Beagle Genetic Tests
Factor VII is a clotting factor synthesized in the liver that is necessary to initiate blood coagulation when vascular injury occurs. Factor VII deficiency is a mild to moderate inherited blood clotting disorder present in Beagle, Airedale, Alaskan Klee Kai, Giant Schnauzer and Scottish Deerhound breeds. It is inherited as an autosomal recessive, thus both females and males can be affected if they carry 2 copies of the defective gene but animals with only 1 copy are not affected.
Results reported as:
|N/N||Normal – no copies of the Factor VII deficiency mutation are present|
|N/FVII||Carrier – 1 copy of the Factor VII deficiency mutation is present. If carriers are bred together, 25% of offspring are expected to be affected.|
This test is specific for the mutation known to cause Factor VII deficiency in Beagle, Airedale, Alaskan Klee Kai, Giant Schnauzer and Scottish Deerhound breed dogs.
Reference: Callan MB, Aljamali MN, Margaritis P, Griot-Wenk ME, Pollak ES, Werner P, Giger U and High KA (2006). A novel missense mutation responsible for factor VII deficiency in research Beagle colonies. Journal of Thrombosis and Haemostasis, 4:2616–2622.
Imerslund-Gräsbeck syndrome (IGS) is a disorder found in Beagles and Border Collies where dietary cobalamin (vitamin B12) is unable to be absorbed through the gut. Both breeds have independent mutations in the cubulin (CUBN) gene. The disease has an autosomal recessive mode of inheritance with both sexes being equally affected. Owners of IGS affected dogs often note a lack of appetite, failure to gain weight, lethargy and malaise that intensifies after eating. Clinically, anemia and excess urine protein is observed. Without chronic treatment, permanent brain and nervous system damage can occur. Dogs with one normal and one mutated IGS gene, carriers, are unaffected but breeding two carriers together would be predicted to produce 25% affected offspring and 50% carriers.
The VGL offers a test for inherited IGS in Beagles and Border Collies 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 IGS mutation; dog is normal|
|N/IGS||1 copy of the IGS mutation; dog is a carrier|
|IGS/IGS||2 copies of the IGS mutation; dog is affected|
Fyfe JC, Hemker SL, Venta PJ, Fitzgerald CA, Outerbridge CA, Myers SL, Giger U. (2013) An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs. Mol Genet Metab. 109(4):390-396.
Drögemüller M, Jagannathan V, Howard J, Bruggmann R, Drögemüller C, Ruetten M, Leeb T, Kook PH. (2013) A frameshift mutation in the cubilin gene (CUBN) in Beagles with Imerslund-Gräsbeck syndrome (selective cobalamin malabsorption). Anim Genet. Oct 27, DOI:10.1111/age.12094.
Musladin-Lueke Syndrome (MLS) is a genetic disease of the Beagle that affects the development and structure of connective tissue. It is multi-systemic, with involvement of multiple organs, including bone, heart, skin, and muscle. MLS is inherited as a recessive trait. Current evidence suggests that dogs that have two copies of the mutant gene are affected with MLS, though the severity of clinical signs can be variable. Dogs inheriting only one copy of the mutant gene can show subtle signs but do not appear to have health-related defects. To the best available knowledge, carriers cannot be identified based on their appearance.
The disorder stems from a single mutation that has been inherited through common descent, such that all affected Beagles share the gene from a common ancestor, perhaps dating back to the foundation stock of the breed. This mutation has been identified by Dr. Mark Neff at the Veterinary Genetics Laboratory, School of Veterinary Medicine, UC Davis.
Research is ongoing and there are still aspects of this disease that are continuing to be investigated such as the geographic distribution of the mutation among purebred Beagle bloodlines, and the variable nature of the disease.
A DNA test for the mutation causing MLS in Beagles is now available through the Veterinary Genetics Laboratory. This test determines whether dogs are normal (clear of the mutation), carrier (have one mutant copy), and affected (have two mutant copies).Dogs that carry two copies of the mutation are susceptible to several health-related consequences. The DNA test can provide a definitive diagnosis for these dogs, but there currently is no established therapeutic intervention.
Results reported as:
|N/N||Normal, the dog does not have the MLS gene|
|N/MLS||Carrier, the dog carries one copy of the MLS gene.|
|MLS/MLS||Affected, the dog has two copies of the MLS gene.|
If a carrier dog (with a single mutant copy of the gene) is used in a mating, an offspring from the cross has a 50% chance of inheriting the mutation from this parent. If two carriers are mated, 25% of the offspring in the litter are expected to have MLS and another 50% of the puppies are expected to be carriers. Mating two clear dogs will only produce clear puppies, which need not be tested by DNA.
Genetic Knowledge of Beagle MLS
The DNA test for Musladin-Lueke Syndrome status is meant to equip owners, breeders, and clinicians with useful information that can be applied in several ways to improve the health of their dogs. It allows owners to establish the MLS-status of their pet and veterinarians to positively diagnose the disease in patients that show MLS-like signs. Test results can be used by breeders to assess potential breeding stock and make fully informed decisions in the choice of mating pairs.The genetic knowledge gained from the test holds promise for eliminating the production of affected dogs in the near-term, and for eliminating the gene defect from the gene pool over time. Submitting a sample for DNA testing is simple. Cheek swabs can be non-invasively collected from a dog in just a few minutes. Samples can be submitted by regular mail.
Bader HL, AL Ruhe, LW Wang et al. An ADAMTSL2 Founder Mutation Causes Musladin-Lueke Syndrome, a Heritable Disorder of Beagle Dogs, Featuring Stiff Skin and Joint Contractures. Plos One 2010, 5(9):e12817.
Inherited neurological degenerative diseases are found in several mammalian species including humans, horses and dogs. Cerebellar cortical degeneration, also called cerebellar abiotrophy, is a disease characterized by ataxia (lack of coordination), broad based stance, loss of balance and intentional tremors. In different breeds of dogs, the onset is variable from neonatal to adult. In Beagles the condition is neonatal and onset is noticed at about 3 weeks of age as puppies begin to walk. The severity of the condition is variable among individuals but progression of clinical signs is minimal. Research identified an 8bp deletion in the Beta III Spectrin Gene (SPTBN2) associated with NCCD in Beagles.
NCCD is inherited as a recessive disease, thus both parents must carry the mutation in order to produce an affected puppy. The VGL offers a test for NCCD in Beagles to assist breeders to identify carriers and affected dogs.
Results reported as:
|N/N||Normal, no copies of the NCCD mutation are present.|
|N/CCD||Carrier, 1 copy of the NCCD mutation is present. Breedings between carriers are expected to produce 25% affected, 50% carrier and 25% clear offspring.|
|CCD/CCD||Affected, animal has 2 copies of the NCCD mutation and is expected to have the disease.|
This test is specific for the 8bp deletion in the SPTBN2 associated with NCCD in Beagles.
Forman OP, De Risio L, Stewart J, Mellersh CS, Beltran E (2012) Genome-wide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation. BMC Genetics 13:55.
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.