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


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.