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- A foal usually inherits a genetic defect from a mutant gene passed on by each parent.
It all begins with a single horse, usually in the earliest embryonic stages, with one mistake in a single piece of DNA. As that DNA fragment, or gene, is replicated in all the cells in his body, so is the "typographical error" in his genetic code.
The result is a different set of instructions for building one protein that becomes part of that developing embryo. From the individual's standpoint, this clerical mistake may not amount to much. After all, he has some 70,000 genes on his 32 pairs of chromosomes, and the vast majority of them work just as intended. Most likely he'll be born apparently healthy, lead a productive life and die from an unrelated cause, taking the mutation with him.
But let's say this horse grows up to become a popular stallion whose "error" produces a potentially debilitating abnormality that's controllable through medication or surgery. As the horse sires offspring, his genes--"typo" and all--are passed to the next generation. That single genetic error can multiply and appear in thousands of individuals over the course of several generations.
Even if the new defect causes severe problems, it could be years before the pattern is suspected as genetic in origin. By then it will be difficult, if not impossible, to erase the error. Many owners will be involved, few of whom are able and willing to sacrifice valuable breeding stock for the greater good of the breed. As the politics drag out, the genetic mutation becomes part of the biological heritage of more and more horses.
Over the past several years, however, researchers have used new and better tools to unlock the mysterious world of equine genetics. Helped greatly by groundbreaking studies of human and other mammalian genetic makeup, these researchers expect to develop a working "dictionary" for the horse's chromosomal lexicon--known as a genetic map. With it, researchers can develop the necessary tests to identify specific mutations and, in theory, selectively eliminate them. The science of horse breeding is about to undergo a transformation.
Genetic Spell-Checking
Genetic defects tend to be recessive, meaning that for a horse to be affected by a given disorder, both parents must possess the mutant gene and pass it along to their foal. If these carriers are never bred, the typo can't be passed on to the next generation. Putting such eugenics into practice is not as easy as it sounds: Unapparent carriers of the gene are physically indistinguishable from noncarriers, and until recently, pedigree research was the only tool breeders had to trace heritable conditions in a horse's family tree.
But pedigree analysis uses statistical probabilities for establishing the heritability of a trait. "You have to have a study of a large enough number of horses and their offspring, normal stallions and affected stallions and look at all their offspring," says Kansas State University researcher Judy Cox, PhD, who has studied the heritability of hyperkalemic periodic paralysis (HYPP) and of retained testicles (cryptorchidism).
Breeders' cooperation and honesty are essential to the success of a study passed on pedigree analysis, and interpreting pedigree information is tricky. "You're going to get an answer, but you have to know how good your data is to know whether to believe the answer or not," says Gus Cothran, Ph.D., a geneticist at the University of Kentucky's Gluck Equine Research Center. "You have to be really careful that you're not just seeing what you want to see."
A much more definitive, but also much more expensive, approach is a controlled-breeding program conducted at a research facility. "It requires a significant research budget," says Cox. "The biggest cost would be the maintenance of the horses. For chryptorchid study, you probably have to keep the offspring around for two years." Typically, controlled-breeding projects take three years and cost $100,000, says Ann Bowling, Ph.D., equine geneticist at the University of California's veterinary genetics laboratory in Davis.
Enter DNA testing. In October 1992, Eric Hoffman, Ph.D., a human geneticist at the University of Pittsburgh, and Sharon Spier, DVM, Ph.D., a UC-Davis equine researcher, published a landmark paper on HYPP in the journal Nature Genetics. Long suspected to be a familial disease, HYPP causes muscle tremors in horses, sometimes leading to "dog sitting," complete paralysis and even death.
Hoffman and Spier discovered a defect in a protein that regulates the flow of sodium into muscle cells, much as a light switch regulates the electricity that reaches a lamp. They further traced the mutation to a single nucleotide error that produced the wrong amino acid (leucine instead of phenylalanine), which in turn produced the faulty sodium-channel gene. In short, one misplaced letter in the genetic sequence--one typo--causes HYPP.
