Genetic Disorders: Breed by Breed

Researchers have defined a number of conditions affecting specific breeds—many of which developed as a result of selective breeding, or breeding for highly desirable qualities such as performance or appearance.

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By knowing what diseases certain horses are predisposed to, owners and breeders can take steps to curb undesirable conditions

Appaloosas are prone to eye problems. Quarter Horses tend to tie up. Arabians can produce immune-deficient foals. Today it’s common knowledge that some breeds are more predisposed to certain conditions than others. But it was only a few decades ago that researchers first identified these genetic disorders in horses. Since then they have defined a number of conditions affecting specific breeds—many of which developed as a result of selective breeding, or breeding for highly desirable qualities such as performance or appearance. 

A classic example is researchers’ discovery that linked the muscle disease hyperkalemic periodic paralysis (HYPP) to the Quarter Horse sire Impressive. In 1996 the American Quarter Horse Association established mandatory testing for all Impressive’s descendants to prevent perpetuating the condition. Now any foal that tests homozygous for HYPP cannot be registered with the organization.

But many owners across a variety of breeds know nothing about their horses’ lineage. This means breeding continues to result in foals with genetic conditions. Knowing which horses could potentially have genetic conditions is important not only for buyers and breeders but also the overall health of the breeds themselves.

Horses are affected by comparatively fewer genetic diseases than humans, but the disorders are still too numerous to cover in one article. Here we will highlight the more common disorders, presented on a breed-by-breed basis. We’ll also describe some not-yet-fully-understood equine conditions that are thought to be caused by genetic anomalies. 

What is a “Breed-Related Disorder?”

This is really a catchall for something that goes wrong with a horse’s genes—the body’s blueprint. The genes control everything from eye and coat color to liver and kidney function. Even behavior has its roots in the DNA, as evidenced by how certain lines are known for being calm or cantankerous. Three types of genetic disorders can occur in horses:

The classic Mendelian or “simple” genetic disorder, passed from one or more parents to the offspring. Most of the well-known disorders fall into this category. Take, for instance, the widely studied severe combined immunodeficiency (SCID), which primarily affects Arabian foals. Before we pull out some of the more technical genetic language, remember that each parent has two copies (alleles) of every gene and randomly gives one of the two copies to their offspring. The SCID disorder is an autosomal recessive mutation, which means two copies of the abnormal gene must be inherited—one from each parent, and not from the sex chromosomes—for the mutation to occur. With SCID the mutation occurs at a specific location on equine chromosome 9 (ECA9), resulting in foals without functional white blood cells, rendering them unable to launch immune responses against pathogens. 

Most other known genetic disorders described in this article are “simple,” following either recessive or dominant modes of inheritance similar to SCID. 

An abnormality in the number of DNA-containing chromosomes that a horse inherits from its parents. The most common type of this abnormality is the “63,X karyotype” that can occur in female horses. Instead of having a full set of 64 chromosomes (32 from the dam and 32 from the sire), including two X chromosomes, affected fillies are missing one X chromosome. Although viable and outwardly normal, they fail to develop a normal reproductive tract. This mutation is spontaneous rather than inherited. 

Genetic disorders arising from abnormalities of more than one gene. This third class of genetic mutation requires the input of several genes, rather than the one gene in simple disorders. With the sequencing of the entire horse genome, a number of equine conditions now have a “genetic” explanation. For example, it has long been suspected that osteochondrosis and recurrent laryngeal neuropathy (“roaring”) have a genetic basis, but researchers are still working to confirm this. 

Genetic Conditions by Breed

Arabians The most important simple genetic conditions affecting Arabians include SCID, lavender foal syndrome (LFS), and cerebellar abiotrophy (CA). 

Foals with SCID are highly susceptible to infections. At birth these foals appear normal because they are receiving antibodies from their dam’s colostrum. But by approximately 6-10 weeks they begin to develop infections that “normal” foals would be able to fight. Affected foals usually die by about five months of age due to a complete lack of B and T -lymphocytes—specialized white blood cells that produce antibodies required to fight infections.

The LFS genetic mutation occurs on ECA1 and results in a dilute coat color (often appearing silver or lavender) as well as fatal neurologic signs. These foals typically die or are euthanized within a few days of birth.

Cerebellar abiotrophy, a recessive genetic disorder due to a mutation on ECA2, results in a foal with an awkward gait, wide stance, and head tremors, among other signs that generally warrant euthanasia. Confirmed CA carriers have been detected very rarely among other breeds—generally those with strong Arabian lineage.

Researchers have described other genetic disorders of Arabians, but the exact location or nature of these mutations remains unknown. Examples include guttural pouch tympany (excess air in the guttural pouches), juvenile epilepsy syndrome (JES, seizures beginning around 6 months of age that typically resolve by 1-2 years of age), and occipitoatlantoaxial malformation (an abnormal fusion of the skull bones with the first cervical vertebra, causing incoordination and weakness). Researchers believe JES to be a dominant trait, with a potential link to LFS.

Quarter Horses Several specific genetic conditions beyond HYPP can plague Quarter Horses:

  • Polysaccharide storage myopathy (PSSM type 1) is caused by a dominant mutation in the GYS1 gene located on ECA10. Clinical signs of PSSM include muscle weakness and atrophy, reluctance to engage the hind end, and muscle soreness. Halter lines of Quarter Horses are affected far more frequently than other types. 
  • Malignant hyperthermia is a skeletal muscle abnormality caused by a specific mutation of ECA10. Inhalant anesthesia can trigger episodes characterized by severely increased body temperature, acidosis (a decrease in body pH), and sometimes death. 
  • Glycogen-branching enzyme deficiency is a mutation on ECA26 affecting a particular glycogen-storage enzyme that results in the overall malfunctioning of various muscles, including the heart. Clinical signs include abortion or stillbirths; if the foal survives until parturition, it experiences progressive weakness, seizures, respiratory and cardiac failure, and sudden death.
  • HERDA (hereditary equine regional dermal asthenia) is caused by a recessive mutation on ECA1. Affected horses have hyperelastic, easily tented skin that does not return to its natural position normally, and they readily develop seromas (fluid-filled pockets under the skin); open wounds that heal slowly; sloughed skin; scars; and white hairs in healed areas. 
  • Overo lethal white syndrome (OLWS) is an underlying recessive mutation caused by an abnormality on ECA17. It appears in newborn foals born to a variety of Paint horse patterns, including frame overo, highly white calico overo, frame blend overo, sabino, tobiano, and even solid-frame breeding stock. Affected foals are white or mostly white and show signs of colic and die within hours of birth. 

Draft Horses Two of the most important genetic conditions in draft horses are PSSM and junctional epidermolysis bullosa (JEB). According to researchers at the University of Minnesota Equine Center, PSSM type 1 prevalence in some draft horse breeds (that were randomly tested) can be quite high.

A recessive mutation on either ECA5 or 8 (two different versions of the condition exist) causes JEB. Affected foals form deep ulcers in the skin following even slight trauma, as well as eye and dental abnormalities. Hooves often slough and foals fail to thrive, prompting euthanasia. 

Warmbloods Researchers believe German Warmbloods have a genetic condition that causes guttural pouch tympany. In one report of a genome-wide analysis involving 373 German Warmbloods, researchers identified a region on ECA3 they say might be responsible, but they note that additional studies are needed to better characterize the exact genetic mutation. 

In a similar study scientists identified a region on ECA20 they think is responsible (or at least plays a role in) equine recurrent uveitis—a leading cause of blindness in Appaloosas, European Warmbloods, and draft horses. 

Friesians These horses appear to be prone to megaesophagus (chronic dilation of the esophagus), aortic rupture, dwarfism, and hydrocephalus (fluid on the brain). Researchers at The Fenway Foundation and the University of Wisconsin have been establishing Friesian breed-specific complete blood count and chemistry value reference intervals to help veterinarians better evaluate and treat these animals. Researchers (Lassaline-Utter, et al. 2014) also recently determined a genetic link between the breed and corneal dystrophy.

Standardbreds, Trotters, Thoroughbreds Though it’s rare, Thoroughbreds can produce foals with OLWS. Thoroughbreds are also known for tying-up, which is thought to have a genetic component. Researchers believe various developmental orthopedic diseases, such as osteochondrosis, have a genetic component in racehorse breeds, in particular. Additionally, in a recent study scientists identified a heritable component to atrial fibrillation (a heart arrhythmia) in horses.

A current genetic puzzle that Samantha Brooks, PhD, of the University of Florida, and colleagues at Cornell University and Michigan State are trying to decipher is the genetic basis for “roaring” in Thoroughbreds. The equine recurrent laryngeal nerve controls the arytenoid cartilages’ motion. If it does not work properly, the cartilages droop into the airway, impeding air flow to the lungs and causing a roaring sound as the horse breathes. Roaring is a common performance-limiting condition in both Thoroughbred racehorses (2-11%) and Draft horses (35-46%).

“Previous research suggests that taller horses are more likely to have recurrent laryngeal neuropathy (RLN) and that affected horses are more likely to produce foals with RLN,” Brooks says. “Both of those findings support a genetic basis to this condition, but few genetics studies have been conducted.”

Brooks and colleagues performed a genome-wide association of 282 affected Thoroughbreds and 268 normal Thoroughbreds, meaning they scanned each horse’s entire genome looking for markers that correlated with the disease, finding a location on ECA3 that appeared to be associated with RLN. That site was also associated with horses’ height, suggesting the link between this height marker and RLN. The study authors identified two other locations, one on ECA18 and one on the X chromosome, with candidate genes potentially capable of influencing muscle physiology and growth. 

“Our study results suggest that RLN is a polygenetic trait and that horses can be selectively bred to reduce the incidence of RLN, but that could result in slightly smaller horses,” Brooks says. “Additional studies further exploring the relationship between genetics, equine growth rate, and the prevalence of RLN are needed. In the long-term, this new genetic information will enable us to better manage RLN in horses.”

Testing for Genetic Disorders

Because the mass institution of equine chastity belts isn’t feasible, the best way to minimize the perpetuation of genetic disorders is testing. A wide range of tests is currently available and, as we’ve noted, some breed associations—such as those for Arabians and Quarter Horses—demand proof of certain test results before you can register your horse. Such groups have demonstrated the benefits to this practice. 

The goal is not to stop breeding carrier horses—and, thus, lose their gene pool—altogether, notes the World Arabian Horse Organization. Rather, testing can help breeders avoid crossing carriers with carriers while still retaining those bloodlines’ desirable pedigrees and associated traits.

In 2013 British researchers highlighted the benefits of genetic testing when they reported that they had identified the genetic mutation responsible for foal immunodeficiency syndrome (FIS) and successfully reduced disease incidence. This disorder, not to be confused with SCID, occurs in Fell and Dales ponies and is caused by a fatal recessive mutation that results in the lack of B lymphocytes. Scientists subsequently developed a test that revealed 38% of tested Fell ponies and 18% of breeding Dales were FIS carriers. After testing and avoiding carrier-to-carrier breeding, the number of affected foals decreased dramatically in just two to three years.

In addition to FIS, there are several other equine genetic diseases for which commercial tests are available (see chart on opposite page).

Take-Home Message

Genetic diseases are rarely as simple as a parent passing a single gene to his or her offspring, and researchers continue to identify “new” genetic conditions. Therefore, it behooves all horse owners to breed responsibly, research a horse’s genetic disease potential prior to purchase, and consider the importance of testing. The equine genome will continue to help scientists identify the genetic basis for many diseases and conditions and, potentially, novel treatments for affected horses.

About the Author

Stacey Oke, DVM, MSc

Stacey Oke, MSc, DVM, is a practicing veterinarian and freelance medical writer and editor. She is interested in both large and small animals, as well as complementary and alternative medicine. Since 2005, she's worked as a research consultant for nutritional supplement companies, assisted physicians and veterinarians in publishing research articles and textbooks, and written for a number of educational magazines and websites.

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