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Interesting AHCY Variations

Discussion in 'Genetic Testing and SNPs' started by Valentijn, Jul 30, 2013.

  1. Valentijn

    Valentijn Senior Member

    AHCY has been studied somewhat, mostly in relation to homocysteine levels and associated disease risk. Missense mutations are underlined, bolded, and orange. Two missense mutations have no research associated with them, but in both cases the minor allele is extremely rare, which might reflect that those alleles are not well-suited to survival (or it might mean nothing at all).

    A712G and C124A are almost synonymous, but not quite, especially in non-European groups. The contradictory results might indicate that there's a bigger factor at play than the alleles themselves - the risk might manifest when the two SNPs are not synonymous for someone.

    None of the Yasko AHCY SNPs are included because there is no research showing that they have any impact on the functioning of the gene.

    rs1205366....A712G...CC...T is protective
  2. Valentijn

    Valentijn Senior Member

    So what is AHCY and why is it relevant?

    AHCY is adenosylhomocysteinase and the gene creates an enzyme (both named AHCY, and also known as SAHH) which can convert homocysteine into SAMe (via SAH) and vice-versa. This can feed into methylation.

    Dysfunction can result in elevated methionine or elevated homocysteine.
    ukxmrv likes this.
  3. Sea

    Sea Senior Member

    NSW Australia
    Sorry I don't understand what you mean by synonymous here

    That is a good statement. I think it is important to be clear on what is backed up by research, what is unresearched and what is disproven. I am uncomfortable making claims about snps that have no research to back them up, but I am also unsettled by statements that assert snps are irrelevant because there is no research, or that there is no impact on gene function because there is no change in protein.

    I don't know enough to know how accurate wikipedia is here, but I found this interesting:

    When a synonymous or silent mutation occurs, the change is often assumed to be neutral, meaning that it does not affect the fitness of the individual carrying the new gene to survive and reproduce.

    Synonymous changes may not be neutral because certain codons are translated more efficiently (faster and/or more accurately) than others. For example, when a handful of synonymous changes in the fruit fly alcohol dehydrogenase gene were introduced, changing several codons to sub-optimal synonyms, production of the encoded enzyme was reduced and the adult flies showed lower ethanol tolerance.
  4. Valentijn

    Valentijn Senior Member

    Sometimes 2 or more SNPs are basically the same - they almost always get inherited together as a chunk. In studies, if both synonymous SNPs are included, they'll be seen as having the same impact. VDR Taq and VDR Bsm are another example of this - if you know what someone has in Taq, you can predict what they have for Bsm.

    So having the risk version of each is not more significant than having the risk version of just one. But, as seems to be the case of VDR Taq/Bsm, there might be a bigger risk associated with the two synonymous SNPs not being in synch with each other.
    Without research, I think it's a matter of looking at the odds. What are the odds that a random SNP is having an impact? Quite small - certainly too small to start a treatment designed around a presumed gene dysfunction based on that random SNP.

    While I wouldn't object to Yasko saying that "I think Autism patients are helped by doing X, Y, and Z", it's very dishonest to pick a random unresearched SNP on a gene and then describe how that gene functions, and conclude that everyone with a certain version of that SNP needs a certain treatment. She's using those SNPs as an authority upon which the treatment is based, when there is absolutely nothing relevant known about many of those SNPs.
    Sorry I wasn't clear ... I meant that the two SNPs are mostly synonymous with each other, not that they create synonymous mutations (which they do, due to the lack of amino acid substitution in the gene).

    I agree that synonymous mutations can definitely have an impact, and they often do. It's just usually a lot less serious than the ones with missense and related mutations. Synonymous mutations tend to have a mild impact in functioning (gene might be a percentage point or two "slower" or "faster"). Whereas missense, stop-gain, splice, and insertion or deletion mutations can range between causing no problem at all (such as when there's a missense mutation involving two very similar amino acids), or rare and severe health problems, or death.

    It really depends on how it affects the protein made by the gene. A missense mutation might result in the protein breaking down a little faster or a lot faster. Or a stop-gain might result in an essential part of the protein being missing. And then it also depends on how vital that protein is - does it have a mild impact when it's malfunctioning, or is it deadly? Can it be compensated for with a supplement or is it incurable? Does it impact the development of children, or does it manifest in adults?

    There's so many variables that it's impossible to predict what any SNP will do, which is why at least some research is necessary before making any assumptions at all. Some of that research can be very basic, such as showing a missense mutation and/or population prevalence. But if there's no mutation and all versions are quite common among healthy people, there's no basis to assume that any version is causing problems.
    Sea likes this.
  5. Bluebell

    Bluebell Senior Member

    I agree.

    Sea, your icon picture exudes coziness. :)

    Makes me want to snuggle under a duvet.

    (perhaps with Paul Newman, around age 30)

    ((well, at least I have the duvet))
    Sea likes this.

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