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Scoliosis genetics - my wild speculation

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  • Scoliosis genetics - my wild speculation

    I just read recently where scientists have found a remarkable amount of difference, much more than expected, in the DNA between identical twins. This, of course, interests me because I have identical twins.

    Anyway, one type of difference noted between ID twins is the number of copies of various genes present. So one twin might have one copy and another might have three of the same gene.

    In my girls, in the same several week period, one girl's curve advanced 10 degrees and the other's had no measurable difference (no brace in either). There is no doubt they are ID twins... there was only one chorion which is dispositive for ID twinning.

    So putting the two observations together (difference in the number of gene copies and my girls having very different trajectories, at least so far), I'm wondering if rate and amount of curve progression might be controlled by the number of copies of one or more genes a person has.

    If true, maybe one day they can determine a priori whether a person's curve will progress to needing surgery or not. Once this is known, then they can see whether any brace will work on curves that are genetically programed to be large. That will be very interesting.

    Just a wild thought.
    Last edited by Pooka1; 05-12-2008, 06:25 AM.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

  • #2
    Sharon,

    I don't believe it's wild speculation at all!

    As I'm sure you know, the first idiopathic scoliosis gene (CHD7) was discovered (and the results published) last year, but they don't yet know ~quite~ what to do with it as it pertains to treatment - or predicting progression.

    Still very exciting news; I've always believed genetic information to be the best hope for a cure or scoliosis effective, on-time treatment. It's certainly a start!

    Control subjects (apologies if that sounds "detached" ... they're kiddos, not merely experiments :-) like your twins, and families with mother/daughter affliction, parent/multiple child diagnoses, and families struck with scoliosis generation after generation will undoubtably provide the best data for researchers as all this moves forward.

    As I've said before, I'd like nothing better than for this board to have no reason to exist: I'm sure I'm overly optimistic, but wouldn't it be wonderful to see this happen in our lifetimes?

    A few links:

    - U of IA News Release
    - Washington University in St. Louis
    - The Journal of Human Genetics
    - Scottish Rite Hospital (Dallas, TX)

    There was also discussion here before about a project underway by Axial Biotech, one TSRH was recruiting for, and others ...


    And, MaryLou (Snoopy), here's one for you specifically related to CMT disease :-). I hope you've been able to locate more on that!

    Best regards,
    Pam
    Last edited by txmarinemom; 05-12-2008, 07:15 AM.
    Fusion is NOT the end of the world.
    AIDS Walk Houston 2008 5K @ 33 days post op!


    41, dx'd JIS & Boston braced @ 10
    Pre-op ±53°, Post-op < 20°
    Fused 2/5/08, T4-L1 ... Darrell S. Hanson, Houston


    VIEW MY X-RAYS
    EMAIL ME

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    • #3
      Originally posted by txmarinemom
      Sharon,

      I don't believe it's wild speculation at all!

      As I'm sure you know, the first idiopathic scoliosis gene (CHD7) was discovered (and the results published) last year, but they don't yet know ~quite~ what to do with it as it pertains to treatment - or predicting progression.
      Yes I knew they found the first (of more?) genes associated with scoliosis. I mentioned that in my (completely useless!) response to sparklegirl in her plaintive thread. What I was suggesting is that it may be the number of copies of this gene correlates with the severity of the scoliosis and not just the presence or absence of the gene. That would explain why ID twins can have different trajectories given that they can have different copy numbers of various genes.

      The research types working on this and the surgeons out there fixing folks give me hope.

      sharon
      Sharon, mother of identical twin girls with scoliosis

      No island of sanity.

      Question: What do you call alternative medicine that works?
      Answer: Medicine


      "We are all African."

      Comment


      • #4
        Thanks Pam. I'll look at the article when I get a few minutes. How are you doing?

        Mary Lou
        Mom to Jamie age 21-diagnosed at age 12-spinal fusion 12/7/2004-fused from T3-L2; and Tracy age 19, mild Scoliosis-diagnosed at age 18.

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        • #5
          I never thought about that but that's definitely not a wild spectulation, that seems very reasonable and could really help to coming closer to Stopping Scoliosis. Thats a good observation :-) I remember hearing about the gene as well it came out the month I learned I had scoliosis.
          Danielle
          14 Freshwoman
          December 1st got no head the boston brace
          Pre Brace Curves:18C 25T 30L
          In brace curves: (1/23/08) 16C 20T 22L
          In brace Curves: (5/21/08) 19C 19T 15L
          We're Bringing CURVY BACK

          Comment


          • #6
            Genetic poymorphism

            Originally posted by Pooka1
            Yes I knew they found the first (of more?) genes associated with scoliosis. I mentioned that in my (completely useless!) response to sparklegirl in her plaintive thread. What I was suggesting is that it may be the number of copies of this gene correlates with the severity of the scoliosis and not just the presence or absence of the gene. That would explain why ID twins can have different trajectories given that they can have different copy numbers of various genes.

            The research types working on this and the surgeons out there fixing folks give me hope.

            sharon

            Sharon.

            You bring up an excellent topic.

            What you are talking about is genetic polymorphism. Polymorphisms don't cause a disease, but they do cause subtle changes in biology. Copy number changes could be answer, but other factors would have to exist as well. Because there is no strict inheritance pattern, this is likely to be a multiple gene problem, similar to diabetes.

            Do you have a reference for identical twins having different genetics? Everything I have read is in population based studies. Usually, the polymorphisms are inherited, so even though there is variation in a population, identical twins should have little differences.

            While identifying a gene that causes disease is important, it doesn't mean that there will be an effective treatment. The research will take a long time and if there is little funding, it takes even longer. Gene therapy isn't likely to be an option for scoliosis since you have to replace the defective gene in every cell that is contributing to the problem. The best one could hope for in the next 20 years is to monitor closely and treat (surgically or otherwise) if necessary.

            There are many researchers that have the same hope as you. They propose that everyone will have their complete genome sequenced shortly after birth, so that each person can have an assessment of what the future holds for them, biologically speaking. It begs the question: Do you really want to know?

            p

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            • #7
              P,

              Thanks for that response. I tried to follow it as best I could not being a biologist (I'm a geochemist).

              The ID twin copy number difference item was just a blurb in a popular science magazine. I didn't track down or read the original reprint. I'll try to find the blurb, get the researchers' names, and track the article down.

              And no, I'm not sure I want to know my biological destiny! Venter knows his and I'm guessing he isn't too thrilled.

              Thanks again,
              sharon
              Sharon, mother of identical twin girls with scoliosis

              No island of sanity.

              Question: What do you call alternative medicine that works?
              Answer: Medicine


              "We are all African."

              Comment


              • #8
                http://www.sciam.com/article.cfm?id=...-not-identical

                This isn't the article I read but it has the same information as far as I can remember.

                From the article...

                "For example, one twin in Bruder's study was missing some genes on particular chromosomes that indicated a risk of leukemia, which he indeed suffered. The other twin did not.

                Bruder therefore believes that the differences in identical twins can be used to identify specific genetic regions that coincide with specific diseases. Next, he plans to examine blood samples from twin pairs in which only one suffers from asthma or psoriasis to see whether he can find gene copy number changes that relate to either of these illnesses."


                sharon
                Last edited by Pooka1; 06-06-2008, 09:37 PM.
                Sharon, mother of identical twin girls with scoliosis

                No island of sanity.

                Question: What do you call alternative medicine that works?
                Answer: Medicine


                "We are all African."

                Comment


                • #9
                  Bruder study

                  I read the article to which you referred me and I read Dr. Bruder's paper in The American Journal of Human Genetics.

                  The article, I think is a little misleading because it confuses differences in inheritance with genome differences in individual cells over a lifetime. What the article addresses is that genes are not stable over one's lifetime. This is not a new idea. For example, we know that some people inherit genetic variations that increase one's risk for cancer, but most of the time, it is an unfortunate genetic change in a single cell. Until recently, scientists have focused on mutation rather than copy number. It is still unclear if there diseases associated with copy number variation.

                  While it is possible to use copy number changes to diagnose a person, you would have to have identical twins, where only one person has the disorder and then you would have to test the right cell. In the case of scoliosis, is that a bone cell? a muscle cell? connective tissue? a nerve? which cell is the right cell? was this a recent genetic change (harder to find) or an old one (more cells would have the defect).

                  Let me know how I did with my explanation. You can ask your questions and I will try to clarify.

                  p

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                  • #10
                    I don't really understand all the genetics of it, but my 3 children and I are all participating in the Axial Biotech study. They sure don't have to prove to me that it's genetic, when all 3 of my kids somehow got my defect.
                    __________________________________________
                    Debbe - 50 yrs old

                    Milwalkee Brace 1976 - 79
                    Told by Dr. my curve would never progress

                    Surgery 10/15/08 in NYC by Dr. Michael Neuwirth
                    Pre-Surgury Thorasic: 66 degrees
                    Pre-Surgery Lumbar: 66 degrees

                    Post-Surgery Thorasic: 34 degrees
                    Post-Surgery Lumbar: 22 degrees

                    Comment


                    • #11
                      You're right.

                      I don't really understand all the genetics of it, but my 3 children and I are all participating in the Axial Biotech study. They sure don't have to prove to me that it's genetic, when all 3 of my kids somehow got my defect.
                      debbei
                      You're right!

                      There are genetic factors that are inherited. Causative disease genes are discovered by comparing "affected" parents/siblings to "normal" parents/siblings, then compared over a large number of families to see what is common.

                      Pooka's idea was regarding identical twins who have inherited identical genes. The article says that the a person's genome can change over time, but these events happen in a single cell which might contribute to only part of the cells in your body.

                      In one situation, you are assuming that every cell has identical genes. In the second situation, you are assuming that there are differences, but you don't know which cells are different.

                      For example, identical twins. Twin A has seizures, twin B doesn't. You can't easily take a piece of brain from twin A and compare to twin B, so you use blood. Testing the blood of the two twins shows 3 differences, but you still don't know if those differences are causing the seizures, because they may not exist in the brain of twin A. You might just as easily find differences between the liver of twin A and the blood of twin A.

                      Does that make it more clear or more confusing?

                      p


                      PS I don't consider you genetically defective. I hope you are not feeling guilty for your children's genetic inheritance.

                      Comment


                      • #12
                        What an interestng discussion! I don't know much about genetics either, but my thinking was totally different in regards to my daughter's scoliosis. Although, i acknowledge it was a wild guess. When she was born, she needed more than a little help entering the world and i think they used forceps, but twisted her rather violently. I figured this somehow caused pressure on her spine and maybe that this set a course of action that led to her scoliosis!!!

                        Is this a possibility???

                        L
                        Mum to Tahlia, aged 15. Fused from T2 - L3, 18/11/08.

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