Colour Dilution Alopecia – not so simple!

In the last week of April, I had the pleasure of chairing another of The Kennel Club’s webinars, organised by the Health Team. It was a free webinar for owners and breeders who wanted to find out more about the dangers of breeding for fashionable colours, using the example of colour dilution alopecia – including what research has told us to date, and how best to support dogs affected with this condition.

Colour Dilution Alopecia (CDA) is a genetic condition found in some breeds that causes hair thinning and loss, which can leave the skin prone to sunburn, infection and dermatitis. The condition is associated with dogs who have a “dilute” colour (e.g. blue, lilac, isabella or silver). While the disorder is commonly described in Dachshunds and Dobermanns, it has also been recognised in other breeds. With the rise in popularity of “fashionable” coloured dogs, it’s crucial to understand the dangers that can be associated with breeding for certain colours and what breeders can do to try to reduce the prevalence of conditions associated with dilute coat colours.

My introduction to the webinar shared some data on the 2021 registration statistics of those breeds where there are Non Breed Standard (NBS) colours in their registration options. This applies to about 10% of the KC’s registered breeds. At one extreme, French Bulldogs had 70% of their 2021 registrations as NBS and 53% for Bulldogs. Labradors had 1% NBS but, with over 61,000 registrations, that still amounts to over 800 NBS dogs.

Colour Dilution Alopecia is a concern to many of us in the Dachshund community because it is reported in the dilute colours (blue and isabella). We ran a breed health survey in 2021, supported by The Kennel Club, specifically to find out how prevalent the condition was. Our 2018 survey had shown skin diseases and allergies to be the second most prevalent health concern in all colours (after IVDD – back disease) and we wanted to find out if this was a particular issue in the increasingly popular dilute colours. Most people will be aware that Mini Smooth Dachshunds have grown in popularity over recent years (under 3000 registered in 2013 and over 15000 registered last year). Shockingly, registrations of dilute Mini Smooths have grown from 0.1% in 2018 to 20% last year. Not only has the breed become extremely fashionable, but “rare” colours have too (often aided by the influence of social media).

In Fitch Daglish’s 1952 book “The Dachshund”, he refers to blue dachshunds, so it is clear that the dilution gene has been in the breed for a very long time. This is not something that has been added by cross-breeding. The high number of dilute puppies now being bred is down to intensive selection for the dilute coat colour in the UK population. Our 2021 health survey showed 80% of blue dachshunds were affected by CDA and 86% of isabellas.

Dr Rosario Cerundolo (Head of Dermatology at Dick White Referrals) presented during the webinar on the signs, diagnosis and treatment of CDA. He showed examples of the condition in several breeds, including Dalmatians, Russian Toy Terriers and Dachshunds. Electron microscope images illustrated the structure of hairs in dilute dogs that causes patches of hair thinning or loss and may also include flaky and/or itchy skin. It is an early-onset, lifelong condition, often being seen from around 6 months of age and cannot be cured; it can only be managed. 

The genetics of CDA

Dr Joanna Ilska (KC Genetics Health Manager) was the second speaker at the webinar and she discussed the research evidence and genetics of CDA. While the gene variants for dilution are now known and can be identified with DNA tests, the gene (or genes) that cause CDA have not been found, to date. Joanna explained that, while dilute colour is a predisposing factor for CDA in Dachshunds, the 2 traits are not irrevocably linked. The fact that dilute colours in some other breeds do not suffer from CDA and not all blue or isabella Dachshunds do either, shows this is not a simple genetic condition. The evidence also does not support the view that other health conditions are caused by the coat colour. So, the fact that many of the dilute dogs in our 2021 survey also suffered from autoimmune conditions is more likely to be a result of close inbreeding, use of popular sires, and strong selection within a narrow population pool.

The scientific evidence on the association between colour dilution and CDA was reviewed by the veterinary and genetics specialists on the KC’s Genetics & Health Screening Dog Health Group and they recommended an educational approach rather than a ban on registration of dilute Dachshunds. This webinar was part of that educational approach. 

Recognising that where there is demand, there will be supply, Joanna stressed the dangers of breeding for “rare” colours and offered some practical advice to minimise the risks. This included carrying out all recommended health screening, breeding from dogs over the age of 2 once they were known to be unaffected by CDA, and avoiding close inbreeding and popular sires.

Discouraging “rare” colours

You may have read the recent press release on the recommendations from the NBS Colour Working Party. The Colour Watch system mentioned in their report will be one element of the KC’s approach and provides a framework for marketing and communication to puppy buyers, breeders and owners. Work is also underway as part of the KC’s strategic review to establish more effective ways within the registration system to promote well-bred puppies with breed standard colours and relevant health-tests. For several breeds, there have also been changes made to Breed Standards and to the lists of BS and NBS colours in the registration process.

How to raise awareness?

The Colour Watch system will be a key element in the KC’s approach to raising awareness of the risks of breeding for so-called rare colours and NBS colours. Several breed club communities are already producing educational materials and we have seen great examples of these at Discover Dogs and on club websites. Clearly, there is a role for breed clubs and councils, as well as the KC. 

The KC would, of course, be pleased to collaborate with breed clubs and their charities on joint campaigns that help raise awareness. One simple step would be for breed clubs to share links to this webinar and the other resources in the KC Health YouTube channel. If breed clubs are serious about protecting the health of their breed, they need to be proactive on social media. On Facebook, there are dozens of Dachshund Facebook Groups and it’s likely the same for other breeds. It is a massive task, though, and we need to address both supply and demand.

‘The greatest enemy of knowledge is not ignorance, it’s the illusion of knowledge’: Stephen Hawking 

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IPFD Dog Health Workshop on Genetic Diversity

On May 3, the International Partnership For Dogs (IPFD) hosted their second virtual workshop. Focusing on genetic diversity (primarily from a genetic tests/tools view), 60 participants – including representatives from IPFD and their partner kennel clubs, genetic test providers, breeders, and other key stakeholders – came together online to identify genetic diversity tools and resources, and to discuss priorities and actions for the benefit of all dogs. Half the attendees had been at the 2021 online workshop which discussed Genetic Test Reporting.

The distinguished panel included Prof. John Woolliams (The Roslin Institute, UK), Samantha Hauser (Embark, USA), Katy Evans (Guide Dogs, USA), Saija Tenhunen (Viking Genetics, FI), Pieter Oliehoek (Dogs Global, NL), and Sally Ricketts (University of Cambridge, UK), who shared their time and expertise with us. These speakers had provided short (YouTube) video presentations ahead of the workshop which were the pre-work for participants. These are available to IPFD website members via the Speciality Forums. The workshop was introduced by Katariina Mäki (Acting CEO, IPFD), a quantitative geneticist who previously worked at the Finnish KC.

International and collaborative genetic diversity management is important because different countries and KCs have different policies and tools available, so there is lots of learning that can be shared. Additionally, international populations of dogs/breeds could be sources of diverse genetic material and, increasingly, there are global breeding strategies being developed. 

The problem of Popular Sires

John Woolliams said that everyone talks about Coefficients of Inbreeding (COI) but KCs and breed clubs should be having conversations about what’s happening in a breed and what else can be looked at, especially rates of inbreeding. KCs should be providing simple summary statistics on genetic diversity to breed clubs. Then, of course, the clubs need to understand how to use that information. The Popular Sire effect is potentially damaging for genetic diversity so, perversely, breed clubs publishing lists of the Top 10 winning show dogs might actually be encouraging less knowledgeable breeders to use these dogs at stud and add to the problem. Another attendee commented that one of the main concerns is that the whole pedigree dog culture is traditionally focused on the single successful specimen (or kennel). How can we shift the focus to the population of the breed as a whole? The issue with Popular Sires is that breeds are sidelining other potential sires who could be contributing to the gene pool.

Most UK breeders will be familiar with the Kennel Club’s online tool for Coefficients of Inbreeding. This is based on pedigree analysis and uses all the available pedigree information behind any particular dog. Joanna Ilska, the UK KC Geneticist, said we are discussing the number of generations to use in COI calculations but will still publish full pedigree values. If KCs worked together we could fill in missing import pedigree information. The UK has seen a reduced rate of inbreeding, reported in a paper published in 2015 (Lewis et al). This is mostly due to increased imports arising from the 2012 quarantine legislation change. Joanna said that an analysis of COI after removing imported dogs from the calculations also showed a reduction in inbreeding, and this occurred after introducing the Mate Select Tool. This may suggest breeder awareness has resulted in a change of behaviour. 

What can breed clubs do?

John Woolliams said that the absolute COI value doesn’t matter and that COI will always increase in a closed gene pool (closed stud book). What matters is the rate of increase of COI. He also talked about some of the actions that breed clubs could (should?) take, for example, looking at pedigrees and average relationships (kinship) between dogs to understand how many different dogs contribute to each year’s puppies. In some countries there is a “neutering culture” where non-show puppies are sold with endorsements or contracts preventing them from being used for breeding. This too, leads to a loss of choice and genetic diversity. One of the participants commented “We, especially breeders, need to campaign that any healthy dog is a potential parent dog. By buying a purebred dog, you have become responsible for the heritage that breed constitutes.”

Jerold Bell emphasised that there are differences between pedigree COI and genomic COI. With the former, every puppy from a given mating would be calculated as having the same COI. The latter enables you to identify differences between individual puppies in a litter, because each puppy will inherit slightly different combinations of genes from their parents. Embark is one of the providers of genomic COI testing and it can sometimes be a shock for breeders to discover that their puppies’ genomic COI is significantly higher than a pedigree COI value. For example, Brenda Bonnett commented that for a sample of GSDs, genomic COI was around 40%, compared with 30% for pedigree COI. Other recent research papers have shown the same thing. Genomic testing is still relatively expensive for breeders to do, though.

Who owns the problem?

For individual breeders making decisions about their next litter, the most important generation is the potential sire and dam you have in front of you. You can’t do much about Great-great Grandparents! Calculating the COI of that potential litter when you know you’re not using the whole gene pool may be interesting but is not going to solve the problem of genetic diversity. The actual percentage of dogs bred from is small in most breeds. In Finland, they have found that only 2% of male dogs are used for breeding. Breeders should consider having more 1-time litters and avoid repeat matings. The idea of using double matings (2 stud dogs on 1 bitch) could be a way to generate a more diverse litter of puppies (who would need DNA parentage profiling).

Kennel Clubs can (and should) provide the tools and education to help manage genetic diversity within breeds, including offering the option to open stud books for appropriate cross-breeding projects. Breed clubs are best placed to look at what is happening across their breed (nationally and internationally) and should be using this information to provide advice and guidance to breeders. 

Pieter Oliehoek made a really important point early in the workshop: the focus should not be on inbreeding but on genetic diversity. Breed clubs and breeders need to understand this important difference.

Brenda Bonnett reminded the attendees that any discussions and decisions on inbreeding or genetic diversity must be considered in the overall context of dog health. Extreme phenotypes bring with them health problems. There is no point “sorting out” genetic diversity if the dogs still can’t breathe, see, move or behave normally as dogs!

You don’t know what you don’t know!

It’s well-known that when you ask people to rate their driving skills, the majority say they are better than the average driver. Clearly, that’s impossible because, by definition, more than 50% of people can’t be “above average”. Apparently, it’s the same when it comes to dog breeders understanding of (even basic) genetics. A recent poll by Carol Beuchat on her Institute of Canine Biology Facebook Group asked people to rate their own understanding of genetic management and that of other people in their breed. On a scale of 1 to 5, most people rated themselves at 3 or more, while rating their breed peers below average (lots of 1s).

This might be another example of the Dunning-Kruger Effect which I have mentioned before. The Dunning-Kruger effect is a cognitive bias where people believe that they are smarter and more capable than they really are. Essentially, some people do not possess the skills needed to recognise their own incompetence. This leads them to overestimate their own capabilities. Charles Darwin wrote in his book The Descent of Man, “Ignorance more frequently begets confidence than does knowledge.“

At the other end of the spectrum, Dunning and Kruger found that highly competent people held more realistic views of their own knowledge and capabilities. Additionally, these experts actually tended to underestimate their own abilities relative to how others did.

Carol went on to explain in her blog why this lack of knowledge about genetic management is such a problem for pedigree dogs. She says: Inbreeding in dogs is FAR higher than in any other mammal, wild or domestic. Inbreeding of wild animal populations is usually in the very low single digits. Breeders of livestock begin to panic as inbreeding approaches 10% because the negative effects are so significant. In fact, they worry about every percentage point of increase.

In a closed gene pool, inbreeding can only increase over generations and the gene pool can only get smaller. With that comes the inevitable consequences of inbreeding depression such as reduced longevity, smaller litter sizes and the appearance of more inherited diseases associated with deleterious mutations.

Breeding strategy

Tom Lewis, formerly the KC’s geneticist, published a paper in 2015 showing data on changes in inbreeding coefficients across numerous KC registered breeds. The data show that breeders are choosing inbreeding as their preferred strategy and, although the data show some evidence of reductions in breed average COI, this is mostly due to the effect of imported dogs with few generations of pedigree data. The data also show COI to be lower than reality because the KC’s pedigree information used in the study only goes back as far as 1980 and therefore excludes breed founders.

In her blog, Carol says there are 2 problems that need to be fixed: firstly, “the significant inbreeding problem that severely imperils essentially every breed”. Then, “we need to breed sustainably” which requires an understanding of the tools used for the management of other animal populations. Clearly, there is much we could learn from the worlds of farm animal production and zoological conservation.

Beyond the Tipping Point?

In some breeds, not only do they face the genetic challenges described above but they also have phenotypic issues associated with exaggerated conformation. You may recall my article last year about the seminar I ran for the Whippet Breed Council. I described the poll we ran for the attendees and their number one concern about the breed for a viable future was conformation and exaggeration. Their number two issue was genetic diversity including inbreeding and popular sires, i.e. everything I have described in the first part of this article.

To me, it was quite surprising that conformation and exaggeration was seen as such a hot topic in Whippets. I’m no expert on the breed, but they don’t strike me as one of the breeds that ought to be overly concerned about that issue. Closer to home, I’m much more concerned about exaggeration in my own breed, Dachshunds. Our Breed Standard was amended last year to make it even more explicit that excessive length of body and a lack of ground clearance were highly undesirable traits. Our health committee produced a paper illustrating a range of types from unacceptably long, heavy and low, through to excessively tall and leggy.

The concept of Tipping Points is, I believe, really useful when considering exaggerated conformation. It is evident from what we see getting awarded in the showring that different judges vary in their view of what is acceptable. The Kennel Club’s Breed Watch programme should be a way to help judges (and exhibitors) recognise the point where exaggeration tips over into visible points of concern, including those with obvious health implications.

Typical dogs

We are also now seeing such discussions about tipping points in published research papers. For example, a paper was published in December 2021 titled: French Bulldogs differ to other dogs in the UK in propensity for many common disorders: a VetCompass study. In it, is this sentence: “In support of a view that French Bulldogs have diverged substantially from the mainstream of dogs in the UK and, are in many respects, no longer even a typical dog, is reflected in their higher differences in disorder propensity.”

I’ve had several interesting conversations about exaggeration recently with vets. Some of those centred around the five welfare needs of dogs which I wrote about in February. We also talked about the dangers of vets (and others) using terms like “normal for a xxx” (insert a breed’s name). The worry here is that we are starting from the perspective of what has become normalised in a particular breed, rather than remembering these should be dogs first. This leads to the question of whether there is a tipping point beyond which a particular breed can no longer be considered to be viable as a dog. When you see pictures of the grossly exaggerated “toadline bulldogs”, it’s pretty clear that a line has been crossed.

For an interesting discussion on exaggeration, listen to Dr Sean McCormack’s wildlife podcast featuring Rowena Packer and Alison Skipper:

play.acast.com/s/seanswildlife/the-flat-faced-dog-dilemma

One person suggested to me that judges’ education should ignore canine conformation and movement and learning should start with looking at horses. That way, judges would learn about virtues and faults without the hindrance of considering what might be “normal for a breed”. I can’t help thinking there is an urgent need for a robust discussion about tipping points and for breeders and judges to go back to basics in defining where we should draw the line on what is acceptable.

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.