Inherited illnesses

04_Fortunately most gundog breeds come from large gene pools4

Inherited illness in dogs is widespread, and although signs of illness can be caused by different diseases, the underlying cause is heavily dependant on the dog’s breed and its genetic make-up.

Vets can use this to their advantage when making an initial assessment. For example, on an autumn day walk a young Springer and a West Highland Terrier suddenly started crying out and rubbing their ears. What caused this sudden pain?

Although either could have hit a variety of problems, my money would be on the Springer having a grass awn down its ear canal and the Westie having an acute flare-up of an inherited skin allergy. Inherited disease is so common that vets recognise and deal with it every day, and dearly wish they did not have to!

The populations of all domesticated dog breeds have a number of diseases which may be inherited, some of which are common, and some of which have only been reported in a handful of animals. Fortunately we live in a period where veterinary science is making rapid progress in the diagnosis of these diseases. This progress significantly accelerated on 14 July 2004.

This was a monumental day in the history of dog breeding and welfare, for it was then that the National Human Genome Research Institute in the USA announced that it had unravelled the entire genetic code for Canis familiaris, the domestic dog. The task had taken years, with over 2.5 billion pairs of code to correctly analyse and sequence, and a budget in excess of $30m.

 This is Tasha, the first dog to have her genome sequenced

This is Tasha, the first dog to have her genome sequenced

The motivation behind the genome project was not purely for dogs’ benefit. When the announcement was made it was hard to understand why the NHGRI, a human genetics organisation, would spend so much time and money analysing a dog’s genes. However, researchers explained that ‘Due to a long history of selective breeding, many types of dogs are prone to genetic diseases that are difficult to study in humans, such as cancer, heart disease, deafness, blindness and autoimmune disorders.

In addition, the dog is an important model for the genetics of behaviour and is used extensively in pharmaceutical research.’ In other words, the research was less about dogs and more about humans. However the spin-off benefits for Canis familiaris are still likely to be enormous.

While geneticists all over the world continue to congratulate themselves on this wonderful achievement, what is the practical benefit? The answer is that we can test for more inherited diseases with greater accuracy, and by breeding selectively reduce the incidence of these diseases.

Although the dog whose genetic code (genome) was worked out was  a boxer dog called Tasha, we have picked a more common gundog breed, the Labrador Retriever, to highlight how influential inheritance might be on future breeding programmes. Anyone who has been involved with breeding will understand how passionately the pros and cons of genetic testing have been argued.
As an example of the limitations of what we currently know, take diseases that affect the Labrador’s athletic ability.

Among the better known are: elbow and hip dysplasia – diseases which lead to pain and malformation of the joints; osteochondrosis dissecans, which is a disease of the joint cartilage; and mypoathies, which are diseases of the muscle. Hip dysplasia is known to be partly inherited and partly due to environmental factors, and studies have shown that a combination of the current British Veterinary Association/Kennel Club Scheme method of assessment using x-ray and estimated breeding values can help significantly reduce the incidence of this disease.

Inherited allergic skin disease in a West Highland Terrier

Inherited allergic skin disease in a West Highland Terrier

The drawback of this is that these diseases become manifest at different rates in different dogs and so the problem may not be diagnosed until the dog has already been bred from, or until it has been overtly affected by the disease. How much better would it be to avoid producing such a dog in the first place, by testing potential parents prior to mating?

This is where things get a bit more complicated. Canis familiaris was selected by NHGRI for its genome study because no other mammal species shows such enormous physical variation (compare a Chihuahua and Great Dane), and yet has highly distinctive breeds that breed true (if you mate two Chihuahuas you get more Chihuahuas). However this has been achieved by careful breeding which has led in a few breeds to closed gene pools. In other words, relatives are interbred to continue desirable characteristics.

The genes from some breeds come from a tiny original population, for example at the end of World War II only eight Leonburgers are believed to have existed and the entire breed is derived from these dogs, and the Irish Wolfhound was derived from just six individuals.

The difficulty of disease control is easily demonstrated in a study of hereditary cataracts, where dogs lose their sight during the first three years of life. Despite screening for eye disease and exclusion of dogs with cataracts from breeding programs, the incidence of HC in Labradors in the Netherlands remained unchanged during 1980-2000, at eight per cent (Kraijer-Huver et al).

Selection for behavioural traits can also add further layers of complexity. For example, studies have shown that gun-shyness has a hereditary component, but if this or other traits such as ‘affability’ or ‘co-operation’ were selected for it may be that other, physical health related traits would be less well controlled. Due to this complexity it is an unrealistic aspiration to breed a purebred gundog that runs no risk of developing inherited disease.

Elbow dysplasia is a common disease in Labrador Retrievers and it has a strong inherited component

Elbow dysplasia is a common disease in Labrador Retrievers and it has a strong inherited component

However a second method of eradication of inherited disease is one that could truly benefit dogs, and is a direct spin-off from the July 2004 genome project.

In man the first method of control, breed selection, is for obvious ethical reasons unrealistic, so a second method, gene therapy, has been examined. There are some stunning cases in man and in experimental mice where this has been effective and although there are huge obstacles, such as cost and other resources, this may be the future treatment for many diseases.

Modern dog breeds do not suffer from the toxic combination of life threatening inherited disease and limited gene pool size seen in some other dog breeds, however greater selectivity within even a well-established breed has a tendency to reduce the gene pool. In certain other breeds it may be that in decades to come litters may be treated for inherited disease by ‘correcting’ the dog’s DNA directly.

Meanwhile dogs of all breeds stand to benefit from the genome project and its spin-off technologies, through collaboration between veterinary and human researchers and the enormous energy that is behind the movement to improve the health of our best-loved breeds.

Harvey Carruthers

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