Genetic Health Screening for Dogs

The American Pet Products Association released a report in late March revealing that spending on veterinary care by U.S. pet owners increased 7.0 percent between 2016 and 2017, from $15.95 billion to $17.07 billion. The association estimates a 6.9 percent increase in spending on veterinary care in 2018, exceeding growth estimates among all spending categories assessed.

Genetic health testing is one of the newest additions to this booming industry.

While most owners are familiar with genetic tests to determine the ancestry of mixed-breed dogs, many are not aware that a number of companies have expanded into testing for genetic health disorders. The companies typically advertise these tests as having the potential to both save money and heartache by giving owners an opportunity to prevent or detect diseases in their earliest stages, in order to add health-filled years to our beloved canine companions’ lives. But is this rosy promise even possible?

Early Days

The simplest answer is yes, but…

A large and ever-growing number of inherited genetic disease mutations are currently known to exist in dogs and research in this emerging field continues. In a 2016 study published in PLOS One, researchers tested 7,000 dogs representing 230 breeds for 93 disease-associated variants, using a custom-designed genotyping microarray (the MyDogDNA panel test). This research revealed 15 previously undocumented risk variants in 34 breeds, bolstering the case for genetic health screening as an increasingly powerful preventative veterinary medical tool.

It is no surprise, then, that laboratories marketing direct-to-consumer genetic health testing products are popping up around the globe. However, the study’s authors noted, “Careful follow-up studies of any unexpected discoveries are essential to establish genotype-phenotype correlations, as is readiness to provide genetic counseling on their implications for the dog and its breed.” (The correlation between genotype and phenotype is a statistical relationship that predicts a physical trait or abnormality in an individual with a given mutation or a group of similar mutations.)

In a cautionary commentary published in the journal Nature in July 2018, several researchers raised important issues regarding the false hope companies are selling through genetic testing for dogs at this point in time. In this paper, it’s pointed out that no regulating body oversees this testing. In the United States, for example, the FDA plays no role in overseeing how these tests are performed, how results are validated, or the best protocol for conveying this complicated data to consumers.

This lack of oversight proved problematic for 23andMe, a human version of genetic health testing. In 2013, the FDA ordered the company to stop selling these tests, citing concerns that people might take drastic medical measures on the basis of their results or seek unnecessary treatment based on false positives. Regulators demanded evidence of the tests’ accuracy and that consumers were well-informed as to the meaning and usefulness of their results.

Alberto Gutierrez, director of the FDA’s Center for Devices and Radiological Health, said in a letter to the company, “FDA is concerned about the public health consequences of inaccurate results” from the Personal Genome Service (PGS), which is what 23andMe calls its test. Some of the intended uses of PGS were “particularly concerning,” the letter continued, because of the potential health risks that could come from a false positive or false negative. “Assessments for drug responses carry the risks that patients relying on such tests may begin to self-manage their treatments through dose changes or even abandon certain therapies depending on the outcome of the assessment,” Gutierrez wrote.

While 23andMe was cleared to resume selling their product, albeit under increased regulatory scrutiny, how successful these measures have been in accurately setting consumer expectations still remains to be seen.

Ironically, the website of Embark, one of the most popular companies offering direct-to-consumer genetic health testing for dogs, includes an enthusiastic customer quote exclaiming: “It’s the 23andMe for dogs!”

Yes it is. Promises, pitfalls, and all.

Experts Advise: Owners Use Caution

Just as the FDA recognized with its human counterpart, “pet genetics needs to be reined in,” according to Jessica Heckman, a veterinarian and postdoctoral associate at the Broad Institute of MIT and Harvard, where she studies the genetics of dog behavior. She recently wrote a piece published in Undark Magazine, saying: “If not [reined in], some companies will continue to profit by selling potentially misleading and often inaccurate information; pets and their owners will suffer needlessly; and opportunities to improve pet health and even to leverage studies in dogs and cats to benefit human health might be lost.”

Discussing genetic health testing further with Dr. Heckman, she encourages consumers to explore what they want the information for and what they plan to do with it prior to investing in it. She explains: “I believe there is a bright future for genetic health testing of dogs, but we just aren’t there yet. Before we can trust these tests, the industry will have to start working harder to validate them, and until that happens, I don’t recommend that important decisions be based on them.”

Screening dogs for genetic disorders has strong potential to guide diagnosis, treatment, and breeding, but since the science and technology are currently in its nascence, too many questions remain. For starters, veterinary healthcare practitioners are left to decide when it’s valuable to screen a dog for all known genetic disorders or restrict screening to disorders recognized for a dog’s particular breed. Then, there are myriad problems that arise in the interpretation of these data.

This dilemma gets increasingly muddied when a veterinarian lacks the necessary training in genetics to make the best decision for/with a patient/client and even more so when non-scientist consumers, who are being marketed to directly by companies, are making these choices based on limited or no knowledge whatsoever. Too often, consumers are left to interpret complicated genetic health data, again based on emerging science, on their own. While many of the direct-to-consumer genetics health tests services provide some form of guidance on the results for customers, it is not the kind of in-depth genetic counseling even a highly educated dog owner requires to be able to effectively integrate these data into the veterinary care of their four-legged friend.

As just one (albeit extreme) example of what can go wrong when less-than-certain results are given to an owner with little or no guidance or counseling, the authors of the Nature article shared the story of a 13-year-old Pug who started having trouble walking and controlling her bladder and bowels.

Then a DNA test revealed (among other things) a mutation that can – but does not always – indicate that its carrier will develop degenerative myelopathy (DM). The owners made the decision to euthanize the dog – perhaps convinced the Pug would die slowly and painfully. Sadly, the mutation for DM is far from perfectly predictive; the mutation does not guarantee a dog has the disease. It’s entirely possible that the Pug’s condition could have been successfully treated.

Mud-Free Zones?

The least muddy areas, it would seem, are genetic screens for disorders recognized for a dog’s particular breed or predominant breed if the dog is a mix. Take, for example, the Multi-Drug Resistance Gene (MDR), which codes for a protein that is responsible for protecting the brain by transporting potentially harmful chemicals away. It is currently known to affect 10 herding breeds, two sighthound breeds, and herding-breed mixed dogs.

In these dogs, an MDR1 mutation causes sensitivity to Ivermectin, Imodium, and a growing list of commonly administered drugs. Dogs that are heterozygous, or have one copy of the gene mutation, can still have a negative reaction to these drugs, but typically at higher doses. Dogs that are homozygous, carrying two copies of the mutation, experience buildup of toxins that results in neurological symptoms, such as seizures, ataxia, or even death.

Since this mutation is most concentrated in Collies, with as many as 70 percent affected, when I added a smooth-coated Collie to my crew a few years back, I became keenly aware of this issue and had him tested through Washington State University’s Veterinary Clinical Pharmacology Laboratory.

Turns out he’s heterozygous at MDR1 and as a result, I stay up to date on the list of drugs to steer clear of and remind my vet of his status whenever we discuss treatment options for him to be sure both of us are keeping a lookout for his best health.

Popular Direct-to-Consumer Genetic Health Testing Services

Embark

Embark uses a proprietary SNP-chip (single nucleotide polymorphism) that evaluates 200,000 locations across your dog’s genome, allowing for comprehensive results on disease risks and traits, testing for over 160 mutations associated with genetic diseases from DNA acquired through a cheek swab. The company works directly with consumers and in partnership with veterinarians.

The Good: Each mutation is queried two to eight times and examined by a team of geneticists and veterinarians to ensure accuracy. As a research partner of the Cornell University College of Veterinary Medicine, Embark is committed to the continued development of the emerging science of genetic health information and shares updated information with consumers as it becomes available.

The Questionable: The mapping of genetic variants to the risk of disease is incredibly challenging and currently based on a nascent science with a lot of noise in the interpretation of the data. As a result, when a dog tests positive for a health risk mutation, owners need to receive these data with skepticism and discuss these results with their veterinarian. While Embark communicates this, it takes a lot of digging to find. The upfront marketing by all of the companies providing this service, lends the impression that their results are much stronger than they actually are.

Wisdom Panel

The health panel offered through Wisdom looks for 3,000 genetic markers, incorporating the MyDogDNA test from Genoscoper Laboratories of Finland. Their mail-in cheek swab tests for breed identification while also screening for the mutations associated with multidrug sensitivity and exercise-induced collapse.

Blood tests that provide breed identification and screening for more than 140 mutations and markers associated with various disorders are available through Banfield Pet Hospital, a Mars Petcare subsidiary, and through veterinarians who offer a test from Royal Canin, another Mars Petcare subsidiary.

The Good: The tests for MDR1 are licensed through Washington State University (WSU), which is the only entity licensed to perform stand-alone MDR1 genotyping in the United States. According to WSU: “Unless testing is conducted by Washington State University’s Veterinary Clinical Pharmacology Laboratory or its licensee Wisdom Health, Washington State University cannot control quality and accuracy of results. Consumers may risk receiving inaccurate results.”

This is particularly important because three different mutations have been associated with this deleterious phenotype, but many genetic-testing companies indicate that they may test for only one. “Thus, a dog declared ‘clear’ for a given gene might still harbor other known, clinically relevant mutations in that gene that the company has not tested for,” according to the paper published in Nature.

The Questionable: If an owner chooses to seek more genetic health information via the blood test route, the testing is guided by a veterinarian at Banfield, a Mars Petcare subsidiary. The blood is then sent to be analyzed by Wisdom, a Mars Petcare subsidiary, and the results interpreted for you by that veterinarian at a hospital owned by Banfield – again, a Mars Petcare subsidiary. This represents a possible conflict of interest.

The authors of the paper in Nature highlight the problems that could arise, given the lack of regulation in the industry, saying: “If the test comes back positive, the clinic’s vet might recommend preventive steps, such as specific pet foods (made by the same company), periodic screening tests (performed by the company’s clinical lab), and more-frequent exams (performed at the company’s vet clinics), even though there may be low or no risk of disease in the first place.”

Vet Programs That Offer Genetic Tests for Dogs

Reputable genetics health tests are offered through a variety of veterinary programs,
offering in-depth consulting from experts in veterinary genetics. However, the tests
offered are breed and disease specific, limiting their usefulness to a subset of dog
owners. Note: This is not intended to be an exhaustive list, but were the most often
referenced by veterinarians consulted about genetics laboratories they trusted and
utilized most often.

What’s A Concerned Owner to Do?

Figuring out where to get good, reliable genetic health information and how to get the most accurate interpretation of the results that is currently available requires a bit of digging, a fair amount of skepticism, and a willingness to ask questions.

While arguably much of the onus is on science and industry to deliver clear and accurate genetic information to the public, as consumers it is our job to be skeptics and demand products of the highest caliber from companies. We need strong data that we can understand, evaluate, and utilize effectively. That may seem like a tall order, but where the health of my dogs is concerned, I refuse to settle for less.

In May 2017, recognizing the increasing numbers of new DNA tests and testing laboratories and the challenge of choosing the best versions of these tests, the International Partnership for Dogs (IPFD) launched an open-access database, the “Harmonization of Genetic Testing for Dogs“. The goal is to make accessing detailed, breed-specific information on genetic traits, including original research and mutation information, less time-consuming and difficult. The new database:

• Catalogs available genetic tests for hundreds of dog breeds and varieties.
• Helps consumers make informed choices when buying DNA tests by describing the expertise, quality-assurance activities, and resources of the providers of genetic tests.
• Describes clinical and genetic information on individual genetic tests and their use.
• Provides information on the original science and research behind genetic tests.
• Includes basic guides for consumers on types of tests as well as testing information to aid veterinary professionals in advising clients.

The database is overseen by a multiple-stakeholder steering committee with funding for the prototype of this online resource provided by IPFD Founding Partners, the Orthopedic Foundation for Animals, and the American Kennel Club Canine Health Foundation.

The resource is still in an early prototype stage, however, so consumers are left to wait and see how useful it ultimately becomes.

Genetic health information is an incredibly promising emerging field grounded in a science that is rapidly developing. As the authors of the commentary in Nature aptly stated: “Done right, the use of genetic testing in companion animals could be a powerful way to better connect people to the possibilities of genetics for treating disease. Done wrong, it could erode trust in science for an increasingly skeptical public.”

GENETIC TESTING FOR DOGS: OVERVIEW

1. Genetic health testing is an emerging field. The tests that have been around the longest, such as the multi-drug resistance genetic test (MDR1), tend to be the most reliable.

2. If your dog’s results contain a mutation that suggest the potential for development of a specific disease, contact the company and ask for additional interpretation and guidance about the relative risks indicated, and discuss this with your veterinarian.

Citations

1. Donner J, Kaukonen M, Anderson H, Möller F, Kyöstilä K, Sankari S, et al. (2016)
“Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the
Breed Distribution of Risk Variants for Canine Hereditary Disorders.” PLOS ONE
11(8): e0161005.
2. Zierath S, Hughes AM, Fretwell N, Dibley M, Ekenstedt KJ. “Frequency of
five disease-causing genetic mutations in a large mixed-breed dog population
(2011-2012).” Wade C, ed. PLOS ONE. 2017;12(11):e0188543.
3. Moses L, Niemi S, and Karlsson E. “Pet genomics medicine runs wild.” Nature,
July 25, 2018.

Kathryn Socie-Dunning lives in Montana with her husband, their newborn baby boy, and three dogs.