variant | Horse Racing Free Tips

Genetics To Blame For Friesian’s Eye Issues

A study team led by Dr. Rebecca Bellone, of the University of California Davis Veterinary Genetics Laboratory, has identified a genetic variant as the cause of a painful eye condition in Friesian horses. The condition, called distichiasis, causes hairs to grow at odd angles along the eyelid; these hairs rub the cornea, making the eye irritated and painful. Severe cases may result in corneal ulceration and possibly the loss of the eye.

Distichiasis can be treated by removing the offending hairs via thermocautery, but the condition recurs in nearly 50 percent of cases. To determine the genetic cause of this condition, the scientists traced the family trees of 14 horses afflicted with the condition. The team discovered a large chromosome deletion between two genes on the ECA13 chromosome strongly associated with distichiasis.

[Story Continues Below]

The team concluded that distichiasis in Friesians is a trait with incomplete penetrance, meaning that the condition may show up in some individuals with two copies of the variant, or the horse may show no sign of the condition at all. The research team noted that testing can avoid crosses that produce animals that are homozygous for the variant. Results can also be used to ensure affected horses are evaluated often to prevent irreversible corneal damage.

To read the full study, click here.

Further Analysis Of March EHV-1 Outbreak Reveals New Variant Of The Disease

In March, eight horses housed at a Pennsylvania show barn were diagnosed with EHV-1 after having elevated temperatures but no other signs of illness. The cause of the outbreak has been found to be a new variant of the EHV-1 H752 genotype. The variant contains the same mutation as the EHV-1 outbreak in France.

EHV-1 can cause respiratory disease in young horses, early death in foals, abortions in mares and occasionally neurological disease. Neurologic issues are fairly uncommon, but can cause the death of the affected horse.

The 31 horses that lived at the affected barn were treated with valacyclovir, and ill horses also received flunixin meglumine and sodium heparin. The investigation team, led by Dr. Nicola Pusterla, believe that the early administration of valacyclovir may have prevented additional horses from falling ill with neurologic complications. Additionally, they note the lack of respiratory symptoms in these cases may be related to the recent administration of EHV vaccinations.

The distribution of the new genotype is not known.

Read the case report here.

UC Davis Researchers Identify Genetic Variant For Fatal Condition In Thoroughbreds

Researchers at the UC Davis School of Veterinary Medicine have identified a genetic cause for the fatal condition equine familial isolated hypoparathyroidism (EFIH) in Thoroughbreds, marking the first genetic variant for hypoparathyroidism identified in any domestic animal species. Additionally, this is the first widely available genetic test for Thoroughbreds.

The study, led by Drs. Carrie Finno and Gary Magdesian, which was reported in the journal PLoS Genetics. Genetic testing can now be performed at the UC Davis Veterinary Genetics Laboratory to identify horses with the variant and avoid mating carriers that could produce affected foals.

“For Thoroughbred owners and breeders, the loss of a foal has tremendous economic and emotional impacts,” says first author Victor Rivas, who conducted the project as part of his undergraduate training in Finno's laboratory. “It is important to promote safe and strategic breeding habits by actively breeding horses genetically screened not only for EFIH, but for other diseases that may impact quality of life.”

Foals affected with EFIH suffer from low blood calcium concentrations, resulting in involuntary muscle contractions, muscle stiffness that leads to a stiff gait and can progress to an inability to stand, seizures, fevers, and an abnormally fast pulse. Parathyroid hormone is typically produced to increase calcium levels in the body, but in these foals, concentrations are low or “inappropriately” normal (i.e. they should be high due to the low calcium). Affected foals die or are euthanized due to poor prognosis. Necropsy results reveal underdeveloped or absent parathyroid glands.

Previously termed idiopathic hypocalcemia, EFIH has been observed in Thoroughbred foals up to 35 days of age. Disease onset and progression are likely determined by the amount of calcium in the diet early in life. This can vary based on dam milk calcium concentration and the amount of milk ingested.

The current study determined an autosomal recessive mode of inheritance and performed whole genome sequencing of two affected foals. A mutation in the rap guanine nucleotide exchange factor 5 (RAPGEF5) gene was present in two copies (homozygous) in both foals. The variant was further analyzed in a frog developmental model and demonstrated loss-of-function of the RAPGEF5 protein leading to aberrant development. Based on this data, the researchers hypothesize that RAPGEF5 may play a role in the derivation of the parathyroid gland during development.

The variant was not identified in individuals from 12 other breeds. The allele frequency for the RAPGEF5 variant in an expanded set of 82 randomly selected, unaffected Thoroughbreds was 0.018. An unbiased allele frequency study has not been performed, so the allele frequency in the larger Thoroughbred population is currently unknown.

“The next steps are to assess the allele frequency in a large population of randomly selected Thoroughbreds,” says Finno. “Additionally, we have discussed collaborating with Dr. Nathan Slovis at Hagyard Equine Medical Institute in Kentucky to test for the variant in cases of 'sudden death' in Thoroughbred foals.”

The clinical presentation of EFIH is similar to human familial hypoparathyroidism. Since the RAPGEF5 gene is highly conserved across species, it is a potential new candidate gene for primary hypoparathyroidism in humans.

“This type of research discovery requires a unique collaboration between clinicians, pathologists and basic researchers,” says Finno. “We were incredibly fortunate to have samples submitted from Drs. Slovis, Daniella Leuthy (University of Pennsylvania) and Laura Javsicas (Rhinebeck Equine) and the expertise of Drs. Brian Caserto (VetPath services) and Andrew Miller (Cornell University). Additionally, the 'proof' of functional results of this genetic mutation would not have been possible without our collaborator from Yale University, Dr. Mustafa Khohka.”

Support for this study was provided by the UC Davis Center for Equine Health.