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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. nandixon

    nandixon Senior Member

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    Hi Valentijn,

    The frequency for the homozygous rare allele result for rs952061 is correct at 1%, but the heterozygous frequency, rather than 10%, is 24% according to HapMap CEU data (http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=952061). This is corroborated by the 22% heterozygous frequency OpenSNP gives as well (http://opensnp.org/snps/rs952061).

    This is still worth finishing an investigation for this SNP, though. Thanks very much for doing this!
    Valentijn and WillowJ like this.
  2. snowathlete

    snowathlete

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    People with 23andme, who use Firefox browser, may like to download the SNP-Tips plugin, as it saves a lot of effort. Basically you point it to the downloaded 23andme raw datafile once and then everytime an RS number appears on any website, forum (including this one) it is displayed green if you have that SNP in your datafile and you can hover the cursor over it and it will display your specific result. Saves you having to go and look manually.

    I am CC.
  3. caledonia

    caledonia

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    I am CC.

    ps. SNP-Tips worked great!
    Valentijn likes this.
  4. Creekee

    Creekee Senior Member

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    Hubby (completely healthy for our purposes) and I are both CC. I am historically ME-diagnosed but recently confirmed Lyme and co-infections...

    Thanks for pursuing this, Valentijn!
    Valentijn likes this.
  5. biophile

    biophile Places I'd rather be.

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    CC for me too.
    Valentijn likes this.
  6. anne_likes_red

    anne_likes_red Senior Member

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    CT here.

    Thanks for your initiative Valentijn. :)
    Valentijn likes this.
  7. wordweaver27

    wordweaver27

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    CC over here :)
    Valentijn likes this.
  8. Aileen

    Aileen Senior Member

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    I'm CT.
    Valentijn likes this.
  9. Valentijn

    Valentijn Activity Level: 3

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    Yes, but we aren't just interested in a relatively inbred group from Utah here. CEU isn't even likely to be particularly representative of European groups, and it definitely excludes the non-white world.

    Basically there's a pretty big chance that uncommon genes are over-represented in such small and homozygous populations. Hence I think it's important to look at the (usually) more diverse results from 1000 Genomes instead, which is also what the NCBI and every other program is doing.
    aimossy and SOC like this.
  10. Valentijn

    Valentijn Activity Level: 3

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    24% = TT (5)
    38% = CT (8)
    38% = CC (8)

    So the results aren't as dramatic as they initially were, but are still quite unusual, especially now that the sample size has grown by a factor of 3 :)

    I plan to take a closer look at the nearby genes, to see if some commonality is present.

    If anyone wants to send me their rare homozygous results generated using the 10_percent file (or their whole file if it's too complicated), that would be great. The more files we have, the more similarities that will pop up, some of which might hold up.
    L'engle and SOC like this.
  11. Ruthie24

    Ruthie24 Senior Member

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    CC here
    Valentijn likes this.
  12. nandixon

    nandixon Senior Member

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    You're accidentally mixing up two different frequency measurements. The 10% frequency for rs952061 from 1000 Genomes is the Minor Allele Frequency (MAF). HapMap CEU gives 13% for this value; OpenSNP gives 12%. So they're all very similar.

    You're accidentally using the 10% MAF value for heterozygous frequency, ie, a Genotype Frequency. The heterozygous frequency is much higher than the MAF, eg, 22-24%, as I noted.
    Valentijn likes this.
  13. Im CC
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  14. Valentijn

    Valentijn Activity Level: 3

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    I must admit I've been a bit confused by that. If there are 0 homozygous TT versions in a population, why is the heterozygous frequency twice as high as the T allele prevalence? The HAPMAP-Mex group should be an easy one to make sense of. There's a sample of 100, with T prevalence of 8% but CT genotype prevalence of 16%.

    So my understanding (now) is that they're counting for chromosomes - but only for alleles, whereas genotypes must be calculating based on the number of people. So out of 100 chromosomes (2 per person) there are 8 which are T. So out of the 50 people tested, 8 have one T and one C, which makes 16% heterozygous people and 84% of people with the common CC version.

    Hence MAF is not reflecting the odds of having that allele for each person, but rather at the odds that each chromosome will have that allele. I think that's the bit I was getting hung up at. So basically the odds of having one minor allele are very approximately twice the MAF.

    I think I've got it now - math really isn't my strong suit :p
    nandixon likes this.
  15. Valentijn

    Valentijn Activity Level: 3

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    TT = 22% (5)
    CT = 35% (8)
    CC = 43% (10)

    And if we look at our Minor Allele Frequency (MAF) as a group, we have 18 T alleles out of 46 total alleles. So our MAF of T is 39%, compared to a MAF of 10% for T in the general public.
    ukxmrv and nandixon like this.
  16. Ema

    Ema Senior Member

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    CC for me.

    @Valentijn, I'm happy to send you my results in general but I'm not sure what format you would prefer? I don't have a lot of experience manipulating this data.
    Valentijn likes this.
  17. Valentijn

    Valentijn Activity Level: 3

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    Text results from the ten_percent file is preferred. Thanks!
  18. nandixon

    nandixon Senior Member

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    Yes, I think that's right. In the Mexican group there were 50 people (100 chromosomes), and they found that 16% of those people were heterozygous. So 8 people were CT.

    And they found that 8% of the total alleles were the minor allele T (MAF = 8%). So they found 8 out of 100 alleles with T.

    Another example is, they might have instead found that 0% were heterozygous and that 8% were homozygous TT. So 4 people would be TT, and the MAF would still be 8%.

    Another example is, they might have found that 8% were heterozygous and that 4% were homozygous TT. So 4 people would be CT, 2 people would be TT, and the MAF would still be 8%.
    Last edited: Oct 26, 2013
    Sea and Valentijn like this.
  19. maryb

    maryb iherb code TAK122

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    @Valentijn
    much as I would like nay love to understand any of this I can't:(
    but if you tell me where to look I will try to find it. also you can have a copy of my results with pleasure.
    Valentijn likes this.
  20. acer2000

    acer2000 Senior Member

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    CC here. Did I win? :)
    Valentijn and Clodomir like this.

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