The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
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Curious about mitochondria...

Discussion in 'Genetic Testing and SNPs' started by Eeyore, Apr 11, 2015.

  1. Eeyore

    Eeyore Senior Member

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    It just occurred to me that it would be really simply to check if there's any prevalence of mitochondrial haplotype in ME patients. Many (but not all) of the genes that code for mitochondrial function are actually present in the mitochondrial genome itself, and not in the chromosomes. These are passed from mother to child. If you have done 23andme (and maybe with other services) you'll get information on your haplogroup. This will be the same as for your siblings (or half siblings by the same mother), maternal blood uncles and aunts, and your maternal grandmother, for example.

    Note: This doesn't account for all mitochondrial function or genetics, but I just thought it would be quick and maybe interesting to see if any group is overrepresented.

    @Valentijn - you may know something about this.

    My maternal haplogroup is H3.
     
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  2. Snowdrop

    Snowdrop Rebel without a biscuit

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    My mother did the Spencer Wells (national Geographic) maternal DNA test. She is haplogroup X.
    I'll have to ask her if she has the info for any subgroup of the X group.
    As I mentioned on another thread it would seem it's possible that an autoimmune component might be in play as transmissible.

    Maybe it would be good for responders to reply with a bit of relevant family history .
     
  3. helen1

    helen1 Senior Member

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    Mine is HV6.
     
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  4. Valentijn

    Valentijn Senior Member

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    I have 23andMe data for 47 ME patients (4 of whom are members of 2 mother/daughter pairs), and maternal haplogroups are as follows:
    D5a2a1
    H
    H
    H1
    H1
    H1
    H1b1
    H1b1b
    H1c
    H1c
    H1c1 (mother/daughter)
    H1c1 (mother/daughter)
    H2a1
    H2a1c (mother/daughter)
    H2a1c (mother/daughter)
    H3h5
    H3y
    H5k
    H6a1b3a
    H13a1a1
    H16
    H18
    H24a
    HV
    I2
    I4a
    I4a1
    J1b1a1
    J1c
    J1c2a2
    J1c2e1
    J2a1a1a2
    K1a1b1a
    K1b1a1c
    L2c
    N1b1b1
    T1a1k
    T2b
    T2b4h
    T2b25
    T2c1d1
    U4a1
    U4a1
    U5a1a1
    U5a2b3
    U5b3b
    W1e1a

    I looked at the mitochondrial DNA a while back, basically adding the alleles for patients versus controls for each SNP, and the biggest anomaly was rs3928306. But that was due to that mutation defining H1 and J1 haplogroups, and naturally that difference disappeared when I began matching controls based on haplogroup.

    It's on my list of things to look at closer as soon as I can, since there does seem to be a lot of mother/child ME issues. But father/child isn't completely unknown either.
     
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  5. Eeyore

    Eeyore Senior Member

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    @Valentijn - I read a paper that fibro is often passed to children by the mother, bu not the father. Trying to find it on pubmed now and will post a link if I succeed.

    I came across this in googling my haplogroup - apparently it's HIV-resistant. Neat - but more interesting for us, it may be related to ATP and ROS generation. Maybe a red herring but enough to make me wonder!
     
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  6. ahmo

    ahmo Senior Member

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    Northcoast NSW, Australia
    K (K1a1b1a)
     
    Last edited: Apr 12, 2015
  7. Valentijn

    Valentijn Senior Member

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    Mine is H1b1, which is actually defined by a supposedly pathogenic missense mutation for adult-onset dystonia :eek: I'm not sure I believe that though, since my maternal relatives haven't had any obvious dystonia, and a mutation prediction model gives it a 60% chance of being harmless.

    The same gene is associated with MELAS however, which does have some symptom similarities with ME/SEID.
     
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  8. Valentijn

    Valentijn Senior Member

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    In case anyone's wondering, this is a different K1a1b1a than is in my list above :D
     
  9. Valentijn

    Valentijn Senior Member

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    By the way, if anyone wants to know their haplogroup more specifically than is given by 23andMe, or at least narrow it down a bit, you can run your 23andMe text file through http://dna.jameslick.com/mthap/mthap.cgi

    For example, 23andMe says I'm H1b, but the website listed above gives me H1b1, with H1b1d or H1b1c being my possible subgroups.
     
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  10. adreno

    adreno PR activist

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    I'm totally ignorant of this stuff. Mine is H5a1, what's that tell me?
     
  11. Valentijn

    Valentijn Senior Member

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    Mostly it just tells you where your maternal line originated :p In the case of H5a1, it's Europe. Sometimes the maternal haplogroup is defined by a missense mutation, which might be relevant to gene functioning, and sometimes studies have found an association between haplogroup and disease risk.

    The H5a group is defined by having the C allele at rs41456348 (i3001462). It was studied a little in this paper: www.ncbi.nlm.nih.gov/pmc/articles/PMC1734884/pdf/v038p00400.pdf starting on page 11. That research is using the older nomenclenture of 4336 to identify it, and is looking at the reverse alignment, so they're talking about the G allele instead of C.
     
  12. adreno

    adreno PR activist

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    Just seems to me that haplogroups are too broad to be much useful as predictors of disease.
     
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  13. nandixon

    nandixon Senior Member

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    Mitochondrial DNA haplogroups may not have much of an effect with respect to whether a person does or does not develop ME/CFS. But there's still the possibility that mtDNA haplogroups may influence phenotype in our disease.

    For example, several studies show that mtDNA from the J haplogroup consistently results in the production of less ATP than H haplogroup mtDNA, all else being equal. (It looks as though this happens because the J haplogroup makes a smaller amount of mtDNA thus resulting in less oxidative phosphorylation capacity. See, e.g.: Oxidative phosphorylation differences between mitochondrial DNA haplogroups modify the risk of Leber's hereditary optic neuropathy)

    I'm J1c, and with my version of ME/CFS, I suffer tremendous fatigue (or total exhaustion or extreme non-sleepy tiredness, call it what you will), and having ME/CFS on a background of a J mtDNA haplgroup, as opposed to an H haplogroup, might possibly explain that, and why some of us have more fatigue than others. Of course, there are potentially many other possibilities for why that may be the case as well.

    I've just barely started looking at this, but there seem to be at least a few different things to try, in theory, to attempt improve the amount of one's mtDNA, like pyrroloquinoline quinone (aka PQQ - unfortunately, this is a severe migraine trigger for me).

    But as a first attempt at trying to improve the inherent J haplogroup OXPHOS problem, I thought I'd give idebenone a try to increase ATP output. (Idebenone is a synthetic coenzyme Q10 analog.) I currently use CoQ10, and it helps a little, but not nearly enough.

    Just to mention also, as @Eeyore quoted above in post #5, the J haplogroup shows an accelerated progression from HIV to AIDS, while other haplogroups can be protective. It's likely a coincidence, but my ME/CFS has been slowly but relentlessly progressive in its worsening for the past 17 years or so, unlike other people who seem to be stable, or improve some, or who even have a relapsing-remitting pattern.
     
    Last edited: Apr 14, 2015
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  14. renerdrat

    renerdrat Every teardrop is a waterfall

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    Temecula
    Interesting, I have J haplo from my moms side and I seem to have inherited most of my moms genes, but my haplo group is r1b1 from my fathers and j2 from my mothers, what's this tell me?
     
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  15. nandixon

    nandixon Senior Member

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    In theory, since you belong to the "J" haplogroup, with all else being equal, you (and I) may be making less ATP than other haplogroups, especially "H."

    How this actually plays out in real life, and whether it's relevant to ME/CFS, is another matter entirely. So to try to gain some insight, I recently made the following poll which I hope you'll also participate in:

    Poll for maternal haplogroup as possible indicator for ME/CFS phenotype
     
  16. Sea

    Sea Senior Member

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    NSW Australia
    Another J here. I am J1C2
     
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  17. ppodhajski

    ppodhajski

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    It could be that it is passed down by the mother because some of the genes that I see cause ME/CFS are only on the X chromosome. This would negate the importance of haplotype.
     
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  18. Valentijn

    Valentijn Senior Member

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    Mitochondrial DNA (and maternal haplogroup) is from the mother. X chromosomes come from both parents for female offspring - one from the mother and one from the father, so wouldn't specifically implicate maternal transmission. Having the disease on the X chromosome also might not fit in with females being far more likely to get ME/SEID than males, since males are more vulnerable to X chromosome mutations due to only having one copy.

    There also haven't been any dysfunctional genes implicated in causing ME/SEID yet. There have been some SNPs with tiny risk elevations, but so far they've been very contradictory and using Fukuda instead of a proper ME/SEID definition. And the ones which have shown altered expression after exertion haven't been on the X chromosome, that I can recall.

    Additionally, haplogroup could be relevant even if mitochondrial DNA is not. Haplogroup is an easy way to determine maternal lineage, due to mitochondrial DNA being mostly unaltered for every new generation. But that lineage might also be associated with problematic mutations which aren't part of the mitochondrial DNA (nor the sex chromosomes). Hence some people with the same haplogroup could have historically developed a high frequency of mutations on any chromosome.
     
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  19. ppodhajski

    ppodhajski

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    Well for men, X chromosomes only come from the mother. I was speaking as a man. :)

    But again, read what I write carefully, I said "some of the genes that I see cause ME/CFS are only on the X chromosome."

    Some, as in not all.

    I believe it is much simpler than you are all making out. I have already helped someone with CFS understand where it was coming from and they no longer suffer from it and I did this for myself as well.

    Most research is looking at genes that we can do nothing about. By focusing on the epigenetic genes I see disease and recovery.

    If a few of you here with CFS/ME would provide your Prometheus file I will show you the similarities and how I think it arises.
     
  20. Valentijn

    Valentijn Senior Member

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    I'm not aware of any. Can you list them, and the source?
     
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