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Mapping the Horse
Targeting disease, scientists leave speed and endurance to breeders
Edward R. Winstead

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Charismatic winning the 1999 Kentucky Derby.

And they're off.

When the thoroughbreds break for the first turn at Churchill Downs on May 6th, Charismatic will be on a farm outside Louisville. Winner of last year's Kentucky Derby and Preakness Stakes, Charismatic was racing's hope for the first Triple Crown in two decades. But the stallion fractured a bone at the Belmont and finished third, leaving the track in an ambulance. The next day, a surgeon successfully inserted four screws into the injured foreleg, and earlier this year Charismatic began a new career: passing on his genes.

"Charismatic is doing great," says a spokeswoman at Land's End Farm in Versailles, Kentucky. "He has many mares in foal, and breeding season goes until late June."

While Charismatic creates offspring (sometimes twice a day), scientists have been creating a map of the horse genome. In 1995, researchers from 21 laboratories around the world came to Lexington, Kentucky, for the first meeting of the Horse Genome Project. Since then, the collaborators have identified nearly 500 genetic landmarks in the horse and are placing them where they belong on the 64 equine chromosomes.

Like maps of the human genome, the horse map will change how researchers study their subject's health. "With the genome map, we now have a tool for investigating the genetic basis of disease and traits in the horse," says Ernest Bailey, the project's coordinator and a researcher at the University of Kentucky's Gluck Equine Research Center in Lexington.

A global collaboration

Horse Genome Project is happening in the USA (California, Texas, Minnesota, Kentucky, New York), Ireland, UK, Germany, Sweden, Norway, France, Czech Republic, Switzerland, Denmark, South Africa, Australia, New Zealand, and Japan.

Today the Horse Genome Project includes 25 laboratories representing the United States, Europe, Japan, Australia and South Africa. "The cooperation among the researchers has been extraordinary," says Gene Pranzo of the Dorothy Russell Havemeyer Foundation. His group has provided grants for periodic mapping workshops. "Scientists come together at workshops to review results and determine the project's next steps," says Pranzo. "They deal with problems that can't be resolved by e-mail or fax."

The horse map is a work in progress. New landmarks will be added as they are discovered, creating a denser, more detailed picture of the genome. At present, there are no plans to sequence the entire horse genome as is being done in human genomics. Eventually researchers will use the map to investigate complex traits involving interactions among many genes. Students in Bailey's laboratory, for example, are interested in genes linked to developmental bone disease, respiratory bleeding, and infectious and muscle diseases.

A healthy horse is a wanted horse

Genes clearly influence speed and endurance, but researchers say they have no plans to use the map to study performance traits. Designing a controlled study of speed, for example, would be difficult because of non-genetic factors like training and diet. Furthermore, many in the racing industry have said they don't want science to somehow lessen racing's mystique. "Breeders probably would rather we stick to curing disease," says Teri Lear, another University of Kentucky researcher on the genome project.

Like the perfect baby, the perfect foal is controversial. And as Bailey points out, horse breeders have successfully selected for performance for centuries: "The best way to confer performance traits to offspring is to raise horses, race them, and select the best performers for breeding, which is what breeders do."

Productive horses have homes

The purpose of the Horse Genome Project, by contrast, is to use veterinary medicine to create a healthier horse. Every horse owner and breeder wants a healthy animal. "One of our goals is to make every horse less likely to suffer," says Bailey. "A healthy and productive horse is a wanted horse. These horses have homes."

An unhealthy horse, on the other hand, has an uncertain future. Charismatic was lucky—at the finish of the Belmont jockey Chris Antley sensed a problem, leapt off and probably prevented further injury by holding the horse's foot. The bone surgery was successful; Charismatic has a home and a stud fee of $35,000. Yet in Bailey's view most breakdowns are a disaster, and a trend in recent years suggests that more and more horses are breaking down on the track.

Charismatic at the Belmont.

One reason for the more frequent injuries may be crowded fields. Major events now include more horses, increasing the odds of collisions and spills. Not since Affirmed in 1978 has a horse won the Triple Crown, and the reason, some say, is there are simply too many horses to beat. The more frequent breakdowns have also been attributed to aggressive trainers and owners who are said to push their horses too hard.

Clearly, the racing industry stands to benefit from advances in veterinary medicine resulting from the gene map: the fastest thoroughbred can't race when sick. But the industry has been reluctant to spend money on the map, according to several researchers. "We need to do a better job convincing people in industry of the utility and applications of the map," says Lear at the University of Kentucky.

No money for the horse

Money has been an issue since Earnest Bailey first proposed the idea of a horse map in the early nineties. Maps for pigs, sheep, cattle, and chickens were then being constructed with funding from the United States Department of Agriculture. But there was no money for a horse map, and no single center had the resources to develop one. Besides, in 1993 the value of such a map was unknown. "Back then, we did not have the critical mass of scientists necessary for the project," recalls James Mickelson, a horse researcher at the University of Minnesota.

Some genetic diseases exist in both humans and horses

Soon, however, researchers began identifying genes for traits of interest in other species. "By the mid-nineties it was pretty clear that genome maps were effective research tools," says Bailey. Then, in 1995, 70 researchers from competing laboratories launched their collaboration at the meeting in Lexington. The project now had momentum but still not much money. No matter, the researchers adopted a comparative approach to mapping that incorporates information from other genome projects.

The comparative strategy works because throughout evolution blocks of mammalian genes have tended to stay together although they may be on different chromosomes in different species. Since work on the human genome is relatively advanced, the horse researchers have tried to identify similar regions in both the human and horse genomes. For example, many genes on horse chromosome 9 are found on human chromosome 8, says Bailey.

Not surprisingly, some genetic disorders exist in both humans and horses. Some Arabian foals, for example, are born without a functioning immune system—the same disorder that forces some humans to live in sterile "bubbles" because they cannot fend off infections. The gene involved in Arabians was identified using information about the disease in humans.

Getting help from the human genome

"Much of the progress that has been made in mapping human genes can be—and is being—applied to horses," says Doug Antczak, director of Cornell University's Institute for Animal Health. He adds that the Horse Genome Project will save millions of dollars and years in time by piggybacking horse research on work done in other species.

The horse map may never contain the structure of every horse gene. "No one is talking seriously about sequencing the horse," says Bailey. "But if we have a good map, the full sequence may not be necessary." With a little help from the human genome, horse researchers may live to see a healthier animal.

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