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The easiest breakthough possible: MBL deficiency and CFS

Discussion in 'Action Alerts and Advocacy' started by Leitwolf, Aug 7, 2011.

  1. Sea

    Sea Senior Member

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    rs5030737 C or T Risk allele T (reported on the minus strand so an A on 23andme) 2.8%
    rs1800450 A or G Risk allele A (reported on the minus strand so a T on 23andme) 5-23% depending on ethnicity

    I have neither of these mutations so as reported by 23andme I am
    rs5030737 GG
    rs1800450 CC
    leela and Hip like this.
  2. Hip

    Hip Senior Member

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    Sea
    Can I ask: how were you able to find out what the risk alleles were for these two SNPs?

    I have always wanted to know how you determine the risk alleles for any given SNP.

    (Also: did you by mistake put the risk alleles the wrong way around? Shouldn't it be: rs5030737 A or G, Risk allele A; and rs1800450 C or T, Risk allele T ? Or does this "minus strand" business reverse everything? I'd be most grateful if you could give some elucidation here, just so I can learn for future reference.)
    leela likes this.
  3. Valentijn

    Valentijn Activity Level: 3

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    Amersfoort, Netherlands
    rs5030737 has Cys associated with the risk, which corresponds with the A allele.
    rs1800450 has Asp associated with the risk, which corresponds with the T allele.

    I'm also AG on the first one and CC on the second one.
  4. Aileen

    Aileen Senior Member

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    My 23andMe results are as follows:
    rs5030737 -- GG
    rs1800450 -- CC

    So, if I am understanding this correctly, that means I do NOT carry any risk for this? That would make sense since until I got this dd I rarely had any infections of any kind.
  5. Sea

    Sea Senior Member

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    I am very new to all of this and still learning as well.

    http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=5030737
    Look under the heading Gene view. The information in this section tells you this snp is a missense variation, the allele change is from C to T, which changes the protein made from R(Arginine) to C(Cysteine).

    That only tells you the change not the risk though. To find the risk you have to look through some of the research to see which protein is associated with any problems if they don't indicate which allele. In this case the research points to Cysteine which is the T allele.

    Sometimes a change can be better for one thing but worse for something else so you can't identify one or the other as the risk allele, only what is risk in the context of the illness or effect you're looking at. Also some changes are better and give a protective effect. This often leads to the unchanged allele being designated a risk when really it's normal.

    Look at your rs5030737 snp on your browse raw data page at 23andme. My genotype in this list is GG. On the left of the snp is a small plus sign. When you click on this a drop down menu appears with reference links to dbSNP and other places. On the right hand side of this menu it has the information about orientation in dbSNP - in this case minus. It also has what your genotype is in this orientation which for me is CC.

    23andme report on the positive strand for all snps. dbSNP and other places sometimes report on the positive sometimes on the negative strand. I don't know why that is. The good thing is that by knowing what is on one strand we can always know what is on the opposite strand because they always pair up in the same way. So if A is on one strand T will be on the other, if C is on one strand G will be on the other.

    When we're discussing snps and sharing data we need to be clear if we're using our data as reported by 23andme or as in the research because it can very easily lead to lots of confusion.
  6. chronix

    chronix

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    Can this deficiency explain the symptoms of CFS/ME?
  7. Hip

    Hip Senior Member

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    Sea
    Thanks for writing that explanation. It is very helpful.

    I noticed just now that SNPedia do actually specify which alleles entail a risk for the disease in question: if you look on the Rs5030737 page for example, on the right hand side, about two-thirds down, in the ClinVar table, you see that they give the risk allleles and the normal alleles, in the following format:

    Risk: rs5030737(T;T)
    Normal:rs5030737(C;C)

    But from what you said, the trick appears to be to know whether these risk and normal alleles are reported on the minus strand or the plus strand. Because if on the minus strand, you have to replace these given risk and normal alleles with their complementary base pairs (A always complements T, and C always complements G), because 23andme always use the convention of reporting on the plus strand.

    What I am not fully clear on is how you can know whether the alleles on SNPedia are reported on the minus strand or the plus strand.

    EDIT: in fact, I now notice that SNPedia provide the orientation (minus or plus) at the very top of the right hand column of the page. So in the case of Rs5030737 it is minus, so in this case we have to take the complementary base pairs.
  8. Sea

    Sea Senior Member

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    Sometimes SNPedia tells you the risk alleles, often not. Sometimes it tells you orientation, often not. Sometimes when you most want to know, it's just not there! SNPedia is a work in progress I think.

    23andme do always show our alleles on the plus strand but the info is also there at 23andme as to whether it is plus or minus at SNPedia in the little drop down menu on the left of your results
  9. Hip

    Hip Senior Member

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    This drop down menu on 23andme, which gives whether it is plus or minus strand on dbSNP: is it safe to assume that in that the convention used by dbSNP will be the same one as used by SNPedia?
  10. Sea

    Sea Senior Member

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    Yes, in SNPedia FAQ they say they use the same orientation as dbSNP
    Hip likes this.
  11. Adster

    Adster Senior Member

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    I don't think anyone could answer that definitively yet. From what I've read, it seems that it could explain it for some people. It might also be just one of multiple problems that add up to the CFS/ME symptoms in some people.
  12. Hip

    Hip Senior Member

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    NOTE: for anyone performing Google searches:

    mannan-binding lectin is also called:
    mannose-binding lectin
    mannan-binding protein
    mannose-binding protein

    HERE is a Google query set up to include all four possibilities.


    Note: when mannan-binding lectin attaches to the surface of a bacterium, virus, protozoan or fungus, this is the first step in activating the lectin pathway of the complement system (the complement system has three pathways: the classical pathway, the alternative pathway, and the lectin pathway).

    So it is a good idea to Google search on the lectin pathway, as in MBL deficiency, the lectin pathway will be weak.
  13. Adster

    Adster Senior Member

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