Equine Genetics and Genomics

Course Information

Course Description

Genetic testing in horses has exploded. Panels from Animal Genetics, the UC Davis Veterinary Genetics Laboratory (VGL), Etalon, and every breed registry are in circulation, and direct-to-consumer results now reach the exam room faster than most practitioners can interpret them. Owners arrive expecting guidance on which results are actionable and which heritable diseases warrant clinical attention—yet most general practitioners have never had a single CE hour on how to read a genetic report. This two-hour program closes that gap. These notes cover four core areas:

• Genetics for Veterinarians: The first-principles foundation needed to read a report without opening a textbook—Mendelian inheritance, codominance and sex linkage, penetrance and expressivity, heterozygous versus homozygous implications, and population-level risk.
• Reading the Direct-to-Consumer Panel: What each commercial laboratory actually measures, where panels disagree, and the specific situations in which a commercial result rules a disease in, out, or neither.
• Mendelian Diseases of the Horse: The clinically important heritable diseases you will encounter—HYPP, PSSM1 and PSSM2, GBED, HERDA, lavender foal syndrome, overo lethal white syndrome, SCID, and JEB—with breed prevalence, clinical signs, and confirmatory diagnostics.
• When Testing Changes Management: The scenarios in which a result changes the plan—breeding decisions, recurrent tying-up, foal mortality—and the common situations where a panel will not change what you do, so you do not sell a client a test that does not earn its keep.

Genetics for Veterinarians

Presenter: Dr. Sian Durward-Akhurst, BVMS, MS, PhD, DACVIM (LAIM)

The first lecture builds the framework needed to read any equine genetic report without reaching for a textbook. A genetic test reports a genotype at one or more loci, and translating that genotype into a clinical statement depends on understanding the inheritance pattern of the trait in question. Horses carry two copies of every autosomal gene, one inherited from each parent. When the two copies at a locus are identical the horse is homozygous; when they differ it is heterozygous. Conventional reporting uses N for the normal (wild-type) allele and a disease-specific letter for the mutation—so a report of N/N indicates a horse that carries no copy of the mutation, N/H indicates a heterozygote, and H/H indicates a homozygote for the mutation. What those genotypes mean for the horse in front of you depends entirely on the inheritance pattern.

Inheritance Patterns That Matter

Most equine genetic diseases follow recognisable Mendelian patterns. In autosomal recessive inheritance a horse must carry two copies of the mutation (H/H) to be affected; a single copy (N/H) makes the horse a clinically normal carrier that can nonetheless pass the mutation to offspring. GBED, HERDA, lavender foal syndrome, SCID, and JEB all follow this pattern, which is why carrier status drives breeding decisions rather than clinical management. In autosomal dominant inheritance a single copy is sufficient to produce disease—HYPP is the classic equine example, where one copy of the mutation in the descendant line of the stallion Impressive can produce clinical signs. Codominant traits express both alleles, so a heterozygote shows an intermediate phenotype, while sex-linked traits map to the sex chromosomes and follow inheritance patterns that differ between colts and fillies.

Penetrance, Expressivity, and Why Genotype Is Not Destiny

Two concepts explain why horses with the same genotype can look different. Penetrance is the proportion of horses with a disease-causing genotype that actually show the phenotype; with incomplete penetrance, some genotypically affected horses appear clinically normal. Expressivity describes the range of severity among horses that do express the trait—the same mutation can cause mild signs in one horse and severe disease in another. Penetrance and expressivity are influenced by zygosity (homozygotes are frequently more severely affected than heterozygotes), modifier genes, and environment. This is why a positive test does not always predict clinical disease, and why a careful clinician interprets a genotype alongside breed, lineage, and the clinical picture rather than treating the report as a verdict.

Population Genetics and Breed-Level Risk

Disease-causing alleles are not distributed evenly across the equine population; they cluster in breeds and bloodlines because of founder effects and selective breeding. HYPP traces to a single influential Quarter Horse stallion; HERDA, GBED, and PSSM1 are concentrated in specific Quarter Horse and stock-horse lines; HERDA and lavender foal syndrome and SCID are Arabian-associated; JEB is seen in draught breeds such as the Belgian. Knowing the breed-level prevalence of each allele lets the practitioner reason about pre-test probability: a recommendation to test for HYPP is sensible in an Impressive-line Quarter Horse and largely pointless in a breed where the allele does not occur. Population genetics, in short, is what turns a menu of available tests into a defensible, breed-specific testing plan.

Reading the Direct-to-Consumer Panel

Presenter: Dr. Sian Durward-Akhurst, BVMS, MS, PhD, DACVIM (LAIM)

Direct-to-consumer genetic panels are now a fixture of equine practice, and the general practitioner is increasingly the person an owner asks to interpret one. Several laboratories dominate the market—Animal Genetics, the UC Davis Veterinary Genetics Laboratory (VGL), and Etalon among them—alongside breed-registry panels such as the AQHA five-panel test required for some Quarter Horse registrations. Each laboratory tests a defined set of variants, and the panels do not all cover the same conditions. The first task in reading any report is therefore simply to establish what the panel did and did not test for, because a result is only as informative as the variant it interrogated.

What a Commercial Test Actually Measures

A commercial genetic test typically genotypes one or a small number of specific, validated variants known to cause or associate with a disease. For a disease caused by a single well-characterised mutation—HYPP, GBED, HERDA, or PSSM1, for example—a panel that interrogates that exact variant gives a reliable answer about that variant. The crucial limitation is that a negative result for a defined variant does not exclude every form of the disease, only the form caused by the tested variant. This matters most for conditions like PSSM2, where the commercial markers offered by some laboratories are not validated to the same standard as the GYS1 mutation that defines PSSM1, and a result must be interpreted with corresponding caution.

Where the Panels Disagree

Laboratories can report apparently conflicting results when they test different variants, use different reference assays, or include research-grade markers of uncertain clinical significance alongside validated ones. A “carrier” result means something very different from one disease to the next: for an autosomal recessive condition a carrier is a clinically normal horse whose status matters only for breeding, whereas for an autosomal dominant condition a single copy means the horse itself is at risk. Translating the report therefore requires pairing each result with the correct inheritance pattern before any conversation with the owner. When a result is internally inconsistent, or a commercial marker is not validated, the appropriate next step is confirmatory testing at a reference laboratory rather than acting on the panel alone.

Rules In, Rules Out, or Neither

The practical question for every reported result is whether it rules the disease in, rules it out, or does neither. A validated test for a fully penetrant variant such as HYPP effectively rules that variant in or out. For a recessive disease, an N/N result rules out that the horse will develop the condition and rules out transmission, while an N/H result rules in carrier status without predicting clinical disease. For conditions with incomplete penetrance, even a positive genotype does not guarantee the phenotype, so the result informs probability rather than delivering a diagnosis. Framing each result in these terms keeps interpretation honest and prevents both false reassurance and unnecessary alarm.

Mendelian Diseases of the Horse

Presenter: Dr. Sian Durward-Akhurst, BVMS, MS, PhD, DACVIM (LAIM)

The second lecture is a clinical walkthrough of the heritable diseases an equine general practitioner will encounter, whether or not a panel is run. Each disease is anchored to a breed, an inheritance pattern, and a recognisable clinical picture, so that the practitioner can connect a presenting horse to the right confirmatory test rather than working blind.

Muscle and Metabolic Diseases

Hyperkalaemic periodic paralysis (HYPP) is an autosomal dominant disorder of the sodium channel traced to the Quarter Horse stallion Impressive. Affected horses experience episodic muscle weakness, fasciculations, and—in severe episodes—respiratory compromise and cardiac arrhythmias associated with hyperkalaemia. Because it is dominant, even a single copy (N/H) can produce clinical signs, and management combines a consistent low-potassium diet with breeding decisions that aim to eliminate the allele. Polysaccharide storage myopathy comes in two forms: PSSM1 is caused by a defined mutation in the GYS1 gene and is reliably detectable by genetic testing, whereas PSSM2 is a clinically defined entity whose commercial markers are far less validated. Both present with tying-up, exercise intolerance, and muscle stiffness, and both are managed primarily through diet (low starch and sugar, added fat) and regular exercise.

Lethal Recessive Diseases of the Foal

Glycogen branching enzyme deficiency (GBED) is an autosomal recessive disease of Quarter Horse and Paint foals that present stillborn, persistently weak, or profoundly hypoglycaemic, because affected foals cannot store and mobilise glycogen; it is uniformly fatal, so the value of testing is entirely in identifying carrier breeding stock. Overo lethal white syndrome (OLWS) is an autosomal recessive condition of overo-patterned Paints in which homozygous foals are born predominantly white and die of intestinal aganglionosis; the Paint breeding math is the practical lesson, since mating two carriers risks a lethal white foal. Severe combined immunodeficiency (SCID) in Arabians and junctional epidermolysis bullosa (JEB) in Belgians and other draught breeds are likewise autosomal recessive and fatal—SCID through absent adaptive immunity and overwhelming infection, JEB through catastrophic sloughing of skin and hoof in the neonate.

Connective Tissue and Coat-Linked Diseases

Hereditary equine regional dermal asthenia (HERDA) is an autosomal recessive collagen disorder concentrated in cutting-bred Quarter Horses, in which the skin—particularly along the back—is fragile, splits under saddle pressure, and heals poorly, typically becoming apparent as the horse enters training. Lavender foal syndrome is an autosomal recessive disease of Arabian foals, especially Egyptian lines, that combines a characteristic dilute (lavender) coat colour with severe neurologic signs from birth. In each case the genetics explain a clinical picture the practitioner may otherwise struggle to attribute, and a carrier test protects future matings.

When Testing Changes Management

Presenter: Dr. Sian Durward-Akhurst, BVMS, MS, PhD, DACVIM (LAIM)

The final theme ties interpretation to action: a genetic result is only worth obtaining when it changes a decision. The clinician's job is to identify the scenarios in which a test alters management and to recognise—just as importantly—the scenarios in which it does not, so that owners are not sold panels that cannot earn their keep.

Scenarios Where Testing Changes the Plan

Three situations reliably justify testing. The pre-purchase examination of a breeding prospect is the clearest: carrier status for a recessive disease, or affected status for a dominant one, directly informs the value and intended use of the horse and the matings it can safely enter. The horse with recurrent tying-up is another, where a GYS1 (PSSM1) result can confirm a heritable myopathy and commit the owner to lifelong dietary and exercise management rather than repeated symptomatic treatment. Foal mortality on a breeding farm is the third—recurrent stillbirths, lethal white foals, or neonatal deaths point toward a recessive disease shared by the mating pair, and testing the breeding stock identifies the carriers that should not be paired again.

When a Panel Will Not Change What You Do

Equally important is the discipline to decline testing that cannot change management. A mature gelding with no breeding future and no clinical signs rarely benefits from a broad panel; an owner’s curiosity is not, on its own, a clinical indication. For conditions where commercial markers are poorly validated—as with some PSSM2 panels—a result may generate more uncertainty than guidance, and the honest recommendation is often to manage the horse on its clinical signs rather than to chase an unvalidated genotype. Recommending against a USD 200 panel that will not alter the plan is sound medicine and builds the trust that makes the next, genuinely useful recommendation credible.

Counseling the Breeder and the Buyer

For recessive diseases the counseling message is consistent: a carrier (N/H) horse is clinically normal and need not be removed from a breeding programme, but it must never be mated to another carrier of the same disease, because each such mating risks an affected (H/H) foal. For dominant diseases such as HYPP, even a single copy carries clinical and welfare implications, and the conversation extends to whether the allele should be propagated at all. Framing each result in terms of what the owner should actually do next—mate, do not mate, manage by diet, or simply monitor—turns a genotype into a decision and is the skill this course is built to develop.

Summary

Reading an equine genetic report rests on a small set of durable principles: identify the inheritance pattern, translate N/N, N/H, and H/H against that pattern, weigh penetrance and expressivity before predicting a phenotype, and anchor every recommendation in breed-level prevalence. The commercial panels measure defined variants, so a negative result excludes only the tested variant, and conflicting or unvalidated markers warrant confirmatory testing. The Mendelian diseases—HYPP, PSSM1 and PSSM2, GBED, HERDA, lavender foal syndrome, OLWS, SCID, and JEB—each map to a breed, a clinical picture, and a confirmatory test. Used together, this framework lets the practitioner order the tests that change a decision, decline the ones that do not, and counsel owners and breeders in terms of the action a result demands.