Making ethical decisions in the face of equine genetic diseases

By Lindsay Day

Recent advances in genetic research have paved the way for more effective identification and screening of genetic diseases in the horse. With these developments come new ethical considerations with respect to breeding practices, testing, and disclosure.

Genetic diseases: 101

Genetic diseases in the horse are caused by a mutation of a specific gene that ultimately results in the symptoms observed. “A mutation is a variation in the DNA code that basically causes the gene to stop functioning like it is supposed to,” explains Arne deKloet, Director of Research at Animal Genetics, a private testing laboratory in Tallahassee, Florida.

While mutations can arise for a number of reasons, and by and large are a naturally occurring phenomenon, they can become concentrated in an animal population as a consequence of breeding selection, particularly when a stallion that is a carrier becomes popular. Assisted breeding technologies like artificial insemination can further amplify their propagation.

“Genetic diseases can either have what we call a dominant or a recessive mode of inheritance,” explains deKloet. In the case of the former, only one copy of the genetic mutation is required for the disease to be expressed, such as with polysaccharide storage myopathy (PSSM), a muscle disorder that results in symptoms associated with tying up.

With a recessive genetic mutation, two copies must be inherited (i.e. one from each parent). This means that a horse can be a “carrier” of the mutation and remain unaffected. However, breeding two carriers together could produce an affected foal, which has a likelihood of happening 25 percent of the time. Breeding a carrier to a normal horse will never produce a horse with two copies of the mutation, though there would be a 50 percent chance the foal would be a carrier.

There are also differences in the severity of the effects of the known genetic diseases, adds deKloet. “You have some that are catastrophic – that is, they result in death. Lethal White Foal is one example, which occurs with inheritance of two copies of the Overo mutation. Then you have something like the LP (Leopard Complex) gene where a horse that has two copies will be born normal, but will tend to have issues related to night-blindness.”

Genetic testing for these known mutations provides a new tool in making breeding decisions. “I think in a perfect world everyone would use the tests and would understand the genetics well enough to understand the consequences,” says deKloet. “Some people are very enthusiastic about using them, but I also know there are some people out there who just don’t see the value of it and say, ‘well I’m just going to roll the dice’.”

Making use of available genetic tests

Several years ago now, after hearing more and more people talking about genetic diseases, Paint and Quarter Horse breeder Dianne Chapman, of Somerset, California, decided to have her horses tested. “I’d never had any problems, but part of the issue is that if you have a horse that’s a carrier [of a recessive trait] you can’t tell any difference in them. I had a colt that was extremely well bred so I thought I would go ahead and get him tested and, low and behold, he tested positive for GBED.”

After the colt’s dam tested negative, Chapman knew that the mutation must have been passed on through the stallion that she had bred to. “I called them to let them know, but they really didn’t seem to care.” Disappointed by their lack of interest and disclosure Chapman was surprised to find that many prominent breeders do not advertise the status of their horses.

Chapman would like to see the perceived stigma of recessive genetic mutations replaced by improved awareness and education. “I don’t think people should be afraid of these tests, or disclosing the status of their animals. We don’t have to avoid them altogether, but it’s important to have the knowledge so you can avoid breeding carriers to each other, so you can prevent these diseases and prevent dead babies.”

With new genetic tests being developed each year, keeping up with the latest information can seem daunting. Dr. Maria Schnobrich, an equine reproduction specialist at Rood and Riddle Equine Hospital in Lexington, Kentucky, suggests that people begin by consulting their breed association or registry. “They will usually alert you to abnormalities they have found in that breed and which they are concerned about, and can often offer advice on what genetic tests are available and where to have them performed. You can also ask your veterinarian if there has been any recent research or new tests for diseases particular to your breed.”

Related: Should You Breed Your Mare?

Hyperkalemic Periodic Paralysis (HYPP) is characterized by sporadic episodes of muscle tremors, weakness, and paralysis. For severe cases in which the horse has collapsed and been unable to stand for an extended period of time, a sling is often utilized to prevent complications that can arise from the horse remaining lying down for overly long. Photo courtesy of Dr. Sharon Spiers, University of California, Davis

In some instances, genetic testing for a particular disease may actually be required to register a foal. The American Quarter Horse Association, for example, requires HYPP testing for all foals descending from bloodlines known to carry the genetic mutation. As of 2007, horses that have two copies of the mutation (notated as H/H) cannot be registered. “You want to be aware of your registry’s current policies before you make your breeding decisions,” counsels Schnobrich. 

Responsible breeding

“Because breeding is an unregulated industry there are no consequences for cavalier or irresponsible breeding practices, and that is something we deal with when we are talking about genetic disease and breeding,” says Nena J. Winand, DVM, PhD, an equine veterinarian and geneticist recently retired from the College of Veterinary Medicine, Cornell University. As she points out, if someone chooses to breed two horses that are both carriers of a fatal recessive genetic defect, there is no consequence other than the risk of financial loss. “In my opinion there is also an ethical consequence, but we don’t have laws that regulate the ethics.”

“If it is perceived as being profitable or desirable to breed horses that are good performers but are carriers of genetic defects, people will continue to do that,” Winand says. “If you look at HERDA [Hereditary Equine Regional Dermal Asthenia] in the cutting horses, certainly some of the top performing animals of all time have been carriers and those bloodlines are still being utilized heavily today.”

Related: Fragile Foal Syndrome Not Confined to Warmbloods

The gene mutation for hyperkalemic periodic paralysis (HYPP) has been found in, and, at present, confirmed cases restricted to, descendants of the American Quarter Horse sire Impressive.

“I think people need to be educated about the breeding decisions they make,” continues Winand. “They need to be aware of the prevalence of undesirable genetic traits and about the bloodlines that they segregate in. And I think they need to do DNA testing for the traits we have tests for. That is really important in my opinion, and it’s very inexpensive.”

For Winand it comes down to an ethical responsibility. “These mutations result in diseases which cause animal welfare and health issues, and therefore it is not desirable to produce affected individuals. Those animals suffer pain and that is the bottom line for me as a vet.”

Winand admits that given the present widespread proliferation of some genetic mutations in certain horse populations, it would not necessarily be advantageous to eliminate carriers from the breeding population altogether. While on the one hand it is not desirable to perpetuate the spread of a deleterious genetic mutation by repeatedly breeding carriers, on the other, removing all such horses from breeding programs could drastically reduce the genetic diversity in a breed and mean the loss of otherwise valuable bloodlines.

“From a practical standpoint, in the cutting industry, for example, the gene pool is so saturated right now that we can’t not breed carriers,” says Winand. “But what you would hope is that over time breeders will have non-carriers that perform at the same level that can be used as bloodstock, and the more performing, normal non-carriers bred, the better off the industry will be in the long run. The goal is to manage the trait and reduce your overall carrier frequency over time. And it does take time. It takes decades. But that should be the goal, in my opinion.”

Horses affected by Hereditary Equine Regional Dermal Asthenia (HERDA) rarely show symptoms until they begin under-saddle work, at which point cases often present with scarring and lesions of the skin. Photo: Dr. Juan Garcia

The big picture

“I use genetic testing as part of my breeding decisions, but it’s not the only factor,” says Quarter Horse breeder Sandy Kirtzinger of Hay Lakes, Alberta. “I think the main thing is to be responsible and know what you are breeding. But you have to look at other traits too. Is it more important to have a quiet horse with a good mind that’s not going to buck you off that is a carrier of a recessive gene, or a have some horse that isn’t a carrier that’s going to dump somebody every time they get on?”

Winand agrees that breeders need to look at the big picture when selecting breeding stock. “You need to look at soundness of limb and wind, and reproductive soundness as well. We want to breed sound, good-minded, trainable individuals that have strong conformation and a good performance record. All of those are things that make a good breeding candidate, and that hasn’t changed over the years.”

“Just because a horse gets hurt and gets turfed out of competition doesn’t mean they automatically make good breeding stock either,” adds Winand. “That is not a sound selection strategy to use.” The more objective you can make your criteria, the better, she says. “If you can set some parameters around things like money earned, height of the horse, certain performance or conformational issues you are not willing to accept – those are more objective things that will help you to weed out your less desirable individuals and will give you a much better chance of producing a quality foal.”

Related: An Inside Look at Equine Cloning

Lethal White Overo (LWO) syndrome occurs when a foal is homozygous for the frame overo gene (see photo below). Affected foals are born white and with intestinal tract abnormalities. Unable to digest their mother’s milk, foals with LWO will die within 72 hours of their birth, and should be humanely euthanized.

Courtesy of Dr. Sharon Spiers, University of California, Davis

Schnobrich emphasizes that it is also important to consider the future use of the foal. “Especially with the economy being what it is in North America and the problem with unwanted horses, I think breeders today really need to look at whether or not there is going to be a job or a market for the horse down the line. There should be something about the pairing you’ve made that is going to make that foal desirable, not just in your own mind, but in terms of the market as well.”

Kirtzinger also underlines the importance of disclosure and honesty in responsible breeding. “As a breeder my job is to produce horses that other people would use and when I offer them for sale to do so honestly. I really believe that is key. If I know that a horse carries the HYPP gene I would let the prospective buyers know, as well as explain to them how to deal with that issue – what to look for and what they can do to prevent it.”

Kirtzinger believes the whole industry suffers when horses are misrepresented. “It can be discouraging. A lot of people, especially novices, get into horses and have a negative experience. And that sort of spoils their future in the horse industry. I think if we are all ethical and disclose everything about our horses and offer some support to the new buyers then we will see a strong industry.”

Ultimately, it is best not to wait for the birth of an abnormal foal or the appearance of symptoms in a purchased horse to become informed about the issues surrounding genetic diseases. By taking a proactive approach and keeping up with the latest information and resources available, you will be in a better position to make informed and ethical decisions about the horses you come to own or choose to breed.

Related: The Equine Heart

Genetic Diseases Identified in the Horse to Date

Cerebellar abiotrophy (CA)

• Arabians and related breeds
• A neurological condition that causes the death of brain cells in the cerebellum. Though often normal at birth, foals typically begin to exhibit neurological symptoms by six weeks to four months of age, such as head tremor and lack of balance and coordination. 
• Autosomal recessive – Two copies of the mutation must be inherited

Congenital Stationary Night Blindness (CSNB)

• Appaloosas
• A condition tied to the Leopard Complex (LP) gene (responsible for a spotted coat pattern) making it difficult or impossible for horses to see in relatively low light.
• Autosomal recessive – Two copies of the mutation must be inherited

Glycogen Branching Enzyme Deficiency (GBED)

• Quarter Horses and related breeds
• A fatal condition that prevents effective glycogen storage such that it is not available in sufficient quantities for proper functioning of the muscles, heart, and brain, resulting in abortion, stillbirth, or early death of the foal. 
• Autosomal recessive – Two copies of the mutation must be inherited

Grey horse melanoma

• Multiple breeds
• A condition associated with the genetic mutation responsible for grey coat colour. Approximately 70 percent of grey horses over the age of 15 develop dermal melanomas most commonly seen around the tail and head.
• Autosomal dominant – Only one copy of the mutation confers susceptibility (and produces a grey horse). Horses with two copies (also grey) are more likely to develop melanomas than those with only one copy.

Hereditary Equine Regional Dermal Asthenia (HERDA)

• Quarter Horses and related breeds
• A severe skin disease that undermines the strength and durability of the skin and often goes unrecognized until the horse begins work under saddle. With no effective treatment available, the majority of diagnosed horses are euthanized.
• Autosomal recessive – Two copies of the mutation must be inherited.

Hyperkalemic Periodic Paralysis (HYPP)

• Quarter Horses and related breeds
• A muscle disorder, tracing back to the Quarter Horse sire Impressive, that predisposes a horse to sporadic attacks of muscle tremors, weakness, or paralysis. Responsive to management/treatment.
• Autosomal co-dominant – One copy of the genetic mutation is sufficient to cause the disease, while horses with two copies are more severely affected.

Junctional Epidermolysis Bullosa (JEB)

• Belgians and related draft breeds, American Saddlebreds 
• A lethal skin condition that inhibits a horse’s ability to produce certain proteins responsible for holding the skin onto the body. 
• Autosomal recessive – Two copies of the mutation must be inherited.

Lavender Foal Syndrome (LFS) Arabians (primarily Egyptian bloodlines)

• A fatal condition causing neurological dysfunction in foals, resulting in seizures, severe hyperextension of limbs, neck, and back, and inability to stand. Foals are typically born with a dilute silvery, pinkish coat colour. 
• Autosomal recessive – Two copies of the mutation must be inherited.

Lethal White Overo (LWO)

• Paints and Quarter Horses, Miniature Horses, and Thoroughbreds with “frame-overo” colour pattern
• A fatal condition resulting in an all-white foal with intestinal tract abnormalities. 
• Autosomal recessive – Two copies of the mutation must be inherited.

Malignant Hyperthermia (MH)

• Quarter Horses and related breeds
• A condition observed in a number of species (including humans) which makes a carrier susceptible to a potentially fatal rise in body temperature associated with abnormal muscle contractions and heart rhythm when undergoing anesthesia with halogenated anesthetics. It may also worsen the symptoms of PSSM.
• Autosomal dominant – Only one copy of the mutation can lead to expression of the disorder.

Myotonia

• New Forest Ponies
• A neuromuscular disorder characterized by foals with abnormal muscle activity, gait abnormalities, and a tendency to spend more time than usual lying down. 
• Autosomal recessive – Two copies of the mutation must be inherited

Polysaccharide Storage Myopathy (PSSM)

• Numerous breeds including Quarter Horses, some draft breeds, Warmbloods, Morgans and others
• A muscle disorder that causes an abnormal accumulation of polysaccharide and glycogen in the muscles, resulting in symptoms associated with tying up such as muscle tremors, stiffness, and reluctance to move. Responsive to management/treatment.
• Autosomal dominant - One copy of the mutation predisposes a horse to the condition.

Severe Combined Immunodeficiency (SCID)

• Arabians
• A fatal condition resulting in a compromised immune system. Foals usually die shortly after birth as the result of infections which their body cannot fight.
• Autosomal recessive – Two copies of the mutation must be inherited.

Related: Equestrianism and Animal Rights

More by Lindsay Day

Lindsay Day is a Registered Equine Massage Therapist and journalist based in Guelph, Ontario