SNPs with GG but Outcome should be CC


#1

I’m new to this so not sure of the correct terms to use. Hope you can figure out what I’m asking and if you can enlighten me to the correct terminology that would be great!

I have a snps that will show GG but when looking at SNPedia, it says the outcome shold be C or T so should be CC, TC or TT. Why does mine show GG then? I’m having a had time deciding what my SNP is showing (normal or not) when the outcome is not as listed. I also have some that are TT and the outcome should be AA for example.

I used Ancestry.com if that makes a difference.

Thank you for your help.


#2

Might have something to do with the chromosome strand. LiveWello (and possibly also AncestryDNA) report genotypes on the FWD strand. It would be helpful to know which SNP you’re referring to.


#3

I am looking into Annexin A11 (ANXA11) gene/SNPs for Sarcoidosis. One of the more researched markers is SNP rs1049550

My ancestry.com, and Livewello, report it as GG but SNPedia uses the CC, CT, TT as well as other medical studies and sites I’ve come across. So I’m having trouble knowing how my result compares to the more used CC, TT results.

This is from Livewello:
Data for rs1049550 obtained from dbSNP shows alternate versions of alleles for this SNP on the REV (minus) strand), are C/G/T.

(my result with name removed) My genotype for ANXA11 rs1049550 is GG

Phenotype analysis for this SNP is not available because the information obtained from dbSNP for rs1049550, is ambiguous.


#4

The difference you note is a common problem that arises from the “directionality” in which base-pairs of the nucleotides (id’d as A, C, G and T), that make up each SNP (segment) of the DNA strand that are identified in the SNP database, are read.

This directionality may be expressed as “orientation”. The problem is that over time, the human genome assembly is “rebuilt”, i.e. each release (to the public) represents a new “build”; and gene direction may be read differently from one build to the next.

The chip that processes your dna sample (such as produced by Ancestry.com) will likely transcribe all the nucleotide base-pairs (from the X and Y chromosomes) from the “forward” or “plus” (+) position, while the SNP database is built from research which sometimes identifies the base pairs from the reverse orientation … i.e. “reverse” or “minus” (-) position; i.e. from a prior build.

These differences also show up between DNA services, by the way. DNA raw data processed by Livewello may be read in some cases differently by Promethease, which for some SNPs will identify the phenotype (the nucleotide letters) from the reverse direction (anti-sense).

So effectively, the problem for us is one of a difference in direction in the reading of the genome. I’m not sure how these differences occurred but possibly they reflect changes in the scientific convention over time.

But what can we do given this discrepancy?
Since we know that in the nucleotide pairs (according to the Watson-Crick model), guanine (G) is paired with cytosine ©, and adenine (A) with thymine (T)… we can infer the following:
You should be able to infer (in homozygous cases) that CC in the “+” position is “GG” in the reverse, and AA in the (+) Position is “TT” in reverse (-) orientation; (and vice-versa for both cases);
while you could translate heterozygosity similarly: A > T (and vice-versa), C> G and vice-versa…

Keep in mind that I’m neither an academic nor otherwise expert on this topic!

P.S. I just found a good page giving more on this: https://www.snpedia.com/index.php/Orientation . (If I’d read that first I’d just give you the link instead of writing the above.)


In dire need of a crash course!
#5

Thank you for taking the time to help me out with this. You made it easy to understand and now I know more of the terminology as well.

I will also read the link you provided. Repetition helps me as well.


#6

You’re most welcome…glad I wasn’t too confusing!