Dr. James Mickelson

Improving Animal and Human Health and Well-Being Dr. James Mickelson
We can now identify simple diseases caused by a single gene, a process that once used to take us years.

Dr. MickelsonDogs are man’s best friend and horses may seem to have an innate connection to their caretakers as they read each other’s emotions and work together in tandem, despite the lack of a common language or appearance.

At the genetic level, scientists have known for decades that mammals share a common genetic heritage.  All mammals, including humans, have nearly three billion base pairs of DNA that are remarkably similar. This is one reason why animal studies are so important to medical research benefitting people.

Over the past two decades, enormous progress made in understanding the genetic makeup of the animal kingdom. With powerful computers churning through millions of DNA base pairs at high processing rates, a torrent of data has begun to unlock the mysteries of how we, and our animals, came to be who we are.

And those same discoveries can shape a future where precision medicine, once science fiction, is becoming a reality for both animals and humans. It’s not quite widespread yet but an explosion of new approaches to diagnose and treat disease seems probable, and the University of Minnesota’s College of Veterinary Medicine is among the institutions leading the way.

The Genetics and Genomics Research Cluster

What scientists associated with the College’s Genetics and Genomics research cluster learn about the genotypes of horses, dogs and other mammals can provide the keys to unlocking the origin of disease and medical conditions in humans, as well as influence the improvement and well-being of animals themselves.

“We’re all mammals, we have genomes and the same number of base pair genes,” said Professor James Mickelson of the Department of Veterinary and Biomedical Sciences. “We know there are many conditions with genetic issues that will happen in related species.”

As one of the College’s first investigators in the modern era of animal genetics and genomics, Mickelson recalled that identifying the genetic underpinning of diseases used to take years of painstaking number crunching on slow, unsophisticated computers and data systems. Today, the College’s computational systems can tap into the U’s renowned Supercomputing Institute or contract with private data firms to run genomic studies and obtain results in months rather than years. 

These advancements have led to greater insights into common medical challenges animals and humans share, such as urinary tract disease, epilepsy, and Parkinson’s Disease.

“We can now identify simple diseases caused by a single gene, a process that once used to take us years,” said Associate Professor Molly McCue of the Department of Veterinary Population Medicine. “We can identify affected horses quite rapidly without having to see them in hundreds of cases. But there are also complex diseases and we have to go further in our research to look at environmental variables that impact genetic markers.”

That’s one of the fundamental mysteries of genetic research. “There’s a large fraction of diseases in domestic animals that is attributable to genetics,” said Mickelson. “It’s hard to put a percentage on that and there’s a lot to learn. Everything at its heart is genetics but we understand that the amount of influence can be quite small in some species and quite big in others.”

Finding a mutation linked to a medical issue does not necessarily lead to a predictable outcome. Just because people, and animals, have a genetic predisposition to a disease does not mean they are guaranteed to suffer from it.

“Looking at patterns in the genomics data can help scientists figure out what risk factors exist and what interventions might cure or ameliorate disease conditions”, says McCue. “When you can ferret out differences in the environment you can begin “treating subgroups differently,” she adds. “That’s what will happen with big data.”

Genetic Research’s Influence

Quarter horses are the most popular breed of horse in the United States. “Researchers in the College of Veterinary Medicine assisted in the discovery of a metabolic disorder that altered the ability of quarter horses to maintain and use glycogen as an energy source”, said Dr. McCue.

The mutation – known as polysaccharide storage myopathy (PSSM) – was discovered to be “far more prevalent than expected,” with as many as 10 percent of all quarter horses carrying it, says McCue.  Horses suffering PSSM have difficulty exercising and suffer severe or mild cramping up or stiffness because glycogen, a stored form of glucose, cannot be maintained in their skeletal muscles.

Environment can greatly affect horses with the PSSM mutation. A diet high in carbohydrates, but low in starch will improve the performance and lengthen the lifespan of quarter horses. “The industry embraced these genetic findings and are working to assisting breeders in improving the health or horses with PSSM,” says McCue, who has received several national grants to study the mutation.

Genetic mapping has now, in fact, become so recognized by the American Quarter Horse Association that it requires breeders to have it done. The association offers a kit to breeders or they can contact the College’s Leatherdale Equine Center for information on testing. The   idea is to eliminate those unwanted traits from the horse population through breeding, says McCue.

Professor Kent Reed in the Department of Veterinary and Biomedical Sciences studies the effects of aflatoxins that are produced in moldy corn and grain, which occasionally contaminate feed and are inadvertently eaten by turkeys. Domesticated turkeys are especially susceptible to the lethal effect of these toxins compared to wild turkeys. 

Producers might introduce selective breeding, or probiotics, to lessen or destroy the effect of aflatoxins on the turkey population. “One goal of this research is to improve the ability of turkeys to biochemically inactivate aflatoxins by altering turkey genetics or manipulating the turkey’s intestinal microbial populations,” he said.

Assistant Professor Eva Furrow in the Department of Veterinary Clinical Sciences studies urinary stones in miniature Schnauzers through grants from the Gray Lady Foundation and the National Institutes of Health, among others. The advantage of studying dogs is that there is familial clustering or breeds which have urinary stones and the genetic markers are roughly the same in humans, she says.

Studying our diverse human population in order to find mutations for kidney stones would have been more difficult. “It would have been much harder to hone in on what genes convey susceptibility to the disease,” she says.

There are several kinds of urinary stones effecting dogs and humans alike. The research of Furrow and others has identified mutations in two analogous genes in dogs and humans afflicted with urinary calcite stones. The next step is to figure out how to prevent stone formation, if possible, through diet or other environmental changes. 

“When we know which genes are causing kidney stones we can help pick different therapies for canine patients,” she says. “After understanding what gene it is we might say ‘we want to test this new treatment that’s never been tried before because it targets that gene.’ We might suggest that a dog gets screened more frequently or change their diet more aggressively.”

Genetic research is all about unfolding the mysteries of illness and life in close collaboration with investigators within the research cluster and across the country. Mickelson and others say the College is a national leader in genetics and genomics research due to the many collaborative interactions that occur constantly among the research investigators in this cluster and the rich number of computational resources available through the University.

Knowing the genetic makeup of animals and humans, and how they overlap, is just the beginning of a journey towards the design, development and implementation of innovative strategies to detect, ameliorate or prevent inherited diseases that affect animals and people.   Simply put, diet, changes in the gut environment, and plenty of exercise remain important priorities in maintaining the health of animals and their human friends.

By Frank Jossi