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Degenerative Myelopathy Testing

A reprint from
 www.caninegeneticdiseases.net/DM/DMtest.htm

A DNA Test for DM

The collaborative efforts of Dr Joan Coates and Dr Gary Johnson and associates at the University of Missouri and Dr Kirsten Lindblad-Toh and Dr Claire Wade and associates at the Broad Institute at MIT/Harvard have resulted in identification of a mutation that is a responsible for the development of Degenerative Myelopathy in many breeds of dogs.

The DNA test for DM is now available from OFA, and also DDC Veterinary.  This test clearly identifies dogs that are normal (have 2 normal copies of the gene), those who are carriers (have one normal copy of the gene and one mutated copy of the gene), and those who are at much higher risk for developing DM (have 2 mutated copies of the gene - designated affected/at risk). The age of onset of symptoms can vary from 6 to 15 years of age or older, and some dogs who are genetically at risk for DM will die from other causes before any DM symptoms appear. Factors that may influence the age of onset of symptoms are the topic of current research - at this time we cannot predict which of the genetically at risk dogs will have an early appearance of clinical signs, and which will have a delayed onset.

A relatively high percentage of dogs in several breeds have the predisposing mutation. With the testing done thus far (thru February 2011), the frequency of the mutation is over 70% in Boxers, Pembroke Welsh Corgis, and Wire Fox Terriers. There are another 10 breeds where the mutation frequency is over 40%. For breeds with a high frequency of the DM mutation, it will take wise use of the test and several generations to maintain a healthy and diverse gene pool while reducing the prevalence of DM. It is important for breeders and owners to keep in mind all the traits present in an individual dog, and not to simply breed a test result. We encourage breeders to DNA test potential breeding stock and consider the results of the DM test as part of their evaluation and decision-making process.

A reprint from
 www.caninegeneticdiseases.net/DM/DMtest.htm

Understanding the DNA Test for Degenerative Myelopathy

We have discovered a mutation in a gene which is associated with development of degenerative myelopathy (DM). In that gene, the DNA occurs in two possible forms (or alleles). The “G” allele is the predominant form in dogs that seldom or never develop DM; you can think of it as the “Good” allele. The “A” allele is more frequent in dogs exhibiting clinical signs of DM; you can think of it as the “Affected” allele.
Summary: “A” allele is associated with DM; “G” allele is not associated with DM.

Since an individual dog inherits two alleles (one from the sire and one from the dam) there are three possible test results: two “A” alleles; one “A” and one “G” allele; and, two “G” alleles. Summary: Test results can be A/A (affected/at risk), A/G (carrier), or G/G (normal) .

Microscopic examination of a section of spinal cord (following euthanasia) is the "gold standard" for diagnosing and confirming DM. We do not have the opportunity to examine cord samples from all the dogs that have died or been euthanized due to DM, but for those cords submitted for evaluation, and where the cellular changes have been consistent with a diagnosis of DM, the dogs have had a DNA test result of A/A in all but 2 individuals. There is additional work being done to better understand these 2 exceptions, but it is clear that the vast majority of real DM cases do have the A/A test result.

Summary: Dogs that test A/G or G/G are very unlikely to develop DM. Dogs that test A/A are likely to develop clinical signs of DM at some point as they age. Additional research now in progress is focused on understanding why some A/A dogs show clinical signs of DM at 7 or 8 years of age while others only begin to show clinical signs at 14 or 15yrs or older, or may die from some other cause without developing recognized clinical signs of DM.

The “A” allele is very common in some breeds. In these breeds, an overly aggressive breeding program to eliminate the dogs testing A/A or A/G might be destructive to the breed as a whole because it would eliminate a large fraction of the high quality dogs that would otherwise contribute desirable qualities to the breed. Nonetheless, DM should be taken seriously. It is a fatal disease with devastating consequences for the dogs and a very unpleasant experience for the owners who care for them. Thus, a realistic approach when considering which dogs to select for breeding would be to consider dogs with the A/A or A/G test result to have a fault, just as a poor top-line or imperfect gait would be considered faults. Dogs that test A/A should be considered to have a worse fault than those that test A/G. Dog breeders could then continue to do what conscientious breeders have always done: make their selections for breeding stock in light of all of the dogs’ good points and all of the dogs’ faults. Using this approach over many generations should substantially reduce the prevalence of DM while continuing to maintain or improve those qualities that have contributed to the various dog breeds.

Summary: We recommend that dog breeders take into consideration the DM test results as they plan their breeding programs; however,breeders should not over-emphasize this test result.  
          Instead, the test result is
one factor among many in a balanced breeding program.

Additional Information on DM,
Description of  Clinical signs, and cell description
 in photos

Degenerative Myelopathy, Disease Basics

DM Research

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