The genetics of DM

The superoxide dismutase 1 gene, or SOD1, has been linked to degenerative myelopathy (DM).

  

The genetic tests for DM in Bernese Mountain Dogs.

• In 2008 a test for a mutation was first used in Bernese Mountain Dogs. That mutation is the SOD1:c.118A, referred to as SOD1-A or exon 2.

• In 2010 a new mutation was discovered in BMDs (and only in BMDs). That mutation is the SOD1:c.52T, referred to as SOD1-B or exon 1.

Two direct DNA tests, one for the A mutation and one for the B mutation, are available that apply to the Bernese Mountain Dog. Many laboratories can perform these two tests, which use DNA from a cheek swab. When the test for SOD1-A is done, a clear result only means that the two genes are clear of that specific SOD1-A mutation; the test for the SOD1-B mutation is necessary to complete the genetic picture. In Bernese it has been determined that the SOD1 gene will have either the A or B mutation, not both. If a Berner is at risk for SOD1-A (both copies of the SOD1 gene have the A mutation), then the DNA test for the SOD1-B mutation does not need to be done, and vice versa. If a Berner is clear or a carrier for one of the mutations, then the test for the other mutation must also be done in order to learn the actual status for both copies of the SOD1 gene.

 

Inheritance

DM is inherited as an autosomal recessive trait with incomplete penetrance. Recessive means that both copies of the gene present in an individual dog have to contain a mutation. In other words, both the mother and father of the dog pass on this mutation to the offspring. The SOD1 gene is not located on the X or Y sex chromosomes, it’s on an autosomal (not sex linked) chromosome.  

 

If a dog gets two mutated SOD1 genes (one from each parent), then that dog is said to be at risk for DM. Because not all of the at risk dogs will become affected, the trait has incomplete penetrance.  

 

• Researchers do not yet know why some at risk dogs get DM and some don’t. We don’t know what percentage of Berners tested shown to be at risk will become affected.

• Perhaps tested dogs determined to be at risk don’t live long enough to show the symptoms.

• Perhaps there are other genes that cause the disease to be triggered, or that cause the disease to be suppressed.

• Perhaps environmental factors play a role.

 

Statistics - Prevalence of SOD1A and SOD1B Clear and Mutations in DM Tested BMDs

 

Cumulative test statistics from GenSol as of June, 2017.

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As the GenSol data shows, well over half of the dogs that have been tested carry at least one copy of a mutated SOD1 gene. The allele frequency is the calculation of mutated genes as a percentage of all copies of the gene. So as many as 37% of all the available genes in the breed are mutated copies.  

 

Using the test for breeding choices

The genetic status of DM in dogs as measured by the current DM tests is one selection criteria among many others that must be considered by breeders. By doing the DM test and wisely interpreting the findings, genetic diversity and positive breed traits can be retained while reducing the incidence of the DM mutations found in the breed. The beauty of direct DNA tests is that no dog needs to be removed from an already limited gene pool.

 

Carrier and at risk dogs can be bred (and should be bred if they are good quality dogs) to dogs that are clear of both mutations in order to minimize the risk of producing at risk puppies that may become affected. In the event that there is a truly compelling reason to breed a carrier to a carrier, a breeder will want to research near relatives and pedigree information to see if both parents come from lines that show no signs of DM – and hope that the possible causative gene is not also present, or that the possible suppressor gene is present. An at risk to an at risk breeding will produce ONLY at risk puppies. Anyone choosing to do such a breeding would also want to have a great deal of pedigree information to use family history to try to minimize the possibility of producing puppies that may become affected.  

 

The goal of breeders should be to gradually breed away from the mutations without creating genetic bottlenecks that may do significant harm to the future wellbeing of the breed as a whole. An example of sound genetic management advice can be found in the Austrian BMD Club’s approach and recommendation which prohibits clear to clear matings. Breeding a DM clear to a DM clear can be done as an exception, but this club’s breeding strategy was adopted to try to preserve overall diversity within the population, given the frequency of gene mutations for DM known to exist in dogs tested for DM.  [Note: A review of this process allowed the club to eliminate this requirement as of January 2017.]

 

An approach involving a radical swift removal of DM carrier and at risk dogs given the high number of dogs with DM mutations will decrease genetic diversity which will not improve the future health of this health challenged breed.  

 

The short term goal needs to be avoidance of producing at risk puppies. A longer term goal is to gradually reduce the incidence of mutated genes as there may be beneficial traits linked to these mutated copies that we want to keep in the breed.

 

Below is a chart that can be used to summarize genetic status. 

 

 

 

 

 

 

 

 

 

*Because the SOD1 gene has only the A or the B mutation and not both, a dog that is at risk for one will be clear of the other.

 

The following chart shows how to make use of those results in order to select a breeding partner to avoid producing at risk puppies.

Breeding combinations to avoid producing at risk puppies. 

See the BMD DM Poster for Mating Outcomes - The Genetics of DM.

 

 

 

 

 

 

 

 

How many at risk dogs will become affected?

We still need to learn what percentage of dogs testing as at risk can be expected to become affected, and we can all help with that. Selecting a large enough sample of at risk dogs that then live long enough to be expected to start showing symptoms, and then doing necropsies on all of those dogs would be a method for determining what percentage of at risk dogs would be expected to become affected. Getting necropsies of at risk dogs to determine whether or not they have DM is key, and it’s a difficult and expensive procedure. The Pearson Fund was created to help support this effort, and it will provide up to $500 toward the cost of the necropsy if needed. Contact the BMDCA Health Committee’s Pearson Fund contact: Pat Long, at pat@bmdinfo.com.  As always, please add information to the Berner-Garde database. If you have an at risk dog, use the database to track the start and progression of symptoms (symptomatic), or the lack of symptoms as the dog ages symptom free (asymptomatic). This can help to track the age when symptoms first appear. Some have shown signs as early as six years – which would mean that this is not a disease of old age. Indicate whether the vets have ruled out other possible causes of rear-end paralysis and show that it is a presumptive case of DM. And do be sure to submit all the information about any necropsy results. It’s never easy, but it’s always greatly appreciated.