Pug Dog Genetic Tests
Approximately 1.2% of Pug dogs die of necrotizing meningoencephalitis (NME), also known as Pug dog encephalitis (PDE). NME is an inflammatory disease of the central nervous system that is usually progressive and fatal. Symptoms of NME include seizures, depression, ataxia, abnormal gait and blindness (1). Female, fawn-colored Pug Dogs younger than 7 years of age are more apt to develop NME than older, male and non-fawn colored individuals (2). Recent research has revealed that susceptibility to NME is associated with the dog leukocyte antigen (DLA) region of dog chromosome 12 (3). The association is at or near the region containing the DLA class II genes. Dogs that have two identical copies of the NME associated markers in this region, have an observed risk (OR) of 12.75 for NME in their lifetime over Pugs that have only one or no copies of these markers (OR 0-1.08).
Results reported as:
|N/N||No copies of the NME associated markers (homozygous for normal). These dogs have a low risk of developing NME.|
|N/S||1 copy of the NME associated markers (heterozygous for susceptibility). These dogs have a low risk of developing NME.|
|S/S||2 copies of the NME susceptibility associated markers. These dogs are 12.75 times more likely to develop NME in their lifetime.|
Outcomes of matings based on NME test results:
1. N/N x N/N = all puppies will have two copies of the low NME risk markers (N/N) and will have a significantly reduced risk of developing NME during their lifetime.
2. N/N x N/S = One half of the puppies will have two copies of the low NME risk markers (N/N), and have a significantly reduced risk of developing NME during their lifetimes. One half of the puppies will carry one copy of the susceptibility markers (N/S), but will also be at low risk for developing NME.
3. N/S x N/S = One fourth of puppies will be N/N and at low risk for NME; one half will be N/S, carry the susceptibility marker, but will also be at low risk for NME; one fourth will be S/S and will be at high risk for NME.
4. N/S x S/S = One half of the puppies will carry the susceptibility marker (N/S), but will not be at increased risk of NME; one half of the puppies will have two copies (S/S) of the susceptibility marker and be at high risk of NME.
5. N/N x S/S = All of the puppies will carry one copy of the susceptibility markers (N/S), and be at low risk for developing NME.
6. S/S x S/S = All of the puppies will carry two copies of the susceptibility marker (S/S) and be at high risk for NME.
Notes: This is not a diagnostic test for NME in Pug Dogs or for NME disease or risk in other breeds. The test is only to determine risk for developing NME in Pug Dogs and for selecting matings that will produce puppies that are at decreased risk (N/N, N/S). Although a significant proportion (11%) of Pug Dogs is S/S, only about 1 in 8 of this group will develop NME during their lifetime.
Also, breeders are advised against breeding out the S genotype, because 40% of Pug Dogs have the S genotype in a heterozygous (N/S = 29%) or homozygous state (S/S = 11%). Eliminating the S genotype will lead to a considerable loss of genetic diversity. Therefore, breeders should carefully select matings that do not produce S/S puppies.
The NME report includes DNA types for a panel of 8 markers selected from the International Society of Animal Genetics (ISAG) canine parentage panel. These markers provide individual identification for each sample tested.
1. Talarico LR, Schatzberg SJ. Idiopathic granulomatous and necrotising inflammatory disorders of the canine central nervous system: a review and future perspectives. J Small Anim Pract 2010: 51: 138–149.
2. Levine JM, Fosgate GT, Porter B et al. Epidemiology of necrotizing meningoencephalitis in Pug dogs. J Vet Intern Med 2008: 22: 961–968.
3. Greer KA, AK Wong, H Liu, TR Famula, NC Pedersen, A Ruhe, M Wallace and MW Neff. Necrotizing meningoencephalitis of Pug Dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis. Tissue Antigens 2010: 76:110-118.
Pyruvate kinase deficiency (PKDef) is an inherited hemolytic anemia caused by a defect in the enzyme pyruvate kinase. Loss of function of this enzyme results in premature death of red blood cells. Affected dogs do not have sufficient quantities of red blood cells to adequately supply the body with oxygen. Observable signs in affected dogs may include lack of energy, low exercise tolerance and fatigue in dogs that appear otherwise fit. Clinically, dogs with PKDef present with a severe anemia, increased iron levels, increased bone density, may have an enlarged spleen and liver as well as fibrous connective tissue replacement of bone marrow cells. Bone marrow and liver failure typically occur by 5 years of age. The disease is inherited as an autosomal recessive disorder thus both sexes are equally affected and two copies of the defective gene must be present for dogs to be affected. Carrier dogs, those with one defective and one normal copy, show no signs but have half the normal level of pyruvate kinase activity. Breeding two carriers is expected to produce 25% affected offspring and 50% carriers of the disease.
Different breed-specific mutations in the Pyruvate Kinase gene have been identified. The VGL offers tests for the PKDef mutations found in Basenji, Beagle and Pug breeds to assist owners and breeders in identifying affected and carrier dogs. The test uses DNA collected from buccal (cheek) swabs, thus avoiding blood sample collection. Breeders can use results from the test as a tool for selection of mating pairs to avoid producing affected dogs.
Results reported as:
|N/N||No copies of the PKDef mutation; dog is normal.|
|N/K||1 copy of the PKDef mutation; dog is a carrier and unaffected but has half the normal Pyruvate Kinase activity of N/N dogs.|
|K/K||2 copies of the PKDef mutation; dog is affected.|
Gultekin GI, K Raj, P Foureman, S Lehman, K Manhart, O Abdulmalik, U Giger (2012) Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs. Journal of Veterinary Internal Medicine 26(4):935-944.
Chapman BL, U Giger (1990) Inherited erythrocyte pyruvate kinase deficiency in the West Highland White Terrier. Journal of Small Animal Practice 31:610-616.
Schaer M, JW Harvey, M Calderwoodmays, U Giger (1992) Pyruvate kinase deficiency causing hemolytic anemia with secondary hemochromatosis in a Cairn Terrier. Journal of the American Animal Hospital Association 28:233-239.