The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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Please provide input on my symptoms and how to handle...

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Mindy, Aug 26, 2013.

  1. Valentijn

    Valentijn Senior Member

    Yup. Just above the map there's "Assembly" then "SNP to Chrom" which says "Rev". If you hover "Rev" it clarifies that it's using the reverse orientation instead of the forward orientation. So their C and T are really G and A when on the forward orientation, which is what 23andMe uses.

    You're good until you assume which allele is the risk one. Only the paper can tell you that for sure. If you look at table 4 it lists both alleles, with one labeled as "coded" and the other as "other". Then in the next column it clarifies that it's looking at the "coded" allele (A) when it lists its frequency. And the beta coefficient is positive, thus A results in higher systolic blood pressure, which is what is associated with that gene (mildly) malfunctioning.
    Okay, you did great until assuming A is the "mutation". The gene is having its alleles reported in reverse, so the mutation is actually A to T, meaning you have the normal version. Figuring this out is quite tricky when the two alleles for the SNP are equivalent to each other when on reverse strands. So it can help to look at another missense mutation on the same gene where the alleles aren't "A and T" or "C and G".

    If we look at a nearby missense mutation on the same gene, such as is at location 104,595,073 (i5001477, rs104894154) we can see that on the missense line it shows G->A when it should be C->T to get the mutation. Thus we know that in a reversed SNP, the alleles are reported in reverse for the missense information, hence what looks like T to A is really A to T.

    Hence with AA reported by 23andMe, you have YY ([tyr]osine) version. Then if go to the variation viewer and look at the OMIM entry ( ), we can find out what's going on. The "T to A" bit doesn't help, because we don't know the orientation. But they clarify that it results in a Y to N mutation in the enzyme, hence N is the risk factor. Looking back at the original SNP page, we see that the N amino acid equates with the A allele, but the allele is reversed, hence it's the T allele from 23andMe results which result in the pathogenic N amino acid in the enzyme.

    There's really no indication of a problem here. You have the normal version of the 2nd SNP, and have a very common heterozygous version of the 1st SNP, which doesn't even have a big impact when it's homozygous.
    Critterina likes this.
  2. Mindy


    A bladder infection
  3. Critterina

    Critterina Senior Member

    Arizona, USA
    This is like when you get your test back and learn more from your mistakes than all the lectures and homework problems combined. Thank you! :hug: I'm going to have to try the next few and have you check me out again.

    That's a big relief! I have normal cholesterol, good HDL/LDL ratios, and am taking plenty of minerals (Bluebonnet chelated multiminerals with boron), but everything from pregnenelone to cortisol and DHEA to estrogens were undetectable, below normal, or in the bottom of the range. Then with low doses of progesterone, DHEA, estradiol, estrone, and testosterone, I went to over 100% (some over 400%) of everything except DHEA, which didn't move...I was looking for a genetic basis - not hoping to find it, but just wanting to know what I'm up against. I should probably post this on a hormone forum and see what feedback I get.
    Valentijn likes this.

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