Page 1 of 3 123 LastLast
Results 1 to 15 of 33

Thread: Is autosomal dominant inheritance universally accepted in AIS?

  1. #1
    Join Date
    Jan 2008
    Location
    NC
    Posts
    8,901

    Is autosomal dominant inheritance universally accepted in AIS?

    Apparently no. From Jack Cheng's "top theories" paper...

    A clear mode of inheritance of AIS has not been confirmed and reports on autosomal dominant,7 dominant major gene di-allele model,8 X-linked,9,10 or multifactorial inheritance pattern 11,12 have all been reported.
    Even in the familial AIS cases, it is likely that multifactorial inheritance is implicated. Another aspect of the genetic study of AIS as a complex trait disease is finding the difference between familial AIS and sporadic ones. In a recent report,27 it was observed that the first-degree familial AIS girls had more severe curve and longer arm span than sporadic ones. Further subgrouping of AIS subjects for genetic analysis would be an important approach.
    Elsewhere, it has been stated that the putatively autosomal dominant form and the mutifactorial form are not distinguishable in many/most(?) regards. I suspect that is why he suggests even what looks like straight autosomal dominant inheritance is probably multifactorial genetic inheritance. This would explain why the cases are not distinguishable according to some.

    And last...

    Multiple reports are available to support the role of inheritance in the development of AIS.
    When you add the Scoliscore work which shows a genetic control on progression (or at least an ability to predict when a curve will not progress to >40*), then both incidence and progression appear to be under genetic control.
    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. #2
    Join Date
    Mar 2010
    Posts
    2,755
    Well it certainly doesn't appear to be dominant in my family. Generations have definitely been skipped. Although, my daughter is affected, but mildly.

  3. #3
    Join Date
    Mar 2009
    Location
    Arizona
    Posts
    948
    If my memory serves me correct 2 out of 3 cases of Scoliosis appear to occur sporadically. 1 in 3 appears to cluster in families.

    Although the ratios may change that's how many (maybe most) common diseases look.
    Last edited by Dingo; 03-21-2011 at 07:23 PM.

  4. #4
    Join Date
    Jan 2008
    Location
    NC
    Posts
    8,901
    As far as I know, not being autosomal dominant means you don't have the strict 25% (AA - affected) - 50% (Aa - affected) - 25% (aa - not affected). It doesn't mean "sporadic." Rohrer01 will hopefully correct me if wrong.

    The incidence among first degree relatives is between about 11% and 33% if I recall correctly (from different pubs) which because it isn't 75% would not be autosomal dominant if I understand this. There are families that appear to have AIS inherited in an autosomal dominant fashion but the Cheng article suggests that it only appears that way and there is evidence ALL cases are multifactorially inherited, I am guessing due the the inabilty to distinguish between the putative autosomal dominant cases and the other cases.

    I am guessing the only truly sporadic cases that are known to be truly sporadic are probably associated with the 25% of Marfans patients who have spontaneous mutations and perhaps spontaneous mutations associated with other connective tissue disorders.
    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."

  5. #5
    Join Date
    Mar 2009
    Posts
    1,090
    Quote Originally Posted by Pooka1 View Post
    Apparently no. From Jack Cheng's "top theories" paper...

    Elsewhere, it has been stated that the putatively autosomal dominant form and the mutifactorial form are not distinguishable in many/most(?) regards. I suspect that is why he suggests even what looks like straight autosomal dominant inheritance is probably multifactorial genetic inheritance. This would explain why the cases are not distinguishable according to some.

    And last...

    When you add the Scoliscore work which shows a genetic control on progression (or at least an ability to predict when a curve will not progress to >40*), then both incidence and progression appear to be under genetic control.
    Please notice that Dr. Cheng specifically discusses familial scoliosis versus sporadic scoliosis. He is specifically categorizing the 75 percent of scoliosis cases without family members with scoliosis in a different category from familial scoliosis.

    He also states that genetics is likely...not proven.

    The twins study you like to quote state high levels of concordance, but the later, larger study of the Danish Twins Registry reports a 13% concordance rate...much lower. You simply can't just decide that this much lower rate is meaningless.

    The fact that some people can't distinguish between the different types of scoliosis doesn't mean much. I see that those with juvenile scoliosis progress to surgical ranges much more determinedly than other scoliosis cases. I would like to know if that is the case with those familial cases of scoliosis that are classified as AIS but end up with lots of juvenile cases in the family tree. I'll bet it would be enlightening. The long arms and possibly more tenacious progression actually reminds me of perhaps a mild case on a Marfan's syndrome spectrum.

    I also see that ballerinas can have large scoliosis curves but typically don't have rib humps..such that some researchers don't even consider them as structural curves to include in research studies....even though some do end up with surgery. Why aren't people investigating this apparently exercise-induced scoliosis as possibly different from possibly other types of scoliosis. The study in Europe was calling for these exercised induced scoliosis cases to be removed from the idiopathic category. Perhaps this could explain why my daughter with her fast progressing curve that was stopped by bracing more easily than other types....because it may be a different type.

    The etiology of idiopathic scoliosis is still unknown. You're entitled to your own opinions....you're not entitled to your own facts.

  6. #6
    Join Date
    Jan 2008
    Location
    NC
    Posts
    8,901
    Quote Originally Posted by Ballet Mom View Post
    The twins study you like to quote state high levels of concordance, but the later, larger study of the Danish Twins Registry reports a 13% concordance rate...much lower. You simply can't just decide that this much lower rate is meaningless.
    That study is GIGO from their own numbers. No guessing involved.
    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."

  7. #7
    Join Date
    Mar 2009
    Posts
    1,090
    Quote Originally Posted by Pooka1 View Post
    That study is GIGO from their own numbers. No guessing involved.
    The researchers who actually did the study disagree with you.

  8. #8
    Join Date
    Jan 2008
    Location
    NC
    Posts
    8,901
    Quote Originally Posted by Ballet Mom View Post
    The researchers who actually did the study disagree with you.
    They can't disagree that their scoliosis rate is too low and their MZ rate is WAAAAAAAAY too high.

    I doubt they would try to argue those points because they aren't nuts.

    Hey, chekc out this blurb on an article with the primate family tree...

    http://www.independent.co.uk/news/sc...e-2245349.html

    Now for the first time scientists have drawn a comprehensive family tree of all living species of primates based on a systematic analysis of scores of key genes embedded within their DNA. It shows that Homo sapiens is just one of dozens of primate species that share a common ancestor, probably a small, shrew-like creature that lived during the age of the dinosaurs some 85 million years ago.
    Here is the article...

    http://www.plosgenetics.org/article/...l.pgen.1001342

    Ain't that the coolest thing!
    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."

  9. #9
    Join Date
    Mar 2010
    Posts
    2,755
    Pooka1,
    I think you are goading Ballet Mom. Play nice.

  10. #10
    Join Date
    Jan 2008
    Location
    NC
    Posts
    8,901
    Quote Originally Posted by rohrer01 View Post
    Pooka1,
    I think you are goading Ballet Mom. Play nice.
    <bows head and kicks the dirt>

    Oh all righhhhtttt....
    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."

  11. #11
    Join Date
    Jan 2008
    Location
    NC
    Posts
    8,901
    Quote Originally Posted by hdugger View Post
    The geneticists use the term "genetic influence" when referring to the role of genetics in scoliosis, not "genetic control." See "Genetics influences progression" at the scoliscore site for one of a multitude of examples. And, to repeat my recently-learned lesson, genetics does not equal inheritance.
    Based on the largish mismatch between what these guys might say and what they are actually studying, I conclude they are engaged in a fair amount of CYA - Cover Your Bases.
    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."

  12. #12
    Join Date
    Mar 2009
    Location
    Arizona
    Posts
    948
    It's important to point out that while Scoliscore may be a great test it's existence doesn't indicate that Scoliosis is genetic.

    Multiple Sclerosis isn't a genetic disorder but if you posess specific genes you may have much worse symptoms.

    Gene Variant May Increase Severity of Multiple Sclerosis
    A new study shows a gene variant may increase the severity of multiple sclerosis (MS) symptoms.
    That's essentially the same thing as Scoliscore. These types of genes may exist for every disease, including infectious diseases.

    BBC: Gene link to meningitis infection
    A set of genes which renders people more prone to meningitis has been pinpointed by researchers.
    Persistent Hepatitis B Infection Associated With Gene Variants in Asian Populations
    A genomewide association study in Japanese and Thai populations has found an association between the risk of developing chronic hepatitis B virus (HBV) infection and variants at 2 gene loci in the human leukocyte antigen (HLA) system — the major histocompatibility complex in humans. The report suggests that the variants influence antigen presentation on immune cells, with a weak or absent immune response permitting HBV infections to become chronic.
    Last edited by Dingo; 03-21-2011 at 11:05 PM.

  13. #13
    Join Date
    Mar 2010
    Posts
    2,755
    ...and your point is??? Aren't you tired of this argument?

  14. #14
    Join Date
    Jan 2010
    Location
    San Bruno, CA
    Posts
    271
    Quote Originally Posted by Pooka1 View Post
    They can't disagree that their scoliosis rate is too low and their MZ rate is WAAAAAAAAY too high.

    I doubt they would try to argue those points because they aren't nuts.
    Their overall scoliosis rate was 1.36% and AIS rate was 1.05%. They reference a Lonstein paper that lists 1.25%. What is the caluclation for the MZ rate and what should it be? You've mentioned it before but I can't remember.

    The article definitely has weaknesses but I don't see it as GIGO. We've talked about this before that a weakness of this study is that they probably missed people with scoliosis because it was self-reported. Also, that you said there were some people who might deny they are twins for various reasons (which is really interesting to me). So an undersampling of twins that actually have scoliosis is probable. But the clinical based populations are obviously oversampling the more severe curves. So, to me, as more severe scoliosis seems to have a measurable genetic component, it would stand to reason that a clinic based population would show a higher concordance.

  15. #15
    Join Date
    Jan 2008
    Location
    NC
    Posts
    8,901
    Quote Originally Posted by skevimc View Post
    Their overall scoliosis rate was 1.36% and AIS rate was 1.05%. They reference a Lonstein paper that lists 1.25%.
    Would you say they possibly cherry-picked a reference with a rate close to theirs as opposed to represented the range of rates in the referred literature (which are a factor of 2 to 4 times higher)?

    What is the calculation for the MZ rate and what should it be? You've mentioned it before but I can't remember.
    Before the devil himself took over with fertility drugs and IVF, the MZ rate was about 1/3 that of the DZ rate IIRC. AFter, it would be lower. They got 0.48 MZ IIRC which is would be waaaaay too high. That actually shocked me that it wasn't low because in real life, I would say I have met at least as many folks who deny the (apparent) MZ status of their twins as who accept it. Researchers who aren't walking around meeting parents of twins will never have a clue about the extent of MZ denial and how that might screw up their questionnaire-based research (please pardon that possible oxymoron).

    So they discuss why their MZ rate is way off?

    The article definitely has weaknesses but I don't see it as GIGO. We've talked about this before that a weakness of this study is that they probably missed people with scoliosis because it was self-reported. Also, that you said there were some people who might deny they are twins for various reasons (which is really interesting to me).
    They deny MZ status. I think the reason is ignorance. They see different freckle locations or different hair whorls or different drug allergies and just assume the kids can't be identical. The Olsen twins of TV and movie fame have used some fallacious reasons for denying their obvious MZ status. All of these things (freckle pattern, etc.) and many more are completely specious.

    So an undersampling of twins that actually have scoliosis is probable. But the clinical based populations are obviously oversampling the more severe curves.
    I don't know how or why you conclude that.

    So, to me, as more severe scoliosis seems to have a measurable genetic component, it would stand to reason that a clinic based population would show a higher concordance.
    I am not sure how you know that more severe scoliosis has a measurable genetic component. It could be that the people with milder curves have more protective genes. Nobody knows.
    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."

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •