Risk factors for equine osteochondrosis - DVM
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Risk factors for equine osteochondrosis
A combination of growth, nutrition and inheritance likely come into play.


DVM360 MAGAZINE


Elucidating the genetics of at-risk horses

McCoy's area of interest is determining the genetic risk factors for osteochondrosis, widely recognized across horse breeds, especially in Warmbloods, Standardbreds and Thoroughbreds. There is also documented evidence from a study done at Kansas State University that it can occur in feral horse populations.11

"The old argument that it's solely a management or nutritional issue has essentially gone by the wayside," McCoy says. "We recognize it as being a complex disease; there are genetic and environmental factors as to whether an individual foal will be affected, ultimately developing disease."

Several groups are attempting to determine the genetic risk factors for osteochondrosis development. One factor might be an underlying shared predisposition to developmental orthopedic disease in general, but researchers must narrow their focus to get at those underlying factors. Researchers have taken a couple of different approaches, says McCoy. One is the candidate gene approach.

"There are certain genes we know are important in skeletal development, in cartilage and joints," says McCoy. "With this approach, it's speculated there are mutations in one or more of these genes that lead to disease development."

In people, a familial form of quite severe developmental orthopedic disease is due to a mutation in a gene that codes a protein important in cartilage. "In horses, we don't think that's the case, though we see a strong predisposition for osteochondrosis development in certain breeds at certain anatomical lesions or within certain family lines," says McCoy. "We don't think there's one gene that causes osteochondrosis or developmental orthopedic disease, but it's much more likely due to a combination of genes that interact with each other."

The newer approach researchers are taking is the genome-wide association study (GWAS), which has become popular not only in the horse genetics community, but in the human genetics community for complex diseases thought to be the result of many genes working together (also known as polygenic traits).

"To investigate these conditions, you look at a large population of horses—hundreds to thousands—and try to figure out what their genetic code is at certain predetermined locations throughout the genome," says McCoy. These are bases known to vary within individuals in a population and are known as single nucleotide polymorphisms.

"Our current technology allows us to evaluate close to 70,000 individual locations throughout the genome," says McCoy. "We then do statistical associations between allele frequencies at the individual locations and disease status. We look to see if there are particular markers more common in horses that have the disease compared to those that don't."

When genomic regions are found to have this statistical association with disease, it allows researchers to focus their efforts. "We don't think those actual markers are going to cause disease, because they're just common markers in the population," McCoy says. "We hope they're tagging the actual variants that are important risk factors for the underlying disease."

That's the approach being taken, not just by the group at the University of Minnesota College of Veterinary Medicine, but by some European groups as well. The EU research is largely in Warmbloods, while the Minnesota research efforts are concentrating on Standardbred racehorses. Both breeds were chosen because of a very high prevalence of osteochondrosis. It's of animal welfare and economic interest in both breeds.

"The current state of genetic knowledge is that several regions of association have been identified that may be contributing to osteochondrosis risk," McCoy says. "The next step, and where our lab group is heading, is harnessing some of the next-generation sequencing technologies that will allow us to focus on the genes in the regions we've identified through our GWAS and actually find gene variants or mutations that combine to produce an increased risk for osteochondrosis."


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Source: DVM360 MAGAZINE,
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