Testing of dogs: DM in Bernese Mountain Dog

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Usual turnaround time: 7 business days
1 test price: 74.00 $ without VAT

Degenerative Myelopathy (DM) in Bernese mountain dog

Degenerative myelopathy (DM) is a progressive neurodegenerative disease which occurs in wide range of dogs approximately at eight years of age. Presently, there are known 124 canine breeds which can suffer from the degenerative myelopathy (Zeng et al. 2014). The widespread distribution of the mutation among the breeds suggests that it originated before diversification of the breeds. The symptoms accompanying this disease are so severe that the dog dies within 3 to 5 years after occurrence of the first signs. From progressive loss of movement and gradual worsening of the condition up to complete paralysis. In many cases, the dog is euthanized approximately one year after symptoms first appear.

The degenerative myelopathy is mostly caused by a mutation in superoxid dismutase 1 gene (SOD1A).  This mutation replaces nucletiode G with nucletiode A  (c.118G>A) within the coding region of the SOD1 gene. The superoxide dismutase I is a generally problematic gene in which 160 various mutations have already been identified (Crisp et al., 2013). Contrary to other dog breeds, the Bernese mountain dogs that are dominantly homozygous for this gene and should be theoretically healthy may die of this disease. It has been discovered that in this breed the disease can be caused by other mutation in SODI gene (SODI B). This mutation replaces the nucleotide A with the nucletiode T (c.52A>T) and is much more rarely than the mutation and occurs only in Bernese Mountain dogs.

DM is a genetic disease inherited in an autosomal recessive manner meaning that the dog must receive the mutated gene from both parents to develop the disease. Rarely, this disease may develop in heterozygotes, although the frequency of occurrence is lower.

As the clinical diagnosis can be performed only post mortem, the molecular genetic analysis presents an excellent method for early determination whether a dog is at risk for degenerative myelopathy or passes the mutation on to the next generation, if the dog is heterozygous for this mutation.

The mode of inheritance of degenerative myelopathy in Bernese Mountain dogs is very complex as it can be caused by two mutations that moreover may manifest themselves by specific symptoms.

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Genotypes SOD1A (c.118G>A) and SOD1B (c.52A>T) in an individual

  • Healthy dog (N/N) = Tested Genetically Normal = a dog without mutations
  • Carrier or a dog at risk (N/P) = Tested Genetically Carrier  = a heterozygote that carries one or both mutation; some carriers of a mutation can be at increased risk of developing degenerative myelopathy
  • Affected dog (P/P) = Tested Genetically Affected = a recessive homozygote carrying two mutations in SOD1A or two mutations in SOD1B or four mutations in SOD1A and SOD1B

* The test of SOD1A is performed by the partner laboratory

SOD1B

SOD1A

G/G (=N/N)

G/A (=N/P)

A/A (=P/P)

A/A (=N/N)

N/N healthy

N/SOD1A (carrier)

SOD1A / SOD1A (DM positive)

A/T (=N/P)

N/SOD1B (carrier)

SOD1A /SOD1B (a carrier of both mutations; if one mutation has been inherited from each parent, the dog is DM positive)

This genotype has not been found in dogs so far.

T/T (=P/P)

SOD1B/SOD1B (DM positive)

This genotype has not been found in dogs so far.

This genotype has not been found in dogs so far.

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Mating of different genotypes

N/N + N/N

If two healthy dogs are mated, 100% offspring in the litter will be healthy as well.

N/N + N/SOD1A

or

N/SOD1B

If a healthy dog (N/N) is mated with a dog heterozygous for one mutation (N/SOD1A or N/SOD1B), so theoretically 50% of the offspring will be healthy (N/N) and 50 % of the offspring will be carriers (N/SOD1A or N/SOD1B).

N/N + SOD1A/SOD1A

or

SOD1B/SOD1B

If a healthy dog (N/N) is mated with an affected dog (SOD1A/SOD1A or SOD1B/SOD1B), so all the offspring will be carriers (N/SOD1A or N/SOD1B).

N/SOD1A or N/SOD1B

+

SOD1A/SOD1A or SOD1B/SOD1B

If a carrier (N/SOD1A or N/SOD1B) is mated with an affected dog (SOD1A/SOD1A or SOD1B/SOD1B), so theoretically 50 % will be affected and 50% will be carriers

N/SOD1A + SOD1B/SOD1B

or

N/SOD1B + SOD1A/SOD1A

If a carrier N/SOD1A is mated with an affected dog SOD1B/SOD1B, so they will produce 50% carriers of the mutation N/SOD1B and 50% offspring will be double heterozygous for SOD1A/ SOD1B. If mating a carrier N/SOD1B with an affected dog SOD1A/SOD1A, so 50% will be carriers N/SOD1A and 50% will be double heterozygous for SOD1A/SOD1B.

N/SOD1A + N/SOD1A

or

N/SOD1B + N/SOD1B

The litter will consist of: 25 % healthy offspring (N/N), 50 % carriers (N/SOD1A or N/SOD1B) and 25 % offspring affected (SOD1A/SOD1A or SOD1B/SOD1B).

N/SOD1A + N/SOD1B

When mating two compound heterozygotes, the litter could theoretically consist of 25 % healthy offspring (N/N), 25 % carriers of N/SOD1A, 25 % carries of N/SOD1B and 25 % will be affected (SOD1A/SOD1B).

SOD1A/ SOD1B + SOD1A/ SOD1B

The litter will consist of 25% affected offspring SOD1A/SOD1A, 25% affected offspring SOD1B/SOD1B and 50% offspring will be double heterozygous for SOD1A/ SOD1B.

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References:

Crisp, Matthew J., et al. "Canine degenerative myelopathy: biochemical characterization of superoxide dismutase 1 in the first naturally occurring non-human amyotrophic lateral sclerosis model." Experimental neurology 248 (2013): 1-9.

Pfahler, S., et al. "Degenerative myelopathy in a SOD1 compound heterozygous Bernese mountain dog." Animal genetics 45.2 (2014): 309-310.

Wininger, F. A., et al. "Degenerative myelopathy in a Bernese Mountain Dog with a novel SOD1 missense mutation." Journal of Veterinary Internal Medicine 25.5 (2011): 1166-1170.

Zeng, R., et al. "Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy." Journal of Veterinary Internal Medicine 28.2 (2014): 515-521.

Breed list

This combined test consists of these basic tests

Usual turnaround time: 7 business days
1 test price: 74.00 $ without VAT