View Full Version : geneticist view of SM and inheritance

17th November 2005, 06:55 PM
Hi all:

I passed along the key points of the comments on syringomyelia and inheritance put forward by Bet Hargreaves -- the main elements that were included in a recent editorial she has posted elsewhere (Rod Russell has posted regarding this editorial here: http://www.cavaliertalk.com/phpBB2/viewtopic.php?t=844 ), and additional comments posted elsewhere regarding whether 10 families of cavaliers would be needed to get any useful insight into inheritance. These points were put to Zoha Kibar, the molecular geneticist in charge of fine mapping and identification of the gene(s) defective in SM for the CKCS genome scan currently underway in Canada. Here is her reply below; crossposting is permitted. A reminder that for those interested in this and other subjects, there are two lists for detailed discussion of SM issues, CKCS-SM and the SM Breeder Support List (breeders only); info on these available here: http://sm.cavaliertalk.com/2005/10/syringomyelia-discussion-lists.html ).


Chiari Malformation (CMI) in humans with or without syringomyelia has been shown to segregate in families, suggesting the involvement of genetic factors in the development of this malformation. The number and identity of these genes remain to be determined. The heritability i.e. the relative contribution of genes vs environment is also not known. In the CKCS breed, dogs were bred for their shape (including their head) and this could explain the presence of this malformation in almost 100% of this breed. Syringomyelia is present in around 60% of human CMI cases suggesting the presence of other factors, genetic and/or environmental, that interact to modulate the incidence and severity of the symptoms.

In the CKCS, I tend to think it is the same story. Clare Rusbridge and Penny Knowler’s study tracing back the affected dogs to one founder and to 6 of 8 grandparents represents strong evidence for the presence of aÂ*founder effect in this breed. Clare Rusbridge is planning to study other determinants in the MRI-ed group and I think this is a very good idea. Not all cavaliers have this SM problem and this is where tracing back to a founder with a disease (i.e. with a mutation or mutations) pinpoints the spreading of this disease to descendents and its high incidence.Â*Founder effects are well-established genetic forces that lead to a disequilibrium in the genetic pool. I am sure all cavaliers will share other traits more than distantly related breeds.

Would SM develop stochastically e.g. the way the dogs are treated as pets? Given the similar incidence in human cases, I doubt this is the case. If the environment is the major culprit, what do these dogs that develop SM have in common?Â*These are not easy questions. In the genome scan, I have included dogs with CMI and with or without SM hoping to be able to identify modifiers. If these modifiers have a small contribution, we will not be able to map them using this approach.

Would MRI-ing 10 families help understand the genetics of SM in this breed? If a detailed MRI is done with the other research ClareÂ*Rusbridge is suggesting to do, that could help. Otherwise, I doubt it. It is more complicated. And what about the age of onset? An MRI study of 10 families would definitely not give a definitive answer.

I understand the fear of genes, which we cannot change, as opposed to environmental factors, which we can (to a certain extent). But unfortunately this trait seems to involve both. Breeders should understand that our study will not be the magic solution that will help them identify dogs that will not develop SM for breeding purposes (at least not in the short term). But identifying a gene will open the door to understanding pathways involved in the development of this disease and hopefully in the long run, a cure for these suffering dogs. Of course we are also interested in the biology.Â*Irrespective of the complexity we are dealing with, we have to try to understand the disease with the tools we have and hence the genetic approach. And irrespective of this complexity, and if we don’t want to think about the multifactorial etiology, the breeding protocol scheme Dr Rusbridge came up with is the best solution for now. Then later we can deal with the causes.

(Zoha Kibar has been appointed as the molecular geneticist in charge of fine mapping and identification of the gene(s) defective in SM in the CKCS breed. Zoha pursued her postdoctoral studies at McGill University working on a mouse model for neural tube defects (NTDs) in humans. She is interested in identification and characterization of the molecular basis of congenital malformations of the central nervous system, particularly NTDs and Chiari malformations and she is planning to pursue her career as an independent researcher in this field.)>>

17th November 2005, 07:25 PM
From what I understand, I just think this is so fascinating. Thanks so much for posting this and keeping us updated! Any news is such a positive step, we're fortunate that people are even willing to research this disease considering there are many diseases that do not get the funding, resources, time, etc. that are so desperately needed.

17th November 2005, 07:29 PM
Thanks for approaching the geneticist to get this information! This should help clear up some of the confusion about genetic vs environmental causes.

Rod Russell
17th November 2005, 07:30 PM
Nice going, Karlin. This certainly is helpful information. Rod Russell

17th November 2005, 10:48 PM
Dear Karlin,
Thank you for the information. You are a tremendous asset to all Cavalier Owners!
JAime Redniss

Rod Russell
18th November 2005, 05:32 PM
I noticed that Karlin posted the same initial message on several lists, and I find it interesting that on Yahoo's CKCS-SM list, for example, there is an abundance of comments from listers, while on another list, dominated by some very opinionated CKCS breeders, I have seen no comment at all thus far.

Rod Russell
Orlando, Florida USA

18th November 2005, 05:36 PM
That is interesting Rod, and frustrating at the same time. :?

18th November 2005, 06:15 PM
People may want time to think it through. Or maybe it is that many who are interested in discussing the post are also over on CKCS-SM, where there is discussion. Sometimes the lists and boards go a bit quiet from Friday through the weekend too.

However people respond (or don't respond!), I'm just happy to see the discussions and comments begin to take in some of the people working in the area. No matter how educated and informed the general discussions may be, it helps to get the perspective of those who are familiar with existing studies, understand genetics and research, and who are seeing dogs with this condition regularly.

Laurie Moon
18th November 2005, 11:29 PM
I am sure people are reading what Karlin is posting...alot of people do not respond and never will....I can almost guarentee that if they ever have to experience this first hand ...they will be very much interested to what Karlins research is finding....Karlin thank you for all you do for our breed !

19th November 2005, 12:51 PM
I've just posted other people's research :) -- so it isn't me doing the research or able to answer many questions beyond offering what I know some informed people have said, but I think it is really important that what IS known or guessed at this time be put out for public discussion and dialogue. Breeders especially need some places to debate and consider and get whatever the latest information might be, as they ultimately are making the decisions that help shape the future of the breed. The more tools they have for making informed choices, the better.

19th November 2005, 05:05 PM
Thanks Karlin,

I think it wil be most interesting to find out what is causing SM, I do think it is a genetic problem and whether it is a defective gene or a gene too few or too many will be really interesting. I wonder if they will also find out from the research whether SM clear parents can have an SM affected puppy. I know from one of the other groups that there is an SM clear bitch that has had an affected pup.

I personally will be more than interested to know if a symptom free and MRI clear dog/bitch can actually carry SM that can be passed onto any offspring. For example people with a family history of haemohillia, the females are usually carriers whilst the males are sufferers.

Hope I haven't confused anyone here....

19th November 2005, 09:40 PM
This is what the last Rusbridge newsletter said:

A number of dogs have a mild malformation but do not have syringomyelia
Clinically affected offspring often have affected (clinically or sub-clinically) parents
Clinically affected parents can produce ‘clear’ offspring

The second point would seem to imply that affected offspring can come from clear parents.

The newsletter is here: http://sm.cavaliertalk.com/smnewssum05.htm

I do know that Clare says very definitely, a clear parent can produce affected offspring.