NEW YORK (GenomeWeb) – As the business of dog genetic testing is taking off, driven by direct-to-consumer tests and an increased interest among breeders and veterinarians, concerns are growing that a lack of regulation and quality standards in the industry has led to erroneous test reports that can negatively affect the health of dogs and their offspring.
As a result, kennel clubs and testing providers have called for the development and implementation of standards. But while many canine genetic testing players agree that rules and guidelines are needed, they differ in what such standards should look like.
Last month, for example, a group of four canine testing labs from the US, the UK, and Austria proposed a set of standards and guidelines that closely mirrors established regulations for human genetic testing. Meanwhile, the International Partnership for Dogs (IPFD), a nonprofit organization that is sponsored by many national kennel clubs and companies, has been developing a database of testing labs that includes information about accreditation and quality metrics. Also, in the absence of an external proficiency testing program, some canine genetics laboratories have taken to informal quality testing with like-minded peers.
Canine genetic testing has been expanding rapidly in recent years, with new players, such as Paw Print Genetics and Embark Veterinary, appearing on the scene and testing volumes growing rapidly. Wisdom Health (formerly called Mars Veterinary), for example, a subsidiary of Mars Petcare that provides canine and feline genetic testing, expects to run tests on 250,000 to 300,000 samples this year, the majority of them ordered by consumers.
While some laboratories, such as Paw Print and OptiGen, primarily provide targeted diagnostic tests and tend to cater to breeders, others, including Wisdom Health and Embark, offer microarray-based screening tests for genetic disease risk and breed identification and target dog owners, breeders, and veterinary professionals.
However, due to a lack of standards, the industry has been grappling with quality issues affecting some labs, according to experts, which can lead to confusion and, in some cases, the breeding of dogs with avoidable genetic diseases.
Lisa Shaffer, founder and CEO of Paw Print Genetics in Spokane, Washington, which offers more than 180 different tests, cited the example of a pair of Labrador retrievers that her lab tested. Only one of them was found to be a carrier for a recessive disease, so they were safe to breed. Their puppies were tested at another laboratory, which reported half the litter to be homozygous for the disease mutation. After retesting the litter for free, Paw Print found the other lab's results to be incorrect, probably due to allele dropout, which could have been picked up with additional quality checks.
Shaffer said this was not an isolated case and her lab comes across cases like this several times a month. "We see it all the time and we have found mistakes from almost every lab in the world," she said, since dogs are shared across borders for breeding and Paw Print sometimes finds discrepancies when testing their offspring. "This isn't to say that Paw Print never makes mistakes — every lab does," she said, but standards would help to minimize testing errors.
Sue Pearce-Kelling, manager of OptiGen — a Cornell University spinout in Ithaca, New York, that provides a variety of canine genetic tests, mainly to breeders, and was acquired by Wisdom Health earlier this year — echoed this sentiment. "We have witnessed some really shoddy players in the field that have issued incorrect results and it's just heartbreaking to see the results of that," she said. For example, a dog that was incorrectly declared to be free of a disease mutation was bred with another dog that was a known disease carrier, leading to a portion of the litter being affected with the disease.
According to Diane Brown, CEO of the American Kennel Club (AKC) Canine Health Foundation, there are no hard numbers available on how often labs issue erroneous genetic test reports. "However, we hear of discordant test results between different companies, test results being provided for conditions that have never been reported/nor occur in a particular breed, and issues with finding accurate test results and/or interpretations of results from the numerous privately held companies that are now aggressively direct-to-consumer advertising for genetic testing for dogs," she said in an email.
As breeders have taken up genetic testing, and technology and cost barriers have come down, the number of suppliers has increased in recent years, and those suppliers often compete on price, according to Tom Lewis, quantitative genetics and genetics research manager for the Kennel Club, which is based in the UK. "While I have no doubt that the vast majority of suppliers are operating professionally, while there are no quality standards or guidelines in place, there is the potential for shoddy or unscrupulous practices," he said in an email. "These can contribute to unnecessary narrowing of the gene pool or, in the worst cases, the production of affected puppies — the very issue genetic testing is employed to avoid."
A lack of regulation of canine DNA testing is mostly to blame for the variation in test quality. "It's something that has been completely lacking in the past. [The field] really is very much self-regulatory still," Pearce-Kelling said.
Shaffer said that even though US veterinary pathology labs, most of which are affiliated with universities, are accredited by the American Association of Veterinary Laboratory Diagnosticians, this does not include veterinary genetics labs. When she started Paw Print Genetics after cofounding and operating a human genetics laboratory, Signature Genomics, for many years, she expected similar regulations, akin to CLIA certification, College of American Pathologists (CAP) accreditation, or the standards and guidelines of the American College of Medical Genetics and Genomics (ACMG). "We were really shocked that there is zero oversight for genetic veterinary laboratories" in the US, she said.
Nevertheless, she set up Paw Print like a human genetics laboratory and adheres to the ACMG standards. "We can't participate in CAP or ACMG external proficiency testing because it's all for human … but we still follow those guidelines," she said.
Last month, Shaffer and colleagues from Feragen in Austria, Animal DNA Diagnostics in the UK, and VetGen in Michigan published a proposed set of standards and guidelines for canine clinical genetic testing laboratories in Human Genetics, which they adapted from the ACMG standards. "Not everything would be applicable to canine testing because obviously, dogs can't talk," she said.
"Really, the main purpose of the standards and guidelines is to try to bring laboratories together to improve across the board," she explained. "If the laboratories were at least to try to adopt these standards and guidelines, I think we would see fewer mistakes in the industry." Along with the guidelines, Shaffer has developed a checklist that labs can use to assess themselves, which she hopes to publish soon.
Not even Paw Print itself can check all the boxes on that checklist at the moment — Shaffer said some changes on its website are needed, for example — but on the laboratory side, the company does follow all required standards, and she believes that others can do so, too. "My hope is that they are also going to use these standards and guidelines to improve internally," she said.
Meanwhile, the IPFD has been working on the Harmonization of Genetic Testing in Dogs (HGTD) initiative, which aims to improve test standardization and counts many canine genetic testing labs — including Embark, Paw Print, OptiGen, and Wisdom Health — among its supporters, and many kennel clubs among its sponsors.
HGTD maintains an online database of canine genetic testing labs that currently lists 59 providers from 17 countries and includes information on quality assurance and accreditation for 26 of them. According to IPFD, the French Kennel Club now requires test results that go into its official records to come from providers that participate in the HGTD initiative, and it hopes that other kennel clubs will follow suit.
According to its website, in 2019, HGTD plans to develop an expert panel for reviewing genetic testing resources, as well as interactive educational tools for consumers. In addition, it is looking to harmonize the nomenclature of canine genetic testing.
In an article posted on the IPFD website this week, CEO Brenda Bonnett commented on the standards and guidelines paper by Shaffer's group, noting that animal labs "can certainly use the accompanying resources/checklist as part of a self-evaluation for quality improvement."
"Hopefully this paper will prompt discussions on whether the authors' guidelines reflect a minimum necessary standard," she wrote. "However, at the moment — or really on the horizon — there is no body or organization in a position to implement these requirements, evaluate labs, or regulate."
Bonnett also cautioned that not many labs might be able to meet all the proposed minimum standards, noting that a lot of canine genetic tests were developed in small academic laboratories that "are diverse in their organization, procedures, people, expertise of staff, etc., but … might generally not be in a position to satisfy human-testing criteria."
Nevertheless, labs should not be excused "from a reasonable level of quality assurance, but there may still be questions as to what is an acceptable level," she wrote. While providers of poor-quality results no doubt exist, other labs may be able to generate accurate results "even without all these quality measures in place. The challenge is to know the good or adequate from the less so."
If the community decides that the standards proposed by Shaffer's paper should be followed, "we will likely end up with a canine genetic testing landscape with many fewer GTPs and higher costs to the consumer," she added. "Would [that] be a good thing? Possibly, but would there be other less-desirable side effects?"
Others argue that quality standards are necessarily for the very reason that so many small labs run their own tests. "Many of the genetic tests currently offered by commercial companies are laboratory-developed tests that may be unique to the laboratory offering the test," Michael Baird, CSO of DNA Diagnostics Center (DDC) in Fairfield, Ohio, said in an email. "Without a quality system in place the laboratory runs the risk of disseminating incorrect results and conclusions."
Like Paw Print, DDC adheres to the same standards used in human genetic testing, primarily because it also tests more than a million human samples per year, including for paternity and forensic testing, and is accredited by several organizations. "DDC has a common quality system established for all genetic testing, including canine, which includes all the necessary elements," he said. While canine testing is performed in a different section of DDC's facility, and uses dedicated instrumentation, it follows the same standards and protocols as the rest of the laboratory, he said. Having a checklist to follow the standards outlined in Shaffer's article is useful, he said, but more is required. "It will take an independent organization to develop appropriate standards, provide proficiency samples, and perform inspections for participating laboratories offering canine genetic testing to have the oversight currently available with human genetic testing."
Implementing laboratory standards comes at a cost, though. Shaffer, for example, employs staff members with doctorates in genetics and veterinary medicine, and Paw Print's tests interrogate every mutation with two primers, which increases the lab's overhead costs. As a result, its prices are undercut by others. "There's one lab that offers testing for $25, and I'm sorry, but you cannot do quality molecular genetics for $25," she said.
OptiGen's Pearce-Kelling, likewise, said that her firm's decision in 2012 to adopt the ISO 17025 laboratory standard turned out to be expensive and labor-intensive. "It's a real commitment of resources, time, and money to attain accreditation," she said, "and it's certainly not cheap, especially for a laboratory like OptiGen that's small," with a staff of fewer than 10.
"But it is, in my opinion, an important expression of how committed a laboratory is to quality control. Everybody can self-regulate till the cows come home but it really isn't until you have an outside third party come in and do an assessment … that you can be assured that it's not just that you're patting yourself on the back and saying 'we're doing a great job,'" she said.
While the ISO 17025 laboratory standard covers a lot of aspects of quality assurance, one area it does not cover is the clinical validity of genetic tests, she said, which IPFD plans to tackle with a discussion forum, she said.
Overall, Pearce-Kelling said, she would welcome mandated accreditation of canine genetic testing labs. "Everybody will complain that it's so laborious and so expensive, and yes, there is a ton of paperwork that at times seems a little bit much, but at least it's proving to the outside world that you're committed, that it matters enough to you to get that accreditation."
Without such a mandate, there is little incentive for labs to invest in quality assurance when nobody else does, "because you have to compete and stay in business," she added.
Other dog genetic testing provider have been outsourcing their testing to other laboratories, which maintain quality standards of their own. Mars' Wisdom Health, for example, contracts its testing out to Neogen GeneSeek in Nebraska, as well as to a Eurofins laboratory in Denmark. According to Angela Hughes, veterinary genetics research manager for Wisdom Health, those labs have ISO 17025 accreditation, and Wisdom Health has programs in place to audit the labs it uses at least annually, and to monitor them throughout the year. The labs also "meet the quality standards that are outlined in the [Shaffer] article," she said.
Embark, likewise, contracts its testing out to another lab, which is CLIA-certified, maintains ISO 13485 certification, and is run by genotyping experts, according to CEO Ryan Boyko. "At a high level, I do think it's important to make standards for canine DNA testing, and I appreciate efforts to push towards those," he said in an email. However, he has some concerns about the standards proposed in Shaffer's paper, which he said do not seem to include non-PCR-based genotyping assays, like the Illumina SNP arrays used by Embark. Also, he said that high-quality results can be obtained even if testing is outsourced to an offsite laboratory, and board certification of a clinical director may not ensure up-to-date knowledge about tests, molecular methods, and specific issues related to canine testing or certain breeds.
"I think the authors are responding to a real need for standards in the industry and they have some good suggestions for some of those standards," he said. "However, I also think that the standards they have suggested represent one particular viewpoint." Instead, he said, test providers should look at the standards used for the approval of direct-to-consumer human genetic health risk tests, like 23andMe's, by the US Food and Drug Administration "and then changing them only where it makes sense because of the differences in test interpretation and use cases between the two species."
Whatever standards canine labs might ultimately follow, it is currently unclear which agency could enforce them. One option might be the various national kennel clubs, which could require certain quality standards for genetic tests to register dogs into their breed health registries. "They, I think are the best gatekeepers at this point of saying what results they're going to accept and why," Pearce-Kelling said.
It is also unclear which organization might be able to implement an external proficiency testing program that dog genetic testing labs could use to assess themselves. Pearce-Kelling said that this is one focus of the HGTD initiative and she expects such a program to launch within the next year or two.
According to Aimée Llwellyn-Zaid, project director for the HGTD initiative, the proficiency testing project was spearheaded by collaborators at the Animal Health Trust in the UK and has made some progress, but because of a lack of funding, there is no timeline yet for its launch.
In the meantime, some labs are planning to engage in informal proficiency testing. Shaffer said she plans to start sending blinded DNA samples between a number of collaborating labs, including the co-authors of her paper.
Pearce-Kelling said that her lab has been sharing reference controls with other labs already, including labs associated with Wisdom Health and friendly competitors, though OptiGen has not participated in any formal proficiency testing.
According to Baird, DDC already participates in a number of human proficiency testing surveys from CAP and performs internal testing when no proficiency testing is available. "An external graded proficiency program is an important method to ensure quality testing," he said.