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HLA DR in 23andMe Gene Set

Discussion in 'Genetic Testing and SNPs' started by Skyline, Apr 19, 2013.

  1. Skyline

    Skyline Senior Member

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    I'm looking into the gene susceptibility to issues with biotoxins at the moment. Using Ritchie Shoemaker's work, you can assess your potential to have issues with molds via the HLA DR PCR test (http://www.survivingmold.com/diagnosis/lab-tests)

    I'm wondering if any of that information is available in the 23andme set and am going to trawl Snpedia for the info (today unfortunately it's not accessible from where I am).

    If anyone has already looked into this, I'd love to know what you found so far.
     
  2. searcher

    searcher

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    My understanding is that you can't figure out your HLA DR from your SNPs-- they either don't know all of the SNPs or there is some sort of epigenetic mechanism that combines with your SNPs to determine your HLA DR. You can narrow down your HLA DRs from your SNPs but not enough to be useful, I think. Please let me know if you find out otherwise!
     
    roxie60 likes this.
  3. Skyline

    Skyline Senior Member

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    Thanks searcher - will let you know what I find.
     
  4. cigana

    cigana Senior Member

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    Hi Skyline, did you ever find out about this?
    Thanks
     
  5. Skyline

    Skyline Senior Member

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    I didn't find it in the 23andme data set, and also the information was so important (define my approach to this whole thing) I wouldn't have relied on their set anyway. The error incidence is too high.

    I read in blogs that it is not available - but didn't check myself.

    As you see from my footer, I got the test down and turned out mold susceptible - was a big turning point for me.
     
  6. cigana

    cigana Senior Member

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    Thanks, very interesting.
     
  7. Valentijn

    Valentijn Activity Level: 3

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    I've been looking into these recently, since they're pretty interesting. Basically the HLA genes are more actively evolving than other genes, hence it might be a place to look at regarding "new" diseases. It's pretty wild, since they've got missense mutations all over the place, and it's quite common to see SNPs there with 3 or 4 possible alleles, instead of the usual 2 (or 1).

    From what I can see, HLA phenotypes are completely determined by SNPs. The primary ones looked at for disease risk and transplant rejections are DRB1 + DQA1 + DQB1. Though I've also seen phenotypes listed for DRA, and was able to determine full DRA phenotypes for 6 ME patients based on their 23andMe data, and narrow it down to three phenotypes for the remaining 5 ME patients, of which each would have two different ones:
    Patients A & B: DRA*010202 (homozygous)
    Patient C: DRA*010101 (homozygous)
    Patients D, E, & F: DRA*010101 + DRA*010203 (heterozygous)
    Patients G, H, I, J, & K: Two of DRA*010101 or DRA*010201 or DRA*010202 (heterozygous)

    Unfortunately DRB1 is exponentially more complex, and the 23andMe testing on the gene is extremely superficial - just 5 or 6 out of 200+ relevant SNPs are tested. And the ones that are tested aren't the useful ones! But it's possible that some of the 23andMe SNPs near the gene will indicate which alleles we have in the relevant SNPs. DQA1 and DQB1 look similarly complex and sparsely tested.
     
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  8. Valentijn

    Valentijn Activity Level: 3

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    Here's the DRA SNPs corresponding to the various phenotypes:
    rs7192 (i6060669) - G = DRA*010101 or DRA*010102
    rs7192 (i6060669) - T = DRA*010201 or DRA*010202 or DRA*010203

    rs8084 (i5015193, i5028329) - C = DRA*010101 or DRA*010201
    rs8084 (i5015193, i5028329) - A = DRA*010202 or DRA*010102 or DRA*010203

    rs11544315 - C = DRA*010101 or DRA*010201 or DRA*010202 or DRA*010203
    rs11544315 - T = DRA*010102

    rs3135391 - A = DRA*010203
    rs3135391 - G = DRA*010101 or DRA*010201 or DRA*010202 or DRA*010102

    As an example, patient A has:
    rs7192 - TT (must have DRA*010201 or DRA*010202 or DRA*010203)
    rs8084 - AA (can't have DRA*010201, must have DRA*010202 or DRA*010203)
    rs11544315 - CC (same as above)
    rs3135391 - GG (can't have DRA*010203, must have DRA*010202, homozygous)
    As a more difficult example, I have:
    rs7192 - GT (could have anything)
    rs8084 - AC (could still have anything, since I don't know if I have GA + TC or GC + TA as my haplotypes from each parent)
    rs11544315 - CC (excludes DRA*010102)
    rs3135391 - GG (excludes DRA*010203)
    This leaves DRA*010101 or DRA*010201 or DRA*010202 as options. Because I'm obviously not homozygous, since some of my genotypes are heterozygous, I must have two different phenotypes, instead of two copies of the same phenotype.
     
    Last edited: Jun 26, 2015
  9. Aileen

    Aileen Senior Member

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    Thanks for the rs#s and all your hard work Valentijn.
    Here are my results per 23andMe:
    rs7192 = GT
    rs8084 = AC
    rs11544315 = CC
    rs3135391 = GG

    No idea what any of this means, but it seems I have the normal (or most common, I should say) alleles for them all.
     
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  10. Valentijn

    Valentijn Activity Level: 3

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    That's the same combination which I have, hence you'd also have two different phenotypes out of these three possibilities: DRA*010101, DRA*010201, and DRA*010202.
     
  11. roxie60

    roxie60 Senior Member

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    http://www.whatayear.org/02_10.html

    here is a discussion about HLA DR4 and DR11 as it relates to inflamation response and lyme. I noticed @Skyline has in signature a reference to post lyme syndrome.....would like to know moew about what this means and did you relate it to specific HLA DR genes snps.
     
  12. Skyline

    Skyline Senior Member

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    Hey @roxie60 if you check out Dr. Shoemaker's framework for analysis of those genes he has found that some genes are post-lyme susceptible, while others are for mycotoxins/ mold. That matrix is freely available on his site if you google for it - you just need your HLA DR test done with Labcorp (perhaps also available via other labs).

    My genes are both mold and post lyme susceptible (i.e. fragments of lyme organism, even though dead, could initiate a similar ongoing inflammatory response in me). I don't have the worst genes according to his map/ research, but not the best either ;-)

    Last point I'll add is that I don't believe this is just a genetic based illness, I think it requires epigenetic switches also (otherwise the 26% of population with Shoemaker identified genes would all be sick, there has to be another mechanism, and I believe it's epigenetics - probably under-methylation of genes). So I'm focused on that at the moment.
     
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  13. roxie60

    roxie60 Senior Member

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    4-3-53

    I currently agree with your @Skyline view about another trigger.

    Im familiar with Shoemaker at high level. Been trying to find his chart, I think I posted it in another thread, but brain just is not cooperating lately. Thanks to Parker for helping me limp along. It appears I am susceptible to post-lyme/chronic lyme.

    I wonder if these genes related to post lyme also apply to the coinfections or if that is another possible set to impact our health given the right triggers
     
    Last edited: Oct 28, 2014
  14. roxie60

    roxie60 Senior Member

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    these are mine as well

    rs7192 = GT
    rs8084 = AC
    rs11544315 = CC
    rs3135391 = GG
     
  15. FightingCFS

    FightingCFS

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    So is there a place that has a list of more of the rsIDs for HLA (mold-type) genes? Thing is, I also ran an AncestryDNA test and that raw data has more SNPs so I'm hoping....
     
  16. Valentijn

    Valentijn Activity Level: 3

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    They probably can't test it usefully either. It requires more sophisticated methods which can handle three or four different possible alleles for each SNP. Cheaper methods seem to only handle binary options.
     
  17. drob31

    drob31 Senior Member

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  18. ebethc

    ebethc Senior Member

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    Hi @Valentijn

    For HLA-DRA, these are my 23andme results for 2 SNPs...
    rs7192 = GT
    rs3135391 = AG

    The other 2 SNPs didn't return any results in 23andme.. Can you tell anything by just these SNPs?

    thanks
     
  19. Valentijn

    Valentijn Activity Level: 3

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    rs3135391 A must be DRA*010203, so that's one of your DRA types. And DRA*010203 has the T allele at rs7192.

    Hence the remaining alleles for your other DRA type must be rs7192 G and rs3135391 G. Rs3135391 G can be any type other than the *010203 we already know that you have, but rs7192 G narrows it down to *010101 or *010102.

    Therefore you have DRA*010203, and either DRA*010101 or DRA*010102.
     
    Last edited: Jun 26, 2015
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  20. Valentijn

    Valentijn Activity Level: 3

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    @ebethc - 23andMe still tests for rs8084, but it's now labeled as i5015193 and i5028329 on the V4 chip. If you can post your result for those I might be able to narrow down your second DRA type a bit further.
     
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