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Thread: Polygenic Inheritance of AIS

  1. #1
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    Polygenic Inheritance of AIS

    Am J Med Genet A. 2010 May;152A(5):1178-88.
    Polygenic inheritance of adolescent idiopathic scoliosis: a study of extended families in Utah.

    Ward K, Ogilvie J, Argyle V, Nelson L, Meade M, Braun J, Chettier R.

    Axial Biotech, Inc., Salt Lake City, Utah 84109, USA. ken.ward@axialbiotech.com
    Abstract

    A heritability study of 69 extended Utah families with a history of adolescent idiopathic scoliosis (AIS) indicates that AIS is a polygenic, multifactorial condition. Each family reported a history of AIS within four generations; a total of 247 individuals were confirmed via X-rays and medical records to have AIS. Coefficient of kinship was more than 25 standard deviations higher for these 69 families than for the general population. Excluding all probands and assuming autosomal dominant inheritance, 1,260 individuals over the age of 16 were determined to be at risk for AIS because they have a parent with AIS. Assuming 50% of these individuals carry the allele, estimated penetrance in at-risk males is approximately 9%, and estimated penetrance in at-risk females is approximately 29%. Recurrence risk in relatives decreases as the degree of relationship to the affected individual becomes more distant; however, the lowest recurrence risk calculated, for third-degree relatives, is still an average of 9%, well above the general population's risk. Onset of AIS appears to be inherited separate from curve pattern and severity. In a study of phenotypes in 36 of the families, the affected individuals were consistent in either curve severity or curve pattern, but not both. It is unclear whether severity or pattern is more heritable, but it is possible that the location of the curve on the spine is the most heritable trait of the phenotype. The study demonstrates the genetic complexity of AIS, including the low penetrance of its cumulative alleles and variable expression. Copyright 2010 Wiley-Liss, Inc.

  2. #2
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    Welp, the germ theory of scoliosis just took a kick to the groin.
    Sharon, mother of identical twin girls with scoliosis

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    Wow. Poor Utah.

    The people of southern Utah also had, and have to deal with all the atomic fallout from all the "shots" (nukes) that were tested in southern Nevada through the years.

    The winds almost always blow east.....
    Ed
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    http://www.scoliosis.org/forum/attac...3&d=1228779258

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    expression

    The study demonstrates the genetic complexity of AIS, including the low penetrance of its cumulative alleles and variable expression.
    Variable expression? I assume he is trying to say that sometimes a gene causes AIS, sometimes it doesn't. Well, that's one possible explanation. Another explanation is that these genes don't cause AIS. They create susceptability to the environmental damage that does.

    A while back people thought MS was caused by genetics. Today scientists know that's not true. Genes create susceptability but the disease is triggered by the environment.

    April 29th, 2010: MS Study Suggests Key Role of Environmental Factor in the Disease

    Scientists are reporting what they say is compelling evidence that some powerful non-heritable, environmental factor likely plays a key role in the development of multiple sclerosis.
    The study was the first to examine all three levels of a human genome at the same time, giving the first full picture of a living genome.
    "Even with the very high resolution at which we sequenced the genomes of our study participants, we did not find evidence for genetic, or epigenetic differences that explained why one sibling developed the disease and the other did not," says the lead author of the study, Sergio Baranzini, PhD, associate adjunct professor of neurology and a member of the Multiple Sclerosis Research Group at University of California, San Francisco.
    I look forward to a time when technology this advanced is used on twins with and without Scoliosis. I'm confident the findings will be similar.
    Last edited by Dingo; 05-01-2010 at 11:00 PM.

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    Quote Originally Posted by Dingo View Post
    Variable expression? I assume he is trying to say that sometimes a gene causes AIS, sometimes it doesn't.
    No. It means exactly what it says.

    http://www.scientificamerican.com/ar...erences-traced
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
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    "We are all African."

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    Clearly this stuff is not only more complicated than a lay person supposes but is more complicated than a lay person can suppose.

    Apologies to J.B. S. Haldane who famously said:

    "My own suspicion is that the Universe is not only queerer than we suppose, but queerer than we can suppose."
    Last edited by Pooka1; 05-02-2010 at 12:09 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."

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    Variable expression means it can be expressed in different ways. The human genome project has only recently been completed, I think. There is so much to learn from here on out. These things take time. I think that the term "gene" is being thrown around too lightly. That is why scientists use the term allele in describing a factor that causes a trait. DNA sequences are very complex, and it is not only the sequence of bases - what we think of as a gene or allele - but there are a whole cascade of other surrounding sequences that can activate or deactivate the gene product (a protien or part of a protein). Like Pooka1 said, way too complicated for the layperson, unless of course, the person is extremely dedicated to learning these things. Take a course in Molecular Biology and also endocrinology, yes I said it ... endocrinology... It will blow you away!

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    Quote Originally Posted by LindaRacine View Post
    Am J Med Genet A. 2010 May;152A(5):1178-88.
    Polygenic inheritance of adolescent idiopathic scoliosis: a study of extended families in Utah.

    Ward K, Ogilvie J, Argyle V, Nelson L, Meade M, Braun J, Chettier R.

    Axial Biotech, Inc., Salt Lake City, Utah 84109, USA. ken.ward@axialbiotech.com
    Abstract

    A heritability study of 69 extended Utah families with a history of adolescent idiopathic scoliosis (AIS) indicates that AIS is a polygenic, multifactorial condition. Each family reported a history of AIS within four generations; a total of 247 individuals were confirmed via X-rays and medical records to have AIS. Coefficient of kinship was more than 25 standard deviations higher for these 69 families than for the general population. Excluding all probands and assuming autosomal dominant inheritance, 1,260 individuals over the age of 16 were determined to be at risk for AIS because they have a parent with AIS. Assuming 50% of these individuals carry the allele, estimated penetrance in at-risk males is approximately 9%, and estimated penetrance in at-risk females is approximately 29%. Recurrence risk in relatives decreases as the degree of relationship to the affected individual becomes more distant; however, the lowest recurrence risk calculated, for third-degree relatives, is still an average of 9%, well above the general population's risk. Onset of AIS appears to be inherited separate from curve pattern and severity. In a study of phenotypes in 36 of the families, the affected individuals were consistent in either curve severity or curve pattern, but not both. It is unclear whether severity or pattern is more heritable, but it is possible that the location of the curve on the spine is the most heritable trait of the phenotype. The study demonstrates the genetic complexity of AIS, including the low penetrance of its cumulative alleles and variable expression. Copyright 2010 Wiley-Liss, Inc.
    Finally!! I think it is even more complicated than this, since girls fare worse than boys for the most part (excluding titaniumEd, of course ).

  9. #9
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    Like I mentioned earlier, I think they should start looking at it from an endocrinological point of view as well, if it is not sex linked. It's a known fact that women have different hormones than men and this must play a role in why girls get a worse slam than most boys.

  10. #10
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    The genetic complexity associated with AIS probably can appear as germ theory to the lay person.

    As the following quote attributed to Socrates goes:

    “True knowledge exists in knowing that you know nothing.”
    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."

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    Quote Originally Posted by Pooka1 View Post
    The genetic complexity associated with AIS probably can appear as germ theory to the lay person.

    As the following quote attributed to Socrates goes:

    “True knowledge exists in knowing that you know nothing.”
    I feel a little bad because I'm not trying to create class distinctions between the "educated" and the layperson. There are plenty of "laypeople" that have IQ's well above many "educated" people. It is just all in opportunity and what is important to a person in life. Not everyone wants to go to college and that's okay. But for those of us who have, the quote above really does apply. The more you know, the more you realize you don't know. That is why medicine is a "practice".

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    Quote Originally Posted by rohrer01 View Post
    I feel a little bad because I'm not trying to create class distinctions between the "educated" and the layperson. There are plenty of "laypeople" that have IQ's well above many "educated" people. It is just all in opportunity and what is important to a person in life. Not everyone wants to go to college and that's okay. But for those of us who have, the quote above really does apply. The more you know, the more you realize you don't know. That is why medicine is a "practice".
    Agreed.

    There is a difference between intelligence and knowledge. It doesn't matter how intelligent you are if you don't have specific knowledge. This genetic variance business really makes that point crystal clear.
    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."

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    Dingo,
    I must give you credit for your efforts to keep up with this research. You are obviously an intelligent man. If you are near a university somewhere, perhaps ASU, NAU or UofA, sometimes a professor will be nice enough to just let you sit in without taking a survey of the class (which you have to pay for). If you could just sit through a class of basic genetics (I mean the whole semester - not just one class), it will greatly help you to understand some of these terms and concepts. If not, you can go to the book store and many times the universities just give away old texts (especially at the end of a semester). I have collected many books that way. If you can get your hands on a genetics textbook and really study it through, it will help you a LOT to understand what is going on with your son. I hope this helps and is not offensive to you in any way.

  14. #14
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    Quote Originally Posted by Dingo View Post
    Genes create susceptability but the disease is triggered by the environment.


    I look forward to a time when technology this advanced is used on twins with and without Scoliosis. I'm confident the findings will be similar.
    Dingo, I am only partially quoting you to make a point. What you say here may be true for some diseases, but it is a proven FACT that it doesn't hold true with all genetic disorders. Down's Syndrome is a genetic disease causeed by a trisomy (meaning there are three copies of a chromosome). However, genetics is more complicated than that. During cell division, sometimes there is not a complete trisomy and only a partial where a piece of one chromosome attaches itself to another chromosome. If it is the right peice, you can still have a child with Down's Syndrome. There is nothing that can trigger someone with this genetic makeup to suddenly express the symptoms of Down's Syndrome. Either the child has it or he/she doesn't. What the environment can do is if the child is worked with intensely, then the child's full intellectual potential can be brought out. This does not negate the fact that the child has Down's Syndrome with all of it's risks including heart problems. If a person with Down's Syndrom has a child with a non-down's person. The baby has a 50/50 chance of having Down's. Genetic disorders are not always triggered by something in the environment. Some are, but a vast amount are not. I think that you are trying to prove in your mind somehow that scoliosis could have been avoided if....
    The more research that is done seems to dispel this belief of yours. Accepting the fact that scoliosis is a genetic disorder will relieve you of any guilt you may be feeling about the what if's. My only guilt in knowing my daughter has scoliosis lies in the fact that I have scoliosis and I passed it on. We can't avoid passing our genetics on to our offspring. Your son's darker skin that you mentioned earlier is simply due to the fact that you live in a hotter climate and he gets more sun exposure at an earlier age, than perhaps you or your wife. Another possibility is that either you or your wife have a dark skinned person in your ancestry, which most, if not ALL of us do. I hope this helps you to understand a little bit of what I'm talking about. I'm certainly not trying to be condescending in any way. It's just hard to give a genetics 101 in a forum. Don't be disappointed to find out it is hereditary, so many good things are, too. Be proud of the little guy and stop beating yourself up over environment, which likely plays very little role in this disease.
    Last edited by rohrer01; 05-02-2010 at 03:54 AM.

  15. #15
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    Quote Originally Posted by rohrer01 View Post
    Dingo, I am only partially quoting you to make a point. What you say here may be true for some diseases, but it is a proven FACT that it doesn't hold true with all genetic disorders. Down's Syndrome is a genetic disease causeed by a trisomy (meaning there are three copies of a chromosome). However, genetics is more complicated than that. During cell division, sometimes there is not a complete trisomy and only a partial where a piece of one chromosome attaches itself to another chromosome. If it is the right peice, you can still have a child with Down's Syndrome. There is nothing that can trigger someone with this genetic makeup to suddenly express the symptoms of Down's Syndrome. Either the child has it or he/she doesn't. What the environment can do is if the child is worked with intensely, then the child's full intellectual potential can be brought out. This does not negate the fact that the child has Down's Syndrome with all of it's risks including heart problems. If a person with Down's Syndrom has a child with a non-down's person. The baby has a 50/50 chance of having Down's. Genetic disorders are not always triggered by something in the environment. Some are, but a vast amount are not. I think that you are trying to prove in your mind somehow that scoliosis could have been avoided if....
    The more research that is done seems to dispel this belief of yours. Accepting the fact that scoliosis is a genetic disorder will relieve you of any guilt you may be feeling about the what if's. My only guilt in knowing my daughter has scoliosis lies in the fact that I have scoliosis and I passed it on. We can't avoid passing our genetics on to our offspring. Your son's darker skin that you mentioned earlier is simply due to the fact that you live in a hotter climate and he gets more sun exposure at an earlier age, than perhaps you or your wife. Another possibility is that either you or your wife have a dark skinned person in your ancestry, which most, if not ALL of us do. I hope this helps you to understand a little bit of what I'm talking about. I'm certainly not trying to be condescending in any way. It's just hard to give a genetics 101 in a forum. Don't be disappointed to find out it is hereditary, so many good things are, too. Be proud of the little guy and stop beating yourself up over environment, which likely plays very little role in this disease.
    Beautifully worded. Right on point. You are such an asset to the group with your training.

    As I said before, we only have two people with any relevant training to my knowledge and Pnuttro can only do so much edifying before exasperation sets in. To her great credit, she tries. But who could have anticipated such an ardent folkscientist trying to prove his pet hypotheses would come on here? I suggest nobody. And what is the point? We aren't sitting here deciding which research to fund. We have scientists, not folkscientists, doing that. There is a reason for that.
    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."

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