Every day is a learning day

One of the potential barriers to improving the health of pedigree dogs is breeders’ lack of understanding of genetics. Most breeders are, by now, familiar with DNA tests for genetic mutations for health conditions such as PRA, CLAD, DM and many more (often also with 2 or 3 letter abbreviations!). The principles of recessive mutations with 3 genotypes; Clear, Carrier and Affected and what these mean in terms of clinically healthy or unhealthy dogs is generally known by breeders. This may be less clearly understood by buyers who may still think that Carriers are likely to be a problem and get ill. 

As we move into discussing which combinations of those 3 genotypes can safely be bred together, there are still a range of opinions on whether DNA Affected dogs should be bred from. As long as an affected dog is mated to a clear dog, any puppies will not be affected but will be carriers. In many breeds, where there are small gene pools, it is reasonable to breed with affected dogs (mating only to clears). While it might be argued that not using affected dogs is a quicker way to remove deleterious mutations, it also has the effect of removing all that dog’s genes from the population. Removing dogs from breeding on the basis of one genetic mutation alone is often not in the best interests of the breed.

When it comes to coats and colours, far fewer breeders seem to be educated or to make the effort to understand the genetics. All too often, discussion of colours seems to be based on historical urban myths or worse, on fashion and personal prejudices. It’s such an emotive topic, as we have seen with numerous discussions over many months about Colour Not Recognised (CNR) and Non Breed Standard (NBS) colours.

Emerging science

What I find really fascinating is the rate at which the science underpinning the genetics of coats and colours is developing. Some of the research is being enabled by Citizen Science where dog owners’ contributions help research teams by providing DNA samples and photographs. One such study published last year resulted in an improved understanding of one of the earliest coat colour mutations, designated as ancient red (eA). This genotype is associated with “domino” in Alaskan Malamute and other Spitz breeds, “grizzle” in Chihuahuas and “pied” in Beagles.

Another new paper (2021) explains variations in the PMEL gene which causes dapple (merle) in Dachshunds. A previous study of this gene in Australian Shepherds had correlated the length of an insertion into the PMEL gene with 4 broad phenotype clusters of merle, described as “cryptic”, “atypical”, “classic” and “harlequin”. This new paper reports on a similar study in Dachshunds and identified numerous cases of “hidden” merle in light red dogs. The paper suggests that the frequent identification of cryptic, hidden and mosaic variants of the merle pattern makes DNA testing critical to avoid producing puppies with serious health problems. Double-merles are known to be at risk of deafness, blindness and microphthalmia (small eyes) and are banned from registration by the KC.

Time for cocoa?

Another lesson I learned recently was the existence of a gene associated with the brown (liver/chocolate) colour. Variants of the B locus are the most common cause of the brown coat colour, with 5 known mutations of the TYRP1 gene that explain the majority of dogs with brown coats and noses. One exception has been the brown or chocolate French Bulldog which, when tested, is found to be BB (i.e. not chocolate as normally expressed). Recent research (2020) has identified a mutation on the HPS3 gene associated with brown in FBs and which has been called “cocoa”, for which a DNA test is now available. 2 recessive copies of this mutation (co/co) are required for the dog to be brown/chocolate.

5, not 4, basic coat colour patterns

The most recent paper I have been reading was published by Dannika Bannasch and her colleagues at the University of Bern. Professor Bannasch and one of her collaborators, Prof. Tosso Leeb, have both been winners of the prestigious International Canine Health Awards. The study clarified how coat colours and patterns are genetically controlled but also discovered that the light coat colour in many modern dog breeds is due to a mutation that originated in an extinct species more than 2 million years ago. 

Dogs can make 2 types of pigment; black (eumelanin) and yellow (pheomelanin). Production of these 2 pigments in the right place on a dog’s body results in very different coat colours and patterns. The agouti signalling protein (ASIP) is the main switch for the production of yellow. Without ASIP, black pigment is formed. 

In addition, there are 2 “promoters” which result in ASIP production on (a) the belly and (b) banded hairs. The study identified 2 versions of the ventral promoter and 3 versions of the hair cycle promoter, resulting in 5 possible combinations which cause different coat colour patterns in dogs. Previously, it had been thought that there were only 4 basic patterns.

Image source: https://www.nature.com/articles/s41559-021-01524-x.pdf

Within each of these 5 pattern types, there may be further variation due to other factors such as the position of the boundary between red and black areas, the shade of red (from dark to nearly white) and the presence of a black facial mask or white spotting caused by genes other than ASIP. 

Prof. Bannasch said: ‘While we think about all this variation in coat colour among dogs, some of it happened long before ‘dogs’ were dogs. The genetics turn out to be a lot more interesting because they tell us something about canid evolution.’

Learning from history

While a lot of the science and understanding of the genetics may be new, many breeds have a wealth of historical information on coats, colours and patterns. Much of that is held in Kennel Club registries or breed archives. These should be essential resources to inform any discussion about colours that can or cannot exist legitimately in any breed. I am aware of a study in one breed, looking at dogs from the early part of the last century, which clearly shows that colours that are not currently fashionable were around over 100 years ago. 

The fact that some of these colours are associated with recessive mutations should make it unsurprising that those colours can still crop up and be bred today. There are plenty of examples of breeds where breeders have specifically selected for a particular colour or pattern and that’s not something new. We should be very careful not to forget our breeds’ histories and their genetic origins, and not fall into the trap of altering Breed Standards simply on the basis of what is or isn’t fashionable today. That, of course, applies to conformation as well as to colours!

Remember, prejudice is a great time-saver; it enables you to form opinions without having to gather the facts.

Breed health improvement: Finding the balance

I was pleased to be invited by the Whippet Breed Council to present a webinar at the end of February as part of their current online education programme. I had to smile when it was first advertised and billed as “an evening with Ian Seath”. I couldn’t help thinking that second prize was “2 evenings with Ian Seath”. Nevertheless, over 80 people signed up to attend. The webinar was titled “Breed Health Improvement: finding the balance” and my invitation was prompted, apparently, by reading the interview Gay Robertson wrote for the Kennel Gazette.

The plan was to talk about approaches to breed health improvement and why every breed needs a health strategy. The Whippet Breed Health and Conservation Plan is still under development with the Kennel Club but there is useful data already available from previous health surveys. The challenge is knowing where it will be best for breeders to put their effort. The presentation covered areas where it might be useful to focus attention and discussed how breeders can make use of DNA tests and clinical screening programmes, as well as some of the pitfalls to be aware of. There was an opportunity for a question and answer discussion after my presentation.

Here are my slides.

It’s time to get a GRIHP – a new resource from the IPFD

We have seen over recent months that the topic of pedigree dog health is truly an international concern. The legislation affecting brachycephalic breeds in the Netherlands has probably been the most high profile but there have been similar moves in France, Germany, and Finland. The proposed German legislation has had a focus of conversations on social media related to the amount of exercise dogs must be given and the potential difficulty of policing any such legislation. However, an aspect that should concern us is the threat to ban dogs with “extreme exaggeration” from participating in dog shows. We can be pretty sure that it won’t just be the brachycephalic breeds that are targeted; short-legged breeds including the Dachshunds are also likely to be within the scope of these proposals.

Dr Brenda Bonnett, CEO of the International Partnership for Dogs said “For many years, lecturing about breed-specific issues in dogs, even before the existence of IPFD, in discussions with the breeding community, veterinarians and others, it was becoming self-evident that if concerns were not addressed by the dog community, society would likely impose ‘solutions’ on them.  This is coming to fruition in many areas, and society and the media wants to move at a much faster pace than many in the pedigreed dog world.”

Shortly after the announcement of the proposed French legislation, our Kennel Club hosted a webcast on the subject of Brachycephalic Obstructive Airway Syndrome (BOAS). KC Chairman Tony Allcock chaired a discussion panel that discussed some of the issues facing brachycephalic breeds and the role the KC is playing in addressing BOAS through the Respiratory Function Grading Scheme (RFGS) developed at Cambridge University. It’s important to recognise that the RFGS is just one strand of work being done here in the UK and it was also useful to hear about the role of the Brachycephalic Working Group during the webcast. This multi-stakeholder group has taken a wide-ranging approach to address the brachycephalic issue, encompassing both the supply side (i.e breeders) and demand side (i.e. buyers). 

I wrote last month about how more data won’t improve breed health. It’s evident from what has happened in the Netherlands that data and evidence have made very little difference to the framing of the legislation affecting brachycephalic breeds. Despite the case presented by the Raad van Beheer (Dutch KC), their government seems to have been persuaded by a small group of vets at Utrecht University that legislation based on measuring the craniofacial ratio is a suitable tool to improve breed health.

Evidence and collaboration

The increasing internationalisation of breed health reinforces the case for the existence of the International Partnership for Dogs (IPFD). Their independent, non-political, position has always been grounded in a combination of evidence and collaboration. Their latest initiative is GRIHP – Globally Relevant Integrated Health Profiles – which has the potential to shape a more balanced conversation about pedigree dog health.

The IPFD website says:

A Globally Relevant Integrated Health Profile (GRIHP) describes the Big Picture of health on (all) conditions that are of interest within a breed and is intended to inform owners, breeders, and those counseling them. Health Strategies are breed-specific recommendations and requirements developed by Health Strategy Providers (HSPs) including, e.g. kennel clubs, breed clubs, and veterinary organizations. Health strategies may encompass detailed descriptions of breed history and development, evidence/ statistics on conditions of interest, health/temperament screening suggestions or official programs, and more, depending on the breed, the HSP, the country, and/or specific organisations. 

The Big Picture for a breed should include information not only on conditions that have genetic or other screening tests available, but also all conditions that may impact the health, behaviour/temperament, well-being, and welfare of individuals and breed populations; ideally accompanied by an indication of the relative importance of each item, which may involve commonness, severity, and other factors.

Depending on the breed these Get a GRIHP articles will include:

  • Breed nomenclature and description of types and characteristics
  • Health and welfare issues, including:
  • statistics on common and high-risk conditions
  • available health, genetic and other screening tests that are recommended or required
  • Population statistics from various countries; statistics on trends in popularity
  • Management strategies and recommendations for owners and breeders, as well as resources to support veterinary-client communication.

Get a GRIHP on Corgis and Dachshunds

Corgis and Dachshunds are the first 2 breeds with GRIHP reports. In the UK, we already have Breed Health and Conservation Plans being developed by our KC and these are focused on action plans for UK breed clubs. The value of GRIHPs is that they open up the scope to reflect internationally available data and evidence of breed improvement strategies.

For example, with the Corgis, you can see international registration statistics from 6 countries. While the UK population may be on the Vulnerable Breeds list, this international perspective shows Finland has seen a significant growth in popularity.

Another useful aspect of the GRIHP reports is that you can see which screening programmes are being implemented in different countries. This helps provide a consensus view of what breed clubs, kennel clubs and breeders are currently focusing on. What it doesn’t necessarily tell us is whether these screening programmes are the most important ones; they might simply be the most readily available ones. Information on DNA tests is already collated by the IPFD. Their Harmonisation of Genetic Testing database now includes a “relevance rating” based on published research evidence to support the use of DNA tests in given breeds. Just because a test is being sold for a breed, doesn’t necessarily mean it is valid and relevant for that breed.

Some of the most useful information in the GRIHP reports is the Swedish Agria mortality (death) and morbidity (illness) data. They compare the featured breed with “all breeds” and other pedigree breeds to give a clear view of relative risks. Interestingly, back disease for Mini Dachshunds is shown as being 5 times more likely than in “all breeds” combined. Other sources typically quote Dachshunds as being 10-12 times more likely to have a back problem. Pekingese are shown as the highest risk breed for back disease in the Swedish data. 

Returning to my initial discussion about legislation that targets specific breeds, the Swedish data on back disease shows that it is not only the short-legged breeds that have an increased risk. The comparator data really do pose some challenging questions for anyone looking to impose apparently simple solutions (such as legislation) on targeted pedigree breeds. Corgis, for example, have a lower mortality rate (Risk Ratio 0.7) than “all breeds” and a marginally higher morbidity rate (RR 1.07). In the Dachshunds, both sizes have a lower mortality rate than “all breeds” and the Standards have a lower morbidity rate. 

We certainly need to see more of these GRIHP reports for other breeds. Not only will they present useful data but they also exemplify the good work being done, internationally, to improve the health of pedigree breeds.

An insight into brachycephalic dog health from The Kennel Club

The Kennel Club has hosted a unique webcast to discuss brachycephalic health and what can be done collaboratively to ensure a healthier future for dogs. Chaired by Kennel Club Chairman, Tony Allcock OBE, the webcast panel comprised Dr Jane Ladlow, European and Royal College Specialist in Small Animal Surgery and leading BOAS researcher; Bill Lambert, Head of Health and Welfare at the Kennel Club; and Charlotte McNamara, Health and Welfare Development Manager at the Kennel Club.

The panel discussed brachycephalic health, approaches across Europe, the need for a collaborative, evidence-based approach, including how the Respiratory Function Grading Scheme can help protect and improve the health of brachycephalic dogs now and in the future, and the importance of data collection and ongoing research into the complex Brachycephalic Obstructive Airways Syndrome (BOAS).

Further information about brachycephalic dog health, what the Kennel Club is doing and which tools and health screening is available to breeders can be found at: https://www.thekennelclub.org.uk/flatfaceddoghealth

To donate and support further research into brachycephalic dog health and BOAS, visit: https://uk.virginmoneygiving.com/charity-web/charity/displayCharityCampaignPage.action?charityCampaignUrl=BDH

Nearly 20 years of DNA testing – what can we learn?

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.

Wider implications?

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.