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Common rarity in 7 out of 7 ME/CFS patients based on 23andMe results

Discussion in 'Genetic Testing and SNPs' started by Valentijn, Oct 25, 2013.

  1. Valentijn

    Valentijn Activity Level: 3

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    I've been sorting through the rare results of ME/CFS patients here with 23andMe results, based on what has been filtered out by the rare gene analyzer at https://sourceforge.net/projects/analyzemygenes/ (10% file is at https://sourceforge.net/projects/analyzemygenes/files/Databases/ ).

    There have been some false positives, but something which looked like it was homozygous in only three out of the seven of us turned out to be heterozygous for the rest of us. 10% of the population is heterozygous, and only 1% is homozygous - so this may be very significant.

    The rsID is rs952061, which can be viewed in your 23andMe files at https://www.23andme.com/you/explorer/snp/?snp_name=rs952061 . The rare allele is T. Thus far we have homozygous results for allyb, GypsyA, roxie60, and heterozygous results for nandixon, Sea, Valentijn, and presumably for GypsyA's daughter, who must have gotten at least one copy from GypsaA but didn't get flagged as having two copies.

    I'd appreciate it if other users with ME/CFS could look up their result for that gene, and let me know if they have CC, CT, or TT.

    More info in following posts.
  2. Valentijn

    Valentijn Activity Level: 3

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    First of all, the results seem accurate. Sometimes 23andMe will report an SNP the wrong way around for everyone. But I checked about 10 random results from https://opensnp.org/genotypes and all were "CC", which is to be expected. http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs952061 also agrees that TT is the rare version. Hence our TT and CT results seem both accurate and genuinely rare.

    The odds of 7 random people on the street having those results are about 0.000001%, if taking into account that one of us has it by chance, and that another has it due to her mother having two copies. So the odds are (I think) about one in 100 million.
    L'engle, WillowJ and SilverbladeTE like this.
  3. Snow Leopard

    Snow Leopard Senior Member

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    Interesting, any idea what gene it is part of?
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  4. adreno

    adreno 3% neanderthal

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    CC here. Then again, I was never diagnosed with ME/CFS.
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  5. Valentijn

    Valentijn Activity Level: 3

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    There are a couple of problems with this result. The first is that rs952061 is located outside of a gene rather than nicely inside of it. So it's in an "intergenic region". Intergenic SNPs aren't directly involved in creating the proteins made by genes.

    However, intergenic SNPs can still promote and enhance nearby genes, thereby regulating them. It is also possible that SNPs currently thought to be intergenic are actually part of discovered genes. Hence rs952061 might be on an undiscovered gene, or it might be affecting the nearby MYBPC1.

    The other problem is that there's been no apparent research into rs952061. Even though the dbSNP shows a couple boxes for it, there's no links to any research. Searching google scholar and google also bring up nothing for rs952061.

    Hence there's no way to be certain that this SNP does anything at all, much less anything relevant to us. Any conclusions are entirely guesswork based on the rarity of our genotypes, our shared disease and symptoms, and the proximity of rs952061 to the MYBPC1 gene.
    WillowJ likes this.
  6. ukxmrv

    ukxmrv Senior Member

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    - thanks for doing this all Valentijn
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  7. Valentijn

    Valentijn Activity Level: 3

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    Since there's no research involving rs952061, the best we can do at this point is look at the functions performed by the nearest gene, MYBPC1. And because SNPs are often inherited in clusters, it is also possible that a rare SNP near MYBPC1 reflects the existence of rare SNPs in the gene itself.

    Its full name is "myosin binding protein C, slow type". http://www.genecards.org/cgi-bin/carddisp.pl?gene=MYBPC1#summaries has two good explanations for it, though they're a bit technical. At the most basic level, it plays a role in muscle function.

    My understanding is that MYBPC1 hooks up the myosin filamints with creatine kinase, thereby allowing skeletal and cardiac muscles to contract in a normal manner. Maybe someone who understands the anatomy and physiology better can expand on this :p

    Some genes which it directly interacts with are TTN, MYH3, MYL1, MYL2, NEB, TPM1, TNNT2, MYL3, USP25, and TNNI2.
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  8. Blue

    Blue

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    I am TT!
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  9. Valentijn

    Valentijn Activity Level: 3

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    So out of ME/CFS patients, that's now 4 with TT, 4 with CT, and 1 with CC.
  10. Thinktank

    Thinktank Senior Member

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    I'm CC
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  11. Hip

    Hip Senior Member

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    I am CC.
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  12. Valentijn

    Valentijn Activity Level: 3

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    4 TT, 4 CT, 3 CC
  13. alex3619

    alex3619 Senior Member

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    One risk of doing these kinds of things, and why validation research and further investigation is necessary, is that in any large genetic assay there will be some percentage of snps in common within any group with small numbers. I have read estimates that only one in a hundred such findings (or was it one in a thousand?) stands under further scrutiny. Having said that its entirely possible that this is important: experimental findings trump speculation.

    Now there is an issue that it might be a possible marker for common nearby clusters in population subsets. So what genes are nearby I wonder?
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  14. Valentijn

    Valentijn Activity Level: 3

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    I agree completely - which is why it's great to get as many results as possible, and especially important that negative results are also included.
    The closest by far is MYBPC1, discussed above. The others in the general area are SPIC, ARL1, UTP20, CHPT1, SYCP3, and GNPTAB. Based on proximity and function, MYBPC1 does seem to be the most interesting of the bunch.
  15. Crux

    Crux Senior Member

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    TT here.
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  16. Clodomir

    Clodomir In hibernation mood

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    I'm CT.
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  17. bel canto

    bel canto Senior Member

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    CT for me.
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  18. Valentijn

    Valentijn Activity Level: 3

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    5 TT, 6 CT, 3 CC. This brings us up to 14 results so far, twice as many as we had this morning :D

    36% = TT (versus 1% in a random sample)
    43% = CT (versus 9-10% in a random sample)
    21% = CC (versus 90% in a random sample)
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  19. bel canto

    bel canto Senior Member

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    Those are very interesting results, Valentijn.

    Looking at the family of genes related to the MYBPC1 gene - the Fibronectin type III domain containing gene family - some of the conditions related are ehlers danlos syndrome and multiple sclerosis - both of which are extensively discussed as having overlapping symptoms with me/cfs.
  20. brenda

    brenda Senior Member

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    I'm CC
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