INHERITED JOINT DISEASE
READING TIME: 4 MINUTES
Dog breeding has been under human control for over 100,000 years. Breeds as diverse as Great Danes and Chihuahuas have a common ancestor, the grey wolf. Humans domesticated wolves by selecting useful traits like tameness and ability to bark. Selection for specialised attributes was a more recent endeavour. Although there are exceptions, most dog breeds have heritages of under 500 years.
We can trace many modern dog breeds to a small number of founders. For example, the modern Irish Wolfhound originated from only six ancestors. In larger populations, genetic diversity was reduced by the use of popular sires. These dogs had physical features which made them particularly successful show dogs. As a result, some produced >100 litters in a lifetime. This means today's purebred dogs represent a limited genetic pool. Unfortunately, artificial selection for desirable traits came at a cost. The trade-off was the accumulation of deleterious genetic mutations.
In 2018, a team of researchers screened over 100,000 dogs for 152 genetic diseases. They found one or two copies of potentially harmful genes in ~4/10 dogs. Knowing the likelihood your dog carries an inherited disorder helps limit risk. Reducing individual risk involves optimising lifestyle to curb expression of harmful genes. Protecting individuals isn't our only responsibility. We must also safeguard future generations. This means identifying carriers and excluding them from the breeding pool.
HOW EASY IS RISK ANALYSIS?
BULLDOGS ILLUSTRATE HIGH GENETIC RISK - DATA SOURCED FROM THE ORTHOPEDIC FOUNDATION FOR ANIMALS
Many social and cultural factors shape our approach to risk. It’s tempting to embrace ideas which suit our personal preferences and reject ideas which don’t. For example, smokers can rationalise that cigarettes suppress appetite. This keeps them lean, which in turn improves health. Comforting narratives make it easier to reject uncomfortable facts.
A veterinary example is the lovable but high-risk Bulldog. Does knowing that Bulldogs have many genetic problems make them less popular? Probably not. Bulldogs are the 5th most popular breed in the USA. In contrast, Whippets don’t make the top 50 even though they’re a very low-risk breed. Whippets teach us that health risk is surprisingly low on a typical priority list. This shouldn’t surprise animal lovers. It’s human nature to reject uncomfortable truths and embrace popular fallacies. Whilst a smoker might believe cigarettes have hidden health benefits, a Bulldog lover might believe supplements can protect them from genetic joint disease.
WHO SUPPLIES TRUSTWORTHY DATA?
Advanced genetic screening systems allow us to access health-related big data. Online Mendelian Inheritance in Animals (OMIA) is the most comprehensive registry. The trade-off for OMIA's detail is its complexity. It isn't a quick reference guide for laypeople.
The Orthopedic Foundation for Animals (OFA) is easier to navigate. They publish breed-specific data on 26 genetic conditions. Dog carers still face the challenge of learning how to interpret the data. It isn't as simple as understanding the probability of a condition. You also need to understand each condition's clinical impact and the available treatments. We've created a resource to help make this easier for you. Our breed statistics pages collate data from official registries and hospital databases. Each page contains simple guides explaining clinical risk and treatment options.
ARE JOINT DYSPLASIAS CONGENITAL?
Dysplasia means abnormal development. Congenital means a physical abnormality is present at birth. As such, joint dysplasias are not congenital. Affected puppies have normal joint conformation at birth. Dysplasias develop during the growth spurt. On average, this occurs between 2 and 8 months of age. Sadly, arthritis doesn't spare young dogs. Every puppy who expresses genes for a joint dysplasia will develop arthritis.
ARE MIXED BREED DOGS LOW RISK?
In the USA, around half of households report having a mixed breed dog. A prevailing view is that mixed breeds have a lower risk of inherited disorders. This theory is supported by robust scientific evidence. For instance, researchers tested the impact of crossing dysplastic dogs with normal dogs. Most studies assessed normal greyhounds crossed with Labradors suffering from hip dysplasia. First-generation Greyadors' risk of hip dysplasia is about halfway between their parent breeds. In effect, the normal genes from one parent dilute the harmful genes from the other parent. A dilution effect is unlikely for hybrids whose parents have similar risk profiles. For example, Labradors and Poodles both have a moderate risk of hip dysplasia. Thus, we shouldn't expect Labradoodles to have a big advantage over their parent breeds. It's worth noting that any hybrid advantage is offset by a higher risk of carrier status. Mixed breed dogs are 1.6 times more likely to be carriers of at least one recessive disease. In one study, mixed breed dogs had a greater probability of cranial cruciate ligament injury.
OTHER GOOD QUESTIONS
READING TIME: 3 MINUTES
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Canine inherited joint diseases are not caused by single gene mutations. Dysplasias are genetically complex. A classic example is a German Shepherd dog with hip dysplasia. According to breed standards, the hindquarters of German Shepherd dogs should be low and sloping. Centuries spent moulding an abnormal pelvic conformation had a negative impact on hip morphology. In effect, the genes responsible for an unnatural body shape overlap the genes which code for hip dysplasia.
German Shepherd dogs aren’t an isolated example. Body composition adapts to intended function in many breeds. For instance, Pitbulls were originally bred for fighting. As such, their bones must be very strong. Pitbull bones can absorb twice the force of Greyhound bones. The trade off is limited durability. Pitbull bones are half as stiff as Greyhound bones. Fortunately, less durable bones are unlikely to cause pain. Even so, the ability of selective breeding to alter bone mechanics provides a vivid illustration. Tampering with evolution has consequences. We have the power to reverse this damage, but only if society agrees to make changes to much loved breeds.
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The relationship between gender and developmental joint disorders is complex. More studies show a higher risk for males, but this relationship is not consistent. Many variables related to gender could affect risk. These include growth rate and body mass index. Dysplasias are commonest in fast growing and overweight puppies.
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Greyhound-Labrador hybrid studies taught us that reduced risk is possible within 2-3 generations. For example, three-quarter Greyhound hybrids rarely develop hip dysplasia. Implementing improvements by creating Greyhound hybrids is easy. Reducing risk whilst maintaining breed standards presents a much greater challenge.
Success or failure of screening schemes means different things to different people. Veterinary associations and kennel clubs judge success over several generations. For example, the Swedish Kennel Club established their open registry in the 1950's. In Sweden, 70% of all dogs are registered with the Swedish Kennel Club. Almost all breeding stock and 30–50% of all dogs are screened for hip dysplasia. How long did it take to reduce the prevalence of moderate and severe hip dysplasia below 10%? For most breeds, it took 40-60 years. This isn't fast enough for a pet owner who needs an instant return. You can't afford to wait a lifetime for genetic improvement.
Sourcing a low-risk purebred puppy requires time and expertise. Owners must identify litters with full pedigrees and proof of radiographic screening. Unfortunately, there's a fundamental problem with this process. If a prospective owner does their homework, it's human nature to expect a guarantee. This isn't possible. At best, radiographs provide an estimate of a dog's genetic risk. If radiographs are a blunt tool, is there a better alternative? Estimated breeding value (EBV) is a more reliable metric for estimating genetic risk. Instead of including only a sire and dam, EBV includes data from many relatives. The Swedish Kennel Club publishes weekly updates on EBV's for 44 breeds. Cornell University is another good source of practical information about EBV.
The first rule of screening is that normal radiographs don't guarantee good genes. The second rule of screening is that abnormal radiographs don't guarantee a bad life. If they did, we would need to outlaw many popular breeds. For example, over 50% of Neapolitan Mastiffs, Dogues de Bordeaux, Bulldogs, and Pugs have abnormal hip radiographs. If abnormal hip radiographs guaranteed chronic pain, only 1 in 3 Pugs would be pain-free. Rejecting this assumption means accepting most dogs with mild hip dysplasia aren't painful. If Pugs and Bulldogs have a low proportion of "normal" animals, how should breed clubs reduce risk? The best strategy is selecting dogs with EBV scores which are better than the breed average. This strategy requires owners to accept an important premise. They are acquiring puppies who are not normal. The best they can do is source puppies who are better than average.
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Society isn't good at accepting complex problems rarely have simple solutions. When radiographic control programmes fell short of public expectations, our attention turned to genetic blood tests. Human genetic screening has become mainstream thanks to companies like 23andMe. Veterinary medicine has taken its first steps in this direction. A molecular test called Dysgen is already available. Unfortunately, Dysgen doesn't predict risk of hip dysplasia as we’d hoped it would. The main challenge for tests like Dysgen is the enormous number of candidate genes. This quote from a canine genome study illustrates the challenge posed by genetic complexity:
To implement genomic prediction, two different statistical methods were employed: Genomic Best Linear Unbiased Prediction (GBLUP) and a Bayesian method called BayesC. The cross-validation results showed that the two methods gave similar prediction accuracy (r 0.3–0.4) for CHD (measured as Norberg angle) and RCCL in the multi-breed population. For CHD, the average correlation of the AUC was 0.71 (BayesC) and 0.70 (GBLUP), which is a medium level of prediction accuracy and consistent with Pearson correlation results.