New genetic discovery explains fatal neurological disease in Quarter Horse foals

   

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Researchers at the UC Davis School of Veterinary Medicine have identified the genetic cause of Equine Juvenile Spinocerebellar Ataxia (EJSCA), a recently recognised and fatal neurological disease affecting American Quarter Horse foals. The discovery not only provides breeders with a genetic test to prevent affected foals from being born, but also advances scientific understanding of neurological disease in both horses and humans.

EJSCA is an inherited neurological disorder that affects foals within the first few weeks of life. Clinical signs typically develop between one and five weeks of age and progress rapidly. Affected foals initially appear uncoordinated and exhibit proprioceptive ataxia, meaning they have difficulty determining the position of their limbs in space. Within days, many develop severe weakness of the hind limbs, become unable to stand without assistance, and eventually require euthanasia on welfare grounds.

The disease results from degeneration of axons, the long nerve fibres that connect neurons and allow communication between the brain, spinal cord and limbs. As these pathways deteriorate, the nervous system can no longer accurately transmit information about movement and body position. Consequently, affected foals lose balance and coordination despite appearing normal at birth.

The first recognised case of EJSCA was identified in 2020 in a Quarter Horse filly known as “Curly Sue.” Veterinarians initially suspected another neurological condition, equine neuroaxonal dystrophy (eNAD), but further investigations revealed that the foal was suffering from a previously unrecognised disease.

To identify the genetic cause, researchers at UCDavis performed whole-genome sequencing on seven affected foals and compared their DNA with that of unaffected relatives and unrelated control horses. The investigation identified an 82-kilobase region on chromosome 11 that contained several candidate genetic variants. Further molecular studies demonstrated that the causative mutation was located within a non-coding region of the ferredoxin reductase (FDXR) gene.

Unlike many disease-causing mutations that alter the protein-coding sequence of a gene, this mutation affects how the gene is processed into messenger RNA. The variant causes the insertion of a cryptic exon - a segment of genetic material that is not normally included in the final RNA transcript. As a result, affected foals produce lower amounts of functional FDXR protein.

This finding is significant because FDXR plays an important role in cellular energy metabolism and nervous system function. Analysis of spinal cord and liver tissues showed that affected foals had substantially reduced FDXR protein concentrations compared with healthy controls. Importantly, mutations in the human FDXR gene are known to cause neurological disease, making EJSCA a potentially valuable natural model for studying similar disorders in people.

The researchers determined that EJSCA follows an autosomal recessive pattern of inheritance. This means that affected foals inherit two copies of the mutation, one from each parent. Horses carrying only one copy remain clinically normal but can pass the variant to their offspring. When two carrier horses are bred together, there is a 25% chance of producing an affected foal.

Screening of more than 1,000 Quarter Horses identified 25 carriers, indicating that the mutation currently occurs at a relatively low frequency within the breed. It has not yet been detected in other horse breeds. Because all known affected foals trace back to a single influential sire, researchers believe the mutation may have arisen relatively recently.

The development of a genetic test by the UC Davis Veterinary Genetics Laboratory now allows breeders to identify carrier animals before breeding. By avoiding carrier-to-carrier matings, breeders can effectively prevent the birth of affected foals while maintaining valuable bloodlines. This discovery represents the first non-coding neurological genetic variant identified in horses and the first known genetic cause of a degenerative axonal disease in the species, marking an important milestone in equine genetics and neurological research.

 

For more details, see:

Brown, B. N., Dahlgren, A. R., Ghosh, S., Durbin-Johnson, B., Willis, A., Olivas, C., York, D., Grahn, R., Bellone, R. R., Cortopassi, G. A., Miller, A. D., Brown, C. T., Woolard, K., & Finno, C. J. (2026).

An intronic variant in Ferredoxin Reductase (FDXR) creates a cryptic exon in Quarter Horses with Equine Juvenile Spinocerebellar Ataxia. 

PLoS genetics, (2026). 22(5), e1012158.

https://doi.org/10.1371/journal.pgen.1012158