Updated on genetic disease in quarter horses and related breeds (Proceedings)

Aug 01, 2010

The Big '6' Genetic Disorders

      1. HERDA
      2. PSSM*
      3. GBED*
      4. HYPP
      5. MH
      6. OLWS

Allele definitions

     • Allele – versions of a gene. Every animal has two alleles (one from each parent)
     • For diseases, there is a 'disease allele' (or gene mutation) and a 'normal allele' present in the population.
     • 'Allele frequency' is an estimate of the frequency of the disease allele in a population


     • Hereditary Equine Regional Dermal Asthenia
     • Quarter horses and related breeds
     • Collagen problem
     • Seromas, hematomas and ulceration primarily along the dorsal aspect, some legs and other
     • Progressive skin disease: age of onset: 1.5-2 years of age
     • Skin has a hyperextensible quality
     • Mutation identified: cyclophilin B gene (PPIB) (Tyron, et al Genomics 2007)
     • Autosomal recessive
     • Heterozygotes are clinically unaffected


     • Polysaccharide Storage Myopathy
     • EPSM – Equine Polysaccharide Storage Myopathy
     • Caused by a mutation in a gene regulating glycogen synthesis
               o Glycogen synthase 1 (GYS1) gene mutation
     • Accumulation of an abnormal glycogen in muscle cells
     • This form of glycogen cannot be used for energy
     • Leads to muscle stiffness, weakness, pain, poor performance and tying up
     • Triggering events:
          o Stress
          o Weaning
          o Onset of training
          o Prolonged rest followed by work
          o High grain (starch, sugar) diets
     • Average age of onset of clinical signs is 5 years
     • Affects a large number of breeds, but most common in:
          o Quarter horses and related breeds
          o Draft horses
     • Dominant gene
          o Only requires one copy of the gene for the horse to be affected
          › Therefore, only one parent must carry the gene
     • At least two forms of the disease in Quarter Horses
          o PSSM type 1 – most common and has a genetic test
          o Type 2 – no DNA test available yet
          o Other forms?


     • Muscle biopsy – diagnosis of both forms of PSSM
          o University of California
          o University of Minnesota
     • DNA test – currently only available for PSSM type 1
          o University of Minnesota


     • Decrease stress
     • Keep the horses fit
          o Regular exercise
          o As much turn out time as possible
     • Strict adherence to diet
          o Low starch and sugar diet
     • No grain/molasses
     • Replace grain calories with fat sources
          o Grass hays are the best hay source
          o Vitamin E and selenium supplementation

GBED-Glycogen Branching Enzyme Deficiency

     • "Glycogen Storage Disease IV"
     • Stop codon in the glycogen branching enzyme gene (GBE1 gene)
     • Affected animals produce an abnormal, less branched glycogen that cannot be utilized for energy
     • The disease is lethal
     • Recessive gene
          o Carriers are phenotypically normal
          o Affected foals die
     • Causes abortion and neonatal mortality
     • Foals are weak from birth
          o Cannot regulate blood glucose
          o Contracted tendons
          o Muscle, liver, heart and lung problems
     • All die by a few weeks of age
     • Diagnosis:
          o Genetic (DNA) test: University of Minnesota
     • This disease is 100 % preventable
          o Identify carriers and don't breed carrier to carrier


     • Mutation in the alpha-subunit of the muscle sodium channel gene
     • Abnormal sodium channels don't close normally, leading to potassium-inducible episodes of muscle fasciculations, contraction followed by paralysis
     • Semi-dominant trait
          o Homozygotes are more severely affected than heterozygotes, but both affected
     • Fasciculations, sweating, anxiety, respiratory noise
     • Weakness, dog-sitting, paralysis
     • Not a true seizure – horses are completely aware
     • Homozygotes exhibit dysphagia or airway narrowing
     • Both NH and HH horses can die during an episode due to complete airway closure or cardiac arrhythmias

Diagnosis and Treatment

     • DNA testing – mandatory of all Impressive descendants in AQHA
     • Management:
          o Low potassium diet (< 1-1.5 % of diet) –No alfalfa, brome, molasses...
          o Acetazolamide
          o Minimize stress
          o Small frequent feedings
          o Regular exercise
     • The AQHA has recently taken a stand to begin elimination of the trait.
     • Beginning with the 2007 foal crop, any homozygous animals can not be registered.
     • H/H horses are completely 100% avoidable
          o Never cross NH to NH

Malignant Hyperthermia

     • MH
     • Newly recognized, still a lot to learn about this disease
     • Dominant gene: Mutation in the Ryanodine Receptor 1 gene
     • Homozygous state lethal in utero?

Clinical findings

     • First cases were found under anesthesia
          o High fevers (> 104 °F)
          o Hypercontraction of muscles
          o Rapid death with rigor mortis
     • Now recognizing cases without anesthesia
          o May appear relatively normal, although heavily muscled
          o Stress seems to play a role with precipitating attacks
          o Severe, rapid myositis (tie up)
          o Persistent fevers and elevated muscle enzymes
     • Well defined and heavy muscles


     • DNA test – University of California, Davis
          o Dr Monica Aleman –Neuromuscular Lab

Overo Lethal White Syndrome
  Ileocecocolic aganglionosis
     • All or nearly all white foals born to two frame overos or horse carrying the gene
     • Normal at birth, but colic soon after
          o Never pass meconium
          o Develop abdominal distention
          o Colic
          o No treatment: surgical resection has been unsuccessful

     • Semi-dominant gene
          o Homozygous state of frame overo
          o Heterozygotes are frame overos
     • Mutation in the endothelin b receptor gene
          o Responsible for neural crest cell migration to the skin (melanocytes) and to the gut (nerve cells)
     • 25 % of frame to frame crosses will result in lethal white foals

Note: Not all white paint foals are lethal !
     • Crosses of frame to sabino, splash, or tobiano or any other combination can produce all white foals
     • Diagnosis of carriers: DNA test, UC Davis
     • This disease is 100 % preventable
          o Never cross two carriers

Available Genetic Tests

     • Hyperkalemic Periodic Paralysis (HYPP)-1992
          o UC Davis
     • Lethal White Foal Syndrome (LWFS)- 1998
          o UC Davis
     • Glycogen storage disease IV (GBED)-2006
          o UC Davis and Univ of Minnesota
     • Hereditary Regional Dermal Asthenia (HERDA)- 2007
          o UC Davis and Cornell University
     • Polysaccharide storage myopathy (PSSM)-2008
          o Univ of Minnesota
     • Malignant Hyperthermia (MH)-2008
          o UC Davis and Univ of Minnesota

Other Breeds:
Hereditary Junctional Epidermolysis Bullosa
Saddlebred horses
     • Partial deletion of the LAMA3 gene
          o Encodes for part of the Laminin 5 basement membrane protein
          o Autosomal recessive
          o Diagnostic test – 9/175 randomly selected America Saddlebreds born in 2007 were found to be carriers.
          o Different gene than in Belgian draft horses (LAMC-2 gene), also of Laminin 5
          o Testing: Gluck Equine Research Center, University of Kentucky

Cerebellar Abiotrophy of Arabians

     • Purkinje cells, after they have been formed, die off
     • Cerebellar signs predominate
     • Autosomal recessive
     • Signs vary in severity and timing
          o May develop from birth to up to 4 months of age
     • Indirect DNA test available –Identified genetic markers associated with CA
          o Gene itself has not yet been identified
          o Available at UC Davis Veterinary Genetics


Tyro RC, White SD, Bannasch DL. Homozygosity mapping approach identifies a missense mutation in equine cyclophilin B (PPIB) associated with HERDA in the American Quarter Horse. Genomics 2007; 90: 93-102.

McCue ME, Valberg SJ, Jackson M, et al. Polysaccharide storage myopathy phenotype in quarter horse-related breeds is modified by the presence of an RYR1 mutation. Neuromuscul Disord 2009; 19: 37-43.

Glycogen branching enzyme (GBE1) mutation causing equine glycogen storage disease IV. Mamm Genome 2004; 15: 570-577.

Aleman M, Nieto JE, Magdesian KG. Malignant hyperthermia associated with ryanodine receptor 1 (C7360G) mutation in Quarter Horses. J Vet Intern Med 2009; 23: 329-334.

Metallinos DL, Bowling AT, Rine J. A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: an equine version of Hirschsprung disease. Mamm Genome 1998; 426-431.

Rudolph JA, Spier SJ, Burns G, et al. Periodic paralysis in quarter horses: a sodium channel mutation disseminated by selective breeding. Nat Genet. 1992; 2: 144-147.

Finno CJ, Spier SJ, Valberg SJ. Equine diseases caused by known genetic mutations. Vet J 2009; 179: 336-347.