Two More DM Results

Wow–they are really getting these tests done quickly. I mailed these (priority) on Friday. They arrived yesterday (Monday) and results are already posted today (Tuesday at noon).

KENLEIGH’S ZEALOUS ZOEY ZOEY F WCC DN07580102	DM	Received: 04/13/2009 Processed: 04/14/2009 Test: Degenerative Myelopathy Results: CLEAR (Homozygous N/N, Clear)
CAYUSE ROWDY RUGBY RUGBY M WCC DL67860706	DM	Received: 04/13/2009 Processed: 04/14/2009 Test: Degenerative Myelopathy Results: CLEAR (Homozygous N/N, Clear)

It looks like two more Cardis have tested ‘at risk’ since the statistics page was last updated.

DM–My Take (Part 5)

I would encourage anyone interested in understanding more about the ‘breed and replace’ method of managing defective genes within a breed to read these two articles:

The Effects of Genetic Testing: Constructive or Destructive?

and 

Breeding Strategies for the Management of Genetic Disorders

 Please note how the author is not saying carrier animals should not be bred–only that they should be bred to clear individuals–and that IF any of the resulting clear offspring are superior to the carrier parent, that offspring should then be used to replace the carrier parent in a breeding program.

 

DM-My Take (Part 4)

Reading story after story today of people who have watched their beloved pets and performance-partners suffer through the progression of DM literally brought me to tears today.

To say, or even suggest, that DM is ‘painless’ makes me cringe. Sorry. I think the dogs do suffer–I think of my own ‘wild child’ Zoey who loves nothing better than running and jumping and I have a difficult time imagining how she would do if she could simply not walk.

To say, or even suggest, that DM is ‘painless’ negates the emotional pain that the disease puts the owners through. These people are very dedicated to their dogs, willing to take their beloved pets to physical therapy sessions (often several times a week), drawing up detailed medical ‘treatment’ plans for their dogs and buying specialized carts for their companions just so they can remain mobile if even just for a few weeks or months.

To say, or even suggest, that DM is ‘painless’ is to imply neither dog nor owner suffers any ill effects from this disease–not the dog that struggles to take every step and not the owner who must struggle every day with ‘quality of life’ decisions.

I wonder how many owners of dogs suffering from DM would say, or even suggest, the disease is ‘painless’?

DM–My Take (Part 3)

A Few Random Thoughts on DM

One thing that strikes me after looking through a number of websites and such today is that the terminology used to describe DM in terms of both phenotype and genotype can be confusing. To say that a dog is ‘affected’ can be ambiguous–are they genetically affected (genotype A/A) or phenotypically affected (showing physiological signs of DM)? If it were up to me, I would use the term ‘affected’ just to describe a genetically A/A dog and ’symptomatic’ to describe a dog showing clinical signs of DM. Of course, a dog could be ‘affected and symptomatic’ or ‘affected and asymptomatic’.

Still need convincing that studying and testing dogs for this disorder is a good thing to do? Certainly one can say dogs will benefit from the research being done on this disorder, but, just as importantly, humans may well benefit too. The SOD1 gene (SOD=SuperOxide Dismutase) is a candidate gene for involvement in some forms of ALS in humans. A nice summary of work in both dogs and humans is HERE.

I see Dr. Joan Coates (last author* on the DM research paper I referenced in my first DM post) is set to give a talk at the 2009 CWCCA national specialty–I’m sure it will be a very informative talk and I look forward to hearing attendees comments about it.  

*For those who may not be familiar with the way authors are listed on papers published in scientific journals, the last author is almost always the senior scientist in whose lab the published work was done.

DM-My Take (Part 2)

What is known about DM?

All of the strictly diagnosed DM affected dogs in the most recent published study were A/A homozygotes–this is a VERY different statement from, “All A/A homozygotes were diagnosed with DM.”

DM, when looked at via genetic analysis of the SOD1 gene mutation, is inherited as an incompletely penetrant autosomal recessive disease. All dogs looked at thus far who have been diagnosed with DM are, genetically, “A/A” at the mutation point within the SOD1 gene. But, all “A/A” dogs do not necessary show outward signs of DM. Chances are good that there are  modifying genes involved in the inheritance of DM–current speculation is focusing on dog autosomes 6,18,20 and 35 as locations for these modifiers. The SOD1 gene itself resides on chromosome 31.

The  only current definitive diagnosis of DM is for the dog to be examined post mortem.

So, if there are modifiers not yet discovered, why test? After all, some A/A dogs may never show (outward) signs of the disease.

For me, the fact that DM is probably NOT a simple recessive disorder  means there is even more reason to test as many dogs as possible, ESPECIALLY those that are related to suspected and known DM affected dogs. If well-documented lineages of dogs known to suffer from DM can be found and their blood used for further studies, it will make it much easier for researchers to track down the absolute underlying cause of DM–be it modifying genes or environmental factors.

This is a disorder that will only disappear with the help of genetic testing–late age-of-onset disorders are always tricky to eliminate from any breeding population, be it humans or dogs because all of your reproduction generally take place years before the phenotype of the disorder shows itself. With dogs and DM, you can’t wait 10-15 years to see if the potential parents of a litter show signs of DM themselves before you decide to breed them.

DM-My Take (Part 1)

I’ve spent quite a bit of time over the past day reading up on degenerative myelopathy. Riley’s test has already been ordered–my other two will be tested soon.

Why test ‘pet’ dogs who are neutered and spayed?

The true frequency of the allele associated with DM won’t be known until many, many dogs are tested–as of right now, the OFA website shows that 72 Cardis have thus far been tested; I have no clue how many Cardis there are worldwide or even just in the US, but I’m guessing that number represents far less than 0.1% of all living Cardis. The stats are HERE.

I, for one, am thankful that a test for one of the candidate genes causing DM has been found–recessive disorders (and right now, the SOD1 gene mutation that is used for the DM test is behaving like an incompletely-penetrating-recessive-gene) are notoriously difficult to eliminate from a breeding population. Carriers (non-phenotypically-affected individuals with a single mutated allele) are able to ‘hide’ in the population, passing the mutation on through multiple generations. By having a test that allows folks to ’see’ (genetically) these carrier animals, there is a huge advantage in the ability to effectively eliminate the mutated, disorder-causing variant (at some point in the future) through selective breeding.

One of the papers I read today suggests that even with the DM marker test available, it will take at least a decade of maker-based breeding before the incidence of DM will be significantly reduced. But a decade isn’t that long, is it? Wouldn’t it be fabulous to know that in just ten years this disease could be a thing of the past?

A recent DM research paper is HERE.

For those who are unfamiliar with the disease, a video of dogs in the various progressive stages of DM is HERE (click on the link, “Download Dataset 1-WMV”).