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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.

Study: Chubby Horses Don’t Eat More Than Leaner Counterparts

Though it's long been assumed that fat horses would eat more than their leaner peers if given an option, a study from North Carolina State University shows that this isn't actually the case. When allowed to make their own choices, chubbier horses not only eat similar quantities of food, they also exercise the same amount as their thinner herd mates.

Drs. Jennifer Moore, Paul Siciliano and Shannon Pratt-Phillips used 10 horses that they separated into two groups: one group included six horses that had body condition scores of more than 7; the other group included leaner horses with body condition scores of 4 or 5. Over the course of 25 days, both groups transitioned from a diet that relied heavily on grazing to one that was based on free-choice hay. Once the horses were transitioned over, the scientists monitored their hay intake and metabolic state for the next 11 days.

Horses had blood drawn regularly throughout the study. Fecal samples were also collected from each horse to determine dry-matter digestibility and gross energy digestibility. The horses also wore heart rate monitors that had GPS trackers that collected data to calculate each horse's energy expenditure.

The study team found no significance difference in the energy intake and expenditures between the two groups of horses. Interestingly, the obese horses were more active for longer periods of time than the lean horses. They also spent less time eating. The scientists concluded that obesity in horses does not appear to be related to excess food intake or reduced activity; obesity is most likely related to metabolic issues.

MARS Equestrian Fellow At UK’s Gluck Equine Research Center Continues To Assist Older Horses

Horses aged 15 and over make up between 20 to 30 percent of the United States equine population. An important milestone will be reached this year in the quest to learn more about this population. October marks the one-year anniversary of Amanda Adams, associate professor at the University of Kentucky Gluck Equine Research Center specializing in aged horse research, becoming the first MARS Equestrian Fellow. This fellowship supports her work to improve not only how the industry cares for senior horses but also how veterinarians can better diagnose the conditions and diseases that affect them.

According to Linda Mars, gaining a better understanding of how nutritional and management requirements change with age and activity will help the industry provide the best possible care to horses and ponies throughout their lives.

As horses age, they face an increased risk for some common conditions and diseases. One of those, pituitary pars intermedia dysfunction, develops in approximately 20 percent of senior horses. Another condition, equine metabolic syndrome, is associated with insulin dysregulation and often obesity. This can occur in all aged animals but may have additional adverse consequences in the older horse. Both are associated with the development of laminitis, a very painful and debilitating condition of the hoof that is often life ending.

These are just two of the key problems that Adams' team has been able to work on with MARS Equestrian support. Her team has established and maintains a unique herd of nearly 80 aged, obese and metabolic syndrome horses. The herd is the only one of its kind in the U.S., and it provides unique opportunities to study geriatric and endocrine diseases in horses.

According to Adams, most of what her team knows and what they are learning about aging and endocrine diseases in this population of special needs horses wouldn't be possible without access to this research herd.

“In a short period of time, we have made major breakthroughs in gaining a better understanding of how to nutritionally manage horses suffering from insulin dysregulation, specifically in equine metabolic syndrome horses. We are also learning that the season has a profound influence on the metabolic responses of these diseased horses, which will help shed light on why these horses may develop laminitis at certain times of the year,” said Adams, a faculty member of the UK College of Agriculture, Food and Environment. “Over the last year, we have also been working to define sarcopenia (an age-related loss of skeletal muscle mass and strength) in aged horses and how specific diet and exercise routines may reverse or improve that muscle loss. Furthermore, we are studying what effect exercise has on the inflammation-aging response in aged horses.”

While the progress is promising, Adams said that more work is needed. In addition to learning how to better manage these horses, there is a need at the basic scientific level to understand how the aging process affects the horse's immunity, metabolic status and nutritional needs.

“The many problems we face with the aging horse are important given the growing senior horse population,” said Pat Harris, Director of Science, MARS Horsecare. “Thus, it is critical that we continue these efforts to advance the field and improve our knowledge in senior horse care,” “ultimately creating a better world for horses” added Bridgett McIntosh, Director of MARS Equestrian.

Thoroughbred Incentive Program, U.S. Polo Association To Offer Thoroughbred Polo Awards

The Thoroughbred Incentive Program (T.I.P.) and United States Polo Association® (USPA) announced today that they will recognize Thoroughbreds that are excelling as polo horses through six awards that will be offered annually, starting this year. For a Thoroughbred to be eligible for these awards, it must have a T.I.P. number. There is no charge for a T.I.P. number.

“Polo is just one of many disciplines in which Thoroughbreds can succeed following their racing careers, and T.I.P. is pleased to partner with the USPA to honor the accomplishments of these horses at all levels of polo,” said Kristin Werner, senior counsel of The Jockey Club and coordinator of T.I.P.

Each award winner will receive an award sash and special logo prizes. The categories for each award are:

High Goal Horse: for a Thoroughbred that has played in at least one USPA Outdoor Tournament in 2020 and scored more than 16 goals in total.
Medium Goal Horse: for a Thoroughbred that has played in at least one USPA Outdoor Tournament in 2020 and scored eight to 16 goals in total.
Low Goal Horse: for a Thoroughbred that has played in at least one USPA Outdoor Tournament in 2020 and scored fewer than eight goals in total.
Arena Polo Horse: for a Thoroughbred that has played in at least one USPA Arena Tournament in 2020.
Lesson Horse: for a Thoroughbred used in a lesson program at a USPA club.
Intercollegiate/Interscholastic (I/I) Horse: for a Thoroughbred that has played in an I/I Regional or National Tournament in 2020.

“The USPA is excited to work with the Thoroughbred Incentive Program to highlight the Thoroughbred's long history in the sport of polo,” said Justin Powers, executive director of the United States Polo Association Polo Development LLC.

Applications will open on the T.I.P. and USPA websites on November 1 and close November 30. The winners will be announced in January and selected based on the application and an essay. Applicants will be judged by a committee formed by the USPA and T.I.P.

Created and announced in October 2011, T.I.P. recognizes and rewards the versatility of the Thoroughbred through sponsorship of Thoroughbred classes and high point awards at sanctioned horse shows, year-end performance awards, a recreational riding program, and non-competition awards. Additional information about T.I.P. is available at tjctip.com and on the T.I.P. Facebook page at facebook.com/tjctip.

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