Horse Health & Disease Genes
Below we have briefly described the various health traits in our diagnostics panel. Keep in mind that these are meant to be basic summaries and provide you with "the least you need to know." Additional information, details and scientific references can be found when clicking of the title of the trait.
Androgen Insensitivity Syndrome (AIS), previously known as Testicular Feminization Sydrome, is a disorder of sexual development resulting in a female horse with XY chromosomes. Horses with AIS exhibit stallion-like behavior such as aggressive behavior toward other horses, Flehman response and vocalization toward cycling mares, and defecation within their enclosures. Typically the mare will have female sexual characteristics (external female genitalia) in addition to undescended testes. Horses can test as clear (N/N),carrier (AIS/N, one normal X chromosome), or affected (AIS/-, one Y chromosome).
Research Confidence: High confidence, findings reproduced in multiple studies
Cerebellar abiotrophy (CA) is a degenerative neurological disorder due to the death of large neurons (Purkinje cells) in the cerebellum. Foals affected by CA begin show symptoms between 6 weeks and 4 months of age. These horses display head tremors, lack of coordination, wide stances, exaggerated gait, difficulty rising, and startle easily. As this disease is an autosomal recessive condition, a horse must inherit two copies of the allele (CA/CA) to show any signs. Horses with only one copy of the allele (CA/N) are known as carriers due to their ability to produce affected foals.
Research Confidence: High confidence, findings reproduced in multiple studies
Also known as “non-sweater”, anhidrosis is the medical term describing a compromised or complete inability to sweat in response to increased body temperature. The presence of this variant indicates potential increased risk for developing chronic anhidrosis when exposed to environmental triggers, such as heat. This condition is dangerous and sometimes life-threatening for horses. Horses regulate their body temperature (thermoregulate) primarily through sweating, which is responsible for 65-70% of cooling, according to AAEP veterinarian Martha Mallicote DVM, Dipl. ACVIM. In the United States, cases of anhidrosis are more commonly observed in the hot and humid Southeastern regions. However, there are also reports in cooler climate regions like the Northern United States, Canada and even Ireland. Anhidrosis can affect several breeds of horses, although previous studies have demonstrated an increased incidence in Thoroughbreds and Warmbloods [1].
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Research Confidence: DISCOVERY STAGE, Cautious optimism
Dwarfism is characterized by abnormal growth, leading to either a disproportionate body type or overall smaller body size. There are many variants for Dwarfism including, but not limited to, ACAN 1-5 (originally found in miniature horses, and Shetland ponies), and B4GALT7 (originally founded in Friesian horses).
Research Confidence: Cautious optimism; findings require multiple studies and further validation
Equine herpesviruses are DNA viruses that are found in most horses all over the world. It is believed that almost all horses have been infected with the viruses and have, most of the time, no serious side effects. Recently, there has been a trend of increasing numbers of outbreaks of a devastating form of EHV-1. Following infection, some horses then suffer equine herpesvirus myeloencephalopathy (EHM), which is accompanied by serious and sometimes fatal neurological effects. Researchers have identified a genetic variant that correlates to a 1.43x increased risk of developing that neurological form (Equine Herpesvirus Myeloencephalopathy, EHM) if infected by Equine Herpes Virus type 1 (EHV-1). Testing for this genetic variant is now available. Explore how to better understand your horse’s risk of developing the neurological form (Equine Herpesvirus Myeloencephalopathy, EHM) if infected by Equine Herpes Virus type 1 (EHV-1).
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Research Confidence: DISCOVERY STAGE, Cautious optimism
Equine Recurrent Uveitis (ERU) is the most common cause of blindness in horses. It is thought to affect 3-15% of the horse population worldwide. With multiple causes, ERU may originate from environmental factors, ocular infection of Leptospira, a genetic predisposition or a combination of these factors. Characterized by episodes of inflammation of the middle layer of the eye, ERU leads to the development of cataracts, glaucoma and eventually complete loss of vision.
In a population of German Warmbloods, a SNP on ECA 20 proved significant in predicting horses affected by ERU...
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Research Confidence: VALIDATION STAGE, Moderate confidence, findings reproduced in some studies
Equine Metabolic Syndrome (EMS) is a wide-spread issue in the horse population. Primarily characterized by hyperinsulinemia (excess insulin circulating in the blood in relation to glucose levels), this metabolic disorder is often present in obese horses and ponies and can be challenging to diagnose as it can be misdiagnosed as "Cushing's" (a pituitary disfunction). Few treatments exist for EMS outside of diet management and exercise, which increases the need for early detection and prevention. Should obesity be allowed to set in, secondary chronic conditions, such as laminitis can easily follow and further compromise the health of the horse.
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Research Confidence: Cautious optimism; strong correlations, multi-breed validation in progress
Foal immunodeficiency syndrome (FIS) is a failure in the development of the adaptive immune system. At 3-6 weeks of age, once the maternal antibodies begin to degrade, foals exhibit signs of anemia, diarrhea, and pneumonia. As these foals fail to respond to treatment for infections, they are humanely euthanized at a young age. FIS is an autosomal recessive condition, thus a horse must inherit two copies of the allele (FIS/FIS) to show any signs. Horses with only one copy of the allele (FIS/N) are known as carriers due to their ability to produce affected foals.
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Research Confidence: High confidence, findings reproduced in multiple studies
Glycogen branching enzyme deficiency is a lethal recessive disorder characterized by seizures, muscle weakness, respiratory failure, and death. Many affected foals do not make it full term and are aborted or stillborn. Carriers (GBED/N) have no known issues. This disorder is analogous to glycogen storage disease type IV in humans and Norwegian forest cats. Studies have indicated that between 4-11% of registered American Quarter Horses and American Paint Horses carry the GBED mutation.
Research Confidence: High confidence, findings reproduced in multiple studies
Glanzmann Thrombasthenia (GT) is an inherited blood platelet function disorder, resulting from a reduction in the platelet fibrinogen receptor protein. Clinical signs can be characterized by bleeding on the skin or from the mouth/nostril/gastrointestinal mucosas, and may include skin rashes with blood spots under the skin, nasal bleeding, gastrointestinal and gingival bleedings. Two mutations in the gene encoding platelet glycoprotein IIb, Integrin Alpha-2B (ITGA2B), have been implicated in the GT condition. Although GT has been associated with a recessive mode of inheritance, heterozygous combinations from both variants have been implicated in GT cases. GT can be a differential diagnosis ​for horses with platelet-type bleeding, especially nasal bleeding not related to exercise or of unknown origin (not thrombocytopenic or from von Willebrand disease).
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Research Confidence: Discovery; findings require further validation.
Hereditary equine regional dermal asthenia (HERDA) is a degenerative skin disease that primarily affects the American Quarter Horse breed. Loose skin is often an early indication of the disease, and severe seromas, hematomas, ulcerations usually develop around 1.5 years of age and progressively worsen. There is no cure, and the majority of affected animals have to be euthanized within 2-4 years. Although the exact cause of the condition is not known, it likely involves an inability to properly regulate inflammation and wound healing. The condition tracks as a recessive disease, meaning that horses can appear normal but be carriers for the condition. If two carrier horses mate, there is a 25% chance that the foal will have HERDA. Studies estimate that ~3.5% of Quarter Horses are carriers.
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Research Confidence: High confidence, findings reproduced in multiple studies
Hoof wall separation disease is characterized by separation and breakage of the dorsal hoof wall extending up from the sole. Affected ponies begin showing symptoms at less than 6 months of age, and often develop chronic laminitis. Frequent hoof trimming and glue on shoes can help manage the condition. Hoof wall separation disease is an autosomal recessive disorder, thus a pony must inherit two copies (HWSD/HWSD) to show symptoms. Ponies with only one allele (HWSD/N) are known as carriers due to their ability to produce affected offspring.
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Research Confidence: High confidence, findings reproduced in multiple studies
Hydrocephalus is an abnormal build up of cerebral spinal fluid around the brain.In the Friesian, it is believed that a narrowing of a passage within the brain prevents normal fluid absorption, leading to an obvious external cranial distension. Affected foals are often stillborn and are associated with dystocia in the dams. Hydrocephalus is an autosomal recessive disorder, thus a foal must inherit two copies of the mutant allele to be affected. Horses with only one copy of the allele are known as carriers due to their ability to produce an affected foal.
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Research Confidence: Moderate confidence, findings reproduced in some studies
Hyperkalemic Periodic Paralysis (HYPP) is a dominant genetic disorder resulting from defects in sodium channels in the muscle. Affected animals experience episodes of muscular weakness or tremors, and can lead to paralysis, collapse, and sudden death. Heterozygous horses (HYPP/N) experience moderate symptoms that can usually be managed through diet and exercise. However, homozygous horses (HYPP/HYPP) are much more severely affected, and some breed registries will not accept these animals.
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Research Confidence: High confidence, findings reproduced in multiple studies
Immune-mediated myositis (IMM) is an autoimmune disease which, when triggered by an infection, or certain vaccinations (i.e. influenza) can cause severe muscle loss (atrophy) within a period of 3 days (up to 40% in 72 hours). Target areas of atrophy include the gluteal and vertebral regions (hind end and topline) as the characteristic inflammation attacks the muscle fibers and surrounding blood vessels. Symptoms include general malaise, muscle stiffness and overall weakness, not associated with exercise, and usually affects horses older than 17 or younger than 8 years of age.
Research Confidence: *DISCOVERY STAGE, Caution is recommended; findings require multiple studies and further validation
In normal fertilization, the the head of a sperm binds to the egg and releases the contents of a structure known as the acrosome. However, some males have otherwise normal sperm that are unable to properly
carry out this process, leading to sub- or infertility due to impaired acrosome reaction. Very little is known about the genetics of male fertility. One study of 7 horses with known IAR, 87 known fertile stallions, and 171 male horses of unknown fertility status found an association with two SNPs in the FKBP6 gene. All 7 case stallions had genotype A/A for both variants, as compared to only 2 known fertile stallions and 3 unknown fertility males. The authors noted that fertility was defined as having at least one foal, though even males with IAR can rarely produce offspring.
Research Confidence: DISCOVERY STAGE, Cautious optimism; findings require multiple studies and further validation
Junctional Epidermolysis Bullosa (JEB), also known as red foot disease or hairless foal syndrome, results in the inability to produce the proteins needed to keep the skin on the body. Affected foals exhibit symptoms within days of birth, including blisters at the pressure points, detatchment of the hooves, and oral ulcers. As there is no treatment, affected foals are humanely euthanized. JEB is an autosomal recessive condition, thus a horse must inherit two copies of the allele (JEB/JEB) to show any signs. Horses with only one copy of the allele (JEB/N) are known as carriers due to their ability to produce affected foals. JEB1 affects Belgians, whereas JEB2 is found in Saddlebreds.​
Research Confidence: High confidence, findings reproduced in multiple studies
Lavender foal syndrome (LFS), also known as coat color dilution lethal, is a neurological dysfunction in newborn foals. Symptoms are apparent at birth and include seizures, severe hyper-extension of limbs, neck and back, stiff paddling leg movements, involuntary eye movement and inability to stand or sit upright. The coat usually has a dilute color that ranges in shade from silver to a pale lavender/pink. As there is no treatment, affected foals are humanely euthanized. LFS is an autosomal recessive condition, thus a horse must inherit two copies of the allele (LFS/LFS) to show any signs. Horses with only one copy of the allele (LFS/N) are known as carriers due to their ability to produce affected foals.
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Research Confidence: High confidence, findings reproduced in multiple studies
Lordosis, also known as "Swayback", is a curvature or dip in the spine that is often seen in older horses. However, in the American Saddlebred, this condition also affects younger horses. These animals do not appear to experience pain from their condition and are still able to be used under saddle. The genetics are likely complex and poorly understood.
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Research Confidence: DISCOVERY STAGE, Cautious Optimism; findings require multiple studies and further validation
Malignant hyperthermia (MH) is a muscle disorder in which anesthesia, stress, or extreme exercise trigger a hyperthermic state. Symptoms include high temperature, increased heart rate, high blood pressure, sweating, acidosis, and muscle rigidity. If symptoms are not immediately resolved, death is likely to occur. As this condition is autosomal dominant, even horses with a single allele (MH/N) exhibit symptoms. One study has shown that horses with both MH and polysaccharide storage myopathy (PSSM) have more severe clinical symptoms.
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Research Confidence: High confidence, findings reproduced in multiple studies
Myotonia is a rare disorder involving a slowed relaxation of muscles after contraction. The most well-known example of myotonia is “fainting goats,” a breed that is characterized by sudden rigidy and/or falling over when startled. In the single documented horse, this resulted in a protruding third eyelid when excited, as well as problems with muscle stiffness (and thus difficulty in rising and movement). This mutation is believed to be a more recent occurrence within the New Forest Pony breed.
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Research Confidence: VALIDATION STAGE, Moderate confidence, findings reproduced in some studies
Polysaccharide Storage Myopathy (PSSM) is a glycogen storage disorder in which affected horses have chronic episodes of exertional rhabdomyolysis (“tying-up”). Acute symptoms are an unwillingness to move and muscle damage following exercise. Heterozygous horses (PSSM1/N) experience moderate symptoms that can usually be managed through a low-sugar/starch diet and exercise. However, homozygous horses (PSSM1/PSSM1) are generally more severely affected and are thus harder to manage. Additionally, one study has found that horses with PSSM1 and a malignant hyperthermia (MH) exhibit more severe clinical symptoms.
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Research Confidence: High confidence, findings reproduced in multiple studies
Recurrent Laryngeal Neuropathy (RLN) is a disease that results in loss of the neurons that open the larynx. Although we do not know what causes RLN, it significantly affects performance in Thoroughbreds and other sport horses. In technical terms, RLN represents a distal axonopathy of the recurrent laryngeal nerves, which is typically expressed only on the left side of the larynx (the left nerve is the longest nerve in horses). RLN is also a mononeuropathy, as other peripheral nerves of the horse remain unaffected. RLN is an important issue for horses in competitive events, because the resultant paralysis of the larynx leads to obstruction of air flow during intense exercise. This obstruction creates the abnormal inspiratory noise that gives RLN its common name: “roaring”.
Research Confidence: VALIDATION STAGE, Moderate confidence, findings reproduced in multiple studies
Severe Combined Immunodeficiency disease is a condition in which a foal has essentially no immune system due to a complete absence of B and T lymphocytes. Affected foals are unable to mount an effective immune response after infection and are unable to recover from infections that unaffected foals would easily resist. The disease is universally fatal in horses, usually within 4-6 months of life. It is a recessive trait, meaning that it requires two mutant alleles to manifest; animals carrying just one copy of the mutant allele are completely healthy and are “carriers”, meaning that they can pass the mutation to their offspring. If two carrier horses mate, there is a 25% chance that the foal will have SCID. It has only been detected in horses of Arabian descent, and studies have determined that ~8% of Arabian horses are carriers of the SCID allele.
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Research Confidence: High confidence, findings reproduced in multiple studies
Squamous Cell Carcinoma is the most common cause of eye cancer in horses. It is also responsible for a large percentage of tumors throughout other parts of the equine body. A recent correlation was discovered between Squamous Cell Carcinoma (SCC) and the DDB2 genetic region. A mutation identified in that region is hypothesized to affect the protein's active role of identifying and signaling DNA regions damaged by UV light for additional “repair” protein mechanisms which attempt to restore the region and thus, prevent tumor or cancer formation. This mutation for Squamous Cell Carcinoma is currently thought an autosomal recessive disorder, thus a horse must inherit two copies (scc/scc) to be at a greatly increased risk for cancer.
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Research Confidence: DISCOVERY STAGE
Cautious optimism, findings in Haflingers and Belgians, but require further studies and validation
"Warmblood" fragile foal syndrome is a connective tissue disorder resulting in joint laxity and extremely thin skin that is only loosely connected to the body. The skin is easily torn, resulting in lacerations, hematomas, and seromas across the foal. Affected foals are euthanized shortly after birth. As Fragile Foal Syndrome is a recessive disorder, horses must inherit two copies (wffs/wffs) to show the disease. Horses with only one allele (wffs/N) are known as carriers due to their ability to produce affected offspring. This disorder is not limited to the Warmblood horse and has been found in many breeds.
Research Confidence: VALIDATION STAGE, Moderate confidence, findings reproduced in some studies
West Nile Virus is a mosquito-borne virus that can infect multiple types of mammals, including horses. Infection can lead to a series of severe symptoms, most commonly encephalitis – acute inflammation of the brain. Severe neurological symptoms develop in ~8% of exposed horses, and once symptoms manifest, the fatality rate ranges from 20-40% and is higher in older horses. Originally found in Africa, it spread to the United States in 1999 and equine cases are currently reported on all continents. Cases of WNV peaked in the USA in 2002, with over fifteen thousands equine cases reported; it has since declined due to the introduction of an equine vaccine.
Research Confidence: DISCOVERY STAGE, Cautious optimism, findings reproduced in other mammals, but require further studies and validation
