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Does a defective gene cause Th1 inflammatory diseases?
We used to think that you needed to carry a defective gene to acquire sarcoidosis or other Th1 inflammatory diseases so we talked about a genetic predisposition.
But Dr. Marshall has been telling us that recent studies of sarcoidosis patients do not show any consistent mutation in the human DNA. Investigators are not seeing any significant genetic predisposition in sarcoidosis patients and there have now been several good studies, on several different populations (countries). This argues against the predisposition being mutation in the human DNA.
Chronic damage to the human body occurs when the pathogens evade phagocytosis in the phagocytes where the genes for most of the body's immune functions are being transcribed, modified, and translated.
It is the ability of the genomes to interact which is key to chronic disease.
Bacteria are capable of mutating and changing genetic expression of cells. The evident communicable nature of these diseases and the fact that up to 25% of the population seem susceptible to Th1 diseases also argues against DNA mutation (genetic defect).
"I don't believe that the HLA axis genetic changes are necessarily handed down in an individual's DNA, I believe that the HLA axis (HLA-DRA, HLA-DRB and HLA-DQ) are all mutations caused by the pathogens responsible for Th1 infection.
"Only that hypothesis explains why so many different diagnoses end up with common HLA haplotypes, yet there is not determinate diagnostic value to be obtained by measuring them. Yes, I know, some of the HLA haplotypes are 50% greater in this, that, or the other diagnosis, but genetics should result in 100% and 0% and anything else is just statistical noise, and should be discarded, IMO.
"I personally feel that if there were some defective human genes involved that they would already have been identified by the genomic studies over the past few years. Yet all that these studies have produced is a vast array of statistical 'noise,' particularly in the area of the HLA-DRB and HLA-DQ genetic axes. I believe that the variability in these regions is because of the impact of the microbial pathogens on these regions.
"The HLA axis genes are almost certainly mutated, or expressing incorrectly, due to pathogenic processes. IMO, there is just no evidence for widespread mendelian variation of the HLA axis in the gene pool alone. Pathogenic activities are the only sensible conclusion.
Of course, if you don't understand DNA and miRNA and all the other factors involved in transcription, if you don't understand errors which can occur in the 'gene measurement' process, and if you don't comprehend the magnitude of the bacterial load homo sapiens is carrying, I can see how it is seductive to assume that individuals somehow "carry bad genes." There is just no real science to back up that view, however."
..Trevor..
"Genetic defects are due to the Th1 pathogens, nothing more. That whole branch of science is built on quicksand, and they are just starting to understand that fact right now...
"This is a lot more cancer genes than we expected to find," says Michael Stratton of the Wellcome Trust's Sanger Institute in Cambridge, UK "
..Trevor..
Genetic mutations
"as for mutations - where do they come from? Caused by the pathogens, of course... Some may just be due to DNA 'noise' arising when genes are being sequenced, when genes are pasted together, even though they don't come from the target organism (Homo sapiens). Not real 'mutations', in that latter case...
..Trevor..
Genetic studies have not yielded any successful treatments
The mistake that all these researchers are making is the assumption that an association between disease symptoms, and mutations in genes, infers that the gene changes lead to the symptoms.
Yet after billions of dollars spent in research, not one gene therapy, not even for the classic genes supposed to be causal for Cystic Fibrosis, not one gene therapy has proven safe or effective.
The reason for this failure-to-perform is that the hypothesis is incorrect. What the researchers are seeing as changes on genes are indeed changes, but they only correlate at low levels of significance because they are due to pathogens. They are due to mutations from chronic infection. Consequently there is no causal effect - only an associative observation.
If you consider that it takes folks on the MP, killing the intracellular bacteria at the fastest rate their bodies can manage, 3 years or more to fully clear the bacterial load in their bodies you can get some idea of the huge amount of pathogenic DNA we are all carrying about. A recent study found 60% of the 'healthy' population are carrying L-forms in their bloodstream.
Part of the problem is that the folks computing the statistics are not the physicians who collected the data, and so there is a disconnect, and two disparate sets of knowledge are not quite meeting when discussing the meaning of statistical certainty. The statistical correlation in every one of these gene studies is very low indeed. Just above the noise.
So once again "the alternate hypothesis" reigns supreme. One that the optimism of modern medicine consistently fails to adequately consider.
..Trevor..
Q: If the mutating agent (chronic inflammation due to infection) is withdrawn (CWDB eliminated), what potential does the organism have to fix the DNA-damage? How well will the DNA repair mechanisms work ?
A: The body has a number of redundant repair mechanisms. Actually I should use the word "complementary" as that is a better description. These defense mechanisms are affected by the pathogens, as evidenced by accelerated aging of folks with Th1 diseases. However it is still unclear to what extent the body's DNA is actually altered, mutated, and to what extent it is changes in the transcription mechanisms which cause the altered proteins in the body.
Based on the healing that we have observed, we do not see any significant remanent degradation, and we do see healing of both cognitive and physical abilities. I would therefore urge you not to worry to much about irreversible damage until we start to observe that it has occurred 
..Trevor..
Fetal development defects
One of the things that fascinated me with the list of genes probably transcribed by the VDR, was the presence of a gene known to be associated with Down Syndrome. Most of the other 27,000 genes have functions which are not identified yet. Yet this one identified linkage makes me think it is certainly possible that a dysfunctional VDR is responsible for some of what we know as "birth defects" but which actually might more accurately be called "fetal developmental defects."
..Trevor.. Nov07
One of the genes known to be trasncribed by the VDR is located in the region known to be responsible for Down Syndrome. The function of this gene is currently unknown, but it certainly seems as though Th1 pathogens might well be involved in this most classic of "birth defects."
ps: interesting that the incidence of DS increases with the age of the mother. Another pointer to Th1 involvement.
..Trevor.. Mar08
The biologists understand what Paul Ewald told Amy in Bacteriality-
http://bacteriality.com/2008/02/11/ewald/
"Evolutionary biologists understand that if an allele (a sequence that codes for a gene) were to code for a disease it would slowly get weeded out of the population, particularly since people who are sick are much less likely to reproduce (especially people with a severe disease like schizophrenia). Yet a person’s chances of getting schizophrenia are 1 in 100. The reality is that faulty genes cannot maintain this frequency. If schizophrenia was a genetic disease, then according to the rules of mathematics, it would only occur in about 1 in every 10,000 people. The current frequency of the disease is just far too high."
Note: it would be so for any disease, not just schizophrenia, such as cystic fibrosis.
June 18, 2008 There is a concept which any successful scientist learns early in their career - it is that some problems are just not deterministic. In this case you have thousands, probably tens of thousands of proteins, enzymes, lipids, steroids, etc being produced by the metagenome, and there is no way you can deterministically account for the effects of them all. The entire field of Genomics at this point in time is spinning its wheels trying to figure out one success - just one success - that they can truly claim to validate their view of the world.
The truth is that their view of the world is limited, that they haven't even conceived the scale of the problem. They think they are working in a deterministic environment, and they are not.
It is pointless trying to figure out relationships when there is such diversity in the metagenome from individual to individual. You have to stand back to smell the roses.
..Trevor..
Jul08...I am not so sure that human DNA is altered to include the symbionts. Indeed,IMO there would be no evolutionary need for this to happen.
Since the metagenomic microbiota has evolved to live in the cytoplasm of nucleated cells, including phagocytes, they not only have access to the DNA transcription machinery of Homo sapiens, they have access to the DNA repair machinery. By interfering with the repair machinery they can induce the multiplicity of SNPs, etc, that we typically see as folk grow sick, and as they grow older. There would be no evolutionary pressure for genomic integration, as far as I can see. The pathogens already have the upper hand.
..Trevor..
Sep08...The next decade will be an exciting one for young scientists. The Human Microbiome project is setting out to identify all the species of bacteria which form part of Homo sapiens:
http://nihroadmap.nih.gov/hmp/
It is estimated that in a single human being there are 25,000 human genes and over a million bacterial and viral genes.
Of the total number of cells in the human body, about 10% are estimated to be human cells, and about 90% are bacterial cells.
..Trevor..
See also:
Bactera vs genes: the spread of chronic disease in families
Koch's Postulates, Horizontal Gene Transfer, and the Era of the Genome
The Bacterial Boom...Implications of the Human Microbiome Project
Last edited on Fri Oct 10th, 2008 16:31 by Foundation Staff
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