Breeder,

The more links you can give me to read the better. It seems there are not many original sources beyond the University of Minn.

Although not a geneticist by any means, I have a science background and can mug through most biochem research papers.

The research was done by a team from U of Minnesota and Saskatchewan. That is why any of the scholarly papers are from those sources. Most (if not all) other information published on EIC is a rehash of the official releases from those two sources. The research was published in Nature Genetics about two years ago. You can either get it from your local library or order a reprint of the article from the Nature website. Here is a link to the information and abstract
http://www.nature.com/ng/journal/v40/n10/full/ng.224.html

Since you are the scientific type, you really don't need anyone to spoon feed you more links - most search engines will find them easily

Actually, it's quite difficult to use a search engine to find and read published research. What's online are abstracts, and accessing whole articles requires payment or paid membership. (And it does matter what is contained in the actual article).

Even if the abstract is online, you need the best source words to find it. And a great deal of research is either not yet published or never will be published.

If you have additional links for the OP, I don't think you would be spoon feeding anyone to post it.

Please read my whole post. The only really useful articles have already been linked. The full research report is not available free unless you check the magazine out at your library. Everything else on the topic is either opinion or a rewrite of the science articles from the researchers. The researchers will have updates from time to time, so I would advise bookmarking the two main research websites. Also be careful about checking the date of any online postings, as some links may have very old, preliminary information.

ALL of the relevant science articles can be found with a Google search on "exercise induced collapse in Labradors" along with the 900+ rehashes, etc. I know, because that is where I found them I don't think any of us mind helping out with information, but the OP could have found the links the same way I did. It is how a lot of us try to "get the facts" these days.

I am a geneticist and cell biologist and have read the original research paper. The most salient points are that the research was done by the traditional method of using pedigrees and LoD scores to establish linkage between a marker and EIC collapses. it was NOT done by the more controversial Genome Wide Association technique. One was found that had an astronomically high LoD score (an indication of linkage). The chromosomal region was then searched for candidate genes, and the most likely one was the gene for dynamin 1, which is a protein involved in recycling synaptic vesicles at the neuromuscular junction, in other words a likely candidate to cause the symptoms of EIC. The team then searched the dynamin 1 gene for polymorphisms that associated with EIC in several pedigrees. They found a single base change that always segregated with EIC and thus is without doubt the mutation that causes EIC. The test is for this mutation. The association of E/E status (homozygous for the mutated form) with EIC collapse is not 100%. About 1-2% of dogs that collapse in a manner consistent with EIC do not have the genetic condition. This proportion is the same for carriers and clears. Also, something like 20% of the E/E dogs do not collapse. So there are other rare conditions that mimic EIC, but carriers do not collapse any more frequently than clears do. And some dogs seem to be protected from the effects of the dynamin 1 mutations, presumably by other genes. All of these data are documented by tables in the paper. There also were large data files available as electronic files at the time the paper was published, and I looked at those, too. The researchers had extensive pedigrees to work with, which were shown in those files. Dogs are not named, only assigned a number. Relationships are shown by horizontal lines to denote matings and vertical lines to denote ancestry, as is standard in genetic research. The only thing the researchers did not do was to use knock-out technology to prove that the dynamin 1 mutation does give the phenotype associated with EIC. There is a mutation in the dynamin 1 gene in fruit flies that causes paralysis, but it is in a different part of the gene.

Thanks for the synopsis of the research article, Peggy. You are better than a "google link" any day

You need to "publish" this somewhere - like on your website - so that others can link to the resource.

Well, it is on this list serve, where it should come up with a search. Truthfully, there is a page on my website about a study I actually did myself on retinal folds that I ought to update and haven't. I think it is great that some people have time to do websites of this sort, but I don't have the time. Maybe when I retire at the end of the 2010-2011 academic year...

MG, I read your whole post, including all the sarcasm.

Get the Facts,

Thank you for confirming why every search I did came up with the same two sources, or obvious paraphrases of them.

Peggy, Thank you for your post.

Bottom line, discounting other possible rare conditions....

1) A homozygous recessive dog many not suffer collapses due to other variables. But a homozygous dominant or heterozygous dog will not collapse due to EIC regardless of the other variables.

2) The tests done by U of Minn and DDC are good tests to determine the presence or absence of the mutated gene in question.

Is this consistent with what you believe to be correct?

I am currently assuming that an affected dog or bitch can be bred as long as only to another who has tested clear.

Having said that, I have not seen anyone comment on if this condition could affect whelping. I am assuming for severe cases it likely could but for mild cases probably not. Please comment.

thanks in advance

The whelping question was brought up a few weeks ago in the thread I started about my gal. Basically there is no evidence of ever a collapse during whelping. We even asked the U of Minn, no documented cases. One breeder posted her bitch collapsed when pregnant and had a normal size litter and delivery. If concerned I imagine you could always do a scheduled c section.

Those are the two research sources with the best (or only) set of facts. Peggy was really helpful with her synopsis of the research paper, but I would recommend you read it sometime (it is a bit data dense) as you may glean something useful for yourself from it.

There are also a few veterinary articles published on EIC. They can be looked up from the reference section of the U of MN webpage:


http://www.vdl.umn.edu/ourservices/canineneuromuscular/eic/scientificreferences/home.html

From U of MN:

http://www.vdl.umn.edu/ourservices/canineneuromuscular/eic/taylor2008/home.html#heat

DIFFERENTIATING EIC FROM HEAT STROKE

There have been a number of good veterinary reviews of heat stroke in dogs recently and the syndrome we are seeing with EIC is very different. With heat stroke - induced collapse in dogs you expect to see a very slow or prolonged recovery that can take hours to days, or else progression to death. Laboratory evaluation reveals a dramatic increase in muscle enzymes (CK usually 7-11X normal). Mentation changes that are severe, progressive and persistent (for hours to days) occur in 80% of affected dogs and significant endothelial injury leads to microvascular thrombosis, DIC, thrombocytopenia and bleeding as well as acute renal failure in most patients. In contrast, dogs with EIC collapse without showing laboratory abnormalities and they recover quickly - happy and running around within 5 to 25 minutes.

And here is a key sign to look for in a true EIC collapse:

http://www.vdl.umn.edu/ourservices/canineneuromuscular/eic/taylor2008/home.html#eval

ervous system examination is normal at rest, but patellar reflexes are diminished or absent in dogs with EIC during collapse and these do not reappear until after the dog has completely recovered, which usually takes 10 to 30 minutes.

Indeed, I have read "the" research article to which I presume you refer. AND I have read research supporting the approach used to identify the gene in the article, the research identifying dynamin 1 in fruit flies, and research about variable expressivity and incomplete penetrance (which may explain why not all dogs who test positive for the gene collapse or have severe episodes). I've also spoken to Katie about the continuing data collection after the publication of the research.

No one should be convinced that they know it all and speak down to others who know less. All research exists in a context of earlier research and continuing into the future. The more I know; the more humble I become about what is known and what is yet to be known. I may be farther down the road of scientific discovery than others, but I am most definitely behind others.

Scientist, Wonderfully expressed thoughts ...

I have learned so much in the past week or so. Thank you to those who have contributed to all of our evolving understanding of this issue.

I found a relatively recent thread on EIC where Jill questioned the accuracy of the test (DDC or Univ of Minn) based on the fact that some affected dogs do not seizure, and some who tested clear or as carriers do. The resulting discussion was fantastic and is the bottom line I think.

Full disclosure, I am the original poster. I used "New to This" on another thread. Both are accurate names.

"No one should be convinced that they know it all and speak down to others who know less."

Thanks for the great example of doing just that

I would caution us all not to refer to EIC episodes as "seizures" unless you are trying to equate seizure disorders with EIC. While it may sound picky to some, using the proper terminology in medical situations is vital to the clarity of the discussion, and future discussions.

That about the reflex is interesting. How does one test for patellar reflexes in a dog, the same as in a human, by striking the knee? I've seen only one collapse that might have been EIC, and it was many years before the condition was generally known, but it would be useful to have a good test to use in case I see another possible EIC collapse. If no one knows, I'll ask my vet the next time I see him.

"Bottom line, discounting other possible rare conditions....

1) A homozygous recessive dog many not suffer collapses due to other variables. But a homozygous dominant or heterozygous dog will not collapse due to EIC regardless of the other variables.

2) The tests done by U of Minn and DDC are good tests to determine the presence or absence of the mutated gene in question.

Is this consistent with what you believe to be correct?"


Yes. That is how I interpret the published research and my conversations with Katie Minor. I believe your question about breeding an affected bitch has already been answered.

Here's a video of how it's done:

http://www.youtube.com/watch?v=BqlvfBDloXw

Thanks for the link! The videos were very interesting.

Just a small suggestion: When giving a website address, it is really easy to make it a direct link (rather than a copy and paste). When you are composing a post, there is a link directly above the input box that says "bb code". It inserts a list of easy codes you can use for adding things to your post. If you use the url code, the web address becomes a link to the page. I notice that only a few people use this and it is a real time saver for the readers.