UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory

Boxer Health Panel

Tests Offered:
DM | HEMA

Degenerative Myelopathy (DM)

Introduction

Degenerative myelopathy (DM) is an inherited neurologic disorder of dogs similar to Lou Gehrig’s disease in humans and results from a mutation (c.118G>A) in the SOD1 gene. Affected dogs usually present clinical signs of disease in adulthood (at least 8 years of age) with gradual muscle wasting and loss of coordination that typically begins in the hind limbs because of nerve degeneration. Disease progression continues until the dog is unable to walk. Small breed dogs tend to progress more slowly. In late stages of the disease, dogs may become incontinent and the forelimbs may be affected. Affected dogs may fully lose the ability to walk 6 months to 2 years after the onset of signs. The disease is inherited in an autosomal recessive fashion with incomplete penetrance. Thus, two copies of the SOD1 mutation (DM/DM) confer increased risk for DM but not all DM/DM dogs across breeds will develop the disease. The variable presentation between breeds suggests that other genetic and environmental factors play a role in disease expression. There is ongoing research to identify other genetic factors that modify risk for DM in different breeds. In addition, similar disease presentation is observed in some animals lacking the SOD1 mutation. Breeding two carriers of the SOD1 mutation together is predicted to produce 25% pups that may develop DM.

The VGL offers a genetic test for the SOD1 c.118G>A mutation. Genetic screening helps breeders establish the genetic status of breeding stock and select mating pairs appropriately to reduce the risk of producing DM-affected offspring.

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Testing recommended for: many breeds

The Degenerative Myelopathy (DM) test is a patented test. The Veterinary Genetics Laboratory is authorized to offer the DM test to residents of the United States, Canada and Australia.

Results reported as:

N/N No copies of the DM mutation
N/DM 1 copy of the DM mutation
DM/DM 2 copies of the DM mutation; dog may develop DM disease

References:

Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O'Brien DP, Lindblad-Toh K, Coates JR. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2009 Feb 24; 106(8):2794-9. [PubMed: 19188595]

Coates JR, March PA, Oglesbee M, Ruaux CG, Olby NJ, Berghaus RD, O'Brien DP, Keating JH, Johnson GS, Williams DA. Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs. J Vet Intern Med. 2007 Nov-Dec; 21(6):1323-31. [PubMed: 18196743]

Shelton GD, Johnson GC, O’Brien DP, Katz ML, Pesayco JP, Chang BJ, Mizisin AP, Coates JR. Degenerative myelopathy associated with a missense mutation in the superoxide dismutase 1 (SOD1) gene progresses to peripheral neuropathy in Pembroke Welsh Corgis and Boxers. J Neurol Sci. 2012 Jul 15;318(1-2):55-64. [PubMed: 22542607]

Zeng R, Coates JR, Johnson GC, Hansen L, Awano T, Kolicheski A, Ivansson E, Perloski M, Lindblad-Toh K, O'Brien DP, Guo J, Katz ML, Johnson GS. Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. J Vet Intern Med. 2014, 28(2):515-521.

Hemophilia A/Factor VIII Deficiency (HEMA)

Introduction

Hemophilia A is an inherited bleeding disorder caused by a deficiency of coagulation factor VIII (F8), an essential protein required for normal blood clotting. Affected dogs have variable presentation of the disease, with mild to moderate bleeding being observed. Additionally, affected dogs may bruise easily or have extended periods of bleeding following trauma. Frequent nosebleeds and stiffness may also indicate F8 deficiency resulting from excessive internal bleeding after damage to muscles and joints. While bleeding is occasionally severe enough to result in death, most affected dogs have a normal lifespan. Variable presentation coupled with a lack of observable incidents with bleeding often results in this condition going undetected until a dog has a surgical procedure or severe trauma.

Two independent mutations in the Factor VIII gene result in German Shepherd Dog F8 deficiency: c.98G>A (reported as HEMA-1) and c.1643G>A (reported as HEMA-2). In Boxers, F8 deficiency results from a c.1412C>G mutation in exon 10 (reported as HEMAbx). The disease is inherited in an X-linked recessive fashion. Females with two defective copies will show disease. Clinical signs are absent in females with one normal and one affected gene (carriers). Males have only one X chromosome. If the inherited allele is affected, males will show disease. If the inherited allele is normal, males do not have the disease.

The Veterinary Genetics Laboratory offers genetic tests for Hemophilia A. Test results assist veterinarians with diagnosis of F8 deficiency and help breeders identify carriers among breeding females and affected breeding males to avoid mating pairs that can produce affected dogs. When a carrier female is bred to a normal male, all female puppies will be normal but 50% of them will be carriers.  Among male puppies from this type of cross, 50% will be normal and 50% will be affected.

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Testing recommended for: German Shepherd Dog, Shiloh Shepherd, White Shepherd Dog, Boxer, (This test does not detect the causative mutations for F8 deficiency in Old English Sheepdog, Irish Setter or Miniature Schnauzer)

Results reported as:

N/N

Normal female - no copies of F8 mutations.

N/HEMA*

Carrier female - 1 copy of the HEMA* mutation

HEMA/HEMA*

Affected female - 2 copies of the HEMA* mutation

N

Normal male - no copies of the F8 mutations

HEMA*

Affected male - 1 copy of the HEMA* mutation

* Report will specify HEMA-1, HEMA-2 or HEMAbx according to breed and mutation present.

References:

Christopherson PW, Bacek LM, King KB, Boudreaux MK. (2014) Two novel missense mutations associated with hemophilia A in a family of Boxers, and a German Shepherd dog. Vet Clin Pathol 43:312-316.

Mischke R, Wilhelm Ch, Czwalinna A, Varvenne M, Narten K, von Depka M. (2011) Canine haemophilia A caused by a mutation leading to a stop codon. Vet Rec 169:496b.

 
Veterinary Genetics Laboratory Tel 530-752-2211 Email VGL