Genetics & Heritable Diseases
Genetic diseases, common in crossbreed and purebred dogs, are typically associated with evolutionarily ancient disease-liability genes that preceded the separation of breeds and are dispersed in the domestic dog genome. In the past century, the most common diseases in dogs have resulted from infectious, nutritional, and environmental causes. As clinicians have learned to manage the causes of these diseases (eg, through vaccination and proper diet), genetic predisposition has become a more frequent etiology of disease. Frequency of common genetic disorders varies among breeds1 and may be caused by random changes (ie, genetic drift), popular sire syndrome, selection for aesthetic traits linked on chromosomes to disease-liability genes, or anatomic or conformational aspects that can alter disease liability.1
The hallmark of inherited disease is predictability of onset and progression. Recognizing predictable triggers and modifying factors that influence the expression of genetic disorders can help improve diagnosis, treatment, and control.
1 Allergic Skin Disease
According to insurance claims and centralized hospital databases, allergic skin disease manifestations (eg, chronic inflammatory otitis, recurrent hot spots) are the most frequent disease presentations in clinical practice.2-5 These presentations are commonly seen in crossbreed and purebred dogs; some breeds have a higher incidence than others.6-8 A study of atopic dermatitis in golden and Labrador retrievers showed heritability (ie, percent of liability due to genetic influence) at 47%, which indicates a significant environmental contribution.9 A molecular genetic study of atopic dermatitis in German shepherd dogs identified an associated segment of chromosome 28.10
No genetic-liability tests are available. Predictable seasonality can be recognized in 15% to 62% (median, 30%) of allergic dogs with chronic presentations.7 For these patients, interventional measures to manage pruritus should be prescribed before it progresses to clinical disease.
2 Canine Hip Dysplasia
Hip dysplasia, which occurs across all crossbreed and purebred dogs, is the most common inherited musculoskeletal disorder.11 Of all dogs for which radiographs are submitted to the Orthopedic Foundation for Animals, 14.59% are rated as dysplastic. This is likely a low estimate, as clinically apparent cases may not be submitted for evaluation.11 Small dogs with hip dysplasia usually do not show the pain and discomfort seen in larger dogs; this demonstrates a size–weight relationship to clinical presentation.12 Radiographic diagnosis is made through ventrodorsal view or distraction index.12
Palpable hip laxity can predict hip dysplasia and later osteoarthritic changes.13 A gentle Ortolani procedure during puppy examinations and palpation for hip laxity under anesthesia during neutering should be performed. Dogs with severe laxity identified at an early age may benefit from interventional surgery.12
Estimated breeding values and genotypic breeding values based on DNA marker panels are being experimentally developed to assist with selection for hip normalcy.14 Breeders should select for familial breadth and depth of normalcy as seen in vertical pedigrees.15
OTHER COMMON CANINE GENETIC DISEASES1-6
- Patella luxation
- Autoimmune thyroiditis
- Cancer predisposition (lymphoma, hemangiosarcoma, mast cell tumor, osteosarcoma)
- Hereditary cataracts
- Nonstruvite bladderstones
- Elbow dysplasia
- Hepatic shunts
- Renal dysplasia
- Addison disease
3 Brachycephalic Obstructive Airway Syndrome
Brachycephalic obstructive airway syndrome (BOAS) is a disorder of breathing difficulty in short-snouted and “bully” breeds.16 Breeds with the highest prevalence include bulldogs, French bulldogs, and pugs.17 BOAS occurs because of a mismatch in the proportions of the skull and soft tissue in the nose and pharynx. Clinical signs include dyspnea, exercise intolerance, heat intolerance, abnormal and increased respiratory noise, cyanosis, syncope, and death.18 In one study, 16.7% of high-risk dogs died of respiratory failure at an average of 8.6 years of age.19
This syndrome includes stenotic nares, an elongated soft palate, everted laryngeal saccules, laryngeal collapse, and/or a hypoplastic trachea.16 Brachycephalic dogs may be presented with facial skin fold dermatitis and corneal ulceration. For dogs experiencing significant morbidity, corrective surgery can include rhinoplasty for stenotic nares, soft palate resection, and laryngeal saccule removal.16,20 Breeders should select for dogs that do not show signs of BOAS and that have a muzzle at least one-half the depth of the cranial length (from occiput to the front of the cranium), a normal-diameter trachea (ratio of lumen diameter at the thoracic inlet to the width of the proximal third rib should be ≥2 on a lateral radiograph), and nostrils that are 33% the width of the nose.18,20
4 Myxomatous Mitral Valve Disease
Myxomatous mitral valve disease (ie, mitral valve endocardiosis) is primarily seen in toy breeds and small patients.21,22 For some breeds (eg, Norfolk terrier, Cavalier King Charles spaniel), it may lead to heart disease at an average age of 6.25 years.23 As this is beyond breeding age, some Cavalier King Charles spaniel clubs have established a generational breeding-control program in which dogs are only bred if both parents are free of a murmur and Doppler evidence of mitral regurgitation. When this program is applied, the frequency of this disorder has decreased.24
5 Cranial Cruciate Ligament Rupture
Cranial cruciate ligament rupture is a common traumatic injury. Although it is not typically considered a hereditary disease, studies show increased risk in rottweilers, West Highland white terriers, golden retrievers, Yorkshire terriers, Staffordshire bull terriers, and some crossbreed dogs.1,25 Studies of cranial cruciate ligament rupture in Newfoundlands show 27% heritability.26,27 Genetic predisposing factors for rupture may include issues with ligament extracellular matrix metabolism, degeneration, and/or inflammation. Other predisposing factors may also involve biomechanical and conformational variations (eg, bone length, stifle angulation, tibial plateau variation, narrowed distal femoral intercondylar notch).28
The WSAVA Canine and Feline Hereditary Disease (DNA) Testing website is an excellent source for DNA tests, lists of susceptible breeds, and testing laboratories.29
Dogs affected by genetic disorders should not be selected for breeding. Because most of these genetic diseases are complexly inherited, genetic risk for carrying disease-liability genes should be based on knowledge of clinical disease or normalcy in first-degree relatives of prospective breeding dogs.
Identified Mendelian Liability Genes: Common Disorders30
- Arrythmogenic right ventricular cardiomyopathy (boxers, boxer crossbreeds)
- MDR1-related ivermectin and drug sensitivity
- Lens luxation
- Degenerative myelopathy
- von Willebrand disease
- Progressive rod-cone degeneration form of progressive retinal atrophy
BOAS = brachycephalic obstructive airway syndrome
Oberbauer AM, Belanger JM, Bellumori T, Bannasch DL, Famula TR. Ten inherited disorders in purebred dogs by functional breed groupings. Canine Genet Epidemiol. 2015;2:9.
Egenvall A, Bonnett BN, Olson P, Hedhammer A. Gender, age and breed pattern of diagnoses for veterinary care in insured dogs in Sweden during 1996. Vet Rec. 2000;146(19):551-557.
Top 10 reasons pets visit vets. Nationwide website. http://www.petinsurance.com/healthzone/pet-articles/pet-health/Top-10-Reasons-Pets-Visit-Vets.aspx. Accessed July 1, 2016.
O’Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC. Prevalence of disorders recorded in dogs attending primary-care veterinary practices in England. PLoS One. 2014;9(3):e90501.
State of Pet Health 2016 Report. Banfield Pet Hospital website. https://www.banfield.com/Banfield/media/PDF/Downloads/soph/Banfield-State-of-Pet-Health-Report-2016.pdf. Accessed July 1, 2016.
Bellumori TP, Famula TR, Bannasch DL, Belanger JM, Oberbauer AM. Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010). J Am Vet Med Assoc. 2013;242(11):1549-1555.
Mazrier H, Vogelnest LJ, Thomson PC, Taylor RM, Williamson P. Canine atopic dermatitis: breed risk in Australia and evidence for a susceptible clade. Vet Dermatol. 2016;27(3):167-e42.
Bizikova P, Santoro D, Marsella R, Nuttall T, Eisenschenk MN, Pucheu-Haston CM. Review: clinical and histological manifestations of canine atopic dermatitis. Vet Dermatol. 2015;26(2):79-e24.
Shaw SC, Wood JL, Freeman J, Littlewood JD, Hannant D. Estimation of heritability of atopic dermatitis in Labrador and golden retrievers. Am J Vet Res. 2004;65(7):1014-1020.
Tengvall K, Kierczak M, Bergvall K, et al. Genome-wide analysis in German shepherd dogs reveals association of a locus on CFA 27 with atopic dermatitis. PLoS Genet. 2013;9(5):e1003475.
Orthopedic Foundation for Animals. OFA website. http://www.ofa.org. Accessed July 1, 2016.
Verhoeven G, Fortrie R, Van Ryssen B, Coopman F. Worldwide screening for canine hip dysplasia: where are we now? Vet Surg. 2012;41(1):10-19.
Gatineau M, Dupuis J, Beauregard G, et al. Palpation and dorsal acetabular rim radiographic projection for early detection of canine hip dysplasia: a prospective study. Vet Surg. 2012;41(1):42-53.
Sánchez-Molano E, Pong-Wong R, Clements DN, Blott SC, Wiener P, Woolliams JA. Genomic prediction of traits related to canine hip dysplasia. Front Genet. 2015;6:97.
Keller GG, Dziuk E, Bell JS. How the Orthopedic Foundation for Animals (OFA) is tackling inherited disorders in the USA: using hip and elbow dysplasia as examples. Vet J. 2011;189(2): 197-202.
Dupré G, Heidenreich D. Brachycephalic syndrome. Vet Clin North Am Small Anim Pract. 2016;46(4):691-707.
Smith S. Most popular dog breeds in America. American Kennel Club website. http://www.akc.org/news/the-most-popular-dog-breeds-in-america. Published February 22, 2016. Accessed July 1, 2016.
Packer RMA, Hendricks A, Tivers MS, Burn CC. Impact of facial conformation on canine health: brachycephalic obstructive airway syndrome. PLoS One. 2015;10(10): e0137496.
O’Neill DG, Jackson C, Guy JH, et al. Epidemiological associations between brachycephaly and upper respiratory tract disorders in dogs attending veterinary practices in England. Canine Genet Epidemiol. 2015;2:10.
Meola SD. Brachycephalic airway syndrome. Top Companion Anim Med. 2013;28(3):91-96.
Mattin MJ, Boswood A, Church DB, et al. Prevalence of and risk factors for degenerative mitral valve disease in dogs attending primary-care veterinary practices in England. J Vet Intern Med. 2015;29(3):847-854.
Parker HG, Kilroy-Glynn P. Myxomatous mitral valve disease in dogs: does size matter? J Vet Cardiol. 2012;14(1):19-29.
Lewis T, Swift S, Woolliams JA, Blott S. Heritability of premature mitral valve disease in Cavalier King Charles spaniels. Vet J. 2011;188(1):73-76.
Birkegård AC, Reimann MJ, Martinussen T, Häggström J, Pedersen HD, Olsen LH. Breeding restrictions decrease the prevalence of myxomatous mitral valve disease in Cavalier King Charles spaniels over an 8- to 10-year period. J Vet Intern Med. 2016;30(1):63-68.
Taylor-Brown FE, Meeson RL, Brodbelt DC, et al. Epidemiology of cranial cruciate ligament disease diagnosis in dogs attending primary-care veterinary practices in England. Vet Surg. 2015;44(6):777-783.
Wilke VL, Conzemius MG, Kinghorn BP, Macrossan PE, Cai W, Rothschild MF. Inheritance of rupture of the cranial cruciate ligament in Newfoundlands. J Am Vet Med Assoc. 2006;228(1): 61-64.
Baird AE, Carter SD, Innes JF, Ollier W, Short A. Genome-wide association study identifies genomic regions of association for cruciate ligament rupture in Newfoundland dogs. Anim Genet. 2014;45(4):542-549.
Comerford EJ, Smith K, Hayashi K. Update on the aetiopathogenesis of canine cranial cruciate ligament disease. Vet Comp Orthop Traumatol. 2011;24(2):91-98.
Slutsky J, Raj K, Yuhnke S, et al. A web resource on DNA tests for canine and feline hereditary diseases. Vet J. 2013;197(2): 182-187.
Mellersh C. DNA testing and domestic dogs. Mamm Genome. 2012;23(1-2):109-123.
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