Welcome to the WSAVA podcast. This episode focuses on genetic testing in practice, what it means for busy clinicians and how it can support decision making in the consulting room. As you follow the discussion, ask yourself, what barriers or opportunities do you see to using genetic testing more widely in practice? Our host, Julian Hoad, is joined first by Leslie Lyons, then by Catherine Mellersh. Let's join the conversation. Hello Leslie, great to have you here.
So genetics in cats, why would you need to test for anything genetic in cats? So they can have things go wrong in those genes that cause them to have inherited diseases, just like we find in humans and dogs and other species as well. And so they will be particular to the cat and if you have an unhealthy cat, certainly don't you wanna know the reason why that cat is unhealthy? And so yeah, that's why we apply genetic testing to cats so that we can actually figure out what's causing their malady.
Why are they at the vet clinic today? Maybe we can figure that out from a genetic test. And is this primarily in pedigree cats or is it also in hybrid cats? All cats have a genome and any given cat can have a health issue caused by a DNA mutation, whether it's a fancy breed or moggy. And so we really wanna make sure that we can do genetic testing that applies to the moggy cat as well as our fancy breeds. And so I'm guessing there's two reasons aren't there for finding out these things.
One is to see whether it's appropriate to breed the parents, but the other one is to see whether the cat you actually have is susceptible to these diseases. Is that right? Yeah. Cat breeders. They want to make sure their cat isn't a carrier or has a genetic mutation that might cause a late onset disease that maybe they haven't recognized yet, but they're ready to breed. So maybe the cat will be older when it actually gets sick.
So you want to know to be able to predict an illness, but then you also don't wanna pass it on to offspring. So that's why generally your fancy breed cats are being genetically tested, but then a moggy cat, the same situation can occur. You could have a brand new genetic mutation that actually causes a health problem. And so if you're a cat, you love your cat just as much, whether it's a moggy or whether it's a fancy breed cat, right?
When you bring that cat into the veterinarian, I wanna know why it's sick. So if it's having a presentation that is similar to a known genetic disease. We get that genetic test done, and then we know, okay, that's what's going on with the cat. But we can also do bigger things now instead of just genetic tests, we can do a whole genome sequence and maybe even predict something that might come as a later onset as well.
Whole genome sequencing, whole exome sequencing, we can pretty much do lickety split. So if we have a DNA sample, we can isolate that DNA and if you're in the queue for the sequencing machine, and boom, they do it right away. Within a few days, you can actually have 3 billion base pairs of DNA. You can have the complete genome sequence of the cat. What takes longer is the analysis and that still slows us down a little bit.
But if we do it properly, and which this is my goal, is to bring precision medicine to our companion animals. But the goal with precision medicine is to use your specific genomic profile of your whole genome. To predict what might happen to you in the future with your health, and then if you're a breeding cat, what you could pass on to your offspring. That's absolutely incredible. So you're talking about genotype to phenotype predictions? Absolutely.
So some people will call it reverse genetics as well 'cause you can look through the genome and find a mutation and then say, Hey, does that cat actually have that issue? Is that something we have to look for? And so you can do it the other way around. Knowing the gene is very helpful, but then the type of mutation is also very helpful as well. That we know, now know, there's different therapeutics that we can apply that might help resolve that condition in the sick cat.
5, 10 years ago, yeah, your cat has this genetic mutation. All you can do is treat the symptoms, and that's what we all hate. Now we're hoping that the genetics will be able to say, ah, here's my toolbox. What do I have on my shelf here? As far as different therapeutics? This one works for that type of condition. Let's give that a whirl. But that is the goal, is to actually use the right therapeutic. Now, can we also maybe correct that by doing gene therapies?
Yes, we are starting to see that we might be able to actually really correct the genetics and then fix it and then there's no long-term therapeutics. Now in the UK, and I know in the states as well, we have the kennel clubs who give advice on what tests the dam and the sire should have when producing puppies. So we have elbow and hip scoring here, we have eye scoring, and we're increasingly seeing recommendations for a number of genetic tests done on dogs.
Is the same thing being recommended more widely for cats in the states? Yes, absolutely.
There are recommendations for genetic testing in specific cat breeds, and so the World Small Animal Vet Association hereditary disease committee, and also the International Society of Animal Genetics, we're working hand in hand to come up with, here's the list, here's your breed, here's the list of genetic tests you should do and we also have genetic tests in cats that are important just for the wellness of a cat. Unlike other species, we can genetically test and know a cat's blood type.
You can't do that in a dog or horse. Then there's also drug resistance genes like MDR1, it's now been renamed to ABCB1, I think. But MDR1 is the gene known for multiple drug resistance. It's very rare. It's not at a high frequency. But maybe good to know if what your cat's DNA type is before you go into the hospital. Also, we know of some coagulation factors, so there's a little list of DNA mutations that any cat should know what they are. So kind of part of a wellness check.
Just as routine is getting your vaccinations, you should probably do these genetic tests and you know these in the background for later times. Coagulation factor, the blood factor, you might wanna know that when you're going in for neuter and spay. Do you see these tests being rolled out as you would test for a serology panel in the future? Are they affordable enough to do that? Yes, absolutely.
So some companies offer big panels of tests and they're a hundred dollars, and you can get hundreds of tests. But what will apply would be the blood type. So there's three different major types. You would wanna know the factor 11 variant, 'cause that affects coagulation. And you would also want to know that MDR1. So regardless you want to know the answers of what mutations they have there.
You can get those for each, maybe $40 a piece, or you can do one of these larger panels that gives you a whole bunch of tests. But in my mind, I would prefer that if you did a whole big panel that before you make a breeding decisions, if you're gonna make a decision on health, I suggest getting that one test run again for sure as a single genetic test so that it's absolutely right before you start making health decisions and breeding decisions on your cats.
So there's a variance in the labs that provide these tests? Absolutely. Yes. Yeah, that's true with anything. Overall, genetic testing has very high sensitivity and specificity, at least for the cat. So speaking for the cat, all our DNA markers are what's called pretty much direct DNA markers. You're directly testing for a specific disease, not something that's called linked or associated with that trait. So cats are a little more simple in that way.
But with a cat a genetic test giving result is fairly pathognomonic for the phenotypic change that's going to be brought about. Yes. Most genetic tests for cats are what we call Mendelian traits and they're pretty much on or off, one or the other. You got it or you don't. And we can predict some that have variable presentation. For example, polycystic kidney disease in cats, you have the DNA mutation. You're gonna get cysts in your kidneys.
The trickiest one, probably for cats is hypertrophic cardiomyopathy, HCM. There's a couple known genetic tests and they're more on the risk factor level that not all cats with the mutation will get disease. And there are other cats that have HCM that don't have this mutation, meaning there's other genetic causes probably out there that we have not yet figured out. Sure. How much of this is a problem we've caused ourselves by line breeding cats and by breeding for exaggerated features?
So you have to look at breeding in two different ways. First off, cats are gonna have DNA mutations. You want that to happen. That creates genetic diversity. Every once in a while you have a bad DNA mutation that occurs and you might not know it's there. Breeding did not cause that mutation to occur. But once you recognize that it's there, now it is your responsibility to do something about it and that's the state we're in now.
So with cats, most of them are at very low level, and we can get rid of most inherited diseases in cats. But then secondly, we do have mutations that are caused by a DNA variant or a presentation that is caused by a DNA variant that we like, but maybe isn't the best thing. And so we have Scottish Fold cats, Manx cats, and we know there is health problems associated with the DNA variant and so if you have the DNA variant some percentage of your cats are also going to have these health mutations.
And that's where again, with WSAVA and the Hereditary Disease Committee, we've asked cat breeders to start thinking about retiring breeds such as Manx and Scottish Folds and so some groups already have done that. They don't accept those breeds and Manx is actually a fairly rare breed and you can actually replace Manx with, change the tail DNA variant to one that is more similar to a Japanese Bobtail.
So you could have the manx genetics, but the Japanese Bobtail mutation and still have short little tail so we can resolve some things. So to paraphrase a, a very common idium in the veterinary profession, cat genes are not small dog genes. Correct. Yeah. Yes. That's one of the things we'd like to promote. Cats are not small dogs and dogs are not large cats, so they do have basically the same genes, but we see that the particular mutation they have may or may not cause the same health condition.
And this is actually why it's important to identify these animals as potential biomedical models. Yeah. Yeah. So if we were to take, say I, I've got a couple of moggys. One of them is 9 years old, one of them was 12 years old. Would there be any benefit in getting them genetically tested now or is it something you'd only want to do to younger cats?
With your older cats, probably it's not going to be so beneficial at this point in time because any genetic trait generally has an earlier age of onset and so you would already know at this point. So mainly we wanna get the younger cats and very young because as we mentioned earlier, we have different wellness DNA variants that would be good to know, your blood type, your coagulation factor types and also your multiple drug response mutations as well.
Leslie, we often hear of coat color being associated with disease. Say we have white cats with blue eyes and they're often deaf. Is coat color a good indicator of the genetic health of a cat? There are a few things in cats that correlate coat color with their health and you mentioned the number one thing, that is white, all dominant white cats, will have a probability of having deafness, but you're gonna find that out early in life.
It's going to be pretty much a congenital onset of deafness and so you'll find that out right away. So we know that color variation is associated with a health issue also, there's a new variant coming out, these cats with dominant blue eyes and we're trying to actually stop the progression of this mutation, 'cause it's a gene called PAX3, and we know that causes Wardenberg syndrome in humans and that's associated with deafness as well.
So one of the, I think there's three or four known different DNA variants for PAX3 in cats. Now we know one is definitely associated with deafness, so let's stop it right now. Let's, let's just not let that go forward. Doing genetic testing for coat colors can be very helpful to the cat. Fantastic. Is there anything else we want to cover or?
Let's see, what we definitely want to do with precision medicine is show veterinarians how it can be used, why is it useful to a veterinarian to think about genomics and genetics, doing genetic tests, how it can be helpful in their practice? And that will be a lot of our discussion at the WSAVA presentations is really getting genetics into the private practice clinic and how will it be useful? How do they even start? Where do I go to? What do I even do?
I think I have a cat with an inherited mutation, or is it inherited? How do I figure that out? And so those are some of the things that we'll be presenting at WSAVA and looking forward to having every veterinarian is on the front line. They can help us find inherited problems and call them from populations, even random bred cats.
They can be from a closed population in a little park or in a town and we can figure out whether they have a mutation, a disease that really we'd like to not see those cats suffer and have, and we have done that with Myotonia Congenita and hopefully our vets can recognize that and help to not only identify what the health problem is, but maybe we can lead to better cures as well. Well let's hope so. And getting the vets to know about it is the crucial role, crucial step, isn't it?
Because we can be pretty sure that a client is gonna come in and say, okay, I want my cat tested for this genetic mutation. And if the vet's not up and saying, yeah, okay, we can do that, then they're going to be ridiculed. You don't want to turn around say the, the whats that? Do we? Is there a test? Is that a thing? Right. Yeah. So the absolute goal is to get veterinarians to realize where can they go for help to get genetic testing accomplished.
There's many of us out there that are there to help. They don't have to completely go get learned and trained in genetics, but they should depend on the resources that are out there. Fantastic. After Leslie Lyons, Julian is joined by Catherine Mellersh for the second part of this discussion. Catherine, genetics, this is a fascinating subject, isn't it?
You can obviously do an awful lot with DNA and find out an awful lot of information about an individual, be that a human, or be that a dog or a cat. So you can tell the breed makeup or the ancestry of a dog from its DNA. But what my research group does, we are particularly concerned with mutations within the DNA that cause or predispose a dog to an inherited health condition.
So we work very closely with stakeholders, so people who breed dogs, and vets, who treat dogs, to recognize conditions, sometimes new inherited diseases, that are segregating within particular breed or a broad breed population. And then we collect DNA from those affected dogs and from their relatives and we literally look in, in the DNA, sequence the DNA and find the precise missed typo, if you like, within the DNA that's causing that inherited disease.
And then once you know that, you know which gene that mutation is in, and you know the protein that's broken and causing that disease, and importantly for future generations, you can develop DNA tests. So preventative tests that ideally the dog breeder does before they've mated particular sire and dam together.
And then they can make those breeding decisions in with an informed, in, from an informed position that the puppies that they breed will have as low a chance as possible of developing those inherited diseases. So it's, our research is really all about prevention and helping breeders breed healthy puppies. Fantastic. And, and presumably you're talking about pure bred dogs, line bred dogs? Mutations can happen in any dog and they happen all the time actually.
There's nothing we can do to prevent that when, so a breed of dog, a breed is a manmade creation, but you can think of it as a sort of a genetically isolated population of dogs that are all relatively inbred or relatively closely related to what, to one another. And when a mutation happens within one of those populations, it can spread very quickly. Particularly if it occurs in a popular sire.
So sometimes closely related breeds will share the same mutation and what that means is a mutation happened a long time ago before those breeds were very robustly separated. And interesting enough, you were telling me earlier that normally we consider things like hybrid vigor when you mix two breeds of dogs. So Cockapoos for example, a very popular breed. Is there not hybrid vigor? Are we not getting a reduction in the risk of genetic illness because we're mixing these two breeds?
So I think the risk of some diseases will be reduced, that's for sure. But I could give you at least one example of an inherited disease mutation that segregates in Cocker Spaniels and Poodles and Labradors. So those two very common, we can call them what we like, hybrid crosses or designer dog, the Labradoodle and the Cockapoo. It's entirely possible that those dogs could inherit a copy of this mutation from both of their parents.
So there, there will be hybrid vigor, but we, people who are buying these dogs shouldn't become complacent, that they're going to be healthy cause they're not pure, pure bred dogs. And we can talk about what a cross breed dog is and what a purebred dog is, because I think there's some misconceptions there as, as well. Well go on then. Let's chat about that.
I've always thought of a pure bred dog as being something like a highly inbred Samoyed or a French Bulldog and the cross breed dog as being a Cockapoo or the good old Heinz 57. Yeah, so I think if you have gone to a breeder and bought, let's say a Samoyed or a Chihuahua or an Akita or something, anything really, particularly if it's a Kennel Club registered dog of those breeds, then both its parents will be that same breed.
But I think when people buy, let's say a Cockapoo or a Labradoodle, they assume that they are buying a puppy, one parent is a Labrador and one parent is a purebred Poodle. That would be called an F1 Cockapoo or Labradoodle. But some breeders of these crosses, they like to, in genetic speak, fix particular conditions, and a lot of people want the the fluffy coat of the poodle that's allegedly a low shedding coat as well.
So they might take a dog that's a cross between a Labrador and a Poodle and cross that back to a Poodle. That would be called an F1B for F1 back cross. So already those puppies have got Poodle on both sides, so that puppy could end up with two copies of that mutation. So that's what I mean by not necessarily being able to be free of the mutations in any of those breeds.
Of course, there's a way around this, and that's by if the breeder uses DNA tests and so geneticists are getting increasingly good at finding mutations that are responsible for inherited diseases in dogs and so it's a relatively easy process to test the DNA of any dog for any mutations at all. So breeders don't have to be breeding in the dark. They can be making very informed decisions about the health of the puppies that they breed.
Now, let's talk about cost of these tests because in the old days when I first graduated, we would send the dam or the sire off for elbow and hip scoring and eye testing. Would you recommend those are still done? Personally, I would, let's talk about eye tests. My research group does a lot of work on inherited eye diseases in dogs. I've had a blind dog myself. I know the impact that going blind can have on a dog and on its family so I feel quite strongly.
Anybody can take their dog, there's a a, an eye screening scheme that's operated by the British Veterinary Association and the Kennel Club and the International Sheep Dog Society, and so that's just abbreviated to the BVA/KC/ISDS screening scheme.
But for the price of approximately a bag of decent dog food, you could take your dog along and have a board certified veterinary ophthalmologist examine the eyes of that dog, non-invasively, but very thoroughly, and report on any evidence of any inherited eye disease that dog might have. And it's about the same cost for a DNA test, actually as well, 40, 50 pounds. So yeah, I think it's a small price to pay to do your best as a breeder to ensure the health of the puppies that you breed.
It sounds like a very low price, doesn't it? As you say these dogs become members of our family and who wouldn't spend a couple of extra dog food bags to, to help a member of their family, and so is there, there's presumably not just one genetic test. You send a sample in and say, could you run a Bulldog panel or could you run a Labrador panel? Is that how it works?
Yes, these days there are, we call them panel tests, and you can send your dog's DNA to a number of companies, and they will screen them for 200 different mutations. Now, most of those mutations will not be relevant to your dog, so if your dog is a Bulldog, for example, then the mutation that causes retinal degeneration in Labradors is not going to be relevant, but it doesn't do any harm to have that information.
And those tests can be a very cost effective way of receiving the genetic test results for lots of different mutations. Now, some breeds have more DNA tests than others, so I think Labradors have, there's maybe six or eight DNA tests that I would recommend that you would do if you are breeding Labradors. So you can probably get that done in one of these panel tests for a little over a hundred pounds actually. So. Two bags of dog food. And that's for the life of that breeding dog, isn't it?
Or the breeding life of that dog? Yes. The DNA doesn't change. So that is different from the eye examination where the, the, depending on the breed, we might recommend sequential eye exams if they have eye problems that maybe don't appear until later in life. But the DNA, you can test DNA from a puppy when it's a few weeks old, really. And then that isn't going to change. So it's very much a one-off test. Can you test? I mentioned hip scoring, elbow scoring.
Is there a genetic test for elbow dysplasia or hip dysplasia at the moment? There's no reliable genetic test at the moment, and that's because hip dysplasia and elbow dysplasia are what we call complex diseases. So they are the result of not just a single mutation, but many mutations. Unfortunately at the moment, to test for your dog's risk of developing hip or elbow dysplasia, you have to rely on a clinical examination.
You mentioned the quality of tests earlier and you said that there are lots of places you can send dogs DNA for testing. Are there bad companies out there? Are there charlatans out there? So there's very little legislation governing who can set themselves up as a DNA testing company. But for example, the Kennel Club in the UK has a list of companies that they the acredit. So that would be a reasonable place to start finding an accredited or a decent laboratory.
There's different companies operating in different countries. It can be tricky, but again, if you are in that breeding community, I would suggest talk to fellow dog breeders and if you are buying a puppy and you want to see evidence that the dog has been DNA tested, there should be, a reputable company will produce a certificate with all the information on that certificate as to what they have tested for, the mutation they have tested for and what the results were.
It really all comes down to education, doesn't it? Not just breeder education, but puppy purchaser education and veterinary education, because I'm not sure that many vets or nurses actually recommend genetic testing yet. It's not really become a industry standard. Yes, I would agree. And I know that you're a vet, but I, I very often say I wish vets knew more genetics and that I think vet students don't get taught maybe as much genetics as they should do, they could do.
Yeah, so I would really like the consumer to become more educated in this region. I always say that a dog is not a fridge, and some people will spend more time researching their next fridge than they will about the puppy that they're about to buy. You hope that this dog is going to be with you for at least as long as your fridge will. So don't make an impulse purchase. Look into the breeds.
So not only decide what type of dog you want in terms of its, how it's gonna fit in with your lifestyle and how much exercise it needs and that sort of thing. But what are the diseases that breed or that crossbred are prone to? What tests are available to minimize the risk of them developing those diseases? Never be afraid to ask the breeder what tests, what health tests have the parents of my puppy had. A good breeder will ask you just as many questions about your lifestyle.
So don't be afraid if the breeder asks you lots of questions. In fact, I would be a little bit worried if the breeder didn't ask me lots of questions about what sort of home I was going to give this puppy. I heartily agree, and I, I'm laughing about the analogy between a, a fridge and a dog but actually that is quite worrying, isn't it?
That people go with their heart and decide for various reasons, various usually emotional reasons, what breed they are most attracted to and quite often that breed may not even be behaviorally a good fit for the family, let alone genetically. Absolutely, absolutely. People like the look of a dog. You know what the, how the dog looks. And again, we can go back to Cockapoos for example. People look at them and they look like little teddy bears, don't they? Especially when they're puppies.
They're cute, they're fluffy. Both Poodles and Cocker Spaniels are very high energy breeds and they need a lot of stimulation. They need a lot of training. They're not just gonna sit in a basket and look cute and fluffy. They need stimulation, they need exercise. And yeah, all of that research, I think is super, super important. People really need to be informed consumers and it's a big purchase, do your research.
You're gonna spend probably a thousand pounds plus on your puppy if it comes from a breeder. Make sure you get a good value for money. Absolutely. Do you see any point in legislation for this? We haven't got any particularly strong legislation on dog ownership at the moment. We don't and I think legislation comes down to policing, doesn't it? And you can have rules and rules in place, but if the resources aren't there to, we used to have dog licensing, didn't we?
And we, we don't have it at anymore. I, yeah. I would love to see people who buy dogs having to go to a compulsory basic dog training course. Yes. And the arguments against making some DNA tests and health checks compulsory is that people will still breed these dogs anyway, and it's very difficult to probably find the puppies that haven't been health tested. And if you, and so you drive the dog breeding underground. Do you see there being a problem with pet insurance?
If it's been tested and one of the parents has a, a, a deleterious gene, could the insurance company turn around and say, we're not covering it for this? I think they could absolutely. Unfortunately, at the moment, DNA testing is not widespread enough for it to be on the health, the insurance company's radar. So I think at the moment you are not going to be penalized that they're not asking the question. So we have these panels of tests.
Are there any more coming on the, the horizon that, that are interesting, unusual, or? DNA mutates. So new mutations occur all the time, and I think this is another misconception of breeders that my, my breed doesn't have any inherited disease. It doesn't have any DNA tests. I don't need to do any DNA testing. DNA mutations happen at random. They're pretty rare, but they can happen in any dog of any breed.
And if they happen in a dog that is bred from, male or female, and passes to the next generation, then there's a chance that within that breed that mutation can become more, more widespread. My research group spends a lot of time hunting for new mutations that are causing new diseases within breeds. So Catherine, to sum up, breeders should have responsibility to say this puppy is going to become a member of someone's family.
I want to make sure it's as healthy as possible, therefore, I'm going to get relevant hip elbow eye scoring done for phenotype changes. But I'm also going to get as much genetic testing as is relevant to this breed, pertinent to the breed, to be Sure. I'm giving it as good a chance for this puppy to be healthy. Is that what you do? You've hit the nail on the head then and summed it up pretty well.
So I think yes, responsibility on both sides, basically, it's the breeders to do everything they absolutely can and that takes reading and researching and asking other breeders of the same breed what health checks should you have done or could you have done?
And responsibility on the part of the puppy buyer to do their research very well, choose a breeder who is taking that responsible, health-focused attitude and yeah, seek out the best quality in terms of health, not in terms of its breed standard or chances of winning in the show ring or anything like that, because most people are gonna buy their dog and it's just gonna be a member of their family. So that's what's important. And there's nothing more important than health, in my opinion.
Can't agree more with you more Catherine Thanks for joining us on the WSAVA Podcast where we are transforming care, one episode at a time. We hope today's discussion was helpful wherever you are in the world. You'll find more information and further resources on the topics discussed in the show notes, and we look forward to sharing our next conversation with you very soon.