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Genomia s.r.o.
Republikánská 6
312 00 Pilsen
e-mail: laborator@genomia.cz
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Testing of dogs: DM* (SOD1A)

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Usual turnaround time: 12 business days
1 test price: 56.00 $ without VAT
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Total 106 related tests Show all Hide related tests

Degenerative Myelopathy

* The tests are performed by the partner laboratory

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. Affected dogs develop non-painful weakness of the pelvic limbs that causes problems with coordination and unsteady gait, than the signs slowly progress to muscle atrophy, ataxia, incontinence and ends with paralysis of hind limbs. The symptoms accompanying this disease are so severe that the dog dies within 3 to 5 years after occurrence of the first signs. However, the dog is euthanized approximately one year after symptoms first appear.

This fatal disease is in most cases caused by a mutation in the superoxide dismutase 1 gene (SOD1), This mutation replaces nucletiode G with nucletiode A  (c.118G>A;  SOD1A) within the coding region of the SOD1 gene. The replacement G with  A in the gene sequence results in nonsense codon  due to which the gene is not correctly transcribed and the  protein superoxide dismutase 1 encoded by SOD1 gene is not produced. Only in Bernese mountain dog, this degenerative myelopathy can be caused by other mutation in the SOD1 gene, which replaces the nucleotide A with the nucletiode T(c.52A>T; SOD1B).  This mutation is however much more rarely than the mutation c.118G>A.

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. A certain percentage of dogs positive for DM did not exhibit clinical signs in their lifetime.  This can be explained either by the death of the dogs before the clinical signs appeared or by existence of modifying genes affecting the symptoms, environmental factors or an incomplete penetrance of the disease among the positive homozygotes.

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 to the next generation, if the dog is heterozygous for this mutation. However, the onset of the first signs and the severity of the course of the disease cannot be determined by this method.

DM occurs in dogs of both sexes with the same frequency. When choosing the breeding pair, the genotypes of the dogs are not important. However, it is important to avoid such combinations of parents which would produce offsprings positive for DM.

  • Healthy/normal dog (N/N) = Tested Genetically Normal = a dog without mutations
  • Carrier or a dog at risk for DM (N/P) = Tested Genetically Carrier = a dog heterozygous for SOD1A mutation
  • Affected dog (P/P) = Tested Genetically Affected = recessive homozygote carrying two mutations in SOD1A gene

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The mating of the below genotypes at risk for DM development is not recommended:

Parental genotypes

Statistical representation of genotypes in offspring

P/P + P/P

100% of the offspring will be at risk for DM development

P/P + N/P

50% of the offspring will be at risk for DM, 50% of the offspring will be a carrier of DM mutation and pass it on to next generations

N/P + N/P

25% of the offspring will be healthy, 50% of the offspring will be a carrier of DM mutation and 25% of the offspring will be at risk for DM

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Combinations which will not produce offspring positive for DM are as follows:

Parental genotypes

Statistical representation of genotypes in the offspring

N/N + N/N

100% of the offspring will be free of DM mutation

N/P + N/N

50% of the offspring will be healthy and 50% of the offspring will be a carrier of DM mutation

P/P + N/N

100% of the offspring will be a carrier of the DM mutation

Note:  It is frequently recommended that dogs homozygous for the mutation (P/P) are not included into the breeding program. In breeds with small gene pool, the elimination of dogs being P/P for DM gene may essentially reduce the genetic variability of the population and could result in occurrence of other undesired genetic load of the breed.

For breeds with small gene pool, it is recommended that inbreeding coefficient in addition to other parameters is considered which can help to select breeding pair that would produce more genetically diverse offspring. For more information see www.genomia.cz/cz/diverzita/

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Reference:

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.

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.

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Breed list - total 133 different breeds. Show list of all breeds Hide breeds

Usual turnaround time: 12 business days
1 test price: 56.00 $ without VAT
CZK / EUR / USD