NEWS
On the brink of the future
Posted: Tuesday, August 31, 2010 12:25 PM
Cindy Mikell photo
by John P. Sparkman
Throughout the history of the Thoroughbred, breeders have struggled to recapture and intensify the abilities of the ancestors of the horses they produce. The countless breeding theories and schemes cooked up by the febrile brains of generations of breeders, journalists, scientists, and, yes, charlatans, share one common goal: manipulating, recapturing, and refining the genetic combinations that produce great racehorses.
Over the last century, science has taught us that the task confronting breeders is far more difficult than they once understood. Although linkages between genes exist, modern genetics teaches that each sperm produced by a stallion and each egg produced by a broodmare receives a basically random selection of the genes possessed by that stallion or mare.
Until the first decade of the 21st century, however, breeders had no way of determining what specific genes any Thoroughbred might have inherited or what they might mean to their career as a racing and breeding animal. Toward the end of the 1990s, geneticists began teasing out the secrets of the genetic code, and that process has accelerated dramatically over the last few years. In 2000, Stephen Harrison, B.Sc., a geneticist with a Ph.D. in genetics from the University of Wales, founded Thoroughbred Genetics Ltd., a company based in Canterbury, England, specializing in genetic testing of Thoroughbreds. In 2006, Harrison published the first peer-reviewed scientific paper showing a connection between specific genes (mitochondrial DNA haplotypes) and racing performance.
Harrison was the first to market DNA tests of Thoroughbreds, but over the last year, competition has appeared. In January, Equinome, based in Dublin, Ireland, and founded by Irish geneticist Emmeline Hill, Ph.D., and Irish trainer Jim Bolger, announced the availability of a new test to detect what they dubbed the “speed gene” based on research published by Hill and others in the online journal PLoS One.
Just a few months later, a Kentucky company joined the fray, when Matthew Binns, Ph.D., and David Lambert, D.V.M., announced the formation of The Genetic Edge, a division of Lambert’s Equine Analysis System Inc., which specializes in genetic testing based on research Binns has completed and will soon publish. Fast on the heels of that announcement came the news that Davanand Doodnauth, M.D.’s LifeLine Labs LLC, another Kentucky company that also offers umbilical stem cell storage, announced that it too was offering genetic tests related to racing performance. Finally, Steve Tammariello, Ph.D.’s ThoroughGen has quietly begun acquiring clients offering a series of tests based on Tammariello’s ongoing research on the equine genome.
Thoroughbred Genetics
“I’ve always been involved in horses, rode in point-to-points and jump races, but I’m too big to be a jockey,” said Harrison, who decided to combine his love for horse racing with his academic career. After earning his Ph.D. in genetics, Harrison saw an opportunity in the Thoroughbred industry.
“It became apparent to me that there was a market for a company that could provide up-to-date genetic science on horses combined with a practical background in horses. To people coming into the industry from outside, one of the things that strikes them is that we’re almost in another century, or we have been until recently.
“It’s a lot more difficult than other breeds because of the expenses involved, and it doesn’t conform to any kind of directed program like in any other livestock breed. One of the problems with Thoroughbreds is that they’re extremely variable, despite the inbreeding. ...There are too many genes in the gene pool for the actual stamina ranges [of races].
“What we’re trying to do is get the best out of the genetics that are available. We try to assemble animals right from the start that are aimed at a specific target.”
Thoroughbred Genetics now has four full-time employees and offers a panel of DNA screens called an EQProfile tailored for racehorses, broodmares, or sires. Different panels in the profiles focus on genes that govern respiration and energy release (stamina); measures of homozygosity or heterozygosity (inbreeding); and what the company calls relatedness or cluster analysis, a panel that relates the genetic profile to previous horses with known abilities.
“The EQProfiles for racehorses, mares, and stallions are the same tests,” Harrison said, “but you’ve obviously got to utilize the information in different ways. The energy/respiratory looks at [mitochondrial DNA] but also some variants on the chromosomes as well. They’re all just components of the profile. No one of them is going to give you the complete answer to the horse.
“There are about 50 sites on the heterozygosity/homozygosity panel. There seems to be an optimal range [degree of inbreeding] there.”
The company’s resources are also available for special projects on a contract basis.
“What we try to do is form a closer working relationship with the clients,” Harrison said. “It’s still a very traditional business. Most of our clients are the major ones that are more innovative.
“It’s an industry that is missing quantifiability. The more you introduce quantifiability, the less certain people’s jobs will be important. The mystique surrounding horse selection is not particularly scientific in many cases.
“There are so many genes involved, but if you can increase probability of success or decrease probability of failure, it’s a big improvement. We provide people with a small piece of advice and they just do their own thing. We can’t claim responsibility. It’s how it all fits together.”
Equinome
The launching of Equinome as a commercial entity was announced with great fanfare in January. A spinoff of University College Dublin’s NovaUCD, an incubation center for new businesses based on university research, Equinome currently has available one genetic test it calls the speed gene test, based on research by Hill, who earned her Ph.D. in genetics under the tutelage of equine genetic research pioneer Patrick Cunningham, Ph.D.
Like Harrison, Hill comes from a racing background. Her grandmother, Charmian Hill, owned and bred Dawn Run, steeplechasing’s greatest racemare. Bolger, trainer of champions Teofilo and New Approach, provided test samples for some of Hill’s research and liked the results so much that he became a partner in the company.
“We were established in August of last year [2009] as a commercial entity,” said Donal Ryan, the company’s managing director. “Dr. Hill’s research had been ongoing for six years, but she made a breakthrough last year with the speed gene. Once she’d made that breakthrough, the setup of the company became a reality.
“We see ourselves as offering a secure, highly confidential testing service founded in world-class science. We offer the service to clients around the globe, and we have a license to import blood samples from all the major bloodstock markets. We already have customers in all the major markets. We’ve seen [an increase] in all the key regions, and have serviced clients in all those jurisdictions.”
Equinome currently boasts seven employees, with the research and development team based at the UCD Conway Institute of Biomolecular and Biomedical Research. The commercial team is based at NovaUCD.
Equinome’s test requires blood samples and a two- to three-week turnaround time, but more tests are under development.
“That’s where we are right now,” Ryan said. “We have quite a dynamic and comprehensive research program, which is ongoing now using genomic technologies to try and identify and characterize the molecular and genetic variants underlying key performance and health traits in the Thoroughbred.
“Through our associations with a number of top Irish breeders and trainers and abroad, that’s given us access to large numbers of top-class horses. They provide subjects for our research program. As a company we’re committed to achieving scientific excellence … so any tests that we commercialize in the future must adhere to those core values.
“We will be developing and adding to our portfolio in the near future.
“Owners and trainers use our service to optimize purchase and training decisions and better target suitable races for their horses. But we’ve also got owner-breeders, commercial breeders, bloodstock agents, and stallion managers who are using the test now to make more precise racing and breeding decisions and to maximize the genetic potential and commercial value of the horses.
“We expect [genetic testing is] going to change how breeders approach selection decisions. We believe that genetic testing using scientifically validated tests will empower breeders to embrace the science and incorporate scientifically sound methodologies into their decision making.”
The Genetic Edge
Lambert has been a familiar figure on the Thoroughbred auction and breeding scene for more than 30 years. A pioneer in heart ultrasound techniques, Lambert’s company, Equine Analysis, also offers biomechanical and other services. Since 2007, Lambert has partnered with Binns, a molecular biologist by training who founded the genetics group at England’s Animal Health Trust, served as a professor of genetics at the Royal Veterinary College in London, and was a founding member of the Equine Genome Project.
“I’m really a molecular biologist,” Binns said, “so my skills are in making DNA jump through hoops, and I’ve applied that to various things in my scientific career.”
Binns had no interest in horses before he was recruited by the Animal Health Trust to bring his molecular biology skills to bear on infectious diseases in horses.
“When you’re doing science, you should understand your constituency. So when I went to Newmarket, I started reading the Racing Post. I started going racing straight away and pretty quickly became fascinated by it as a puzzle.”
Binns’ skills and interests soon were diverted to genetics.
“Very quickly I became intrigued by performance,” he said. “It was uncharted territory.”
Binns recently published a book written with longtime Racing Post pedigree writer Tony Morris titled Thoroughbred Breeding: Pedigree Theories and the Science of Genetics.
In July, Lambert and Binns formally launched The Genetic Edge, a division of Equine Analysis specializing in DNA testing based on Binns’ research, though the tests had been available since March. The tests include a distance panel similar to Equinome’s speed gene test, a racing surface preference panel, a graded stakes performance panel, and a height panel, which predicts mature height.
“We wanted to look at performance, and we wanted to use Grade 1 winners, because we believe that there’s less variability there,” Binns said. “We take those horses as our good horses [in the experimental design], and the bad horses we define as under-60 Beyers [Speed Figure] that had run at least three times. We decided on comparing sprint versus distance, dirt versus turf, small versus tall horses, and looked for markers associated with those traits.
“In our study we had about 30 Grade 1-winning sprinters, and they were all homozygous [for the heavier muscle gene]. If you want to win a sprint at that top level, you’ve got to be homozygous for sprinting.
“It measures optimum distance, but that is severely influenced by the pace at which races are run. A homozygous sprinter can win the [Kentucky] Derby (G1), possibly a heterozygous stayer can win it, but it depends on pace.”
Binns’ graded stakes panel grades horses A, B, C, or D, based on the number of markers associated with graded stakes ability their genome contains.
“We’ve got markers associated with G1 ability, and we’ve taken nearly 300 samples from [the] Keeneland September [yearling sale] and tested them against that panel. It gets complicated, but when you look at an elite sale, about 70% are As and Bs, and the percentage comes down as you go through the books as you’d expect. Eighty-five percent of G1 winners are A and B horses. About 10% of the population are Ds. We don’t think Ds will do the job.”
The graded stakes panel offers breeders as well as buyers a useful tool.
“The day that foal hits the ground you could get your genetics,” Binns said. “Culling is such an important thing. You can replace that 10% [Ds] with a better 10%. If you have a genetic C, you’ve got a 1 in 3 chance compared to As and Bs.
“We are continually analyzing the data and new data to refine our understanding of the genetics of performance.”
Said Lambert, “[Genetic testing] could potentially hurt the current situation for certain people, but it’s going to be for the long-term good. If you can introduce tests like this and help someone accomplish more, then it will hopefully keep our owners in the game a bit longer, and maybe we can get people developing plans that have some longevity to them.”
LifeLine Labs Pegasus Profile
The most recent newcomer to the genetic testing market is Doodnauth’s Lifeline Labs, a Lexington-based company that announced the availability of its Pegasus Profile genetic tests in May.
A native of Long Island, Doodnauth went to the racetrack regularly as a child with his father, a native of Guyana who is of Indian extraction.
“I learned to enjoy horse racing at a very early age before I understood anything about gambling,” said Doodnauth, who earned an undergraduate degree in evolutionary biology from Harvard University, and then worked in research at the National Institutes of Health and at the University of Maryland for several years before deciding to go to medical school at Howard University in Washington, D.C.
“After med school I wanted to marry the two passions that I had, one for research and the other for Thoroughbred racing. It was very easy for me to look at cutting-edge technologies and see how they could be suited to the Thoroughbred industry.”
Doodnauth founded LifeLine Labs in 2005 as a biotech company specializing in the isolation and cryo-preservation of stem cells processed from equine umbilical cords. Umbilical stem cells may be useful later in life for treatment of musculo-skeletal defects or bone or soft tissue injuries.
“There probably will be a transition [in the future] to a universal stem cell line, and we hope to become that company. I’m trying to transition our company to be on the next edge, and I think genetics is the next edge.
“We started out cataloging our stem cell lines based on genetic markers so that I could uniquely identify cells that were stored. Looking to the future, I started looking at retired horses and looking at genetic markers for performance. We’ve looked at a panel of markers and are continuing to look at more and more markers.
“We think we’ve developed a product that can be useful for any horseman, whether you’re at the top of the game or have one or two horses.”
The Pegasus Profile compares the genetic markers at more than 40 sites on the equine genome to markers at the same sites in horses with known performance in a genetic database and provides clients with information on the performance of the ten closest matches to the subject horse.
Information provided for the client includes highest performance level, black-type status, average earnings per start, best Beyer rating, best two-year-old Beyer rating, average winning distance, and winning distance range for the closest matches. The profile also provides a measure of “graded stakes likelihood” based on the similarity of the subject horse to graded stakes-caliber horses in the company’s database of more than 1,000 retired horses.
“We’re looking at multiple genes on multiple chromosomes, and we’re still developing the science,” Doodnauth said. “We’re tweaking our algorithms and making adjustments, but what we do know is that the horses in our database have a fixed performance record. If we can provide that to the client, they might be better suited to make sense or nonsense from that information.
“The average person without any science can look at the information and see that if eight out of ten horses [with similar genetics] are bums that it’s likely that the horse doesn’t have the genetics for performing at a very high level.
“On the graded stakes likelihood, we look at the frequencies of certain alleles at these genetic marker locations on diverse chromosomes, compare that in the graded stakes group, and then see what it’s like in the general population, and you get a ratio.”
ThoroughGen
Though not from a racing background, Tammariello grew up near Erie, Pennsylvania, in a family that regularly patronized now-defunct Commodore Downs. After earning his Ph.D. in molecular entomology from Ohio State University, he completed a postdoctoral fellowship working on Alzheimer’s disease at the University of Kentucky Medical Center in Lexington.
Tammariello is now an associate professor of molecular genetics at Binghamton University in Binghamton, New York, and currently owns one horse racing on the Pennsylvania-West Virginia circuit.
“My research line for Binghamton University is in Parkinson’s disease,” Tammariello said. “As sort of an offshoot, since I am a molecular geneticist, I decided to start looking at genetic traits that could be important in the athleticism of humans and of horses.
“I started looking at genes that in the literature were important in humans or racing dogs, or anything that I could find that would link to what I thought would be a physiological trait in horses. We have screened 150 genes now.
“By the spring of 2009, I had collected approximately 250 Thoroughbred samples and another 150 from other breeds of horses. What we were interested in, number one, is what makes a Thoroughbred a Thoroughbred and, number two, what makes a good Thoroughbred a good Thoroughbred. There are all sorts of variables in that.
“We found different polymorphisms, which are changes in the DNA, that seemed to be linked to certain physical characteristics that would be important in racing. We were able to locate and identify upwards of 75 different polymorphisms. When we compared those to the performance records of horses, we narrowed that down to about ten that we think are very important to the racing industry. They range from genes related to muscle to bone density and some behavioral traits.”
Tammariello had planned to delay developing a commercial company, but the launch of Equinome in early 2010 changed that calculation somewhat.
“Equinome hit everything, the Wall Street Journal and Science, and everything else, so in March of 2010, I sat down with some associates, and said we should think about making ourselves known,” he said. “We decided to focus more on meeting some of the people in the industry, so we’ve been going to the sales and farms.”
ThoroughGen currently offers three basic tests commercially. The energy gene test is related to racing class, as is the energy gene plus muscle gene number one test. The energy gene plus muscle genes one and two test is a predictor for both class and stamina.
“What we’re really doing is we’re trying to assess what makes a bad racehorse,” Tammariello said. “It’s going to be almost impossible to look at a genetic screen and say that you’re going to have a champion horse. What we will be able to do, and what we can do right now is, with the ten genes we’re looking at, we can tell breeders what horses maybe shouldn’t be crossed.
ThoroughGen aims to provide information on the probability of success by taking out the bad horses first.
“Two of our polymorphisms work 100% of the time,” Tammariello said. “If they have a certain mutation, the horse will never make it to the track. We have seven other polymorphisms that we’re able to do linked to bone density and behavior, but we don’t really know how useful that’s going to be yet.
“Personally, I don’t think genetic screening is going to create faster horses. This is just one puzzle piece that could help breeders and trainers make a plan for breeding pairs and training regimens.”
John P. Sparkman is bloodstock editor of THOROUGHBRED TIMES and author of Foundation Mares. More of his work can be viewed at http://pedigreecurmudgeon.blogspot.com.
