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Confused about alleles...

Discussion in 'Genetic Testing and SNPs' started by spaceboy3000, Mar 12, 2014.

  1. spaceboy3000

    spaceboy3000

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    Atlanta
    Hi All,

    I'm SURE this is a very basic question for you folks, but I'm still new to this stuff.

    I've looked at my 23andMe results through a few different analyses, and I've noticed some discrepancies. One is from "livewello.com" I believe, and the other analysis is the "Sterling" analysis done through MTHFRsupport.com

    For example:
    The "Sterling" analysis shows my results for NOS2 (rs2248814):
    "risk allele: A
    my results: GG"
    Thus, it reports that I am "-/-" for NOS2

    MEANWHILE, My "Livewello" report, run on the SAME data set, for NOS2 (rs2248814) shows:
    "risk allele: A
    my results: AA"
    Thus it reports that I am "+/+" for NOS2, just the opposite of the other report's finding!

    I gather that not everybody will always agree upon which allele is the "risky" one. But to me it looks like the two different analyses both agree that "A" is the risky allele, but also seem to think that MY alleles are different in one interpretation from the other. What am I missing here?

    Thanks!
  2. spaceboy3000

    spaceboy3000

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    Atlanta
    ALSO,

    I just opened up the BIG raw data file from my 23andMe results and searched for the gene. Here's how it reads:

    "rsid chromosome position genotype......

    rs2248814 17 26100321 GG"
  3. Valentijn

    Valentijn Activity Level: 3

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    Amersfoort, Netherlands
    Sounds like Livewello has some issues :p
  4. jepps

    jepps

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    Hello together,

    I´m also confused about alleles: the SNP für Aldolase B, which plays a key role in carbohydrate metabolism http://en.wikipedia.org/wiki/Aldolase_B rs1800546. A lack of functional Aldolase B results in accumulation of Fructose-1-phosphate in liver cells, the buildup is toxic, and results in the death of liver cells over time. http://ghr.nlm.nih.gov/gene/ALDOB


    SNPedia indicates as risk allele "C":

    "Since this is a minus strand SNP, it is an ambiguous flip prone to some confusion, but to be clear, in SNPedia the orientation for the ancestral allele of this SNP is G, while the risk-associated allele is C"

    while dbSNP indicates as minor allele "G".

    Does anyone know, what´s now the correct risk allele to have a Mutation in the Aldolase B-Gen? Thank you for your reply!!!! jepps
  5. Valentijn

    Valentijn Activity Level: 3

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    Amersfoort, Netherlands
    In your 23andMe results, the risky allele would be reported as G.
  6. jepps

    jepps

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    Many thanks, Valentijn, but does this mean, the SNPedia is wrong in this case? Livewello indicates as minor allele "C".

    I looked at the 23andme-test from other people, and all have "CC".

    I don´t eat fructose because of my dysbiosis. But previously I had never prompt reactions, when I ate fruits. So 23andme and SNPdp seems to be right in this case, and Livewello and SNPedia seems to be wrong.

    Best Regards, jepps
    Last edited: Mar 19, 2014
  7. Valentijn

    Valentijn Activity Level: 3

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    Amersfoort, Netherlands
    Then they're reporting it backwards. In the forward orientation, and on 23andMe, C is the normal result.
    Yes, because CC is the common version. Almost no one has CG, and no one has GG.
  8. jepps

    jepps

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    So this means, that we must turn the interpretation of SNPedia and 23andMe to have the same result. Many thanks for your answer,

    jepps
    Last edited: Mar 22, 2014
  9. FightingCFS

    FightingCFS

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    I am following this conversation on facebook where Livewello talks about the Allele issue: https://www.facebook.com/Livewellov...?comment_id=5782404&offset=0&total_comments=6

    "Why 23andMe Variance Report results sometimes differ depending on the app used to generate it.

    This sort of ambiguity regarding the meaning of genetic test results, is the very reason that we do not give an opinion on how we believe these reports affect people personally or even why a particular allele is or isn’t a variant allele. We try as much as possible to stick to the Research data - reporting only what the data shows:

    --All of LiveWello's Minor Allele information is retrieved directly from dbSNP. A link to dbSNP is added to every SNP in a Livewello Gene Variance Report. That way, a user and their Practitioner can verify minor allele information for themselves.

    --At Livewello, we only use the forward strand for interpreting all our SNPs. This is because it is the same strand that is used by 23andMe where the Gene Tests are done. Be aware that other reporting authorities/ apps do not consistently do this, and will sometimes report minor alleles from the minus strand.

    --Our goal at LiveWello is to make our Gene App reporting more consistent and reproducible by using the same methodology for analyzing each and every SNP, rather than by using ad hoc techniques. As such, we have chosen to use a more consistent approach which shows a person’s actual phenotype, to be based on the presence or absence of a minor allele

    We do however realize that the nature of this emerging industry makes it very difficult to do this. Even the methodology used to determine a minor allele has been hotly debated. The challenge with genetic data interpretation has been very well documented in literature and articulated in the links below:

    http://www.informatics.jax.org/userhelp/SNP_terms_help.shtml

    http://www.ncbi.nlm.nih.gov/books/NBK44427/#Reports.rs61734154_maps_to_the_reference

    http://www.openbioinformatics.org/gengen/tutorial_allele_coding.html

    To make matters worse, the criteria seems to be constantly changing, probably because this a relatively new and rapidly evolving field of science.

    To quote openbioinformatics.org :

    "One obvious problem with this coding scheme is that one must know the "forward strand" with certainty, but this is usually not the case. Even for the well studied human genome, there are still many holes to be filled. It is possible that a sequence is assembled into the forward strand in 2004 human genome assembly, but it becomes reverse strand in the 2006 human genome assembly. It is also possible that a sequence cannot be assigned into either forward or reverse strand, so it's annotated as something like chr1_random in many genome databases. It is also possible that a stretch of forward strand becomes reverse strand in a particular subject due to inversion in this region.”

    As you can see, it is rather complicated. What we know is that minor allele information could change based on research which, as it happens, is being added to those 4 Databases in your Livewello Report, almost daily. This is the reason why Livewello App users are privy to free, no-hassle App updates. In one-click, Livewello users are able to take advantage of this information instantly. They are not stuck with a static PDF Report but rather, one that keeps them constantly connected with emerging research information. Livewello offers users 4 Major sources of research Data that is conveniently categorized by SNP and with one click, easily accessible from their Report: PubMed, dbSNP, SNPedia and Ensembl. If you look at the SNPedia entry for this SNP for example, you will see that it says that more research work needs to be done to resolve the issue with this and many other Genes for that matter. Until then, we just don't know, and we can only work with the information available which is referenced when you click on the SNP and you go to the Research Reference Page that the App has provided.

    Livewello is not a seer. It is a tool and like we stated before, a qualified and experienced Health Practitioner should always take into consideration a host of other contributing factors like your signs, symptoms and a variety of other Lab results when devising your health plan.

    Nonetheless, the issue of Minor Alleles and DNA strand orientation remains at the forefront of our focus at Livewello as we try to bring you the very best translation of your 23andMe genome report. This was the motivating factor and the reason why we added the free SNP Sandbox feature.

    SNP Sandbox offers Livewello users deeper access to their results beyond the 300 SNPs in standard variance reports. With this tool, Livewello users can create custom SNP tables containing their results on any of the 300,000 Disease related SNPs in their 23andMe Raw Data. We know that though the research available today is vast, there is ample potential for more. For instance our 23andMe Raw Data alone, contains our information on 600,000 genes.

    Finally, for users like yourself who have particular research or literature that they’d rather rely on, the free SNP Sandbox tool gives you the ability to edit minor alleles, to see what your phenotype would look like using different values. A note showing that this information was edited can be seen online in the user's report. The intent of this feature is to offer flexibility as Livewello users utilize their Variance Application. Read more about SNP Sandbox here: https://docs.google.com/document/d/1IrRpSqjVjPylUZ8bJvndF9u69YpiukfZvSXVUEvrT6E/edit?usp=sharing

    If you visit Livewello’s SNP Library, you will also see that there are hundreds of SNP Templates shared by other users some of which may even share your opinion on this particular SNP. The library can be accessed at: https://livewello.com/snp-templates

    We feel that we have adequately explained our standpoint regarding this issue. Please feel free to share this information with your Chat group as we think they deserve to know too. In the future, if you’d like a quicker response to your queries, please email us at support@livewello.com where we strive to respond to questions within an hour during business hours. All the best.

    P.S.
    Everything You Ever Needed to Know About What To Do with Your 23andMe Raw Data Results:
    https://docs.google.com/document/d/1gpsKey8mCkYfuvy8Lhd4oIXkru4qum0LJmDB3l3JDno
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