Gene info from ME site ( Long)

Discussion in 'Fibromyalgia Main Forum' started by sues1, Jun 11, 2006.

  1. sues1

    sues1 New Member

    Since I have problems following a long in reading.......I read more complex things more slowly and I use my mouse pointer to follow along...makes it easier to follow.
    I thought this was interesting and worth reading.

    From Jill McLaughlin, as posted to the list CFS_Research:

    Genes are the units of heredity. They contain the information necessary to construct the products/chemicals (proteins etc.) needed for the organism to function. Genes are encoded in the organism's genetic material (DNA) and control the development and behavior of the organism.

    DNA consists of a double-helix molecule (which was discovered by Watson and Crick in the 1950's) found in the cell nucleus that incorporates a sequence of nucleotides, each made up of one of four bases (adenine, guanine, thymine or cytosine), a sugar (deoxyribose) and a phosphate group (hence the name deoxyribonucleic acid). A sequence of three nucleotides in the DNA molecule, known as a codon, codes for each different amino acid which forms protein. RNA is an intermediate product in the process of manufacturing proteins from
    genes, known as transcription and translation, so if you hear these terms you'll at least know where they fit in.

    The word gene has increasingly reflected its meaning in molecular biology, i.e., the segments of DNA which cells transcribe into RNA and translates into proteins. "Gene expression," goes beyond the presence or absence of a particular gene, but is the degree to which the code for that particular enzyme has been "expressed" i.e., translated into making a certain enzyme or protein. The DNA strand is expressed into a trait only if it is transcribed to RNA, which is what gene expression refers to. In eukaryotic species, very little of the DNA in the genome encodes proteins.

    In common usage, gene is often used to refer to the hereditary cause of a trait, disease or condition. In the Mendelian sense, traits are rather straightforward, dependant on whether a gene is dominant or recessive, such as eye color, hair color, blood type etc. However it is well known that factors other than genes determine many other characteristics or conditions or susceptibility to them: diet, exercise, environmental exposures, culture etc. The term phenotype refers to the characteristics that result from this interplay.

    Mutations are changes or errors in the sequence of a gene which may arise. Mutations may occur in the DNA of the sperm or eggs of a particular person. From there, the mutations are passed on to the offspring of that person, and they become part of the DNA of every cell in the body, including the germ cells (testes and ovaries) that they pass on to their offspring. We inherit mutations from our parents, and we pass them on to our children.

    There are several possible types of mutation. One type of mutation is a "single nucleotide polymorphism," or SNP. An SNP is a small genetic
    change, or variation, that can occur within a person's DNA sequence. Although SNPs do not usually produce physical changes in people, they may predispose people to disease or determine the severity or progression of disease or even influence their response to treatment or medications.

    Some mutations render certain reactions and products completely absent or nonfunctional. If this product affects a reaction that is essential for life, such a mutation is considered lethal and is fatal to the organism. Other mutations cause the affected enzyme to be less efficient than the normal form of the enzyme, in varying degrees, depending on the particular mutation. (This is what may account for the low molecular weight RNase-L abnormality, which is the type of thing that CDC should have studied instead of taking the very broad approach of looking at all genes and finding abnormalities - which may overlap with other conditions - and focusing on a few involving neuroendocrine HPA axis abnormalities involved in the stress response. Or at least this is what they reported on.)

    Over a million different SNPs have been found in the entire human
    genome. We all have some of them. It's just a question of which ones we have. The differences between the set of SNPs that anyone has contributes to the different susceptibilities to various diseases or toxic insults etc. SNP's may account for our unique biochemical individualities.

    In this type, one nucleotide has been changed in the normal gene sequence and the importance is in how it relates to protein synthesis (enzymes are proteins).

    Enzymes are a type of protein, and they are formed by the cell as
    chains of amino acids. The particular sequence of amino acids for each enzyme is coded in the gene (the DNA sequence found in the cell nucleus) for that enzyme.

    Once an SNP has occurred and a person has a particular SNP, all the copies of the particular product that is coded for by the gene that has this SNP will have the same abnormality (i.e., amino acid change) from the normal enzyme. Depending on where in the sequence this change has occurred, it can have a minor or pronounced effect on the enzymes efficiency in promoting its particular biochemical reaction and thus on the organism as a whole. Because SNPs are inherited and do not change much from generation to generation, following them during population studies is straightforward.

    A mutation refers to a change in the sequence of nucleotides in the
    DNA, and it can be caused by many things, such as radiation, chemicals, toxins and viruses. Cause may be important on some levels but practically this is what is happening regardless of the cause, and different causes may produce the same damage and results. On a practical level, the discovery of the cause of polio did not get people out of iron lungs. For those who are sick now, what
    is happening and the effects - regardless of why - and determining how to abrogate them may be the best approach. Sure we need to know more, but how can we use what we do know to our best advantage. We cannot wait until all issues are conclusively resolved to be able to get good treatment and adequate care.

    And a follow-up by Rich Van Konynenburg:

    I think that was an excellent explanation of polymorphisms, Jill!

    There's one thing about the CDC studies, though, that has been
    misconstrued by reviewers, I think because the CDC and their
    collaborators did not make it clear.

    There are now believed to be over 10 million existing SNPs in the
    total human genome of the world's population. The CDC and its
    collaborators did not search the entire genomes of the Wichita
    subjects they studied. They focused only on a few SNPs that are known
    to occur in enzymes and other proteins involved with the stress
    response system and the neurotransmitter system. I think they chose
    these because they suspected that there were issues in these systems.

    My hope is that researchers will look elsewhere in addition. I am
    particularly interested in the entire sulfur metabolism (including the
    methylation cycle and the transsulfuration pathway, the folate
    metabolism and the biopterin cycle, the detox system, the antioxidant
    system, and the immune system. Gradually papers are starting to come
    out about SNPs in CFS in these systems, and I hope we see more of it,
    because I think that will give a more complete picture.

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