The Principles of Genetic Research and its Impact on the Thoroughbred Racing World

Article by Holly Robilliard and Cassie Fraser

GMO Thoroughbreds? Superhorses created in the lab? Is genetic doping a real “thing”? It’s time for a reality check and a good, hard look at what’s real, or even possible, and how it can hurt or help the Thoroughbred industry.

Breeders, trainers, and owners continually seek a competitive edge, striving to produce horses with the speed, stamina, and resilience needed to succeed on the racetrack. Concurrently, there is increasing pressure and responsibility to minimize animal discomfort, injury, and death in a public forum. Therefore we must carefully examine and balance all the tools at our disposal before determining which ones to use and how.  

Interestingly, there is a growing technology that may be of more notable controversy than even horse racing: The power of genetics. Perhaps the greatest power man has ever wielded, genetics has sparked numerous debates over the good and evil it can bring. As with most new things, there is a significant fear of the unknown, so how do we even begin to understand it? In short: research, homework, and fact-finding. Let’s look at what is fact, scientifically known, and possible today, and then consider what may be possible in the future. 

Genetic Influences on Equine Performance

DNA, often called the “blueprint of life,” holds the key to a horse’s inheritance and development, from its physical prowess, size, and speed, to temperament and abilities. By studying their genetics, we can unravel the intricate code that dictates the pre-existing traits and characteristics of these powerful athletes. This information can then be utilized in our breeding and performance programs to improve suitability and success, all while upholding ethical standards and preserving the integrity of the sport.

The general rule for Mendelian traits is that a foal inherits one allele from each parent for a given gene. If the inherited alleles are the same, the horse is called homozygous for that gene. If they are different, they are heterozygous. As heterozygosity goes up, genetic diversity is increased, resulting in more variation in the genetic content. This results in a greater adaptability to environmental stressors and change, leading to a more robust animal and population. With equine genetics, we tend to focus on three kinds of genes: Causatives - genes/variants that directly cause a trait or condition, Correlatives - genes/variants that appear alongside, or in common, with a trait or condition, and Risks - genes/variants that increase their likelihood/risk of acquiring that trait or condition. 

A Thoroughbred study by Momozawa et al. found an association between the dopamine d4 receptor (DRD4) gene and a measure of temperament. In the study, “curiosity”, defined as, “an interest in novel objects and a willingness to approach them”, was prevalent in horses with a particular gene variant. Horses preferring to observe carefully, from a distance, were of the opposite variant type, named “vigilance”. Although further research is required, it is not unreasonable to consider that temperament affects a horse's ability to learn, break from the gate, or handle the pressure of large crowds on race day.

Another performance trait, perhaps of more notable interest to Thoroughbred enthusiasts is the “speed” gene, myostatin (MSTN). This insertion results in increased muscle growth in horses and other mammals. Genetically, horses can have two copies of the “Sprint” variant, two copies of the “Endurance” variant, or one copy of each, “Sprint/Endurance.” Thoroughbreds homozygous for the Sprint variant tend to excel earlier in age, at shorter distances (8 furlongs or less) with quick bursts of speed. Horses homozygous for Endurance excel later, and at longer distances (9 furlongs or more). However, heterozygous horses won at all distances, having both quick bursts of speed  and endurance capabilities (Fig 1).

Using genome-wide association studies (GWAS), scientists can analyze equine DNA and identify specific genes associated with various health and performance traits. This research holds immense promise, pinpointing genes responsible for desirable traits like speed, temperament, gait, size, and overall health. So how can we use it to produce horses with optimized genetic profiles for racing, while minimizing risk and injury? The answer lies within our breeding programs.

Breeding & Buying Optimized With Genetics

For generations, breeders have been making selections for observed traits, such as pedigree, racing history, prior offspring performance, and conformation. Additionally, “Nicking,” the strategic crossing of certain lines with an observed affinity for one another, is another well-known method used to make breeding decisions. These techniques may be successful, as the chosen bloodlines possess underlying genetic traits that express and complement one another. Given science today, the next evolutionary step in this process is to genetically test and confirm the desired traits are present and will be passed on in the most advantageous combinations.

Inbreeding (having drastically reduced genetic diversity) poses a significant challenge within the Thoroughbred racing industry due to the closed nature of the studbook. Science shows that a 10% increase in inbreeding reduces a horse’s likelihood of successful racing by 7%. Essentially, higher genomic inbreeding correlates with poorer performance. Traditionally, we have relied on pedigree and conformation to make mating decisions. Today, using actual genetics, we can calculate accurate genomic inbreeding and work toward decreasing it. On paper, two mares (full siblings) would appear to have the same inbreeding value. In reality, they can differ greatly, and if bred to the same stallion, may produce foals with drastically higher, or lower, genomic inbreeding values.

Using myostatin again, let’s look at a stallion that, by conformation and pedigree, appears to be the perfect match for your mare. Genetically, the mare is Sprint/Endurance and the stallion is Sprint/Sprint. This would result in a foal who is 50% likely to be Sprint/Endurance and 50% likely to be Sprint/Sprint. Now, if you breed that same mare with a stallion who has, at a minimum, one copy of endurance, the foal would still have a 25% chance of being Sprint/Sprint. However, it would also have a 50% chance of being Sprint/Endurance, and a 25% likelihood of being Endurance/Endurance, giving it longer-distance capabilities.

Beyond discovering performance-related traits, genetic research plays a vital role in promoting the overall health and sustainability of the breed. Health and soundness risks, such as Recurrent Laryngeal Neuropathy (RLN), or “roaring”, Kissing Spines, and Tendinopathy are being actively developed as genetically testable variants. Some of these traits can limit a Thoroughbred's pre- or post-racing career. Other predispositions, like Chronic Idiopathic Anhidrosis (CIA), or “non-sweater,” or Fracture Risk, can be life-ending if they go undetected. 

Through the use of genetic testing and associated technologies, breeders can “Build-A-Horse” to their specifications by crossing specific sires and dams using confirmed, heritable genetics, that create that optimal foal. By making breeding decisions based on math and science, we can reduce the presence of undesirable health traits in our programs.

As more Thoroughbred owners utilize genetics, collaborating researchers will continue identifying areas of strength and vulnerability in health and performance. This knowledge empowers breeders and buyers to make informed decisions that preserve genetic diversity and ensure the long-term strength of Thoroughbred bloodlines. Given the considerable investment of both resources and effort involved in the production and training of horses destined for the track, decreasing risk and increasing financial management is paramount. Remarkably, the cost of utilizing genetic testing to ascertain a horse’s optimal race distance is less than one week's feed, and can ultimately save owners and breeders both time and money.

Navigating Ethical Considerations

As genetic research becomes increasingly integrated into the Thoroughbred racing industry, it’s wise to approach this technology with foresight instead of fear. Whilst it offers unprecedented opportunities for improvement and advancement, this research also carries the potential for unintended consequences and ethical dilemmas that must be carefully navigated. 

The topic of cloning has been hotly debated in the last decade. The first reaction appears to be to “ban” it in certain registries and competitions. Interestingly, the fears stoked by this technology have not materialized into truth for a seemingly simple reason: You can replicate the genetic code of an animal, but it’s another thing entirely to replicate the uterine environment, the training, feeding, life experiences, and competition circumstances.

Another recent concern within the industry is the concept of “gene doping” to create superhorses, which involves artificially modifying an athlete's genes to enhance their performance. For example, the myostatin gene may become the target of genome editing in horses, as it alters the amount and composition of muscle fiber types. Although there are no known foals born, to date, with genetically altered myostatin, could it happen? Maybe. Would the effect be instant in something like myostatin? No. Why? Because that’s not how it works! A live animal has a fully formed physical plan in place, especially for things such as muscle, tendons, and bone. Today’s most advanced gene therapies tend to be extremely targeted regions, take months to years to work, and are extraordinarily expensive. 

Assuming it’s possible to change the myostatin disposition of a horse, could we detect that it was manipulated? The answer, according to multiple experts, is a very strong, “maybe”. Technique and timing would matter as would the simple question of, “Could this foal’s parents have passed on this genotype?” As technology advances and provides the opportunity for a competitive edge, it’s safe to say that someone will try it. What then? The answer may just come down to numbers, like everything else on the track.

So, with all of this knowledge, can someone choose a bunch of genetic traits and create a Superhorse? Although you hear about it every day, complex genetic editing is just in its infancy. It is possible to change a gene or variant within an embryo- We’ve been doing it for decades already. So why not a Superhorse? Well…consider the following:

1. It’s not easy to insert a single correct genetic edit that results in a living animal. 

2. It takes a large number of iterations and time for that one change.

3. The process can be super expensive. Multiply this by many dollars and much more time for every additional genetic change you wish to add.

4. Once you’ve produced genetic change, now you have to wait years to see the foal perform at which point your choice of changes may no longer be the winning combination!

Although we are likely years away from this being a feasible, let alone common, issue, we need to take steps now to understand genetics and devise a reasonable path forward. Preventing the misuse of gene editing could be as simple as creating a standardized genetic testing requirement via hair sample in addition to the standard parentage verification. This initial hair sample would serve as a genetic baseline, offering a comparison for those taken at a later date when genetic modifications are suspected. 

By adhering to rigorous standards of ethical conduct, transparency, and accountability, we can harness the full potential of genetic research while safeguarding the welfare and integrity of Thoroughbred racing.

Conclusion

Genetic research and testing represent a game-changing advancement for the Thoroughbred racing industry. It is a powerful tool for enhancing the quality, health, and performance of racehorses- all of which are required to maintain the sport's integrity. As we increase our understanding of equine genetics and discover new traits applicable to the Thoroughbred, we can produce healthier, more competitive horses, while reducing the historical struggles of inbreeding and breakdown. Although we must be careful to adhere to the ethical code set forth within the industry, by utilizing genetics to build the next generation of improved thoroughbreds, we can take ownership of the technology and usher in a new era of excellence and innovation within the sport.

Sources

Hill, E. W., Stoffel, M. A., McGivney, B. A., MacHugh, D. E., & Pemberton, J. M. (2022). Inbreeding depression and the probability of racing in the Thoroughbred horse. Proceedings of the Royal Society B, 289(1977). https://doi.org/10.1098/rspb.2022.0487.

Momozawa, Y., Takeuchi, Y., Kusunose, R., Kikusui, T., & Mori, Y. (2005). Association between equine temperament and polymorphisms in dopamine D4 receptor gene. Mammalian genome, 16, 538-544. https://doi.org/10.1007/s00335-005-0021-3

Rooney, M. F., Hill, E. W., Kelly, V. P., & Porter, R. K. (2018). The “speed gene” effect of myostatin arises in Thoroughbred horses due to a promoter proximal SINE insertion. PLoS One, 13(10). https://doi.org/10.1371/journal.pone.0205664 

Tozaki, T., Ohnuma, A., Nakamura, K., Hano, K., Takasu, M., Takahashi, Y., ... & Nagata, S. I. (2022). Detection of indiscriminate genetic manipulation in Thoroughbred racehorses by targeted resequencing for gene-doping control. Genes, 13(9), 1589. https://doi.org/10.3390/genes13091589