Allele Frequencies of Inherited Diseases in the American Quarter Horse
ACVIM 2008
Danika Bannasch, DVM, PhD
Davis, CA, USA

Inherited Diseases

A number of inherited diseases in the American Quarter Horse have been characterized at the molecular level. This has led to the commercialization of DNA tests for breeders. The American Quarter Horse Association and the American Quarter Horse Foundation have been providing funding for research on inherited diseases in this breed for many years culminating in the availability of these tests for this particular breed. In addition to disease tests there are a number of DNA based tests for coat color available for the American Quarter horse as well as other breeds which will not be addressed in this session.

A candidate gene approach identified a mutation in the sodium channel SCN4A which is responsible for potassium-induced paralysis, commonly known as hyperkalemic periodic paralysis (HYPP).1 This disease is inherited as a semi-dominant disorder meaning that animals that carry one copy of the mutation show a phenotype (muscle hypertrophy and sometimes attacks of paralysis) whereas animals with two copies of the mutation have a more severe phenotype. In fact, homozygous animals are often euthanized due to the severity of their clinical signs.2 This disease is thought to be more common in "halter" type Quarter horses.

Three research groups independently identified a two base pair mutation in the endothelin B receptor (EDNRB) as the cause of Lethal White Foal Syndrome (LWFS).3,4,5 This disease is seen most commonly in the American Paint horse, a breed related to the American Quarter Horse; however there have been reports in the literature of purebred American Quarter Horses carrying the mutation.4,6 LWFS is also inherited as a semi-dominant disease since animals carrying one copy of the mutation exhibit white spotting in the coat and sometimes deafness while animals carrying two copies are born completely white, deaf and have aganglionic megacolon which is always ultimately lethal. This disease is clearly more common in the American Paint Horse breed which registers American Quarter Horse and Thoroughbreds born with white spotting.

The molecular basis for a disease of abnormal glycogen accumulation has been determined to be a mutation in the glycogen branching enzyme.7 Glycogen branching enzyme deficiency (GBED) is inherited as an autosomal recessive disorder and presents either as late term abortions or early neonatal mortality.8 The recessive nature of the disease means that animals carrying one copy of the mutation are completely normal. Animals must carry two copies of the mutation in order to be affected with the disorder.

Recently, the mutation that causes the inherited skin disease hereditary equine regional dermal asthenia (HERDA) has been identified. This disease is characterized by young adult onset of dorsalized skin lesions. There are currently no treatment options for this disease and affected horses cannot be ridden due to the severity of the lesions. HERDA is caused by a mutation in the cyclophilin B (PPIB) gene.9 It is also inherited as an autosomal recessive disorder so carriers display no obvious phenotype.10

Most recently, the mutation that causes one form of dominant polysaccharide storage myopathy (PSSM) has been reported.11 This disease is inherited as an autosomal dominant trait meaning that animals will show clinical signs of the disease when they carry only one copy of the mutation.

These five disease mutation tests are, or soon will be, available commercially. Costs for the currently available tests are $40-$50. Two factors are important for determining which animals should be tested for these diseases. The first is the severity of the disease phenotype. The second is the allele frequency of the disease paired with the mode of inheritance. The costs of the tests are so reasonable (less than the cost of a CBC) that money should not be the deciding factor.

Subpopulations Within the American Quarter Horse

The American Quarter Horse is one of the largest breeds of horse in the world. The world population size has been estimated at 3.24 million.12 The breed originated as a ranch horse used to handle the large groups of cattle needed to feed the American expansion out west. The breed name came from the fact that Quarter horses are the fastest horses over short distances (1/4 of a mile). Today American Quarter Horses are still used to handle cattle but they also compete in the show ring. Within this large diverse population, subtypes have emerged that excel at particular aspects of the competition. Some of the competitions are based on structure (halter), others on skills that were necessary for a working horse (cutting, reining, working cow horse) and still others based on speed (barrel racing and racing). Breeders refined and selected for attributes that gave their horses the winning edge within each discipline. Today, although these horses are registered as one, there are clearly distinct subtypes of American Quarter horses. The top winning cutting horse and top winning halter horse look so different from each other that they could be mistaken for different breeds.

The inherited diseases described above are popularly known to occur in specific subtypes of the breed. The diseases most relevant to a breeder of halter style American Quarter Horses might not be the same as those important for breeders of reining horses. In order to investigate this difference, a means of defining a horse into a subtype is necessary. Towards this end, we used DNA samples from elite performance horses from the different relevant divisions of the breed: Halter, Pleasure, Cutting, Reining, Working Cow Horse, Barrel racing and Racing, in order to estimate allele frequencies within the subpopulations.

Estimates of Allele Frequencies

The allele frequency is the frequency that a disease mutation occurs within the population. Since all horses have two copies of each gene, the population has twice as many alleles as individuals. The allele frequency is calculated as the percentage of relative frequency of the allele amongst all alleles present. For recessive traits, the carrier frequency is also an important number for breeders and counselors to know. It is the frequency of individuals heterozygous for the mutation. For lethal disorders, the carrier frequency is twice the allele frequency. Accurate estimates of allele frequencies are difficult to obtain. Often researchers working on the disease only have access to a biased sample set since they have usually collected DNA from affected animals and their relatives. Testing laboratories have equally biased sample sets since tests will often be submitted for animals related to affected animals. The ideal sample set for estimating the population allele frequency will be unbiased with respect to research on the disease and voluntary submission by owners.

Estimates of the breed allele frequencies of the five diseases found in the American Quarter Horse and American Paint horse were determined. The American Quarter Horse breed has high allele frequencies for PSSM (0.06) and GBED (0.06), with a lower, yet significant, prevalence of HERDA (0.02) and HYPP (0.008). American Paint Horses have a notably high allele frequency for LWFS (0.11) and an increased risk of HYPP (0.03) relative to American Quarter Horses. Estimates of the allele frequencies within subpopulations of the American Quarter Horse breed revealed significant differences between subpopulations. Halter horses had high allele frequencies of both HYPP (O.30) and PSSM (0.15), while cutting horses had high allele frequencies for HERDA (0.14). Barrel racing and racing horses had very low allele frequencies for these five diseases. Pleasure, reining and working cow horses had intermediate levels of PSSM, HERDA and GBED.


The mode of inheritance is important to factor into discussions of counseling. If a horse with a dominant disorder is bred, 50% of its offspring will also have the disease. If two carriers of a recessive disorder are bred to each other, 25% of the offspring will be affected with the disorder. It is possible to maintain a recessive disease allele in the population by testing each generation in order to identify future carriers and avoid producing affected progeny. This is done quite commonly in dog breeds with small gene pools in order to maintain diversity. In the case of dominant disorders, an affected horse that is bred will produce affected progeny and there is no way to avoid this with managed breeding. For a disease like LWFS where heterozygous animals display a coat color phenotype but not a disease, management can be accomplished with careful breeding decisions. Now that the tools are available, the ultimate goal of all breeders should be to eliminate these inherited diseases.


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12. American Quarter Horse Association website. Accessed January 3, 2008.

Speaker Information
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Danika Bannasch, DVM, PhD
University of California
Davis, CA