Greater awareness and ongoing research mean fewer foals are being born with this genetic skin condition

Attention stock horse owners: Have you heard of HERDA? For the past 20 years, learning about hereditary equine regional dermal asthenia (HERDA) has been a major goal of stock horse associations and HERDA researchers alike. Up to 3.8% of Quarter Horses—and specifically up to 28.3% of those in the cow horse population—are carriers for this debilitating genetic condition that causes horses’ skin to wrinkle, stretch, and slough. While HERDA horses can be maintained with specialized management, most affected animals are euthanized due to the impracticalities of that care, the inability to be ridden, and painful scarring.

With simple genetic testing, though, owners can find out if their animals are affected by or carriers of HERDA so they can make sound management and breeding decisions. As awareness increases, the industry should see fewer foals born with HERDA—and aim to eliminate clinical cases altogether.

How HERDA Happens

In 1978 scientists first described an unusual super-elastic skin condition and suspected it might have a hereditary link. They were right: In 2007 scientists discovered HERDA arises from a simple mutation on a gene called PPIB, located on Chromosome 1. If a foal inherits that same mutation from both parents, he or she will develop clinical signs of the disease, says Rebecca Bellone, PhD, Veterinary Genetics Laboratory director and a professor at the University of California, Davis.

Scientists traced the mutation back to its origin, a 1944 foundation Quarter Horse colt named Poco Bueno, who sired 405 registered foals. The stallion possessed mutated genetic codes for defective collagen processing. Collagens build connective tissues in skin as well as in cartilage, bones, tendons, ligaments, neurological membranes, and some other tissues. The most obvious effect of these defects is abnormally stretchy and wrinkly skin, with layers often detaching from each other so the skin peels away and sloughs. These gaping skin wounds—along with any other contact wounds—heal slowly and poorly, leaving disfiguring scars.

Owners might first notice frequent lacerations, cuts, or scrapes on young horses eventually diagnosed with HERDA, but the strongest clue appears when these animals are first saddled. At this point they often start to develop wounds along the back and neck. Ultraviolet rays from the sun seem to make the condition even worse, creating new lesions and exacerbating existing ones.

However, because horses have connective tissue throughout their bodies, they might also develop problems elsewhere, says Abby McElroy, DVM, MS, PhD candidate and researcher at the University of Massachusetts Chan Medical School, in Worcester. In particular, researchers know HERDA to be associated with an increased risk of corneal ulcers as well as abnormal heart valves, she says.

“If you have an affected horse, it’s obviously very serious for both the horse and the owner,” says Tammy Canida, registrar at the American Quarter Horse Association (AQHA), whose headquarters are in Amarillo, Texas. “The humane thing to do is put the horses down in most cases.”

It Just Takes Two Alleles

Early research in 2009 revealed 3-4% of Quarter Horses, Paint Horses, and other stock horses probably have the HERDA mutation. However, most of these horses show no signs of disease because they’re merely heterozygous carriers, meaning they have only one copy of the HERDA mutation.

Genetic material comes from both parents equally, as genes from the mother line up in the DNA on the chromosome with matching genes from the father, Bellone explains. Genes often exist in alternate forms, which are called alleles. If an individual gets a different allele from each parent for the same gene, he or she is heterozygous for that gene. If the alleles are the same, though, the individual is homozygous.

Because HERDA is recessive, horses must have acquired the mutated allele from both parents—meaning they’re homozygous—to show clinical signs, Bellone says. Therefore, horses that acquire the mutation from the dam or the sire alone are heterozygous and seem perfectly healthy. Meanwhile, they’re carrying the DNA for the disease. If heterozygous horses are bred to other heterozygous horses, their offspring could inherit the mutated allele from both parents, Bellone says. The resulting cross has a 25% chance of producing a homozygous individual—one with clinical HERDA.

Before 2007 breeders sometimes used trial and error to identify silent HERDA carriers in their breeding stock. But since the development of the DNA test for the HERDA allele, breeders have had a simple tool for recognizing carriers, Bellone says.

“That’s the thing about HERDA; it’s recessive,” she says. “So you can avoid producing an affected animal by knowing what the genotypes of the parents are.”

High-Performance HERDA Carriers

If there’s a DNA test for HERDA carriers, why wouldn’t we just sterilize all mutant-gene horses and eliminate the allele entirely?

The answer might be due to an ironic HERDA twist. As it turns out, there might be a link between a single HERDA allele and good athletic performance. In fact, three of today’s top cutting horse sires are HERDA carriers, says McElroy. So the demand for these genetic lines remains high. And that’s no secret to the AQHA.

“It seems to be in popular lineages that are performing well in the industry,” Canida says.

The reason for that link remains a mystery, says McElroy. “I think that’s a big question within the industry: Why are there so many super-performing carriers?” she says, adding that research is lacking.

Some people in the stock horse industry suspect the mutation might code for more joint mobility in heterozygous horses without causing the deleterious effects of the gene, she explains. “Maybe they have a little bit of the phenotype,” she says, a technical term for observable characteristics.

McElroy wonders if subtle changes in connective tissue might improve performance in athletes in general—both horse and human. “You look at swimmers and gymnasts, for example,” she says. “They’re obviously incredibly hypermobile. But they’re not ill. And for horses working in cutting and reining, that hypermobility would give them a huge athletic advantage.”

Even so, if the allele endows stock horses with a “superpower” that garners many winnings early in the horses’ careers but then leads to bone and joint conditions such as osteoarthritis later in life, it could pose a welfare issue, McElroy adds.

Thus far, scientists have neither studied these questions nor measured the degrees of equine or human joint hypermobility with regard to connective tissue quality. And there has been no research completed on bone and joint health specifically in HERDA carriers. “That’s something that really needs to be studied, in my opinion,” McElroy says. “At this point, it’s unclear if an athletic advantage truly exists. It’s also unclear if any perceived advantage comes from the HERDA mutation or another gene.”

DNA Testing: Quick, Easy, Affordable, and Important

With HERDA carriers’ successful performance careers and breeding popularity, genetic testing has never been more important, our sources say. “The number of carriers right now is astronomical,” McElroy says. “So people really need to make informed decisions before breeding.”

The AQHA and American Paint Horse Association (APHA) agree. To minimize the breeding of homozygous foals, the associations have teamed up with Bellone and other experts to create educational materials and offer easy instructions for owners to have their horses’ DNA tested. A simple HERDA DNA test requires a few strands of mane and costs $45 through the UC Davis Veterinary Genetics Laboratory, or $100 as part of the full AQHA/APHA genetic testing panel.

Since 2015 the AQHA has required that owners of all breeding stallions have their studs’ genetic HERDA information on file and accessible to mare owners. In 2018 the APHA followed suit. Foals can only be registered with the AQHA and APHA if their sires’ genetic information, including HERDA status, is on file with the association.

Being heterozygous doesn’t exclude the stallions from breeding, however. Canida explains that the goals of the test are purely informational. “We always recommend that mare owners ask stallion owners for the information that would impact their breeding choices,” she says. “But we also make it public information, so that they can always pull the record and see it on our files as well.”

The associations do not require owners to test broodmares, but they strongly encourage it—especially when considering breeding to a heterozygous stallion. “If mare owners are aware that the stallion they want to breed to is a carrier, then they need to test the mare to ensure that they don’t produce any affected animals,” Bellone says.

 “We feel that our goal is to educate the members about it so they can make the choices for their breeding barn,” says Canida. “We just want them to be aware of what a horse may or may not have.”

“And under current rules, it will not be eliminated,” she adds. The AQHA’s focus, she says, is on education so as “to avoid getting those (clinically) affected horses.”

Meanwhile, nonbreeding stock can also undergo DNA testing if their owners suspect they’re homozygous or even heterozygous for HERDA, or if they’re just curious, our sources say. Both the AQHA and APHA websites provide educational tools that help owners understand DNA test results and how to manage their horses accordingly.

Importantly, awareness—even of the tests themselves—remains key, stresses Bellone. “If the genetic test exists, but people aren’t using it, it’s not helping,” she says.

Managing (and Surviving) HERDA

While the main goal is preventing the birth of any homozygous foals, the harsh reality is such births persist, our sources say. Our sources say most affected adult horses end up being euthanized, some are shipped for slaughter, and a few are rescued by nonprofit organizations. Some homozygous mares serve as embryo transfer recipient mares. Occasionally, owners keep their own homozygous foals as well-protected pets. McElroy says she recalls the case of a homozygous horse that successfully worked cattle for eight years—although it’s possible the horse had, for reasons unknown, a milder form of the disease.

If their quality of life permits it, HERDA horses could be kept in indoor conditions during daytime hours to prevent sun rays from breaking down collagen, she says. Owners would have to ensure the environment is low-risk for contact injuries—even rubbing against surfaces—and for insect bites. “There are owners who have kept these horses going for many years, keeping them inside during the day, turned out at night with intensive fly management, staying away from … anything that’s going to traumatize the skin,” McElroy says.

Management methods for similar connective tissue disorders in humans and smaller animals have progressed in recent years because these individuals’ environments can be more easily controlled. Unfortunately, that’s not the case for horses. “We just don’t know much about keeping these horses going longer,” she says.

“At this point, we don’t have a lot of therapies or treatments,” McElroy says. “It would really just be intensive management.”

HERDA on the Horizon

In the past two decades, HERDA researchers have mostly studied the condition’s effects on the skin, but they’ve started looking into its effects elsewhere in the horse’s body. For example, homozygous horses have thinner corneas with more frequent ulcers, and they have weakened heart valves.

“Collagen is everywhere, so it affects every bodily system,” says McElroy, who studies HERDA as an equine model for Ehlers-Danlos syndrome—the general HERDA analog affecting humans, rabbits, cats, dogs, cattle, sheep, and mink. “There’s a lot we don’t know about. Do they have bone fragility? What’s going on with their GI tract? Are they more likely to colic? Are they more likely to have bladder ruptures as foals?” Her own work has focused on the nervous system and confirms—like in humans with Ehlers-Danlos Syndrome—HERDA horses have abnormal spinal cord regions in the sacrum area, although the physical implications remain unclear.

Scientists are also considering whether HERDA affects some horses more severely than others—with some, like the exceptional HERDA working cow horse, having such mild disease it might even go unnoticed. “For me the question has always been, ‘Are there some underlying genetics that can protect some horses?’ ” Bellone says. “And also, ‘Is there any hope of testing for something like that, or doing any kind of research on it?’ ” To her knowledge, at this time, there is not.

An upcoming research area for such diseases is gene therapy, which essentially involves injecting the healthy allele via a viruslike vector into newborns, effectively replacing the bad allele, McElroy says. Better yet, gene therapy could start after genetic testing of the embryo. While progress is underway for humans, the astronomical price of such therapy—reaching seven figures—is likely to preclude its commercial use in horses. “It would be more like on a research basis,” she says, adding that costs might drop over time and especially with prenatal treatment.

Meanwhile, scientists and associations are continuing to focus on awareness, making sure owners understand what HERDA is and how to prevent it through DNA testing and wise breeding. Efforts so far have been fruitful, McElroy adds, with a drop in the number of homozygous foals born.

Whether the incidence of the allele itself is dropping remains hard to say, notes Bellone. With the steep increase in testing, it’s difficult to compare today’s rates with those from the mere hundreds of horses tested 15 years ago. Even so, ongoing analyses suggest there’s a trend toward a drop in allele frequency, she explains.

“We need to continue that push for education and make sure that people really understand the genetics of a recessive disease, and make sure they understand the risk of carrier-to-carrier matings,” McElroy says.

Take-Home Message

As scientists progress in their understanding of HERDA, so must the owners and breeders managing and producing the horses that carry the alleles responsible for this recessive disorder. With improved awareness and ongoing investigation into the whole-body effects of this disease, the industry is striving toward prevention and—potentially in the distant future—a hope for therapeutic management.