Progress in Solving the Horse Genome Puzzle

Equine researchers around the world are gearing up for the sixth International Equine Genome Workshop, to be held in Dublin, Ireland, this summer. The meeting will allow participating scientists to move one step closer to achieving their collective goal: Cracking the equine genetic code.

The Workshop is coordinated by Ernest Bailey, PhD, a geneticist and professor of veterinary science at the University of Kentucky's Gluck Equine Research Center. For nearly a decade, Bailey has organized the collaborative efforts of more than 100 animal researchers representing 25 laboratories in 15 countries. When they meet this year, the group will add pieces to a genetic puzzle that, when completed, promises to unlock many mysteries of the horse.

The first meeting of the International Equine Genome Workshop was held in Lexington, Ky., in 1995. "The original goal of the Workshop," says Bailey, "was to develop a gene map that would be useful for identifying genes that cause hereditary diseases in horses." Toward that end, significant progress has been made. Researchers have successfully pinpointed the genetic glitches responsible for several deadly equine diseases, such as severe combined immunodeficiency disorder (SCID) in Arabian horses and hyperkalemic periodic paralysis (HYPP) in Quarter Horses.

A simple DNA blood test now makes it possible for horse owners and veterinarians to detect illnesses, including SCID in Arabians and HYPP in Quarter Horses. DNA testing in overo Paint horses can help breeders avoid the tragedy of producing a foal with lethal white foal syndrome, a genetic disorder associated with fatal flaws of the gastrointestinal tract.
 
As a bonus, the scientists have gained a better understanding of the genetics of coat color. A single hair plucked from a mare's mane can—in some breeds—help predict the color and markings of the foals she'll produce. Tests for coat color genetics are currently available to horse owners for around $25.

Although progress is being made toward the completion of the horse genome project, the pace is frustratingly slow. It isn't a lack of intellectual talent or technology that's holding the researchers back: Gene mapping became a matter of basic science during the 13-year quest to crack the human genetic code.

Financial Restraints
Lack of financial support has been a major deterrent to the completion of the equine genome project. Compared to the $3 billion in funding that was consumed by the human genome effort, the price tag of the horse genome project is relatively modest, estimated to be somewhere in the neighborhood of $25 to $50 million. Nonetheless, it's money that's hard to come by for equine researchers.

While the U.S. Department of Energy and National Institutes of Health made hefty contributions toward cracking the human genetic code, these government agencies did not set aside funds for mapping the equine genome. Currently, the horse genome project receives financial support from the USDA and several private donors, including Morris Animal Foundation, the American Quarter Horse Foundation, and the Dorothy Russell Havemeyer Foundation (a New York organization that supports several areas of equine research).

Limited funding has put the equine genome project far behind the gene mapping efforts of other agricultural species. "Genomics was deemed very important to animals like cows, sheep, pigs, and chickens," says Bailey, "because you can use this science to increase the production of food, and that makes it easier assign a dollar value to it. You can't do that with horses, because increased production isn't the real issue."

Horse Industry as Heavyweight
Still, as Bailey points out, the economic impact of the horse should not be taken lightly. The horse industry plays a major role in the U.S. economy, contributing some $112.1 billion to the nation's gross domestic product. Representing nearly seven million horses and seven million people in the United States, the horse industry provides Americans with around 1½-million jobs annually, more than the number of jobs provided by the railroad industry, radio and television broadcasting, and even the manufacture of tobacco products.

When it comes to the allocation of resources for gene mapping projects for agricultural animals, "the horse is at the bottom of the barnyard pile," jokes Doug Antczak, VDM, PhD, director of the James A. Baker Institute for Animal Health at Cornell University. "If there were more money available, we'd be able to complete the project in about a year. As it stands, we'll probably finish it in three or four years."

If there is any advantage to lagging behind in terms of research, it is that equine geneticists can follow in the footsteps left by scientists working on mapping the genomes for other species, particularly humans.

"The sequencing of the human genome lent a huge amount of information to the horse research community," says Gérard Guérin, director of horse genomic research at the National Institute for Research on Animals in Jouy-en-Josas, France.

Bailey explains, "The more we studied the human genome, the more we realized that we could use it to predict the structure and organization of the horse genome. All of the genes on chromosome 9 in the horse, for example, are located on human chromosome 8." Similarities between the horse and human exist because throughout mammalian evolution, large chunks of genetic material have remained intact from species to species.

Genes, Chromosomes, and DNA
Every creature, including the horse, has a unique set of chemical blueprints that determines not only how it looks, but how every single cell in its body functions. These blueprints are contained in the animal's DNA. Specific segments of DNA make up genes, and genes, in turn, are neatly packaged within structures called chromosomes.
The human has 23 pairs of chromosomes; the horse has 32 pairs. According to Bailey, "We want to be able to know which genes are on each of these chromosomes in the horse, so this is the point of mapping them."

Mapping genes to their respective chromosomes is only half the battle. Once researchers know where the genes reside, they'll be better able to determine their functions. "We want to know how genes impact many aspects of equine health," Bailey explains. "We want to identify the hereditary components of developmental bone diseases, respiratory conditions, and reproductive disorders."

Equine scientists emphasize that cracking the equine genetic code is not an end in itself, but rather a means to an end. "The horse genome is a tool, just like a microscope, or a centrifuge, or any other tool in the lab," says Antczak, whose research involves understanding the interactions of the immune systems of mares and foals during gestation. "My projects require information and knowledge about immunology, reproduction, and genetics."

Most of the scientists that comprise the International Equine Genome Workshop are not strictly equine geneticists by trade. In their own laboratories, Antczak explains, they spend the majority of their time working on their respective areas of research, which range from equine metabolic disorders to mammalian evolution.

"A lot of the Workshop members work on the horse genome project in their spare time, during the evening hours," Antczak notes. The scientists are willing to work overtime in the area of genetics, he says, because they need this information to make advances in their own areas of scientific research. At this point in the Workshop's history, Antczak says, "we're kind of like primitive man. We're in the tool-building stage. Once we've designed the tools we need, we're all going to go out and hunt different animals."

Bailey, whose research at the Gluck 1Center focuses on the interface of immunology with genetics in horses, agrees, saying, "The horse genome is a necessary research tool. Without it, I can't make progress in my research."

Nature vs Nurture
With the equine genome as a tool, Bailey believes, each of the equine researchers will be able to gain knowledge and understanding that will ultimately be used to improve the health and welfare of all horses.

Using the science of genetics to improve equine health is a noble quest, but there's a very real possibility that the same science eventually could be manipulated to enhance performance in the show ring or on the racetrack. Could a simple blood test or a hair sample be used to identify genetic markers for superior performance, allowing the wealthiest breeders to mass-produce horses of exceptional quality?

Bailey doubts that the science of genetics will ever replace the art of horse breeding, largely because there will always be multiple genetic pathways leading to successful performance in horses.

"Genes have lots of small effects," he explains. There is really no single gene responsible for speed or endurance. Genetic tests aren't going to be 100% predictive, because in the end, genes aren't everything."

Even genetic superstars require proper nurturing and management. Starting in the uterus, the environment in which the horse is raised is critical to ensuring that the animal realizes its full genetic potential. According to James Murray, PhD, a 15-year veteran of equine genetics research at the University of California, Davis, School of Veterinary Medicine, "An animal's genetic makeup is only part of what the animal is. The other two parts are the environment in which it lives, and the interactions between its genes and the environment."

The real value of mapping the horse genome, researchers say, lies not in its potential to enhance an individual horse's performance, but rather to facilitate the development of new tests, vaccines, and therapeutic drugs that will benefit all horses. "The use of these tests," says Guérin, "will result in improved soundness of horses. We also anticipate that they will improve the quality and competitiveness of the animals, and the breeds that they represent."

Gene Expression Influences Horse Health
One of the fundamental changes associated with the development of diseases in horses is an alteration in the expression of various genes. Gene expression can change in response to inflammation, infection, exercise, and variations in the daily routine. In horses, changes in gene expression can lead to conditions like laminitis, respiratory illnesses, metabolic diseases, and muscle disorders.

"If we find out which genes are being expressed in certain disease processes," Bailey explains, "we'll know which therapies or treatments will be the most effective early on. Or we'll be able to avoid putting a horse in a situation in which he's likely to become ill."

Bailey says that once they're developed, genetic tests will likely be readily available and affordable to all horse owners. "These tests are going to be used just like the tests we're using now. The vet will come out and draw a sample of blood or hair and send it off to the laboratory. The lab will send back answers about which genes are being expressed."

What will be different, he believes, are the drugs that are used to treat the illnesses and disease processes that are identified. "We'll have new treatments and therapies that are more effective than the ones we have now, because we'll have a better understanding of what's going on in the horse." Bailey says. The end result, Bailey predicts, will be sounder, healthier horses.

A Work in Progress
Before new diagnostic tests and treatments can be developed, much work remains to be done. Horse geneticists expect that by the end of 2005, they'll have mapped approximately 4,000 of the estimated 25,000 equine genes.

"Right now," Antczak explains, "the appearance of the horse genome is comparable to a map of the Earth generated by a satellite. We can see a broad outline, but we don't have the fine details. When the project is finished, we'll have a better picture, like a roadmap. We'll be able to see the individual street signs."

Creating a high-resolution map, like the one that exists for the human genome, is a goal shared by all of the horse researchers of the International Equine Genome Workshop. When they meet in Dublin this summer, they plan to take a few more strides toward achieving that goal.

About the Author

Rallie McAllister, MD

Rallie McAllister, MD, grew up on a horse farm in Tennessee, and has raised and trained horses all of her life. She now lives in Lexington, Ky., on a horse farm with her husband and three sons. In addition to her practice of emergency and corporate medicine, she is a syndicated columnist (Your Health by Dr. Rallie McAllister), and the author of four health-realted books, including Riding For Life, published by Eclipse Press and available at www.ExclusivelyEquine.com or by calling 800/582-5604.

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