2
$\begingroup$

In genetic research I often come across references to single-nucleotide polymorphisms (SNPs). An example is rs3184504(C;T). As far as I understand it: In this case rs3184504 refers to a specific point in the DNA genome, and (because this one occurs in a non-sex human chromosome) it indicates the nucleotides at that point in each copy of that chromosome.

But how does one determine which strand of the DNA helix it references? Is there a convention? Or is the strand indicated in the SNP reference (in this case rs3184504)?

If one strand is C;T then the opposing strand will be G;A ... but in the context of the gene in question I assume it matters which strand is referenced in the SNP. E.g., if the code following this SNP on the chromosome in which rs3184504 has C is:

CTCGA...
GAGCT... 

this is a different genotype from the SNP indicating a C on the other strand:

GTCGA...
CAGCT... 

So the SNP description is only meaningful if it also indicates the strand, right? If so, how does the SNP descriptor do that?

$\endgroup$
2
$\begingroup$

@WYSIWYG is correct, but in view of the brevity of his answer (and a second answer contradicting him) I provide chapter and verse.

The definition of RefSNP reference number is given by NCBI as:

“A reference SNP ID number, or “rs” ID, is an identification tag assigned by NCBI to a group (or cluster) of SNPs that map to an identical location.”

It is important to realize that this number bears no relationship to the numbering of the DNA sequence:

“The rs ID number, or rs tag, is assigned after submission.”

To find information about the position of an SNP from its rs number one can search the NCBI dbSNP. In the case of rs1384504 the first few lines of the first entry in the search results is:

Variant type:   SNV
Alleles:        T>A,C,G
Chromosome:     12:111446804 (GRCh38)

This indicates that the SNP is at position 111446804 on Chromosome 12, which has a T in the reference genome, and this lies in a gene designated SH2B3. (You can find this from the links on this page.)

It can be seen on this page that the orientation of this gene happens to coincide with that of the reference chromosome. However a nearby gene, PPP1CC, is in the opposite orientation and contains a SNP rs367543175 C/T. The start of the entry for this is

Variant type:   SNV
Alleles:        C>T 
Chromosome:     12:110720185 (GRCh38)

…indicating that the SNP is at position 110720185 on Chromosome 12, which has a C in the reference genome, i.e. on the anti-sense strand of this gene.

Two SNPs on genes with opposite orientations

And, of course, most human SNPs lie outside genes, so the concept of sense and anti-sense strand does not apply.

Conclusion

To find out whether the reference base in a designation for a SNP lying in the coding region of gene corresponds to the sense or anti-sense strand of that gene, one has to access the documentation for that SNP. This information is not embodied in the allele data appended to the reference SNP ID number.

| improve this answer | |
$\endgroup$
2
$\begingroup$

It is described with respect to the reference sequence. See the VCF format description.

| improve this answer | |
$\endgroup$
2
$\begingroup$

DNA has a "sense" strand and an antisense strand. The sense strand for that gene is the one you care about when discussing SNPs in that gene, because its the one being transcribed (and, as a result, the one affecting the organism). For more information about sense and antisense strands, there are some pretty good explanatory youtube videos and Wikipedia entries.

| improve this answer | |
$\endgroup$
  • 1
    $\begingroup$ Whether or not you are interested in the sense strand of a gene (and most SNPs fall outside genes) the allele variation in an RefSNP reference number, about which the poster asks, does not necessarily relate to that strand. @WYSIWYG was correct, as I document in my own answer. $\endgroup$ – David May 9 at 12:19

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.