Brenda N. Bonnett, DVM, PhD
This paper is the first in a series on Health Breeding, including the veterinarian's role. Here we look at what is included under the heading of 'inherited disease' and identify opportunities and challenges as veterinarians address these issues.
What Disorders Do Veterinarians See in Practice?
From the UK, VetCompass data say ears, teeth, anal sacs, nails, arthritis, diarrhea, obesity and injuries top the list.1 These include the most common and routine conditions that may affect any dog. From Swedish insurance data (2006–2013) (Personal communication, Bonnett BN), where routine procedures like nail trims and teeth cleaning are not covered, the most common conditions were vomiting/diarrhea/gastroenteritis; skin tumours; skin trauma; otitis; pain/locomotor problems; inflammatory skin problems; pyometra; mammary tumours; anal/perianal problems; nail trauma; and itching. Which of these conditions might be considered inherited? Well, there may be a genetic predisposition for 'everything.' Are Jack Russells predisposed to have vehicular accidents because of their inherent temperament? Perhaps, but for the sake of discussion, let's address this in terms of how inherited disease might present to a veterinarian with reference to testing.
Who Comes to Veterinarians Asking for or Needing 'DNA Tests'?
1. Individual owners with a pet dog. What does inherited disease mean to them?
a. Symptomatic dog: diagnosis and prognosis; e.g.:
i. Potential response to treatment (e.g., genomics to optimize cancer chemotherapy)2
ii. Genetic typing on tissues (e.g., tumours)
iii. Why did this happen? What or who is to blame?
b. Asymptomatic dogs: identifying increased risk; early detection (e.g., bladder cancer; however, this needs to be accompanied by an effective intervention)
c. Interpreting the results of ancestry tests submitted by the owner. Just for fun? Or can these be used to inform care?
d. Identification and parentage testing for forensic, or legal reasons.
2. Breeders — a casual breeder vs. a registered breeder vs. commercial breeders.
a. Decisions about the individual dog, mate selection, etc.
b. Complying with regulations/recommendations
i. Impact on the breed/population; concerns about genetic diversity3
So, there is a wide range of interactions in practice that might involve inheritance and genetic testing. One hears a lot in the media about inherited disease in pets, especially dogs. However, decision-making based on the media or discussions on Facebook is not necessarily the best for health and welfare of dogs. A television documentary, Pedigree Dogs Exposed, for example, highlighted syringomyelia in Cavalier King Charles Spaniels as a terrible disease affecting young dogs. The reaction led to worldwide calls for health programs for this disease. Notwithstanding the importance of this disease, it is not the most common nor highest risk cause of death in this breed (Figure 1); we should promote a balanced approach to breed-specific health issues that considers all health problems in a breed.
|Figure 1. Most common causes of mortality: rates from Swedish insurance data 2006–2011|
The Prevalence of Inherited Disease in Dogs: Information and Misinformation
We know that veterinarians and clients have access to massive amounts of 'information' on the internet. There is an abundance of sophisticated marketing; exaggerations and inaccuracies lurk amid useful information; differentiation may be challenging. However, defining the most important health issues requires that we understand both prevalence and risk of various conditions.
Various websites on dog health and breeding make claims that dogs have the highest number of genetic disorders among domesticated animals, with numbers ranging from 225 to as high as 619. The message being sent is that there is a large and increasing number of genetic diseases in dogs. To keep things in perspective, the OMIM catalog of disease phenotypes (humans) lists approximately 8500 identified mutations and the WHO estimates that over 10,000 human diseases are known to be monogenic. Remembering that humans and dogs share 84 percent of their DNA, why should we be so shocked at the number of conditions in dogs?
The relationship between human and dog genetics, however, has an even bigger impact on our understanding of inherited disease in dogs. Here are quotes from refereed publications:
- A majority of canine genetic diseases have their counterparts in humans and thus dogs are considered as a very important ... animal model in human biomedicine.4
- Millions of children worldwide are born with rare and debilitating ... disorders each year. ... Dogs are coming to the rescue ... Hundreds of spontaneous genetic conditions have been described in dogs, most with close counterparts to human rare disorders. ... examples include the canine models of human Caffey (SLC37A2), van den Ende-Gupta (SCARF2) and Raine (FAM20C) syndromes.5
The cautions we should take away include: many of the diseases studied in dogs and the resultant DNA tests, came/come about because of research focused on (and funded because of) corresponding diseases in humans. Many of these are rare in humans and extremely rare in dogs. There is a heavy emphasis on monogenic conditions. The number of inherited conditions so far discovered in any species or breed is primarily influenced by research funding and focus. Just because a disease has been studied and a test has been developed does not mean it is an important disease for the breed or the dog population in general. There will always be an increasing number of inherited diseases discovered. We must learn to balance evidence on importance, application, validity, etc., to appropriately take advantage of the tremendous potential for advanced technologies to inform our practice.
Purebreds vs. Mixed-Breed Dogs
It is important to realize that many inherited conditions occur across all dogs; some breeds have an increased risk of specific conditions. A study from 2013 compared mixed and purebred dogs.6 Results indicated that:
Of the 24 disorders assessed, 13 had no significant difference in the mean proportion of purebred and mixed-breed dogs with the disorder when matched for age, sex, and body weight. Potentially inherited disorders without a significant predisposition included, e.g., all the neoplasms, several cardiac conditions; hip dysplasia and patellar luxation; hypo- and hyperadrenocorticism; and lens luxation. Ten disorders were more prevalent in purebred dogs (e.g., aortic stenosis and dilated cardiomyopathy, hypothyroidism, elbow dysplasia and IVDD, and atopy or allergic dermatitis, bloat, cataracts, epilepsy, and portosystemic shunt). Some of the odds ratios were not large, indicating that even if there is an increased risk for purebreds, the conditions also occur in mixed-breed dogs. This study and others show that the situation is complex; we cannot blame all inherited disease on selective breeding; and inherited disease is common in all dogs.
There are several other questions that need to be considered:
- Is it just about purebreds vs. non-purebred dogs? What about source? In many countries less than 20% of apparent purebred dogs come from breeders associated with a national kennel or breed club; the majority come from other sources, including commercial breeders. This has major implications on the options to institute programs aimed at health breeding.
- What are the human-animal interactions in breed popularity and inherited disorders, especially those related to appearance and personality?
- Have the profession and individual veterinarians been complicit in problems of inherited disease in purebred dogs? Each veterinary practitioner should consider what they can do - from being aware of the messages they send on their clinic Facebook page to whether they implicitly or explicitly accept as 'normal' abnormalities in certain breeds, and whether they comply with efforts to improve data sharing.
It is clear that no veterinarian in practice can keep up with all developments in genetics, genomics and epigenetics; burgeoning numbers of tests and labs; or regulations and recommendations. Veterinarians must avail themselves of all strategies at their disposal, including partnership building with clients, recognizing when the situation is beyond their experience or expertise, and knowing where to go to find help (experts or information). All stakeholders in dog health must work to develop and share information and tools to help practitioners [e.g., WSAVA Hereditary Disease Committee and database (wsava.org) and the International Partnership for Dogs and their Harmonization of Genetic Testing for Dogs initiative (DogWellNet.com)]. There are exciting multi-stakeholder, international efforts underway and together we can make a difference in the health and welfare of our cherished pet populations.
1. O'Neill DG, Church DB, et al. Prevalence of disorders recorded in dogs attending primary-care veterinary practices in England. PLoS One. 2014;9(3):e90501.
2. Davis BW, Ostrander EA. Domestic dogs and cancer research: a breed-based genomics approach. ILAR J. 2014;55(1):59–68.
3. Farrell LL, Schoenebeck JJ, et al. The challenges of pedigree dog health: approaches to combating inherited disease. Canine Genet Epidemiol. 2015;2:3
4. Switonski M. Dog as a model in studies on human hereditary diseases and their gene therapy. Reprod Biol. 2014;14(1):44–50.
5. Hytönen MK, Lohi H. Canine models of human rare disorders. Rare Dis. 2016;4(1):e1241362.
6. Bellumori TP, Famula TR, et al. Prevalence of inherited disorders among mixed breed and purebred dogs: 27,254 cases (1995–2010). J Am Vet Med Assoc. 2013;242(11):1549–55.