Working together to significantly improve the lives of dogs

The Centre aims to understand the genetic basis of inherited diseases in dogs and to develop DNA tests which, together with breeding advice, will improve the health and welfare of generations of dogs.

We know that inherited diseases resulting from single gene mutations are likely to become more prevalent in purebred dog populations than in crossbreeds, and that these can lead to significant welfare issues. The Kennel Club Genetics Centre at the Animal Health Trust was created to tackle this.

Dr Cathryn Mellersh (front right) Head of the Kennel Club Genetics Centre at the Animal Health Trust with her research team and the AHT's DNA Testing Service.

Using the Animal Health Trust’s unparalleled level of skill and expertise within canine genetics, since the inception of the Centre 22 DNA tests have been developed to identify carrier and affected dogs from 50 breeds.

One of the first mutations to be discovered and be developed into a DNA test was for a painful and blinding condition called primary lens luxation (PLL), a disease that affects around 20 different breeds. Following the PLL success, a further 21 tests have been developed by the KCGC team. Through the AHT’s DNA Testing service alone more than 65,000 dogs have been tested for these mutations, resulting in more than 164,000 hereditarily clear puppies born free from debilitating or blinding inherited conditions.

At the beginning, my team and I were very excited about the prospect of what we could achieve. I am convinced The Kennel Club and AHT partnership has significantly improved the lives of dogs.

Dr Cathryn Mellersh
Dr Cathryn Mellersh, Head of Canine Genetics

Dr Cathryn Mellersh, Head of the Canine Genetics Centre at the AHT, added: “We have worked with the relevant purebred dog stakeholder groups to identify problems and, where possible, provide solutions which, without doubt, are changing dogs’ lives. Technology has also advanced significantly in the last 10 years, so going forward there is so much more we can achieve.”

WHOLE GENOME SEQUENCING

In 2015, thanks to advancements in genome sequencing technology, scientists in The KCGC at the AHT were able to identify the mutation responsible for a rare, neurological condition, cerebellar ataxia, in smooth-haired Hungarian Vizslas and develop a DNA test for this condition.

What was novel about this research was that in order to find the mutation responsible, the AHT used whole genome sequencing to study all 2.4 billion letters of DNA from just one affected Vizsla. Traditionally, a genetic investigation into a disease of this nature would require DNA samples from at least twelve affected dogs and the same number of healthy dogs from the same breed.

Dr Cathryn Mellersh, said: “The combination of advances in genome sequencing technology, alongside our expertise and bespoke computer analysis, has paved the way for our Give a Dog a Genome project. We came up with the concept that we could use whole genome sequencing to directly identify disease mutations.  We aimed to create the UK’s largest canine genome bank to make it much easier to investigate all of a dog’s DNA, and find rare genetic mutations relatively quickly. We can do this by comparing the genomes of affected dogs with the genomes of healthy dogs from different breeds, as we did for cerebellar ataxia in the Vizsla.”

Launching the Give a Dog a Genome project at Crufts in 2016.

GIVE A DOG A GENOME

The Kennel Club Charitable Trust agreed additional funding to enable the AHT to create the canine genome bank and develop more DNA tests to help even more dogs. The project, which became known as Give a Dog a Genome (GDG), received huge support from breed communities, and very quickly 75 breeds were signed up to complete health questionnaires and provide DNA samples to be whole genome sequenced.

By gaining a wealth of new information about the canine genome, from a vast number of breeds, the project aimed to make the process of finding genetic mutations even more effective and efficient in the future.

Dr Mellersh, added: “At the time, and even more so now, we felt GDG had unprecedented potential. Through this we can have a substantial impact on the health and welfare of purebred dogs. The GDG project is another excellent example of the pioneering work which has come out of The Kennel Club and AHT partnership.”

By the end of 2018, 89 dogs from 77 breeds had been sequenced, and their data added to what has now become the UK’s largest canine genome bank. Now, the AHT’s scientists need to analyse all of the whole genome sequence data – with each genome being 2.4 billion letters long, if you read it like a book, it would be equivalent to reading the Harry Potter series 440 times per genome!

Once fully analysed, this information will significantly aid future canine genetics research – at the AHT and around the world, as the charity publishes what it learns.

Of the 77 breeds sequenced, Shetland Sheepdogs are one of the first breeds expected to benefit directly from the GDG project. Breeders of these dogs were concerned about another blinding condition called progressive retinal atrophy (PRA), which is found in the breed.

By comparing the whole genome sequence of a single PRA-affected Sheltie to the GDG bank of genomes from other breeds, the AHT has identified one variant in a retinal gene that is a very strong candidate for causing PRA in this breed. The variant still needs to be fully validated but the KCGC team are very hopeful a DNA test will be available before the end of the year.

IMPACT OF DNA TESTING

Just last year, the partnership looked at the impact DNA testing is having on canine disease. It is clear that the use of DNA testing can stop affected dogs being bred immediately, and testing also allows a controlled decline in carrier dogs, ensuring gene diversity within a breed.

Scientists looked at data collected at least five years after DNA tests were developed for eight diseases in eight breeds: Labrador Retrievers, Parson Russell Terriers, Gordon Setters, Irish Setters, Cavalier King Charles Spaniels, Miniature Bull Terriers, Cocker Spaniels and Staffordshire Bull Terriers. Results show that, thanks to responsible breeders using DNA testing, frequency of disease mutations has reduced by up to a staggering 90%.

We’re delighted to be able to demonstrate the real-life, positive impact DNA testing can have on disease prevalence, and in turn how that is benefiting thousands of dogs.

Dr Cathryn Mellersh
Dr Cathryn Mellersh, Head of Canine Genetics

WHAT DOES THE FUTURE HOLD

This partnership has made significant improvements to dog health and welfare over the last 10 years. With the knowledge that can now be gained from analysis of DNA sequenced data in the canine genome bank, we could very quickly accelerate forward another 20 years. Scientists in the KCGC at the AHT aim to get better and faster at identifying mutations using smaller numbers of dogs and improved technology.

One of the key benefits of finding mutations in this way is that a disease can often be stamped out before it takes hold in a breed.

The KCGC team also plan to tackle complex genetic diseases, such as epilepsy, as these diseases potentially compromise the health of the greatest number of dogs. Of the 489 currently known genetic diseases in dogs, 72% are believed to be complex.

Raising awareness of health testing among puppy buyers is also key. There are still too many people unaware of what health tests are available and not checking that parent dogs have been tested for known conditions. The partnership wants to ensure potential puppy buyers know what they should be asking, so they purchase not only an appropriate puppy for their lifestyle, but also one that has benefited from health testing and will have the very best start in life.

Cathryn Mellersh summarised: “The last ten years have been incredibly important to dog health. Thanks to the partnership with The Kennel Club so many dogs are benefitting from DNA tests, and that’s improving the lives of generations of animals. Great things can and are being achieved through genetic research. With humans suffering many of the same diseases as dogs, there is always the possibility that our research is going to help human medicine as well.

“We are incredibly grateful to The Kennel Club Charitable Trust and its members for its ongoing support, and look forward to continuing to make life better for thousands of dogs.”