Professor & patients' paper on the solvable biological challenge of ME/CFS: reader-friendly version
Simon McGrath provides a patient-friendly version of a peer-reviewed paper which highlights some of the most promising biomedical research on ME/CFS ...
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basic question about gene expression

Discussion in 'Genetic Testing and SNPs' started by Aerose91, Nov 26, 2015.

  1. Aerose91

    Aerose91 Senior Member

    Im just not quite sure the answer to this. When we talk about epigenetics and gene expression, does it not matter if we have snp's or not?

    For instance, if you have +/- then you could be expressing either the mutation or correct gene because you have both options.

    If you're +/+, or contrary, -/- does gene expression even matter since both copies of your genes are the same so you can't really "express" something different?
  2. Sea

    Sea Senior Member

    NSW Australia
    Most of the groups I've seen trying to provide people with health information based on their snps "expressing" really have no understanding about gene expression.

    Google snps gene expression and do some reading from pubmed or scholarly articles and you will get far more understanding.
    Valentijn likes this.
  3. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    You have reason to be confused about this. Even prominent research groups working on molecular biology quite often present findings in a way that seems to confuse these things. Gene expression really has pretty little to do with genetics. Epigenetics is a word that nobody can agree the meaning of. There are a few unusual situations where 'epigenetic' is useful to refer to odd patterns of transmission of gene methylation from parent to child but otherwise I think things would be clearer if the word was abolished. It is only used to write trendy grant applications and sound slick.

    Gene expression refers to how much messenger RNA a particular cell type is making from particular genes, with the expectation that that will indicate how much protein it is making from those genes. It is quite separate from genetics per se. So if someone studies gene expression of a cytokine gene after exercise that has nothing to do with genetics, it has to do with cellular signalling. Clearly if the gene is missing there will be no expression, but there is no need to study exercise to find that out.

    SNPs are single base alternatives in DNA sequences. They are not necessarily 'mutations' and 'correct genes'. Often genes just come in more than one variant and it may be hard to say if one variant is 'better' than another. For HLA genes there are lots of variants and no one is better than another. If the alternative is in the part of the gene that codes protein sequence then two variants will produce slightly different proteins. In some cases one of those proteins is no use but more often it just has a slightly different binding strength or something like that. But the alternatives of the SNP may be outside the protein encoding region (or even outside the gene and be completely 'silent'). If the SNP is in the promoter or controller region of the gene then it may change the amount of gene expression you get in response to a signal in the cell - it might mean you only make 50% as much protein with one variant as with the alternative variant.

    But by and large whatever difference in gene function there is between one variant of an SNP and another that difference will be constant throughout life regardless of how much the gene is being expressed. Genetics is like the size of your car engine. Gene expression is like how fast you try and drive it. Because most genes have complex feedback control systems it is likely that you get much the same amount of protein function despite small variations in terms of SNPs. If the speed limit is 50mph then everyone drives that fast, regardless of the size of their car engine. But in some instances SNPs will put a cap on the protein function in a given situation.

    To be honest it all seems pretty academic for ME'CFS since we do not know of any SNP based gene variations being relevant to the condition. The main reason for looking at genetics in ME/CFS to my mind is to establish whether or not there is a genetic predisposition at all - which would help establish the physical nature of the condition. Since we have no idea what, if any, molecular pathways might be abnormal (the abnormality would have to be very slight since people are healthy before they get ME) I doubt that knowing about any particular genes is of much relevance.
    Sea, barbc56, voner and 2 others like this.
  4. Valentijn

    Valentijn Senior Member

    I think @Jonathan Edwards explained expression pretty well. It's not really like you have some dormant freakish mutation which suddenly comes to life and tries to eat you. It's more of a tweaking in regulation which happens outside of the strictly genetic aspect.
    That wouldn't really be about expressing, but about the SNPs themselves. If the SNP has been studied, then the size of the impact is usually known. +/- doesn't mean a 50/50 chance of it working or not, but rather how that SNP impacts gene functioning. On some genes, +/- for a SNP means that the gene functions at or near 100%, even if being +/+ means a drastic alteration in gene functioning. On other genes, a +/- SNP can be enough to cause a disease, or cause a big alteration in gene functioning - it depends on the gene and the way it operates.

    A good example is MTRR versus MTHFR. To have a big reduction in MTRR functionality, it has to be +/+ for a SNP, or compound heterozygous (one from each parent) on two missense mutations which are capable of causing problems. But for MTHFR, being +/- on an important missense mutations will have a big impact, albeit less of an impact than being +/+. This is quite consistent for all of the missense mutations I've seen research for on those genes. They each have a different rule, but follow their own rule very consistently.

    If someone is talking about gene expression on the internet (blog, forum, etc) as being an explanation for yours (or others) specific genetic results, they're usually just talking out of their rectum. Basically they have invested in making ridiculous claims about specific SNPs which are based on Yasko's bizarre claims, which are usually contradicted by the research when there is any. They cannot deny that those claims about the SNPs are wrong, so now they invent vague and completely unsubstantiated claims regarding "expression" of genes. Apparently they expect these SNPs to behave in a radically different manner when some mythical trigger comes along, despite the complete lack of scientific support for these claims.

    If someone's talking about "genetic expression" in that context, it's a good sign that they're a quack, or a wannabe quack.
    Sea, barbc56 and voner like this.
  5. Aerose91

    Aerose91 Senior Member

    Those are both really thourough explanations, and much more in depth than i had learned prior. Thank you guys for breaking it down.

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