Identification of Putative Genetic Mutations Associated with Equine Neuroaxonal Dystrophy (15-03)


Carrie Finno, DVM, Ph.D., DACVIM
Erin Burns, B.S.

Equine neuroaxonal dystrophy (eNAD) is a devastating neurological condition that develops during the first year of life in genetically predisposed foals maintained on a vitamin E deficient diet. Affected horses suffer from incoordination, preventing their use as a riding animal. To develop a genetic test for eNAD, an adequate number of horses (eNAD-affected and unaffected) and genetic markers (DNA sequence on a chromosome) are required. Previous attempts at identifying the gene involved in eNAD were limited to only 54,000-70,000 genetic markers, whereas the newest marker test contains 670,000 markers. Horses affected with eNAD have very low vitamin E levels, supporting the idea that a genetic mutation involved in vitamin E transport or metabolism is responsible for the disease.


This study identified a region on equine chromosome 7 for further evaluation for eNAD. Using the combination of genotyping and sequencing data, the region was explored for haplotypes (i.e. markers on stretches of chromosome that are inherited together) that could be associated with the disease. With continued investigation of the region on chromosome 7, investigators hope to develop a genetic test for eNAD, thereby allowing breeders to determine the need for supplementation of pregnant mares and foals to prevent the disease.

Genetic Investigation of Juvenile Idiopathic Epilepsy in Arabian Foals (15-10)


Monica Aleman, MVZ, Ph.D., DACVIM
Carrie Finno, DVM, Ph.D., DACVIM

Juvenile ldiopathic Epilepsy (JIE) is a disorder in Egyptian Arabian foals that causes seizures. Potential life-threatening complications include head injury and aspiration pneumonia. Although the disorder is heritable, the genetic mutation is not yet identified. This project investigated the genetic cause of JIE by performing a genome-wide association study. A region on chromosome 1 was identified as significantly associated with the JIE phenotype. Two JIE-affected horses underwent whole genome sequencing and candidate genetic mutations have been identified.


The identification of a region on chromosome 1 is a significant step forward. Additional studies are underway to determine which of these genetic mutations may be responsible for JIE in Arabian foals and allow for the development of a genetic test. This will provide breeders the ability to screen mares and stallions for JIE prior to breeding.

Identifying a Genetic Basis of Unexplained Sudden Death in Racehorses (15-26)


Joshua Stern, DVM, Ph.D., DACVIM

Despite thorough pathologic and toxicologic investigations, no unifying, definitive cause has been identified to explain the increase in sudden cardiac death events of racing Thoroughbred. Similar events are observed in human athletes and are often attributed to genetic mutations and predisposition to abnormal conduction within their hearts, yet no genetic investigation into these equine sudden death cases has been performed. This study sought to identify genetic markers associated with sudden death to provide a foundation for future investigations.

The DNA was obtained from 20 horses that died suddenly with no clear cause of death and compared to DNA of 28 matched control horses that were euthanized due to orthopedic injury and then compared across the entire genome to obtain a list of genetic markers for analysis. The study’s results did not identify a significant area of the genome associated with sudden death.


This work confirmed that future genetic investigations of sudden death require fresh tissue samples or blood samples to be stored and high-quality DNA samples extracted as soon as possible. The study also showed that the number of cases and controls was insufficient and future evaluations should aim for a sample size that considers this condition to be polygenic or multifactorial. Finally, this data supports that continued efforts looking for environmental causes of sudden death in the Thoroughbred racehorse are warranted.

Genetic Investigation of Limbal Squamous Cell Carcinoma in Haflinger Horses (15-12)


Rebecca Bellone, Ph.D.
Mary Lassaline, DVM, Ph.D., M.A., DACVO

Squamous cell carcinoma (SCC) is the most common cancer of the equine eye and the second most common tumor of the horse overall. SCC frequently originates in a region of the eye known as the limbus and can quickly spread to other parts of the eye, leading to vision loss and destruction of the eye. Haflinger horses are over-represented for this disease, on average are affected at a younger age, and affected horses trace back to a common ancestor; making this an important breed to study the genetics of the disease. This study sought to identify and investigate the DNA mutations that cause this disease. A genetic variant was identified with a strongly associated risk for cancer in Haflingers.


This work led to the development of a commercially available DNA test offered at the Veterinary Genetics Laboratory, UC Davis. Clinicians are utilizing the DNA test to identifying Haflinger horses at highest risk for this cancer so that these animals can be examined earlier and more frequently. Breeders are also utilizing this test to make informed breeding decisions, which should help to lower the incidence of cancer in the breed.

Because this genetic variant does not explain all of the limdal SCC cases observed, data analysis is in progress to determine if additional genetic variants are involved. In the long term, understanding the genes and biological pathways disrupted in ocular SCC may lead to the development of new and more effective treatments and thereby prevent visual impairment associated with loss of the eye.

The study was published in the International Journal of Cancer 141(2):342-353.

Study of Genetic Cause of Melanoma Cancers in Connemara Ponies (14-22)


Alain Theon, DVM, MS, Ph.D., DACVR

Connemara Ponies, similar to other horses with a graying hair coat, have an 80% lifetime risk of developing melanomas. Although Connemara ponies are not predisposed to melanoma cancer, they have an increased risk due to selective breeding for gray phenotype. The study focused on identifying actionable genomic targets associated with melanoma that could be manipulated through genetic screening and careful breeding to decrease or eliminate the risk of developing melanomas in Connemara ponies and other breeds. The investigation also sought to further define the molecular mechanisms responsible for development of melanomas in patients at risk, which will aid in targeting treatment development efforts.

The study required the establishment of a biobank to provide quality samples for research. Through the support of the American Connemara Pony Society, the UC Davis Center for Equine Health and the Cunningham and Doyle Charitable Trust Fund, biospecimens of 72 pure-bred Connemara ponies were collected from across the U.S.


Preliminary identification of genetic variants was accomplished, which will help to guide future studies with the ultimate goal of being able to develop genetic testing tools to inform the Connemara pony community and potentially breeding decisions to decrease the disease prevalence. The establishment of the biobank with the Connemara pony biospecimens will aide future genetic studies targeted to this breed.

Chronic Progressive Lymphedema (14-21)


Danika L. Bannasch, DVM, Ph.D.
Verena K. Affolter, DVM, Ph.D.
Claudia Sonder, DVM
Brittany Dally, M.S. student

Chronic progressive lymphedema (CPL) in the horse is a disabling condition that stems from a buildup of lymph fluid in the lower limbs. Draft horses (especially Shires, Belgians, Clydesdales, Gypsy Vanners, and Friesians) are most commonly affected by this condition, with the majority of animals presenting with varying severities of clinical signs. Due to the large number of horses displaying clinical signs of CPL in affected breeds, a genetic predisposition is suspected.

Two genome-wide association studies were conducted to identify a genetic component within the Friesian horse breed that may cause CPL or predispose them to the condition. Unfortunately, neither of these studies was able to identify a genomic region on a chromosome that was associated with CPL. As this form of lymphedema appears to be predominantly in draft horse breeds, the size of the horse was investigated as a potential contributing factor or indicator of CPL development. Height, weight, and limb measurements at four locations were obtained from a total of 37 horses (28 cases and 9 controls). Of these measurements, significance was achieved for two measurement locations, forearm (radius and ulna) and gaskin lengths, demonstrating a potential correlation between animal size and CPL status within the Friesian breed.


Increased understanding of the cause and predisposition of this condition in draft horse breeds will assist veterinarians in developing more consistent treatment plans to manage this condition and provide lifelong support to keep affected horses comfortable and mobile. These study results will help to inform future studies aimed at identifying a genetic cause and the potential development of a genetic test which would assist breeders.