Last week in Dealer’s Choice, co-written with
executive editor John Pricci, HRI did something seldom done anywhere: Sharing
science prior to its appearance in a major peer-reviewed medical journal.
Most scientists publish their findings in a journal first–before the media learns of it. But not Dr. Nena Winand. She scooped herself, acting in the best interests of Thoroughbred horses. (See: Mutant Gene Causes Horse Bleeding and Breakdowns – HRI – April 3, 2019. https://bit.ly/2K3Xrgz)
Routinely, a scientific paper is released first, and Winand initially requested that I not share her research until the findings were published. But after Arms Dealer became the 23rd equine fatality at Santa Anita Park since DEC 26, 2018, she granted HRI permission to run with the story.
Dr. Winand, DMV, PhD in genetic scientist, identified Warmblood Fragile Foal Syndrome [WFFS] at Cornell University in April, 2011.
Dr. Winand’s research found that a mutant gene is present in at least 15% of all Thoroughbreds, and may be as high as 30% or more in the U.S., where lines of bleeders have been highly selected.
In brief, WFFS prevents collagen–the body’s most abundant protein and the glue that holds together all living things–from forming properly, thus keeping the protein from doing its job.
Collagen is necessary to form strong cell walls that keep blood vessels from bursting under pressure. Collagen also is involved in the creation of strong bones, helping to keep them from shattering under stress. Collagen also forms connective tissue that keeps muscles attached to bone.
Rebecca Bellone commented on the story April 5, stating “I was contacted by one of the writers this week but was not able to respond in time, so I am responding now.
“As Director of the Veterinary Genetics Laboratory [at the University of California Davis] and an equine geneticist, I would like to communicate with your readership that there are no reported cases in scientific literature to substantiate these connections. The [WFFS] mutation has not been linked to bleeding disorders or poor bone formation in the Thoroughbred.
“Our laboratory did identify the allele for Fragile Foal in the Thoroughbred breed, but it was determined to be at a very low frequency (less than 4%). Furthermore, in Warmbloods, it has been shown to only behave in a recessive fashion.
“This means that for a horse to be affected it needs to be homozygous, or have two copies of the mutation. We have not identified any Thoroughbreds who are homozygous for the Fragile Foal mutation.
“Based on all of the available data, it is highly unlikely that this mutation has anything to do with bleeding or breakdowns,” concluded Bellone.
“Well that’s incorrect but I didn’t discuss it with her,” Winand responded. In fairness to Bellone, she did not read Winand’s work as it is yet to be published. “She also is not a veterinarian [and] not really capable of identifying phenotype herself.” But that’s only part of the issue.
“[Their research] only looked at 95 Thoroughbreds which is an inadequate sample. Obviously they are not doing more population screens, which I thought they would do because they could have had a good paper.
“Of course, they haven’t identified any Thoroughbreds with two gene copies. They don’t test aborted foals for this, especially Thoroughbred foals. She doesn’t understand that the stillbirth/abortion/weak foal phenotype is one of several phenotypes seen in EDS VI, the others being bone fragility and bleeding.
“The effect on lysine hydroxylation is so severe that homozygosity is basically a lethal phenotype. It mimics a recessive because there is adequate lysine hydroxylation to make a normal appearing horse with weak bone and cardiovascular tissue that fails under stress.
“Our understanding of the critical role of lysine hydroxylation in the integrity of bone and cardiovascular structures is well established in the human EDS VI literature, as well as in veterinary studies in the horse.
“Although the reproductive loss/fragile foal phenotype gives the appearance of behaving as a recessive trait, it is important to understand that EDS VI involves multiple phenotypes and that it is common for some genetic disorders to have both recessive and dominant phenotypes depending on the nature of the specific mutations involved.
“It is also not uncommon for the distinction between recessive versus dominant behavior to breakdown when inherited disorders are studied at the tissue, cellular, biochemical and biophysical levels.”
Even before Winand’s findings become public, it is fair to ask two questions:
How many more horses will die as a result of the presence of this mutant gene? Further, doesn’t The Jockey Club have a duty to warn breeders, owners and horsemen who work with today’s Thoroughbreds?
“In the end, it will become clear like so many things after the fact,” said Winand.
At 4”45 pm today, HRI received an email from The Jockey Club president, Jim Gagliano stating:
“John and Mark –
I read with great interest the article of April 3, 2019 Mutant Gene Causes Horse Bleeding and Breakdowns at http://www.horseraceinsider.com/HRI-Feature/comments/04032019-mutant-gene-causes-horse-bleeding-and-breakdowns/.
In the article, conclusions from research that had yet to be published in peer-reviewed journals were cited as, “Horses that test positive for WFFS should not be allowed to race; they are ticking time bombs.” We find this type of reporting disturbing because (i) it appears to be based upon evidence that no one has had the benefit of assessing the credibility and (ii) it is written to create an incendiary impact given the proximity to the recent spate of racing and training fatalities at Santa Anita Park.
Based upon consultation with our subject matter experts at the Veterinary Genetics Laboratory at the University of California Davis, the test for the mutation referenced is principally recommended for all Warmblood/Sport Horse populations http://www.vgl.ucdavis.edu/services/horse/WFFS.php. They indicate the incidence of carriers in the population of Sport Horses to be approximately 9-11% and that the defect attributed to this mutation requires two copies to demonstrate symptoms.
In contrast to the work cited in your article, equine genetics experts indicate that in the Thoroughbred, “the investigation on breed distribution of this mutation is ongoing.” This statement would imply that the frequency and risk of this mutation in the Thoroughbred is currently unknown.
Unfortunately, that did not seem to affect the decision to rely upon data that has yet to see the light of day as if it were on par with credible, peer-reviewed findings that have withstood critical review by a panel of subject matter experts. Based upon responses from equine genetics experts to the article, it would appear that the results you have cited are speculative at best and false at worst. We suggest you correct it.
Unless and until a peer-reviewed journal article results, we would suggest a disclaimer indicating that neither the data nor the conclusions have been reviewed for accuracy and that any opinions expressed are that of the author.
A copy of the letter we are sending to the researcher will follow.
Please contact us if you have any questions or comments.
© 2019 Mark Berner, HorseRaceInsider.com