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Rare Coenzyme Q10 gene variations in ME patients

Discussion in 'Genetic Testing and SNPs' started by Valentijn, Jul 22, 2014.

  1. Leopardtail

    Leopardtail Senior Member

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    @Valentijn

    You will know half of this, but including info for all who read.

    The role of ubiquionol in the electron transport chain (ETC) is very simple it's one of the links in the chain. In order to make a new ATP synthase (the physical enzyme that implements the ETC) you need a ubiquinol molecule - each mitochondria needs very many of that enzyme hence very many Ubiquinol molecules. In simple terms the ETC is nothing more than a series of molecules that accept, then pass on electrons it's like a uni-directional 'copper wire'. At the end of that 'wire' ATP is made. Most cells also need many mitochondria.

    Hence requirement = many (per mito) x many (#mitos)

    Each mito should have a functional life of six weeks then divide into younger fresher mitos:

    Hence requirement = many (per mito) x many (#mitos) x few (semi-frequent division)

    Next we have to account for the 'oxidative stress' in PWME - ubiquinol 'disarms' free radicals but becomes the useless (for the ETC) ubiquinone meaning
    Hence requirement = many (per mito) x many (#mitos) x few (semi-frequent division) x very many (oxidative loss)

    Add in poor production of CoQ10 and you end up with
    Mito status Status = Production (low) / Requirement (very high)

    This seems likely to result in very few, or very geriatric mitos since you can't make functional mitos without the 'right CoQ10' = ubiquiniol.
     
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  2. SDSue

    SDSue Florida

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    @Valentijn Such interesting stuff - thanks for putting it all together. I know very little except that NDUF7 rs7258846 is the known SNP associated with Leigh Syndrome, an early onset severe form of MD.

    Any idea what to make of my NDUF7's? It doesn't seem to paint a pretty picture.
    Screen Shot 2014-07-27 at 9.59.53 AM.png
     
  3. Leopardtail

    Leopardtail Senior Member

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    is this a simple matter of pasting data from an old spreadsheet into a new one?
     
  4. Valentijn

    Valentijn Activity Level: 3

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    Nope. The problem is that the older set of data has 960,000 SNPs, and the newer set has 600,000+ SNPs. These two sets need to be merged, but Excel hits the limit of its rows well before 1,600,000. So I can't even get both sets into the same sheet as would be needed to merge them. Which is annoying, because they'd definitely be under the limit once merged.

    What I really need to do is switch to using a database instead of a spread sheet. That will also make it easier to automate the calculation of expected genotype prevalence, tagging each SNP with the name of the gene it's on, tagging known missense and/or pathogenic mutations, converting "i" numbers to "rs" numbers, etc etc.
     
  5. Valentijn

    Valentijn Activity Level: 3

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    All versions of those SNPs are very common. And 4 of them are tightly linked, so having all 4 is no more relevant than just having one. Ironically, those linked ones include 3 "red" results and one "green" result, so they're essentially contradicting themselves by flagging 3 of them but not the 4th. Or they're deliberately raising a false alarm, as everyone will have to be red for either one or the other three of the SNPs.
     
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  6. Leopardtail

    Leopardtail Senior Member

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    I don't any data on that on V's report sue - I'm confused!
     
    SDSue likes this.
  7. Leopardtail

    Leopardtail Senior Member

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    It's definitely a job for a database, but would likely break Access as well. I suspect that's going to be a job for mysql (faster) or postgreSQL (more robust with complex queries).

    How IT literate is your fiance when it comes to complex databases?
     
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  8. Valentijn

    Valentijn Activity Level: 3

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    That's because I'm only listing rare SNPs. The ones in SDSue's report have alleles with 38% and 45% prevalence in the general population. So approximately 15% of humanity is also homozygous for one set, and 20% are homozygous for the other set.
     
    Last edited: Jul 27, 2014
  9. Valentijn

    Valentijn Activity Level: 3

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    Extremely :D He also has a dim view of Access, as it's actually pretty much a spreadsheet as well and not a proper database program. The new PC is planned to have Linux installed as we both hate Windows 7 and 8, and XP is too old to work well with the 8 core processor. Though it sounds like Windows in general doesn't utilize multi-core processors very effectively anyhow.
     
  10. Leopardtail

    Leopardtail Senior Member

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    so does the original data set have un-needed SNPs that could be removed (thus producing a clean data set)?

    Are they for different populations of patients without intersection?
     
  11. Leopardtail

    Leopardtail Senior Member

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    I had real issues with 64 bit linux, be careful there unless you are much better at LINUX than me
     
  12. adreno

    adreno 3% neanderthal

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    @Leopardtail

    So you think PWMEs would benefit more from supplementing ubiquinol, rather than ubiquinone, even though they should interconvert?
     
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  13. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Are people really seeing a difference between ubiquinone and ubiquinol?

    I have read a few things of late that it doesn't make a difference and more a marketing ploy to sell more expensive q10.

    I have only used ubiquinone so I can't give an opinion either way other then since using high dose of ubiquinone, that it has helped.
     
  14. Valentijn

    Valentijn Activity Level: 3

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    I've actually already tried removing entries where all 12 ME patients and controls have exactly the same results, and that takes us down from 960,000 rows to 842,000 rows. But it's still too many for Excel when adding the newer 23andMe results, especially if I want to be able to manipulate data after adding additional patients and/or controls. That approach would also risk missing rare results from new patients whose data is added, if those SNPs have been filtered out.

    The fiance thinks mysql and postgresql wouldn't be able to handle the number of columns which will be needed in a proper database. He wants us to use the Apache Cassandra database management system, which should be able to handle it. And he's quite good with Linux too, so shouldn't have any problem getting me set up :D
     
  15. Valentijn

    Valentijn Activity Level: 3

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    Actually, maybe I can merge approximately half of the new and old 23andMe chips' data at a time, pending my new system being set up. It might work - if having the extra patients and controls doesn't kill Excel once the merged halves are then merged together :D
     
  16. Leopardtail

    Leopardtail Senior Member

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    There is not solid science on that yet. What's certain is that during mito division we need ubiqinol, and ATP must be available to make it from ubiquinone.

    The strategy I am trialling at the moment is mixed supplementation with 200mg ..ol and 200mg ...one at different times totalling 400mg / per day. The bit of Q10 I understand well at the moment is the ATP synthase part, with heavy fatigue I strongly suspect Ubiquinol is needed, but it's vastly more expensive and harder to get (you can buy powdered ubiquinone). I have still to do work on the other functions so not sure how things lie there yet. I did find that link on Cholesterol and CQ10 though. My suspicion is always the body makes different use of different versions of things.

    I have a lot of ME 'triggers' at the moment, so hard to know for certain how well it's working.
     
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  17. Leopardtail

    Leopardtail Senior Member

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    Why does he want to use so many columns rather than separate the results into a separate line data table? That would lead to far more options for reporting, quizing, and stats.
     
  18. Leopardtail

    Leopardtail Senior Member

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    there is science to indicate differences, but not impact on ME patients. It's like the comparison between r5p and riboflavin.
     
  19. Leopardtail

    Leopardtail Senior Member

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    not used cassandra so look forward to hearing how you get on.
     
    Valentijn likes this.
  20. SDSue

    SDSue Florida

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