

2. Ms. Angelique Levert of France and her beautiful featured horse Chelsea Dancin Wood - You have been an incredible source and we love that you joined us for the journey - Merci!! https://painthorseangels.com/

3. Gaikwad Rohini P., Mukherjee Sampica, Saha Abhijit, Naphade Poonam. (2015) Waardenburg syndrome type 2

4. All of our collaborators, scientists and horse people alike who make these discoveries possible. We are so privileged to have this opportunity and look forward to the next exciting discovery. #MakingaDifferenceTogether