The new genetic tests available through ADDL will help dog breeders eliminate specific diseases


Monday 19 June 2023

Shawna swabs the cheek of a miniature American Shepherd in Dr. Ekenstedt's lab.
Shawna Cook, a miniature American Shepherd owner and recent PhD graduate, has researched juvenile-onset cataracts and neuraxonal dystrophy in the breed. The swab to collect DNA samples was an important step in the various research projects she conducted in Dr. Kari Ekenstedt’s canine genetics laboratory.

Research findings by genetic scientists at Purdue University College of Veterinary Medicine have the power to eradicate specific genetic diseases within certain dog breeds. Testing for genetic mutations will be offered by Purdue’s Animal Disease Diagnostic Laboratory (ADDL). As the first tests of their kind offered to the public for three new canine genetic diseases, these screenings will allow breeders to identify which dogs carry a disease and could possibly pass it on to their offspring. By ensuring that two carriers are not bred together, the disease can be stopped before it spreads throughout the breed.

Dr. Kari Ekenstedt, assistant professor of anatomy and genetics in the Department of Basic Medical Sciences at the College of Veterinary Medicine, holds both a doctorate in veterinary medicine and a Ph.D. in mammalian genetics. His Canine Genetics Laboratory recently fixed one genetic disease in Basset Hounds and two genetic diseases in Miniature American Shepherds. All three diseases are autosomal recessive, meaning that the mutated gene is not sex-linked and two copies of the mutation are required to cause the disease. In other words, dogs with only one copy of the mutation (carriers) are healthy, but ideally should only be bred to shedding dogs to avoid producing affected puppies.

“We are thrilled to partner with Dr. Ekenstedt to provide these tests for animals,” said Dr. Animal genetic testing is a new addition to the ADDL and we can only provide this service because of Dr. Ekenstedt’s expertise in the field. She discovered the genetic changes we will be testing for that cause these diseases, which can lead to the death of affected puppies. Through these tests and the genetic counseling offered by Dr. Ekenstedt, we will work with breeders to eliminate these genetic diseases in these dog breeds.

Jeanna Blake, a third-year PhD student in Dr. Ekenstedts’ lab, has done most of the research on glycogen storage disease in Basset Hounds. This disease affects the body’s ability to store glucose in the liver and muscles and then break it down to create energy. The accumulation of glycogen in the heart muscle can cause heart failure in dogs.

This disease came to my attention after two litters died very young from heart failure, Dr. Ekenstedt said. The pathologist who conducted the autopsies sent me the tissue, which gave us a set of sibling DNA that could be whole genome sequencing.

To fix a genetic disease by identifying a causal mutation, Dr. Ekenstedts’ team uses whole genome sequencing on the DNA of an affected dog and compares it to other whole genome sequences in a database of nearly 1,000 control samples. Complex computational algorithms sort through billions of pieces of data to help the team narrow down specific genes using an established data analysis pipeline. The whole process can take more than a year.

I was surprised to discover a new cause of glycogen storage disease in dogs, Blake said as he described his role in the research project. Mutations in the causal gene have been seen in humans, but are new to the dog world. The findings of this study add to the mutational spectrum of glycogen storage diseases in dogs. The more disease-causing mutations we know about, the more extensive genetic testing we can perform, resulting in earlier disease detection and disease prevention through targeted breeding strategies. The discovery and testing of this mutation will allow Basset Hounds to be born free of this specific glycogen storage disease.

Blake explained that his hope with canine genetic research is to help dog breeders make informed breeding decisions and avoid breeding dogs with inherited genetic mutations by phasing out the genetic diseases of different dog breeds. I have always wanted to help dogs through scientific research. Having the opportunity to contribute to this groundbreaking research means everything to me. I can wake up and live my dream every day by contributing to research that directly impacts dog health.

Dr. Ekenstedt and her lab team gather around the Continuum sculpture outside Lynn Hall
Purdue researchers at the College of Veterinary Medicines Canine Genetics Laboratory (left-right): Shawna Cook (PU PhD 2023); Jeanna Blake, MS, a third-year doctoral student; Dr. Kari Ekenstedt; Maeve Sheehy (PU BS 2023) holding a Boxer puppy; Nayan Bhowmik, PhD, postdoctoral researcher; and Jessica Clark (PU MS 2023).

Blake said knowing that the work done in the Canine Genetics Lab could prevent even one Basset Hound puppy from being affected by glycogen storage disease is worth all the work. The impact this research may have on the canine world further strengthens my commitment to canine genetics. I want to help more dogs through my research.

The two diseases in miniature American shepherds, juvenile cataract and neuraxonal dystrophy, have been studied extensively by Dr. Shawna Cook (PU PhD 23), now a postdoctoral researcher at Cornell University. The research was especially significant for Cook, who is the owner of a miniature American Shepherd.

I was thrilled, Cook said when asked about her reaction to the opportunity to contribute to a research project that has the potential to benefit the breed of dog she keeps as a pet. She definitely pushed him into passion project territory. Not only have I been given the opportunity to help dog owners and breeders that I know personally, but I have also been able to help the breed as a whole. Everyone says getting a puppy is a lot of work, but my Miniature American Shepherd, Helix, has given it a new definition! He is only three years old and he has given me a lot to do! Without her I would never have met the owners and breeders who have entrusted me to conduct this research.

Cook’s personal connection to the research proved inspiring. The personal connection I already had to the race prompted me to be a better scientist and take responsibility for my own research, Cook said. Weekend, late night; I was always ready to look at the data, collect samples and chat with the owners.

While juvenile cataracts are not fatal, they are still undesirable for breeders and their customers who both want healthy animals. Neuroaxonal dystrophy, however, causes the animal’s nervous system to degenerate, causing a wobbly gait and progressively worsening until the animal completely loses the ability to walk.

These are preventable genetic diseases, Dr. Ekenstedt said. By identifying carriers and breeding them to healthy dogs, we can retain all other desirable genetics while avoiding the disease entirely. The goal is to test and slowly replace carrier animals over several generations. We don’t want to immediately stop breeding every carrier dog because this could have an overall negative effect on the genetic diversity of the breed.

Cook said both miniature American shepherd projects were close to her heart. To be able to tell breeders that they will be able to breed these diseases out of their dogs was just amazing. Now we can provide the tools you need to help prevent these hereditary diseases. However, there will continue to be hereditary diseases, both simple and complex, that exist in our canine companions. Regardless of breed, I want to be able to contribute to the breeding of genetically healthy puppies. These projects have really cemented the fact that I’m doing what I’m supposed to be doing. I couldn’t imagine doing anything else.

Dr. Ekenstedt describes her research as exploratory, meaning the scientists working in her lab aren’t developing a specific hypothesis and then testing it to prove or disprove it. Instead, they learn about abnormalities occurring in a particular breed and analyze the DNA of affected animals to identify the specific mutation causing the genetic disease.

Just like humans, animal genomes mutate with each generation, said Dr. Ekenstedt. These natural diseases are generated through spontaneous mutations. Many breeders are doing absolutely everything possible to produce healthy dogs, but genetic diseases will continue to appear. Having tools to identify disease carriers will be essential to producing healthy puppies, especially in long-standing purebreds with limited gene pools.

Many of the student researchers in the lab work on single-gene mutations that are usually relatively simple to fix. The lab is also working on several more genetically complex diseases that cannot be linked to a single gene. But there is a disease of pigmentary uveitis in Golden Retrievers that Dr. Ekenstedt considers her white whale. She and Dr. Wendy Townsend, professor of ophthalmology in the Department of Veterinary Clinical Sciences, have collaborated for years to try to decipher the genetic code of the disease that affects up to a third of Golden Retrievers.

The problem with pigmentary uveitis is that it’s painful and inflammatory enough that dogs sometimes end up with enucleated eyes, Dr. Ekenstedt said. We used all the same techniques to analyze the whole genome sequence, but it was very difficult to identify the mutations. There are a number of reasons why it remains elusive, making it a really fun puzzle, but also a frustrating one to solve. I would be so thrilled if we could find the answer why there are so many Golden Retrievers in the world and eliminating that disease would have a tremendously positive impact on the breed.

With more than 200 dog breeds registered with the American Kennel Club and new breed-specific genetic disorders emerging all the time, Dr. Ekenstedts’ lab will continue to troubleshoot genetic disorders and offer those tests through the ADDL as they become available. Revenue generated from test sales is channeled back into the ADDL and Dr. Ekenstedts’ laboratory to fund further research.

Offering genetic testing through the ADDL establishes Purdues’ reputation as a pioneering institution in canine genetics, a somewhat neglected field of research within the profession. Dr. Ekenstedt estimates that there are only a dozen labs in North America that conduct canine genetic testing. I have a group of brilliant scientists working in my lab, Dr. Ekenstedt said. I am confident in our team’s ability to solve many other genetic diseases.

Kat Braz |

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