A University of California, Davis study has found no link between a gene mutation in Warmbloods and breakdowns in thoroughbred racehorses. The study involved DNA sample testing and genomic analysis of 716 thoroughbreds currently campaigning in the United States. Of the 716 horses selected for genetic testing, 22 suffered catastrophic breakdowns on the racetrack and had to be euthanized. Thirteen of those 22 breakdowns were injured during a race, while the remaining nine were injured during training sessions.
Researchers were interested in discovering what, if any, individual genetic variances played a part in the 22 fatalities.
It is well known that the cycle loading of a horse’s legs during workout or racing can aggravate pre-existing lesions at the distal end of metacarpal and metatarsal bones – resulting in catastrophic fetlock injuries. Furthermore, cumulative damage to articular cartilage and subchondral bones over long periods of intensive cycle loading is thought to impair bone remodelling, resulting in skeletal breaks or fractures.
However, since many racehorses do not suffer breakdowns – only 3.07 per cent involved in the UC Davis study were fatally injured – there may be some type of inherited predisposition toward injury at work.
This is why the Davis research tried to limit the effect of environmental variabilities by only collecting sample of horses that primarily raced and trained at one particular American track over the course of a single racing season.
It is also why they chose to focus on the possible connection between fatal bone and tissue injuries and an inherited autosomal disorder known as Warmblood Fragile Foals Syndrome (WFFS).
WFFS is the result of a defect in the development of connective tissues and mucous membranes and is caused by a single mutation to the PLOD1 gene.
WFFS manifests as extremely delicate skin that tears or ulcerates easily and loose, hyperextensible joints – providing the foal actually survives the birth. There is no cure, with euthanasia as the only option. (Laboklin photo)
PLOD1, or Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 1, is important modifier of lysine. When lysine undergoes a process of oxidation by lysyl hydroxylase enzymes it becomes hydroxylysine, and hydroxylysine is one of the key ingredients of collagen. Collagen, in turn, is what provides support and structure to the skin, tendons, ligaments, muscles, and skeletal system.
In humans, PLOD1 mutations cause connective tissue disorders collectively known as Ehlers-Danlos-like Syndrome, or EDLS. A total of 13 types of EDLS have been identified to date, ranging in severity from easy bruising, frequent joint dislocations and abnormally stretchable skin to cardiovascular weakness, gastro-intestinal immobility and crippling pain.
In horses, the PLOD1 mutation tends to cause lax musculature and abnormally soft internal organs. Afflicted animals present with such tell-tale indicators as floppy ears, hyper-flexible tendons, soft bones, hematomas, and subcutaneous emphysema.
Most mares abort WFFS-affected embryos. It is extremely rare for a live foal to be born, and those that are almost always have to be euthanized within the first week after birth for humane reasons. At present there are no known living WFFS weanling, yearling or adult horses.
The PLOD1 defect is a recessive trait which, in scientific terms, means the transmission of the gene to a foal by one carrier parent is a 50 per cent possibility. In other words, approximately half of the offspring of a carrier parent will be carriers themselves.
A mating between two carriers has a 25 per cent chance of producing an afflicted offspring. Since 100 per cent of afflicted cases are non-viable, every breeding between two carrier parents has a one-in-four chance of producing a terminal foal.
The PLOD1 mutation is a relatively recent discovery. In 2007, Dr. Nena Winand, a senior research associate at the College of Veterinary Medicine at Cornell University, was contacted by John Baird from the University of Guelph after a student of Baird’s necropsied a warmblood foal that had extreme connective tissue fragility. Winand immediately began DNA testing the dead foal’s tissue.
By 2013, Winand had identified the defective gene and produced a DNA test for WFFS.
Although the disorder is called Warmblood Fragile Foals Syndrome, thoroughbreds were hypothesized to also be affected by the disorder due to the inclusion of thoroughbreds in warmblood breeding.
To be clear, the term “warmblood” can be used to categorize either: any horse that is produced by crossing a draft breed with a thoroughbred or an Arabian, or; Continental-based riding horse breeds such as Trakehner, Holsteiner, Hanoverian and Selle Francais.
These four foundation breeds have given rise to other, nationally-based breeding registries such as the KWPN in Holland, the Swedish Warmblood and the Canadian Warmblood. And, all four foundation breeds have had little or no draft influence.
They do have strong pedigree influence from the limited inclusion of the so-called refining breeds – in particular, English thoroughbreds and Arabians.
Dr. Winand believes the origin of the PLOD1 mutation can be traced back to a thoroughbred called Dark Ronald. Born in England in 1905, Dark Ronald was a highly prized sire in warmblood breeding, producing some famous linebred Hanoverian and Holsteiner sons like Cor de la Bryere, Lord and Landgraf I. These sires can be found in the pedigrees of many current Olympic champions.
Every single warmblood identified by Winand’s DNA test as a carrier of the PLOD1 defect has Dark Ronald in its pedigree, and those breeds with heavy Dark Ronald influence have a higher carrier rate. So, for example, the Hanoverian carrier rate is around 20 per cent, Holsteiners are at seven per cent, while Trakehners are at two per cent.
According to Winand’s research, the carrier frequency for pure thoroughbreds is between two and four per cent – likely because Dark Ronald had less of genetic influence as compared to warmbloods. However, the UC Davis study found the carrier rate among their American-based study population was 2.4 per cent.
What wasn’t definitively known prior to the Davis if simply carrying a copy of a defective PLOD1 gene was enough to increase the risk of catastrophic breakdown. Now that the study is complete, the answer clear.
None of the horses involved in the study had two copies of the mutation and just 17 of the 716 horses were identified as carriers. More importantly, only one of the 22 catastrophic breakdown cases carried the PLOD1 mutation.
A press release from UC Davis’ Veterinary Genetics Laboratory states conclusively that there is no substantiate link between the WFFS mutation and breakdowns in thoroughbreds. Additionally, there is absolutely no evidence of a link between the defective gene and bleeding episodes in thoroughbreds.
So, if there is a genetic factor that makes some thoroughbreds more prone to fatal ontrack injuries more than others, a single recessive copy of the WFFS-causing PLOD1 mutation is not it.
