Polygenic Inheritance of AIS

[Dingo]

the disconnect

rohrer01

As far as getting a textbook on AIS genetics, I have no idea where to find one. You might try the book store. But IF you find one, chances are it will have been written by Dr. Ogillvie.

I think this is where our disconnect resides. Dr. Ogilvie has not found compelling evidence that AIS is triggered by heredity. He's found some interesting correlations that suggest that certain children have an increased susceptability. Someday he may find the genetic blueprint that triggers Scoliosis. But until that time he's got a hypothesis.

I should add that certain genes make us more or less susceptible to the flu virus.

Scientists pinpoint flu gene

An unlucky combination of "vulnerable" genes could explain why some people recover from the flu overnight and others struggle to shake off the virus for weeks.

Somebody correct me if I'm wrong but that's roughly what Dr. Ogilvie has found for Scoliosis.

[Dingo]

heredity

rohrer01

If the trauma, disease, or other environmental factors cause damage to the DNA in the gametes(eggs or sperm), the disease then becomes and inherited one. This is so because the defective DNA can then be passed on to offspring. That's what heredity is. Therefore all heredity is not "good" as you have previously stated.

Our DNA certainly isn't the Death Star. It can be damaged like anything else. If this damage is passed onto the next generation that would be an example of heredity. The resulting childhood disease would be rare, and stay rare because of natural selection.

There are a few flukey reasons that harmful genes can become common. However even in those cases these genes are ultimately whittled away over time if they don't serve a beneficial purpose. To the best of my knowledge all of these diseases are regional.

For example Cystic Fibrosis hits about 1 in 3,000 caucasians. That breaks the 1 in 10,000 barrier which means it's exceedingly common for a genetic disease. However Asians are hit at a rate of something like 1 in 30,000. That's pretty normal for a genetic disease.

Scoliosis hits roughly 2% of people around the world. When I hear guys like Dr. Ogilvie call it a genetic disease I know he's going to be wrong. Genes probably play a role in susceptability and that's about it.

[Pooka1]

To the best of my knowledge

Through all your posts, you show that your knowledge is COMPLETELY insufficient to be discussing this stuff.

[mamamax]

Epigenetic Influences etc

Dingo - when CD used to post here, he once said that you reminded him of Augusto Odone. I agree. I'm sure Augusto (and his wife) endured much skepticism and scoffing. And yet, this lay parent was the first to scientifically resolve the "how to" of normalizing very long chain fatty acid levels. Because of his work, there now exists Lorenzo's Oil, which prevents illness in those whose genes make them vulnerable to developing ALD symptoms. For those who do not know the story: http://www.myelin.org/LorenzosOiMovie/

Just stopping by to offer my encouragement Dingo, and some additional references for your file:

http://www.nature.com/scitable/topic...nd-disease-895

http://www.ayugen.com/scienetificInformation.htm

http://www.nature.com/scitable/topic...ader-willi-923

[Pooka1]

To the extent Odone worked independently from researchers, he was doing SCIENCE to his great credit. He put in the time to understand a condition that was far far far simpler than scoliosis. He did not make up etiologies for the disease as the etiology was known. He did not do FOLKSCIENCE, FOLKMEDICINE or FOLKBIOLOGY. Researchers already KNEW what the deal was with that disease unlike with scoliosis. The problem was defined when Odone stepped in. With scoliosis, the problem isn't defined as evidenced by the several separate avenues simultaneously being investigated by researchers. The problem is intrinsically harder.

There is little chance a lay person is going to define the scoliosis problem with no relevant training whatsoever just as there was little chance Odone could have done so even with that far far far simpler disease.

A lay person can put in the time and get the right training to come up to speed on this. But scoliosis is known to be is a far far far more difficult problem. Hence the amount of time and the amount of training required is far far far more. And with a track record of misunderstanding practically every paper posted, it isn't looking good.

Finally, for every Odone there are a million lay people who tried and failed to help. It's admirable that they tried but there is a reason training is required to do research and it can be easily seen in that huge failure rate. By your mention of Odone in this context, you have made the mistake of counting the ONE hit and ignoring the MILLION misses. And in this case, Odone's hit occurred in a situation completely dissimilar to that for scoliosis.

Details matter to those who care to get the story straight and not inadvertently mislead.

[Dingo]

kudos back atcha

Mamamax

First of all thanks for the links! Those go in my favorites.

I'm not sure if I'm the same caliber of person as Augusto Odone, however I have a pretty good stink bomb detector. I smell some BS.

Scoliosis doesn't look like a genetic disease. It's very common and it hits Japanese, Nigerians, Swedes and everyone inbetween. Twin concordance isn't 100% and although a few unlucky families are hit hard 2 out of 3 cases occur sporadically. Time (and a lot of research) will tell but I'm confident that Scoliosis isn't any different than Multiple Sclerosis or Type 1 Diabetes. Genes create susceptability and environmental damage or misdevelopment causes the disease. Furthermore when the disease occurs specific genes allow for worse symptoms.

When the next big twin study comes out and researchers find "much lower concordance than expected" watch these guys backtrack.

[rohrer01]

Dingo, don't misunderstand...

Even if "genes" only cause a susceptibility or predisposition to a disease, it is still hereditary and worth investigating which genes are causing the problem. There are cancer "genes" that make people susceptible to breast cancer, BRCA1 for example. Not everyone who carries these genes gets breast cancer, but it is still genetic (with an environmental trigger), and there are still women out there that know that they are carriers and get mastectomies as a prevention. Please, I'm not trying to be condescending in any way by advising you to get a genetics textbook and learn about what genetics and heredity are really all about. You have the intelligence to do that. If you can invest all this time and energy in reading papers that you have a hard time understanding (you have misunderstood simple layman's terms), you can invest time in putting yourself through a genetics course. This would really help you to understand what you are reading. Like I said, a lack of 100% concordance in MZ twins doesn't really mean that much if the incidence of MZ twins both having the disease is statistically significant. To understand why this is, you would need to study Molecular Biology. There are a whole cascade of DNA sequences that are responsible for turning a "gene" on or off. No one is disputing that environment may have a role in this, and it may be a significant role. I've said that about 100 times already. That doesn't mean it's not genetic, or inherited. I really don't know what your argument is. I know you must be feeling picked on, it is just frustrating that you won't take the advice. You make really off the wall statements that are completely false and can be proven such. If you really want to know what Ogillvie is up to, then you need to educate yourself on what he is doing, either formally (as in a college course or two) or informally (self-taught with a legitimate textbook that is credible). THEN you can make an intelligent argument that others can at least follow. More important than that, you will be in a better position to help your son being informed on what is real and what is not.

I feel bad that I am 41 years old and am just now taking the time to learn about my own disease that I have suffered with for decades. I feel like a failure because I didn't take the time to really understand it when my daughter was underage and I could make good medical choices for her. My ignorance led me to make poor medical choices for her and now she is of age and doesn't want to listen to me... Don't let that happen to you. This is really about getting the best care for our children, not who wins the argument.

[Dingo]

genetics

rohrer01

You have to understand there is a big difference between a disease spread by heredity and a disease caused by environmental damage in genetically susceptible people.

For starters don't be surprised if we learn that any child can have Scoliosis. Somewhere around 2% of people have it which suggests that just about anyone might be vulnerable. Genes may make the disease more likely and particular genes may allow for much worse symptoms. But of course the same is true for the flu. Anyone can get the flu but specific genes allow for much worse symptoms. Someday we'll vaccinate children against the flu. If we knew what the environmental component was that triggered Scoliosis we might be able to vaccinate against it as well. That would make it like Polio, not Cystic Fibrosis.

As for the BRCA1 and BRCA2 mutations it's my sense that they can directly lead to cancer because of the way they operate. Unlike a lot of genes that scientists associate with illness these two are well studied and the mechanism that leads to cancer is understood. And of course if these genes caused cancer in 5 year olds instead of 45 year olds they would be extremely rare.

BTW I try to keep my posts simple but I do know quite a bit about genetics. To most people "scrambled" makes more sense and has more meaning than the word Trisomy. To say that sometimes a gene causes a disease and sometimes it doesn't has more meaning to most people than "genetic expression".

[Pooka1]

So now we have someone who misunderstands even layman's plain English when used in a scientific context making an effort to "dumb it down" for the rest of us. Of course it's already at rock bottom so that isn't possible.

Are we on Candid Camera? That is the only hope here.

[rohrer01]

scoliosis is NOT like the flu

Influenza is a virus. You can not trace it in a family tree. EVERYONE gets the flu at some point in their life. Just so you know, they ARE vaccinating children for the flu. Just an educated guess, but I would say that they will NEVER be vaccinating people against scoliosis. You can't keep comparing the flu with scoliosis because everyone gets the flu. Only ~2% of the population get scoliosis. And as I said before, other inherited diseases aren't that common because the children born with them die before they can pass it on to the next generation.

The BRCA1 and BRCA2 genes are well studied, yes. Is the mode of action well understood by scientists? NO, otherwise they would not still be studying it. Women who carry the genes would not be getting mastectomies out of fear of contracting cancer because they would already know the risk factors for if or when they would develop cancer.

Scrambled and trisomy are not synonymous, so it doesn't help the average person to understand. Cell division is a complicated process. Meiosis and mitosis work differently. I do not find your "talking things down" so everyone can understand very logical. I haven't had any complaints about people not knowing what I'm talking about. You can be scientifically accurate and still put things in terms that people understand.

I will admit when I don't know something, like who this Odone fellow is, or what his accomplishments were. I'm really not trying to put you down. You just need to educate yourself. You do NOT understand genetics, heredity, and molecular biology as well as you think you do. I think a measure of humility is needed here.

I feel bad that Mamamax feels the need to jump in and defend you. But I'm really not trying to be insulting or mean. I've given you some very good advice on how to gain the knowledge you need to make your argument valid. I think Pooka1 says the things she does out of sheer frustration. I for one, don't believe that everyone needs to go to college to be a productive member of society. I went to college because I was in a situation that I felt compelled to have an education that would allow me to use my brain so that I could get a job, since I could not do manual labor, like waitressing because of my back. The subject matter I studied was pre-med and then some because I wanted to be a Physicians Assistant. Do I claim to know as much as a doctor? NO. But I did learn a lot about the human body, and my particular field of study was in genetics and molecular biology. I chose not to continue on in school because my children needed me at home. That was my choice. I don't even understand everything these researchers are doing, and to be honest as time goes by, I forget things. But basic things tend to stick with you. It's like riding a bike. You never forget.

Because of my experience, the next step for research in scoliosis, in my opinion, when they get the genetic thing figured out, would be to look at the endocrinological aspect of the disease. This is becaues there is a disparagement between males and females when it comes to progression. Environmentally, men stereotypically do more heavy lifting, work outside more, are exposed to more external factors that you would think would contribute to scoliosis (if you believe it is viral, bacterial, chemical toxins, or the such), especially viruses and germs. Think of plumbers, carpenters, and electricians crawling in all those aweful places to fix old houses, or worse yet, city sewage and sanitation. Not that women don't ever have those types of jobs, but those fields are dominated by men. This is partly why I find your germ theory hard to swallow. So please, don't be so quippy with me. I'm not being mean. I don't like to argue and accuse. I like to discuss ideas. But those ideas need to be reasonable and have a solid knowledge base. You can't compare scoliosis to every other disease out there. I admit I have done some comparisons, but only to make a point on how genetics and heredity work, not to say scoliosis is like.... So if your point is to continue to senselessly argue, I don't want to waste my time. If you want to reasonably discuss something, I'm all ears.

[Pooka1]

Influenza is a virus. You can not trace it in a family tree. EVERYONE gets the flu at some point in their life. Just so you know, they ARE vaccinating children for the flu. Just an educated guess, but I would say that they will NEVER be vaccinating people against scoliosis. You can't keep comparing the flu with scoliosis because everyone gets the flu. Only ~2% of the population get scoliosis. And as I said before, other inherited diseases aren't that common because the children born with them die before they can pass it on to the next generation.

The BRCA1 and BRCA2 genes are well studied, yes. Is the mode of action well understood by scientists? NO, otherwise they would not still be studying it. Women who carry the genes would not be getting mastectomies out of fear of contracting cancer because they would already know the risk factors for if or when they would develop cancer.

Scrambled and trisomy are not synonymous, so it doesn't help the average person to understand. Cell division is a complicated process. Meiosis and mitosis work differently. I do not find your "talking things down" so everyone can understand very logical. I haven't had any complaints about people not knowing what I'm talking about. You can be scientifically accurate and still put things in terms that people understand.

I will admit when I don't know something, like who this Odone fellow is, or what his accomplishments were. I'm really not trying to put you down. You just need to educate yourself. You do NOT understand genetics, heredity, and molecular biology as well as you think you do. I think a measure of humility is needed here.

I feel bad tha Mamamax feels the need to jump in and defend you. But I'm really not trying to be insulting or mean. I've given you some very good advice on how to gain the knowledge you need to make your argument valid. I think Pooka1 says the things she does out of sheer frustration. I for one, don't believe that everyone needs to go to college to be a productive member of society. I went to college because I was in a situation that I felt compelled to have an education that would allow me to use my brain so that I could get a job, since I could not do manual labor, like waitressing because of my back. The subject matter I studied was pre-med and then some because I wanted to be a Physicians Assistant. Do I claim to know as much as a doctor? NO. But I did learn a lot about the human body, and my particular field of study was in genetics and molecular biology. I chose not to continue on in school because my children needed me at home. That was my choice. I don't even understand everything these researchers are doing, and to be honest as time goes by, I forget things. But basic things tend to stick with you. It's like riding a bike. You never forget.

Because of my experience, the next step for research in scoliosis, in my opinion, when they get the genetic thing figured out, would be to look at the endocrinological aspect of the disease. This is becaues there is a disparagement between males and females when it comes to progression. Environmentally, men stereotypically do more heavy lifting, work outside more, are exposed to more external factors that you would think would contribute to scoliosis (if you believe it is viral, bacterial, chemical toxins, or the such), especially viruses and germs. Think of plumbers, carpenters, and electricians crawling in all those aweful places to fix old houses, or worse yet, city sewage and sanitation. Not that women don't ever have those types of jobs, but those fields are dominated by men. This is partly why I find your germ theory hard to swallow. So please, don't be so quippy with me. I'm not being mean. I don't like to argue and accuse. I like to discuss ideas. But those ideas need to be reasonable and have a solid knowledge base. You can't compare scoliosis to every other disease out there. I admit I have done some comparisons, but only to make a point on how genetics and heredity work, not to say scoliosis is like.... So if your point is to continue to senselessly argue, I don't want to waste my time. If you want to reasonably discuss something, I'm all ears.

Post of the month nomination.

I admire your restraint. The rest of us have been us against this stuff for a long time. Edification is futile. We have a person who clearly feels he is an inadequate parent if he isn't pretending to understand the science of scoliosis. I understand that but that shouldn't mean he gets carte blanche to post anything that pops into his head that doesn't even come close to being science or even rational at times.

Odone is a father of a patient with adrenoleukodystrophy (ALD). From the wiki page:

This severe form of adrenoleukodystrophy was first described by Ernst Siemerling and Hans Gerhard Creutzfeldt in 1923.[3] Lorenzo was diagnosed in 1984, using a new blood test that had been recently developed. People with the disease were usually young boys (5–10 years old), who would gradually become mute, deaf, unable to move, and blind, and would typically die within two years from aspiration or other neurologic causes.

Augusto and Michaela refused to accept this grim prognosis, and fought to find a treatment for their son's fatal disease, clashing time after time with doctors, specialists, and support groups, some of whom were skeptical that two average citizens could produce a cure. With the help of Hugo Moser,[4] and through long hours of research and study, the Odones, who had had no previous medical background, came up with a treatment. This treatment involved the consumption of a specially prepared oil, which became known as "Lorenzo's oil".[5] Lorenzo's Oil has been shown to be ineffective in patients with a related condition, adrenomyeloneuropathy[6].

The Odones had an important role both in developing Lorenzo's oil and in setting up the Myelin Project, which promotes and carries out research on ALD and other similar disorders. Michaela also insisted on continuing to treat her incapacitated son as a human being and not a "vegetable", helping him devise a means of communicating with her and others through the blinking of his eyes and the wiggling of his fingers.

These parents put in the hard work to actually understand the issues enough to propose a rational dietary treatment. But ALD and AIS could not be more different in terms of what is known about each. The situation with AIS is nowhere near as well known and we have various groups of researchers investigating completely different hypotheses. So unlike ALD where not only is it known to be genetic but they knew the entire biochemistry of the problem, the only thing known about AIS is that it has a strong genetic component. The Odones had a huge advantage dealing with ALD where so much more was known.

[Dingo]

Scoliosis

Rohrer01

Influenza is a virus. You can not trace it in a family tree. EVERYONE gets the flu at some point in their life.

The flu virus causes the flu, but it's not that simple. It might also cause diseases like Schizophrenia and Autism.

Flu During Pregnancy May Increase Risk Of Schizophrenia In Certain Offspring

When mothers become infected with influenza during their pregnancy, it may increase the risk for schizophrenia in their offspring. Influenza is a very common virus and so there has been substantial concern about this association. A new study in the June 15th issue of Biological Psychiatry suggests that the observed association depends upon a pre-existing vulnerability in the fetus.

Lucky for us a universal flu shot is in clinical trials right now. Vaccinating against the flu may reduce the incidence of Schizophrenia, Autism and many other diseases.

For arguments sake let's pretend that the environmental component of Scoliosis is the flu virus. Exposure to a particular strain of the flu, in a high enough dose at the wrong time may trigger the nervous system damage that leads to Scoliosis, especially in genetically susceptible children. In that case vaccination against the flu would eliminate Scoliosis just like the Polio vaccine eliminated Polio.

Most people don't realize that very few children who were exposed to the Polio virus suffered any permanent damage. Wiki: Polio Most kids had no symptoms and a few simply came down with what felt like a cold. However a small minority of children weren't so lucky. Something like 1 in 1,000 children suffered paralysis. No doubt many of the most severely affected children had a genetic susceptability to the Polio virus. I've seen old news clippings with headlines that showed that in some families multiple children were killed by Polio.

[rohrer01]

Rohrer01




For arguments sake let's pretend that the environmental component of Scoliosis is the flu virus. Exposure to a particular strain of the flu, in a high enough dose at the wrong time may trigger the nervous system damage that leads to Scoliosis, especially in genetically susceptible children. In that case vaccination against the flu would eliminate Scoliosis just like the Polio vaccine eliminated Polio.

Most people don't realize that very few children who were exposed to the Polio virus suffered any permanent damage. Wiki: Polio Most kids had no symptoms and a few simply came down with what felt like a cold. However a small minority of children weren't so lucky. Something like 1 in 1,000 children suffered paralysis. No doubt many of the most severely affected children had a genetic susceptability to the Polio virus. I've seen old news clippings with headlines that showed that in some families multiple children were killed by Polio.

I would be more inclined to believe that a scoliosis trigger may be a lack of enough folic acid during pregnancy. At least in my case, I also have spina bifida occulta. Spina bifida is connected to folic acid deficiency, and possibly heredity as well, as my son also has it. Both my mother and myself were very diligent about taking our folic acid during pregnancy. However, when I was undergoing fertility treatments and they found out about all of my back issues, they put me on mega doses of folic acid, 4mg/day. The usual amount in a non-prescription prenatal vitamin is 0.8mg/day and a prescription prenatal vitamin is 1.0mg/day. Maybe that is the environmental trigger? Many things can happen in-utero to affect the child. High fevers, german measles can really do a number on a baby, and several other things, including stress. I'm having a hard time accepting your germ theory because there are families, like mine, that are extrememly hard hit by scoliosis. These are genetic patterns, again not saying environment has nothing to do with it. But my biggest guess is that environment in which something is triggered to turn on the scoliosis genes is probably during gestation. The other factors are hormonal (endocrinological), due to the fact that girls go through a more harsh and sudden production of hormones that are constantly fluctuating, and not just estrogen. They continue with their menstrual cycle throughout their child-bearing years and guess what? Women progress more than men do. Just plain old deduction. What makes girls different from boys. Thankfully you have a SON with scoliosis and not a daughter. Not saying that he will never progress, no one can know that. It's too early in the game for that. But at least he has gender on his side. You are going to have to come up with some pretty severe "proofs" to convince anyone that scoliosis is caused by a flulike virus simply because it has such close ties to families, which indicated a genetic disorder. BUT if you do your research from legitimate sources - I suggest putting you on the trail of gestational diseases (whether viral or not) and hormonal imbalances. It would be nice to vaccinate our children for scoliosis, but I'm afraid that it is predetermined before the child is born. I hope you are focusing most of your research on treatment options for your child and finding out what works and what doesn't and WHY. I think that would be time best spent. They grow up so fast and it makes you wonder where the time went. Worry about him right now, then when he is grown focus on the how's of the disease. I wish I had done more for my daughter, as I previously stated. Don't get so caught up in these discussions and debates that you forget to get him the best treatment for him. Just a word of advice from one parent to another.

As far as Polio's effect on people. I've only known two people with Polio and BOTH had paralysis from it. My grandmother was one of them and she suffered terribly from Post-Polio syndrome. She had extreme pain as an adult (in her 40's and 50's) and died at the age of 59. No one knows what she died from. I don't know that much about Post-Polio syndrome.

Also, remember that while wikipedia is a good source for information. It is not "official" and can be changed by anyone. You seem to get a lot of information from there. A good place to go for accurate data is PubMed through nih (National Institute of Health) and the CDC.

[Pooka1]

Gestational issues are a factor

Maybe that is the environmental trigger? Many things can happen in-utero to affect the child.

I think it was Ogilvie who when asked about why monozygotic twins were not 100% concordant he replied something along the lines that twins studies are not necessarily a good model for studying scoliosis because it is a midline developmental disorder and monozygotic twins at least are known not to always split evenly or along the same axis or something.

So he was saying that there are physiological reasons NOT to expect monozygotic twins to be concordant. No need to discard the genetic basis when noting they are not 100% discordant. Researchers working in this field know these things... lay, untrained parents, not so much.

Just like I know things in my field that someone even in an allied field may not. And it matters critically in some cases... it is hard to have to suggest rejecting a paper for a journal when the person has missed a critical detail that undermines the results. In this case, if enough is known about splitting of the fertilized egg then they had better somehow control for that in the studies or these twins studies on scoliosis possibly should not continue to be published.

And for every issue like this that have been identified there are a million left to be identified. So even something like using mono- and dizygotic twins to study scoliosis which might seem okay at first may not be.

It is very easy to see why most published research results are false despite the best efforts of the researchers.

And it is very easy to see why a lay, untrained parent may think the problem is defined and that the literature is perfect when in fact neither might be the case.

[Pooka1]

From that wiki page I posted...

With the help of Hugo Moser,[4] and through long hours of research and study, the Odones, who had had no previous medical background, came up with a treatment.

Note start of the sentence, "With the help of Hugo Moser." So they were working closely with a researcher. Imagine the sheer number of edifications that must have occurred given the lack of medical training of the Odones. And then imagnie how they took that edification on board and used it to develop the suggested dietary treatment.

A random lay parent NOT working closely with a researcher NOR accepting edification about even basic stuff NOR getting appropriate training is not in the same category as the Odones.