What's In Your Horse's DNA?

Breeders have always been barnyard geneticists, taking a critical look at their broodmares and stallions to create foals with the traits they want, such as color, conformation, speed, athleticism, personality, intelligence, and health.

Photo: Anne M. Eberhardt/The Horse

Breeders have always been barnyard geneticists, taking a critical look at their broodmares and stallions to create foals with the traits they want, such as color, conformation, speed, athleticism, personality, intelligence, and health.

In recent years, laboratory geneticists have created tools and tests that enhance the possibility of producing healthy foals. Furthermore, the equine genome--the complete sequence of DNA bases, the genes (pieces of DNA that encode molecules such as proteins and determine hereditary traits), and chromosomes (large segments of DNA in each cell's nucleus)--has been determined. The total amount of DNA and number of genes is broadly similar between horses and other mammals. However, how the DNA is divided into chromosomes varies, explains Ernie Bailey, PhD, geneticist and professor of veterinary science at the University of Kentucky's Gluck Equine Research Center in Lexington. Each horse cell has 32 pairs of chromosomes--more than human cells, which have 23 pairs each.

All foals inherit their genes from the sire and dam, who each provide one copy of a gene to create a pair. If the two genes are the same type (they have the same DNA sequence or have the same effect), the foal is homozygous for that gene. If the two genes are different, the foal is heterozygous for that gene, Bailey says.

Dominant genes are always expressed when present, and there is a 50-50 chance the parent will pass that dominant gene on to its offspring. An example of a dominant gene is that of gray coat color: Gray offspring always have at least one gray parent. "Only one copy of a dominant gene need be inherited for the offspring to express that trait," says Bailey.

Conversely, recessive genes are only expressed if the offspring inherits a copy from each parent (is homozygous). Chestnut coat color is an example of a recessive gene: Two bay parents can produce a chestnut offspring if they each carry a single copy of the gene for chestnut, but a chestnut parent has two copies of the ¬recessive gene, so all matings of chestnut parents produce chestnut offspring.

"It is clearly important for breeders to know whether or not genes are dominant or recessive," Bailey says.

When scientists started studying the genetics behind equine hereditary diseases, they looked at those that had traits in common with human diseases, as the human genome had been mapped but the equine had not. After scientists determined a genetic mutation, equine geneticists knew what to look for and where to find it.

Inherited Disorders in Horses 2010*
Disease Trait Genetic Test Affected breeds
GBED R Yes Quarter Horses and related breeds
HERDA R Yes Quarter Horses
HYPP D Yes Quarter Horses, Paints, Appaloosas
JEB R Yes Belgians and similar horses, American Saddlebreds
LFS R Yes Arabians
MH D Yes Quarter Horses


Paints, pintos
PSSM type1 D


>20 breeds, including Quarter Horse- related breeds, continental European draft breeds, and some Warmbloods, Quarter Horses, Arabians, and other light breeds
PSSM type 2 ? No  
RER D No Thoroughbreds
SCID R Yes Arabians
*As work continues in this field, more traits and diseases will be identified
R=Recessive D=Dominant
Source: International Horse Genome Workshop: www.uky.edu/Ag/Horsemap/hgpgenomics.htm


GBED: glycogen branching enzyme deficiency
HERDA: hereditary equine regional dermal asthenia
HYPP: hyperkalemic periodic paralysis
JEB: junctional epidermolysis bullosa
LFS: lavender foal syndrome
MH: malignant hyperthermia
OLWS: overo lethal white syndrome
PSSM: polysaccharide storage myopathy
RER: recurrent exertional rhabdomyolysis
SCID: severe combined immunodeficiency

But now that the equine genome is sequenced (an effort supported by many researchers around the world and completed at the Broad Institute of the Massachusetts Institute of Technology and Harvard University, described here: www.uky.edu/Ag/Horsemap), geneticists can tackle genetic causes for diseases that occur only in horses.

"We basically apply the same technology that they use in humans to identify a gene for breast cancer or schizophrenia or addictive behavior; we can apply that technology to equine health," says James N. MacLeod, VMD, PhD, John and Elizabeth Knight Chair and professor of veterinary science at the Gluck Center.

Researchers have so far identified the genetic mutation in nine equine diseases: hereditary equine regional dermal asthenia (HERDA), hyperkalemic periodic paralysis (HYPP), glycogen branching enzyme deficiency (GBED), junctional epidermolysis bullosa (JEB), lavender foal syndrome (LFS), malignant hyperthermia (MH), overo lethal white syndrome (OLWS), polysaccharide storage myopathy (PSSM), and severe combined immunodeficiency (SCID).

Eye of the Beholder

At first some breeders were wary about genetics' intrusion into horse husbandry. They didn't want to produce foals with se-rious diseases such as OLWS (in which the digestive tracts of white foals, most commonly overos, don't develop completely; the foals typically die in the womb or less than 12 hours after birth), but they also did not want the world to think they had defective mares and stallions that could not produce healthy foals. Who would want to breed with them?

"There are the same issues in human health," explains MacLeod. "If I have a gene that predisposes me to a heart attack at age 55, I would like to know that for my medical care, but I don't want an insurance company to tell me that I am no longer insurable because of that genetic trait.

"We don't want to destroy someone's livelihood and lifetime efforts, but at the same time, if we know there is a problem in a line of horses, and we think it is inherited, we need to put this information out on the table," adds MacLeod. "This individual had this trait and this problem. Then, we can work toward a solution."

People seem most reluctant to talk about potential hereditary problems before a test is developed, adds Samantha A. Brooks, PhD, assistant professor of equine genetics at Cornell University in New York.

"When we are investigating a potential hereditary disorder and we are trying to put together case studies and looking for samples from potentially affected horses, it can be a minefield," Brooks says. "There is a long tradition in horse breeding, and reputation counts a lot. We have very strict confidentiality (rules). We have to go to farms with healthy horses as well as those with sick horses, because we have to make comparisons. So no one will know if your horse is affected or not (if they hear about geneticists visiting the farm)."

Powerful Tools

Knowledge is power, and the genetic tests that have been developed are powerful tools that enhance breeders' abilities to evaluate their horses and produce healthy foals.

"I strongly feel that the artistry of horsemanship is not threatened by this new knowledge, any more than the artistry of horsemanship is threatened by knowing a lot more about equine nutrition," says MacLeod. "Understanding the nutrient needs of a horse to make a better horse feed and to grow better hay is a good thing. Understanding some of these inherited genetic components and how they influence horse health or behavior or other traits of interest is a good thing, too."

For instance, before the gene for the muscle disorder polysaccharide storage myopathy (which appears in draft horses, Warmbloods, and Quarter Horses and causes muscle pain, stiffness, and cramping) was determined, a veterinarian who suspected a horse had the disease had to take a muscle biopsy to diagnose it, explains Stephanie Valberg, DVM, PhD, Dipl. ACVIM, professor of large animal medicine and director of the University of Minnesota Equine Center. Now that scientists have discovered the genetic mutation for PSSM, a simple blood test can provide the diagnosis and help owners decide whether that horse would benefit from dietary changes.

"They can know, based on a pain-free test, why horses have this muscle condition, and they can avoid perpetuating it," says Valberg, who holds the patent for the PSSM test.

But with great knowledge comes a great dilemma. Now that owners and veterinarians know the basis of nine genetic diseases and have tests for most of them, is it right to breed carriers?

At first glance the answer might seem simple--don't breed horses that carry a defect they might pass on to a foal. However, experts agree that the issues are as complex as the equine genome. And genetic testing allows you to make an informed decision, notes MacLeod.

Certainly no one wants to have a foal with a serious condition such as SCID, found in Arabian horses, where the foal is born without a working immune system. But what if it's not a life-threatening condition and the stallion is a Kentucky Derby winner or the mare has delivered several champions?

"It takes more thought to decide (what to do)," says Valberg. "What sort of disease would (the offspring) get? How severe would it be? What is the risk? And what am I going to do if I have a foal that is born with the disease?"

Ultimately, the most important information to know is whether your horse's genetic mutation is a recessive or dominant trait (see chart on page 23). If the trait is recessive, such as is the case with GBED, HERDA, JEB, OLWS, LFS, and SCID, the foal must inherit two copies of the gene from the sire and the dam. Therefore, a carrier can be bred to a noncarrier and produce a foal without the condition.

"As long as you know that your mare is a carrier of that recessive gene, you can make sure that the sire does not carry the gene; then you can keep breeding your mare and avoid having an affected foal," Valberg says.

It's important to remember that the foal will be a carrier that could then pass the gene on to his offspring.

Some diseases such as PSSM, MH, and HYPP are dominant traits, which means the foal only needs one copy of the gene to have the disease. "In that scenario, no matter who you bred your mare or stallion to, there would be a 50% chance of the foal being affected by the disease," she says.

Sometimes breeders want their offspring to carry some traits but not others, which is the case with the gene for OLWS. People love the distinctive coat pattern seen in pintos and Paints, but they don't want to produce a foal with the fatal condition. As mentioned before about managing a recessive condition, in this case owners can breed carriers to noncarriers to produce a disease-free animal.

Several breed organizations have been proactive in introducing rules to regulate breeding and registry of horses with genetic conditions, and they are demanding that carriers of certain genetic traits be listed. Other organizations are still debating the issue and trying to determine what information they should require when a horse is registered.

Brooks observes, "Of course, we should work progressively to limit the production of horses that may carry genetic diseases, but just because an animal is a carrier doesn't mean it doesn't have other qualities that would make it beneficial as breeding stock as long as you apply the tests that we've developed to avoid unnecessary suffering by affected offspring."

Eye on the Future

Genetics research will not only give breeders an opportunity to eliminate some diseases but also will help them eventually guide the veterinary care of their horses. Many diseases, from osteochondritis dissecans (a disease process of the articular surface of joints) to metabolic syndrome, probably have a genetic component to them, and being able to determine the genes that put a horse at risk could change the way horses are managed.

"There are a lot of researchers working toward identifying susceptibilities to conditions that would not be due to one gene but would be due to many genes," says Valberg.

For instance, some researchers are looking for the genes that put a horse at risk for metabolic syndrome, which can predispose horses to laminitis.

"If we can do a screening test early in the horse's life and say this combination of genes gives your horse a 70% risk of developing metabolic syndrome, you can start nutritional changes early and make sure he doesn't become overweight (which could lead to metabolic syndrome)," she adds.

Brooks agrees. "We are working on diseases that are very complex, like heaves and laminitis, which might have an environmental component as well as a genetic component. Therefore, you have the option of potentially preventing it because you can test the foal ahead of time and avoid the environmental factors that can contribute to the disease."

MacLeod summarizes, "I think as we learn about the genomics of horses, there is so much opportunity to gain understanding of all sorts of disease processes, to get important diagnostic tests, and to develop powerful new therapies for diseases. We have only just begun to realize these potentials."

About the Author

Marie Rosenthal, MS

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