Nearly 20 years of DNA testing – what can we learn? – my February 2019 “Best of Health” article
Doctors Tom Lewis (KC) and Cathryn Mellersh (AHT) recently published an Open Access paper where they analysed trends in DNA testing for 8 autosomally recessive conditions in 8 breeds. A headline in the Vet Times said “Study reveals ‘fantastic work’ of DNA testing”. The sub-headline stated that “A study has revealed responsible breeders are reducing the number of pedigree dogs at risk of often painful and debilitating inherited diseases by around 90%”.
This paper is exactly the sort of great work we have come to expect from the KC’s Health Team and their partners at the Animal Health Trust. I believe it could be one of the most influential papers that might be published this year because of its potential to influence breed health policy and strategy, as well as the behaviour of breeders and buyers.
I don’t want to dwell on the detail of the research; you can read that for yourself, here: https://goo.gl/PiQmMF – I want to discuss how and why this paper might be important. The study covers the results of 8 DNA tests in 8 breeds for the period 2000 to 2017. 2 of the DNA tests applied to 2 breeds, resulting in 10 test+breed combinations. The key metric used to measure progress was the Mutation Frequency which is more useful than simply counting the number or calculating the proportions of Clear, Carrier and Affected dogs. It is calculated as [(2 x No. of Affected) + No. of Carriers]/(2 x No. of dogs with a known result).
Measures of progress
Previously, many reports on the progress of DNA testing have simply shown the proportion of Clear, Carrier and Affected dogs tested each year and that’s what we used to report in our Dachshund Annual Health Report. However, as tests become more established, the KC is able to deduce the status of untested dogs and assign their hereditary status. For many tests we are now able to identify Hereditary Clear, Hereditary Carrier and Hereditary Affected dogs based on test results from their parents. That still leaves a proportion of dogs in the KC database without known or deduced status and the researchers acknowledged this in their analysis but were able to calculate a “worst case” view of mutation frequency in each breed. Those of us reporting on DNA testing in our breed should be asking the KC Health Team for Hereditary results so we can give a more accurate picture of the impact being made. The difference can be quite significant, for example 50% of the test results for PRA-rcd4 in Gordon Setters were “Clear” in 2017 but, when hereditary status is taken into account, 95% of the breed was “Clear”. When you’re telling the story of what’s been achieved, that’s a big difference.
Another aspect of the paper is the data on trends in uptake and usage of DNA tests. For most breeds, unsurprisingly, the peak uptake of DNA tests was around the time it became commercially available and subsequently tailing off. The one exception to this was Exercise Induced Collapse in Labradors where use of the test has grown steadily since its launch. The peak around launch may reflect the fact that breed club communities are often actively involved in developing a test and are therefore keen to make use of it as soon as it becomes available. The challenge for all of us in breed clubs is how to educate and influence those outside our community to make use of these tests.
The paper also shows that there is an inverse relationship between the size of a breed and the take-up rate of tests. The slowest rate of increase occurred in the 2 numerically largest breeds, Labradors and Cockers. In smaller breeds, it’s more likely that breed clubs have influence over a higher proportion of breeders. The Labrador/Cocker effect may also be related to the split of working, show and pet breeders, making it more difficult to reach a more diverse group of owners. It may also be the case that, in breeds where multiple DNA tests exist, like Labradors (5 tests according to the KC) and Cockers (4 tests), it is more difficult to persuade breeders to make use of what might be seen as “yet another test”.
Another consideration related to uptake of a test is breeders’ perception of the need to use it. The severity of the condition, its age of onset and how widespread affected dogs are in the population are all factors that individual breeders will consider when prioritising whether or not to use a test. In some cases, breeders simply don’t want to know despite the seriousness of a condition and prefer to bury their heads in the sand. All of this gets me back on my change management hobby-horse; it’s important to communicate much more than just the launch or availability of a new test.
In some cases, the launch of a new test could actually make things worse in a breed. The paper notes the evidence of selection – breeders intentionally avoiding producing affected puppies. In some breeds we have seen unhelpful selection strategies such as Affecteds or Carriers being removed from the breeding population completely, when they could quite safely be mated to Clear dogs. Another unhelpful approach is when people rush to use the small number of Clear stud dogs available and we may end up with the so-called Popular Sire Syndrome and all the adverse consequences that go with that. So, while DNA tests do indeed have the potential to prevent the breeding of more affected puppies, breeders must consider the bigger picture of genetic diversity. Reducing the gene pool makes it even more likely that hitherto unseen recessive mutations will “pop up” as undesirable health problems.
There are over 700 inherited disorders and traits in dogs, of which around 300 have a genetically simple mode of inheritance and around 150 available DNA tests. This tells us that we should not rely on DNA testing to solve the “problem” of diseases in pedigree dogs.
This new paper therefore gives the KC and breed clubs an opportunity to educate (or re-educate) owners and breeders on how DNA tests can be used within an overall breed health strategy. As well as celebrating the fantastic work done by so many committed breed enthusiasts, the messaging needs to be wider than “DNA testing improves dog health”.
I also wonder to what extent this paper might cause the KC to review its policies on the registration system, particularly given that there have long been calls for responsible breeders to be recognised for their commitment. It’s no good saying that’s what the ABS is for when so many good breeders have chosen not to join. Last year, Our Dogs wrote “A Manifesto for Change”, directed at the KC Board. Among other things, it said there was a need to address (or justify clearly) long-standing issues related to the registration system such as the ABS, DNA identification and the requirements for health testing. I hope the Lewis & Mellersh paper provides part of the evidence-base for those discussions.