View Full Version : good news on the gene marker front!

13th August 2005, 11:46 PM
With some of the more worrying statistics about the percentages of cavaliers that seem to have SM and the malformation, this bit of fantastic news deserves some highlighting. I understand this to mean that the researchers have decided that from the DNA they have examined, they believe it will be possible to find a genetic marker for SM.

But better yet, that it won't be necessary to find an exact marker because given the information they already have, they believe there will be enough indications of the probability that a cavalier has the likelihood of having or passing along SM. That means people could do a sinple DNA test without needing a very expensive MRI, and also that it should be possible to start predicting which dogs have a higher likelihood of passing along more serious forms of SM. I'm hoping I am understanding all of that right! It will be kind of cool to have a cavalier genome too!

Marie Pierre Dube has completed a preliminary analysis of the initial scan and the good news is that the chosen markers are sufficiently informative enough to justify a whole genome scan in the CKCS breed. This first stage of gene mapping will involve around 500 markers and 200 dogs. Marie Pierre, a genetics epidemiologist, has recently taken on a position at the Montreal Heart Institute where she heads a research team in genetics of cardiology. She has a particular interest in MVD.

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.

She says: ”Genetic analysis is more definitive and accurate and of course cheaper than MRI. I have to stress the fact that we don't need to wait for identification of the gene for genotyping the dogs. Once we map the gene to a genomic region, we can select a few informative polymorphic markers that are tightly linked to the segregating phenotype (and hence the gene) and we can develop a genetic test that will give a probability value of carrying the defective gene. Of course identification of the gene and the underlying mutation will give a more clear-cut answer where sequencing the DNA will give a definitive genotype.”

15th August 2005, 12:48 AM
Wow, this is incredible!

15th August 2005, 05:54 PM
Oh yayyyyyyyyyyyyyyyyyyyy that's fantastic :D Thanks for letting us know Karlin :D XX

15th August 2005, 07:05 PM
This is an email from Penny Knowler, who works with Clare, discussing the genetic research. It is a hard area to understand so I'd asked her to explain what is happening, and she said it is fine to crosspost:

Undertaking a whole genome scan to locate a gene is not the same as working out the full genome sequence (they have done this for the dog though - can't remember the breed -cross.) In order to locate the gene they have to identify where, and on which chromosome it is. They do this with markers which only indicate the general area in which the gene lies and does not involve any sequencing. In principle the marker allows a comparative analysis of affected and unaffected dogs and can be used to provide a "DNA test". Such a test does not identify the molecular nature of the condition i.e. it permits easy diagnosis but does not explain the disease. There are many existing DNA tests that use markers - they are very valuable but not necessarily not 100% accurate. Understanding the molecular nature of the disease will require precise identification and sequencing of the gene as a first step in analysing what has gone wrong - this is what Zoha will be doing. It is much more difficult and expensive undertaking compared to identifying markers and requires lots of DNA. Human geneticists like Zoha are interested in validating these findings in humans. Identification and characterization of genetic factors predisposing to Chiari malformation 1 (CMI -human condition) would help the understanding of the pathophysiology of SM for better diagnosis, clinical management and ultimate prevention. For biologists, these studies will provide new insights into the poorly understood process of normal development of craniocerebral structures of the central nervous system. It is all very exciting!! So many people worldwide will benefit from this research - and its really nice that so many 'ordinary' people worldwide are contributing to make it possible.

15th August 2005, 10:49 PM
Do they still need DNA, Karlin? If they do can you ask Claire how to go about donating etc? They can have some of Maxx's if they need it - I'm sure he won't mind...

16th August 2005, 12:09 AM
They definitely need blood -- if he has had an MRI this is very valuable. If you look in the faqs under the DNa project there's a link to download the forms for this plus an explanation for your vet. The blood goes to Manchester; the scan should go to Clare; I think they need 3-5 generation pedigrees for this to be valuable but you can email the contact on the CKCS club site in the UK for the project and they can clarify if you don;t have a pedigree.

16th August 2005, 03:24 AM
Karlin -- someone on the L list asked about sending the markers they already have from the aKC or CKCSC and I wanted to mention that the markers they need for testing for any disease are very specific and different from the parentage markers. The markers are basically a sequence of genomic data that is "linked" to the phenotype/disease (in this case, SM).

Do they still think it's polygenic? I'm guessing not since they are talking about a linkage test? That would most likely just link to one gene....

16th August 2005, 10:07 AM
They do think it is polygenic, according to Clare in the newsletter. But then maybe they are doing a whoke range of tests; this is stuff I don;t really know much about!

16th August 2005, 10:53 AM
Thanks Karlin, Maxx does have a pedigree - one littered with Champions - it just makes me question the overbreeding of the sires yet again :cry:

16th August 2005, 10:55 AM
Thanks Karlin, Maxx does have a pedigree - one littered with Champions - it just makes me question the overbreeding of the sires yet again :cry:

17th August 2005, 02:10 PM
According to the newsletter they are still thinking it is either polygenic or dominant with incomplete or variable penetrance. I think, if anything, they are leaning towards the dominant with incomplete or variable penetrance mode of inheritance as the basic route with the possibility of another gene being involved as well--since they went into more detailed explanation of that.

If it is all dominant or mainly dominant it should be much easier to find a marker. At least we can hope so.

17th August 2005, 07:01 PM
I emailed Penny Knowler and she is guessing about 3 years to get the gene results.