Photo: Anne M. Eberhardt/The Horse
Most owners and breeders wouldn't gaze at a pasture filled with weanlings and picture those same horses 25-30 years later, with sway backs or graying coats. With increasing attention being paid to geriatric horses' care, however, it behooves us to look at horses' longevity from a different angle--at the beginning rather than at the end.
"Great," you might say. "Can I design my perfect horse--one that I can ride and love for decades?" Sorry, the answer, unfortunately, is no--or, at least, not yet. While our understanding of the equine genome is growing by leaps and bounds, our current genomic knowledge is the tip of a very complicated iceberg. An individual horse's physiology is shaped not only by his parents' genes but also by his environment, from feed and management styles to climate and exercise load. As Molly McCue, DVM, MS, PhD, assistant professor in veterinary population medicine at the University of Minnesota Equine Center, says, "We're reaching a place of realization about how much genetics and environment combine."
Genetics and Genomics
As scientists have sequenced and learned to manipulate pieces of the genetic puzzle, the picture that puzzle's creating has become visible. Welcome to genomics.
While "genetics" examines one gene at a time, "genomics" is the study of all of the genetic material contained within an organism. In 2003 The Human Genome project completed the 13-year task of sequencing the full complement of human DNA and identifying all of the more than 20,000 genes that encode proteins. In 2007 the equine genome sequence was completed.
The sequence of the equine genome provides researchers with a critical starting point or reference for specific genetic investigations.
Ernest Bailey, PhD, immunogenetics and genomics researcher at the University of Kentucky's (UK) Gluck Equine Research Center, described the significance of equine genomic research in a 2005 white paper on behalf of the Equine Research Coordination Group prior to the landmark sequencing: "The point is to understand the interplay of genes and management, then allow breeders and horse owners to continue doing what they have always done, while making informed choices." He also noted in the paper that "the real benefit of genomics for horses will be to understand complex diseases that have frustrated horse owners and veterinarians since the time of domestication."
The Horse and His Human Architects
Long before genomics, Mendel, or even the microscope, humans were manipulating horses genetically, breeding for traits that suited specific human needs or desires. McCue refers to this 6,000-year period of human intervention in the development of the horse as evolution within a compressed time frame.
In some ways the horse might have benefited from our interference. "As athletic working animals, horses have been selected for health and performance over thousands of years," writes Bailey. "Consequently, horses have few purely genetic diseases."
Indeed, James MacLeod, VMD, PhD, John S. and Elizabeth A. Knight chair, professor of veterinary science, and director of UK's Equine Initiative, comments that while there might be "some phenotypes (physical expressions of genetic traits) selected for that aren't the best when it comes to health, the horse is nothing compared to some purebred dog breeds." In other words, horses are generally bred for athletic abilities rather than for wrinkly skin or floppy ears. Thus, less physiologically-sound animals were left out of the mix and many of the human-driven health issues plaguing more ornamental companion animals haven't developed.
However, selection for athleticism comes with its own price. McCue points out that "the horse was domesticated for a work animal. (This led to) accelerated breeding for metabolic efficiency." In other words, horses, like humans, have evolved to do work with far fewer calories than are available to them. In humans, an abundant food supply that exceeds metabolic needs has led to conditions such as obesity and Type 2 diabetes. In horses, feeding carbohydrate-rich diets to animals that have been bred for generations to perform heavy work on scant feed results in conditions such as equine metabolic syndrome (EMS).
Is Inbreeding Bad?
A joke told in livestock circles goes something like this: "When it works it's line-breeding; when it doesn't, it's inbreeding." But what are the risks, benefits, and possible consequences of breeding near-relatives in an attempt to enhance or "lock-in" specific desirable traits?
McCue discusses a phenomenon called "inbreeding depression," which is defined as "the reduced survival and fertility of offspring of related individuals."1 How this phenomenon contributes to or detracts from an individual's longevity is not yet known, but McCue points out that "within every genome, there are a certain number of deleterious mutations. Breeding close relatives produces an increased likelihood of an offspring with two copies of a deleterious mutation.
"By doing a lot of inbreeding, we're probably breeding in life-limiting traits," she continues. "By concentrating bad mutations, we're probably decreasing longevity even if we can't yet put a finger on (the specific cause)."
To help avoid these life-limiting traits, horse breeders should keep up-to-date on genetic discoveries within their breeds and seek to understand the complex interactions of genetics and management.
Applying Genomic Knowledge
While the past 15-20 years have seen the development of numerous diagnostic tests for specific genes linked to a variety of equine diseases (see table), the consensus among researchers seems to be that these single-gene-associated diseases will prove to be the exception rather than the rule. MacLeod comments that many single-gene traits are well-defined. However, he looks toward the more complex traits as showing us opportunities to advance equine health in the future: "I get most excited about the health-related studies (based on genomics). Those will continue to pay dividends." MacLeod hopes that this work will give the veterinary community a better understanding of the genetic determinants for health conditions.
McCue agrees, adding that she sees genetics as preventive medicine that can lead to "understanding disease risk and making choices that minimize risk over time."
Take one of the more recognized life-limiting conditions in the older horse, for instance: laminitis secondary to EMS. Nat Messer, DVM, Dipl. ABVP, professor in the Equine Clinic at the University of Missouri College of Veterinary Medicine, points out that "more and more horses are being raised in a semi-sedentary lifestyle and being fed improperly for that lifestyle."
Results from a 2006 study of 160 ponies2 found that "a previous diagnosis of laminitis was consistent with the expected inheritance of a dominant major gene or genes with reduced penetrance." In these ponies, "determination of prelaminitic metabolic syndrome in March predicted 11 of 13 cases of clinical laminitis observed in May when pasture starch concentration was high."
According to McCue, scientists now believe that more than one gene is involved in a horse's risk of developing EMS. "I think the answer is going to be multiple genes that have alleles (variant forms of the same gene) that increase risk when put together over a lifetime," she says.
Researchers are also investigating possible genetic components to conditions such as developmental orthopedic disease (DOD), wobbler syndrome, equine melanoma, equine recurrent uveitis in Appaloosas, and recurrent airway obstruction.
With diseases such as EMS, the environmental component (improper diet and exercise, as mentioned) is well-recognized. What has been less understood is the reason for varying responses among horses on the same pasture. "In a group of horses," says McCue, "not all of them may be at risk for obesity on grass."
The true value of recognizing some of the more complex conditions' genetic components will likely lie in how it modifies the ways we manage these horses. With DOD, researchers are examining the question of predisposition toward certain conformation types and their correlation with lameness, says Messer.
Of the possibility of identifying a genetic predisposition toward wobbler syndrome, MacLeod says, "if we knew the genetic determinants that place horses at risk for the disease, we might start preventative management practices when the foal is born."
So shouldn't our goal be to eliminate undesirable and life-shortening traits from the genome and, thus, the horse population? MacLeod points out that a horse identified with a certain predisposition "may have a myriad of other wonderful traits. We may want most of what that horse represents, but perhaps modify some management parameter early in life because of a known genetic susceptibility and also consider these genetic issues when making future breeding plans."
Applying Knowledge to Reality
"One of the horse's best and worst attributes is that it lives a long time," says Messer. While horses routinely live into their 20s, with reports of ponies reaching 50 or older, quality of life and usefulness are as important as chronological longevity. We might not find ways of selecting longer-lived horses, but we can try to identify and manage genetic predispositions toward diseases that shorten horses' lives.
Rather than rushing out to have your horse's genome sequenced, McCue suggests horse owners:
1. Educate themselves. Know the mutations in the breed and test for them. Avoid breeding simple traits that are known to have the potential for detrimental health consequences.
2. Know that genetics isn't going away. Breeders, says McCue, should learn about genetic concepts such as dominance, recession, and partial expression. It is important to understand the complexities of genetic expression rather than to look for a "yes or no" answer on whether to breed a mare. Consulting with a veterinarian is key to understanding these concepts.
With access to a wealth of new research and available tests for "simple" genetic diseases, it might be easy to forget some basic principles: Certain conformation traits can predispose to lameness and these should be eliminated through responsible breeding.
As mentioned, lameness and chronic laminitis secondary to EMS lead the list of life-limiting conditions in the horse. Changing nutritional management after a diagnosis of laminitis in a middle aged horse or developmental orthopedic disease in a young horse might be akin to closing the proverbial barn door as the hoofbeats echo down the road. However, looking at longevity and performance lifespan at the beginning could make a great deal of difference in the end.
1. Charlesworth Deborah, Willis John. "The Genetics of Inbreeding Depression," Nature Reviews Genetics. (10) 783-796. November 2009
2. Kibby H. Treiber, MS; David S. Kronfeld, PhD, DSc, MVSc; Tanja M. Hess, DVM, PhD; Bridgett M. Byrd, MS; Rebecca K. Splan, PhD; W. Burton Staniar, PhD. "Evaluation of genetic and metabolic predispositions and nutritional risk factors for pasture-associated laminitis in ponies," JAVMA. Vol 228(10), 1538-1545. May 15, 2006
3. Baxter, G. Adams & Stashak's Lameness in Horses, 6th Ed. Wiley-Blackwell, 2011 p. 73
4. Madhu P. Katepalli, Amanda A. Adams, Teri L. Lear, David W. Horohov," The Effect of Age and Immune Function on Telomere Length in the Horse," Developmental and Comparative Immunology, 32(12) 2008
About the Author
Christy Corp-Minamiji, DVM, practices large animal medicine in Northern California, with particular interests in equine wound management and geriatric equine care. She and her husband have three children, and she writes fiction and creative nonfiction in her spare time.
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