MTHFR & base pair basics

[pberry]

Need some help clarifying MTHFR SNPs and understanding allele basics.

SNPedia (and TEOA Program) say that MTHFR C677T has rsid rs1801133 and can take values C or T (https://www.snpedia.com/index.php/MTHFR);

• Ancestry and 23andme raw data say that my rs1801133 = AA. I am not sure if Ancestry and 23andme rsid's are out of alignment with the other sources or if you can have an A when a C or T is expected.

Similarly confusing, SNPedia says that MTHFR A1298C has rsid rs1801131 and values A or C;

• Ancestry and 23andme raw data say that my rs1801131 = TT.

I had always thought base pairs had to be either G-C or A-T. Can anyone explain or provide links to some online primers that do?

[SusanJ]

I had always thought base pairs had to be either G-C or A-T.

From 23andme:

Each chromosome consists of two strands of DNA that are complementary to each other. The DNA nucleotide base adenine (A) always pairs with thymine (T) and the base guanine (G) always pairs with cytosine (C) across these two strands. One strand is called the positive (+) strand and the other is called the negative (-) strand. 23andMe always reports genotypes on the positive strand of the specified reference genome assembly.

https://customercare.23andme.com/hc/en- ... andMe-Use-

So the positive strand had an A at the location for rs1801133. If they had read the negative strand, it would have been reported as T.

[NF52]

Need some help clarifying MTHFR SNPs and understanding allele basics.

SNPedia (and TEOA Program) say that MTHFR C677T has rsid rs1801133 and can take values C or T (https://www.snpedia.com/index.php/MTHFR);

• Ancestry and 23andme raw data say that my rs1801133 = AA. I am not sure if Ancestry and 23andme rsid's are out of alignment with the other sources or if you can have an A when a C or T is expected.

Similarly confusing, SNPedia says that MTHFR A1298C has rsid rs1801131 and values A or C;

• Ancestry and 23andme raw data say that my rs1801131 = TT.

I had always thought base pairs had to be either G-C or A-T. Can anyone explain or provide links to some online primers that do?

Hi pberry!

I remember this same frustration! Susan's answer is the thorough one, but here's the one I use for a "cheat sheet" from snpedia:

Companies follow their own protocols, which are often different. 23andMe currently reports all genotype data based on the plus strand of GRCh3.... This often leads to confusion since a 23andMe customer may see a genotype in their raw data that will not match the genotypes defined by dbSNP, in SNPedia, or in their Promethease report...In these cases, the alleles need to be "flipped" to match:

A->T
T->A
C->G
G->C

Thinking of the shapes of the letters, I remember the code as "A and T are tall twins; C & G are round twins".

Your rs1801133=AA on 23&me in Snpedia would be T/T. And Snpedia's MTHFR A1298C's possible A/C combos in 23&me would show as TT, GG, T/G or GG.

[SandyZ]

Need some help clarifying MTHFR SNPs and understanding allele basics.

.....

Hi pberry,

As a welcome intern, I wanted to welcome you and make sure you were familiar with the site. I'm glad you found us and have been able to already receive some answers to your question.

If you would like to deepen your understanding regarding ApoE4, the Primer is a detailed and informative resource written by a practicing Medical Doctor with ApoE4/4.

In addition, the How to Guide offers tips on how to navigate forums, including how to quote members when you respond to posts so they get an email notification of your post (tip: use the quotation icon in the upper right of any post). The How to Guide also demonstrates how to use the Search function for topics and how to subscribe to topics of interest in the forums.

The Wiki is another resource full of information that you might helpful.

Finally, if you would like to learn more about other community members' experiences or even continue to share more about your own, feel free to link to Our Stories.

I hope this information is helpful.

Please reach out for assistance as you navigate the site.

In gratitude,

SandyZ

One more thing...Here is a quick link to the section in the Wiki regarding Methylation.

[pberry]

Susanj NF52 It's starting to make more sense now. Thanks for the very helpful quotes and links.