Dr. Emmeline Hill is an Irish equine geneticist and horsewoman who has dedicated her career to understanding the genetics behind thoroughbreds.

An early fascination with genetics led her to study human genetics and cattle genetics during her PhD. However, time and time again, she found herself drawn back to horses and the thoroughbred industry at large.  With the advent of new molecular tools and the sequencing of the human genome, Dr.Hill came to realise that she could apply these tools to study the horse genome. In 2009, she discovered the speed gene, a powerful biomarker that has revolutionised the fields of equine genomics and greatly contributed to thoroughbred genetic research.

Horses and People spoke with Dr. Hill about the current direction and future applications of her research on equine genes.

When did you first become interested in genetics?

My choices were hugely influenced by my family’s involvement in racing and the thoroughbred industry. My family bred thoroughbreds and as a child, I rode ponies- not at any sort of high level, but I was always around them. And then I was always going to go down the science track. I had lots of questions about the world in general, but I was particularly interested in evolution. That was kind of what really sparked my interest in genetics and population genetics.

So how did you end up working with horses in particular?

Well, I always knew people liked to talk about bloodlines and inheritance, through pedigrees. Pedigrees, of course, are genetics, and genetics are, you know, pedigrees. So I realized that even though a lot of people maybe didn’t know it, they were always considering genetics when they were looking at a pedigree.

When I was in university, it was an exciting time to be working in the field of genetics, because the human genome was being sequenced at that time. All these new molecular tools were being developed. And so, I thought, what if we could apply these tools that are being developed in the area of human genetics to other species? What if we could apply them to answer questions about horses? And that’s sort of where it all started.

Dr Hill’s research warns that inbreeding in thoroughbreds has lead to exposure of harmful mutations, which can be detrimental to the breed. Photo by Fennell Photography.

Can you tell me about your research on horse genetics over the years?

When I was a PhD student, I actually studied human genetics and then I went on to work in cattle genetics. It was getting slightly closer to horses because at that time there really wasn’t such a thing as horse genetics as we now know it. It was an emerging nascent field of research.

Now, of course, there’s an international workshop studying equine genomics, which I’m a part of. However, when I was a student, the tools, and technologies for studying horse genomics were not very well developed, and as horses were not considered an agricultural species or a model for human research, the technology lagged behind. In any case, now we’ve caught up, which is great.

I was first awarded a grant from Science Foundation Ireland to try to address some of the questions that I had. What are the genes that make thoroughbreds? What are the genes that differentiate them from other horses? What are the genes that make some horses faster than others? They seem simple questions, but they hadn’t been asked in this way before.

It was during that research that we made the discovery of what we now call the speed gene, which allows us to read the DNA of an individual horse and make a very accurate prediction about how horses are likely to perform on the racecourse in terms of distance aptitude.

When it comes to the speed gene, there are three different categories, and it’s based on an actual reading of the DNA. We refer to them as CC, CT, and TT types, the CC being the horses suited to short-distance sprints, CTs middle distance, and TTs to long distance.

Can you explain a little more about the speed gene and what it means for horse racing?

Sure. The reason for the difference in racing distance between the categories of horses is that the mutation in the myostatin gene has a significant effect on the different muscle fiber types that a horse develops.

CC horses have a higher proportion of fast-twitch muscle fibres which are the muscle fibres that are required for power and short bursts of speed, and the mutation significantly influences the rate of development of muscle – so CC horses are more precocious in their muscle growth and growth rate compared to TT horses.

How can we use this genetic information to add another layer to help inform training and race planning?

Genetic information can certainly help guide training and race preparation. The speed gene information allows trainers to remove the element of guess work. Most trainers look at the pedigree and the physical individual and what the horse is showing them at home on the gallops and on the racecourse. This can be informative, but it is not always accurate, because full siblings with identical pedigree pages can be completely different genetically. Using the speed gene information can give strong guidance to sit alongside what the trainer is seeing.

Sure. You’ve also studied inbreeding in thoroughbreds. Could you tell us more about your recent papers on that subject?

Yes, we did a study on inbreeding based on measurements at the DNA level across the whole genome. Inbreeding in horses can be good or bad. Good inbreeding is used to concentrate the favourable versions of genes in progeny, which is a strategy that’s been used for centuries and has made the thoroughbred the thoroughbred. Recent inbreeding, on the other hand, can lead to exposure of harmful mutations, which can be detrimental to the breed.

Our research found that recent inbreeding is significantly associated with a lower probability of a horse ever actually racing. We were able to pinpoint a specific region of the genome that, when double copy or homozygous, is associated with horses with that signature to have a significantly lower chance of ever racing.

Do you have any insights into why the horses with that marker have a significantly lower chance of ever racing?

No, we don’t know the reason why that is the case yet. The only data that we have is from race records at the moment, so we can only see if those horses made a race start or not. We don’t know why, and that’s what we want to delve into a little bit more.

Speaking of racing, the proportion of horses who don’t ever make a racecourse start is incredibly high. What are your thoughts on this?

When you consider that racing is the breeding goal, because if you don’t race, you can’t win and you can’t demonstrate value, the fact that there’s somewhere between 35 and 55% of foals born that don’t ever start in a race suggests that the breeding goal for a large proportion of thoroughbreds is not being met. Furthermore, the thoroughbred gene pool is getting smaller, and the population is much more highly related than other breeds of horses, which accentuates the possibility of exposure to harmful mutations. These can be selected out of the population, but it takes some time.

You mentioned earlier that you want to provide information to breeders to help them make better decisions. Can you talk more about that?

Yes, absolutely. We want to be able to provide finer resolution information to breeders that goes beyond the pedigree so that they can make better-informed decisions about which horses to breed to which. This is in their interest because the goal of breeding and training horses is to get them to the racetrack and if they aren’t making it there in the end, it’s a waste of resources. So, if the industry wants to have a thriving and sustainable population of horses in the future, then it’s really something that should be looked at.

In our research we have seen that the TT type of thoroughbred is dying out. There are very few of them around and very few being bred internationally at the moment. This has been going on for the past 15 to 20 years, and we have only seen a significant increase in CC types over time.

This is a concern because if there are no opportunities for these horses, then that trend will continue. There have to be opportunities in the race program, and there has to be value associated with that type of horse in order for those horses to be maintained within the population.

For example, reducing the Derby from 12 furlongs to 10 furlongs, as was done in France, would exacerbate the problem in this part of the world. The British Horseracing Authority has made some strides to try to boost the production of more staying-type horses, but unless the financial rewards are there, that’s not going to happen.

In Australia, there’s a huge emphasis on precocious early two-year-old-type racing, which is great, but there’s a risk of completely losing these TT types. We may not just be losing the TT version of the speed gene; we could also be losing all of the other genetic attributes that go along with that, such as durability and other aspects.

A few years ago, we went back and tested a lot of the older historical horses like Eclipse and found that they were mostly TT types. So, we’re also losing the original thoroughbred in a sense because thoroughbred racing 150 to 200 years ago was very different from the two-year-old races we see today. In some parts of the world, it has become more like quarter horse racing in a way, with short sprints, and that change happened at the turn of the last century when two-year-old racing became more popular and sprint racing became more mainstream.

Apparently, the aristocracy got bored with watching long 4-mile races, waiting for the horses to emerge out of the fog on the back straight, and they wanted races to be quick and right in front of the stands so they could see all the action from start to finish. And that’s really what happened. They moved from these match races of four miles where they’d head off into the distance and punters couldn’t see them until they came back and were all strung out. Short sprints on the other hand could be viewed by everyone. That was 150 years ago, and it was around that time that the horses that were CC types then propagated and became more popular, and then you see this increase over time of CC types in the population. But that’s been even more accentuated now with the demands of the type of racing that’s on offer.

Our goal in the future is to provide breeders with better information to make informed decisions about breeding, especially for maintaining the TT type of thoroughbred in the population. The loss of this type of thoroughbred has been going on for some time, and we must act to preserve it for the future of the industry.

—

Shortly after our interview, Hill’s team published a paper about a topic she had briefly talked about during our meeting but couldn’t delve into until it was officially released.

The paper investigated stress responses and behaviours in young thoroughbreds and was titled “Integrative Genomics Analysis Highlights Functionally Relevant Genes for Equine Behavior”  and examined 100 thoroughbred yearlings over four years as they were prepared mentally and physically for their racing careers. This research is especially transformative for racing industry, since breeders and owners can now use genetic information to make more informed decisions about training based on genetic factors. To succeed in the racing industry, a horse’s ability to handle environmental stress is crucial, regardless of its individual talent or pedigree, since genetic markers that predict anxiety, fearfulness and dominance behaviour can influence a horse’s mental and psychological responses to new situations, training methods and high-stress environments, such as racing stables. This knowledge has significance for the welfare of racehorses and can help handlers to better identify horses with a more tractable genotype that can adapt to new environments and conditions faster than horses with genetic markers indicating less behavioural plasticity.

Hill played a key role in the study, which examined genetic markers that can impact a horse’s coping ability to new stimuli in a training environment. The study revealed interesting links between different horses’ stress hormone levels, behaviour, and genetics pertaining to all aspects of training – from stabling to first backing, to first trained in long reins, to the first time they cantered on the gallop in a group.

Stress and coping traits have welfare and economic implications since they can also affect handler and rider safety. However, not every horse raised in the same environment faces the same amount of stress or copes with it in the same way. Some horses develop an “active coping style” characterised by behavioural hyperactivity and an inability to express intellectual flexibility, which can impair training performance, affect body condition, and make them more susceptible to disease.

In the study, Dr. Hill and her team compared genetic profiles of yearlings that coped well with early training and those that didn’t and tested neural tissues that control fear responses and behaviour modification to pinpoint which genes would most likely influence these responses.

Using this approach, they found genetic markers linked to stress-induced anxiety, depression, suicide, neurodevelopmental disorders, inflammatory diseases, fear-triggered behaviours, and addiction to alcohol and cocaine in other animal species and identified markers associated with stress and coping in a training environment.

A key finding of the research was that yearling behaviour was often inconsistent with cortisol levels measured, suggesting that cortisol detects just one aspect of a horse’s stress response, and this is often misinterpreted by humans.

Dr. Hill said, “This means that some horses experience stress without acting out, and this could have detrimental long-term effects if it cannot be managed appropriately. Identifying genetic markers for the stress response could, therefore, have value in identifying horses most susceptible to stress.” The identification of genetic variants that contribute to behaviour has the potential to develop not only a test for biological markers of stress response but also for improved breeding and management decisions to identify horses that may be best suited to racing and training environments.

“This concept, “aligns with the proposal to update animal welfare thinking beyond the ‘five freedoms’ to a ‘life worth living’ and the ‘opportunity to thrive’.”