Degenerative myelopathy - Page 5

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by Blitzen on 08 July 2015 - 22:07

Villa, this might help you make a decision too:

 DDC Veterinary's DNA test reveals one of the 3 possible genotypes for degenerative myelopathy:

  • CLEAR (those having 2 copies of the normal allele and appear to be normal).
  • CARRIER (those having 1 copy of the normal allele and 1 copy of the mutation and most appear to be normal).
  • AT RISK (those having 2 copies of the mutation and will likely show clinical signs.)



 

It is important to note that although carriers usually will not show clinical signs for the disease, if used for breeding, they will pass on the mutation about 50% of the time, therefore a carrier x carrier mating will likely result in producing at risk pups in 25% of the offspring.

Canine DNA frequently asked questions

For more information about how these test results can be used for registration, contact the Orthopedic Foundation for Animals (OFA) or the Canine Health Information Center (CHIC).


by joanro on 08 July 2015 - 23:07

'How did you decide that, Joan?'

Lack of conviction by the lab, indicated through use of the word I capitalized.
The word 'mutation' continually shows up, so, as I have said before, testing is not going to eliminate the disease. Nor is testing a reliable predictor of occurrence of DM. I still don't believe they've found the gene responsible....why else would the wire fox terrier test as 'at risk' at least 92% of dogs tested, yet there has never been a clinical expression of the disease in the breed...

by Blitzen on 08 July 2015 - 23:07

I see,  thanks. I believe 'suggested" is the usual term used when researchers refer to the outcome of a specific study as opposed to "have proven", but I could be wrong.


by Blitzen on 08 July 2015 - 23:07

I wonder if some breeders think that GSD's truly can be "DM free" due to this statement on the DDC website:

Degenerative Myelopathy (DM) Test

Canine Degenerative Myelopathy (DM) is a devastating degenerative disease of the spinal cord that can progress rapidly and cause weakness in the hind limbs and eventually paraplegia among genotypically affected dogs.

This test is available for all dog breeds. Initially, this inherited recessive disorder was thought to only affect German Shepherd Dogs; however, degenerative myelopathy has been recently diagnosed in several other dog breeds.

The DNA test is an accurate, convenient, and affordable tool to help breeders avoid producing DM at risk offspring and significantly reduce the gene frequency in future generations. DDC Veterinary's DNA test reveals one of the 3 possible genotypes for degenerative myelopathy: this is followed by the chart I posted above.

I think the OFA does a much better job of accurately describing the test results and their usefullness for breeders.


by joanro on 09 July 2015 - 02:07

Right. They say 'suggested' because they aren't certain.

by foreversolucky on 09 July 2015 - 02:07

I shouldn't wade into this because all it does is piss me off, but here we go. 

Joan, the word "mutation" is all over the place because there is a change in the genetic sequence (mutation) compared with the majority of the population (wildtype).  That's it.  It doesn't imply goodness or badness or causation.  Stop reading into things because the word is scary.

My interpretation of "SUGGESTED" is that there is, firstly, obviously more things at play than SOD1.  It's not like Huntington's in humans, where presence of the mutation means that you get the disease.  Full stop.  My analogy is breast cancer diagnostics - BRCA mutations only cause 5-10% of breast cancers (all stats from Komen), but if you have that mutation you've got a 45-65% chance of developing breast cancer by 70.  Many women with BRCA mutations will not develop breast cancer, but they have a 6-8x higher risk of it than women without the mutation (~8% chance of breast cancer by 70).  Similarly, many dogs testing At Risk won't develop DM.  That's why the label is "AT RISK" and not "DM positive" or something like that.  The A/A dog is more at risk than the general population.  The N/N dog has a lower lifetime risk of developing DM.

Since it's more complicated than just A/A = Must Develop DM, you get other factors leading to clinical DM.  Also, no test is perfect.  If you have a diagnostic test with 98% sensitivity and 100% specificity, that's a damned good test.  It also means that 2 out of 100 tests are wrong.  For reference, rapid influenza tests have sensitivities around 35-65%, and doctors still use those despite having as much reliability as a coin flip.  There have been almost 5000 GSDs tested with results in the OFA database, so if the test was as good as 98% sens/100% spec, we'd expect to see 100 wrong calls.  That leads back to my second reason why the lab uses "suggested" - without postmortem sampling of the spinal cord, you CAN NOT say a dog had DM.  Period.  Since there aren't large numbers of DM-suspected and case-control GSDs going in for necropsy, it's unlikely that there are enough data points for strong statistical significance.  The lab, being good scientists, are therefore going to SUGGEST a link, despite the overwhelming evidence of a link.


by joanro on 09 July 2015 - 02:07

Forever so lucky. I'm not sceereded....mutation is used by offa in their explanation why they don't accept clear through parentage beyond first generation..in other words, after the first batch of pups from 'clear' parents, the pups from those pups must be tested because of MUTATION possibility. So don't be pissed at me, get pissed at the directors of the DM DNA program. I didn't read any of the rest of your post. No point in reading it. The second sentence was enough to disregard the rest.:-)

by foreversolucky on 09 July 2015 - 03:07

For everyone who's actually reasonable, here's the explanation for the nonsense above.  The polymerase enzyme which duplicates DNA is somewhat glitchy by nature and makes mistakes (ahem, mutations) at a certain rate.  There is a proofreading function but sometimes an error slips through and is passed to the daughter cell.  If it occurs in a gamete, an offspring from that gamete will inherit the mutation not seen in the parents.  In humans, the stat I found is 1 mutation for 10 million bases or 0.32 mutations per genome, per division.  The dog genome is about the same size.  Add up the number of cells and multiply it by the number of replications, and you get a significant number of mutation events. Since DM is such a devastating disease, you don't want to miss one of those spontaneous mutations.  Not such a big deal if - whoops - the dog turns out to carry longcoat when the parents didn't, but they want to make sure to catch unanticipated At Risks.


by joanro on 09 July 2015 - 12:07

That's why the disease won't be eliminated, no matter if you test the parent dogs, because of Mutations. Testing the owners would eliminate the disease just a soon. Again, more bs.

by Blitzen on 09 July 2015 - 12:07

You said it much better that I ever could have, Lucky.






 


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