1
$\begingroup$

This in fact has bugged me for years, but now I finally remembered to ask.

I suppose that if one variation is more frequent, it can be labeled as the default, but what about variations that are equally as common?
The example that I just saw, it seems that the frequency of both variants is the same, and yet somebody claims that G is the default and C is the polymorphism:
Polymorphism with genotypes CC, CG and GG occuring in 30, 40 and 30% of the control group, respectively http://hell.org.pl/~kamyk/stackexchange/Zorena1.jpg

Maybe it is possible to determine which one was first, but how? Is there ancient data about polymorphism frequencies?

$\endgroup$
2
$\begingroup$

A DNA locus may have two (or more) variants (alleles), but there isn't one termed a main or default variant. In the example you cite, Myśliwska 2009, the only asymmetric distinction between the G and C alleles that I could see was in this passage:

The polymorphic region −174G>C of IL-6 encoding gene is implicated in transcription of this cytokine. The G>C nucleotide substitution creates...

This passage uses "substitution" (and "G>C" in −174G>C), which suggests that "G" is what is termed the ancestral variant, and "C" a later variant. The ancestral variant was the form that is believed to have been essentially the only form in some ancestral population; the later variant is a mutation (substitution in this example) which became established in part of a later occurring population.

Not all polymorphisms have their variants characterized in this way. Those that do usually have DNA sequence evidence showing that species other than humans have a homologous gene, and those genes appear to have only the "ancestral" variant. For the locus in the example you cite, the human IL6 -174 locus, a early paper by Fishman et al. (1998) says this:

Considerable interethnic variation in the frequencies of these polymorphisms has been demonstrated (39), which is consistent with our data for the -174C allele, which is considerably rarer in Gujarati Indians and Afro-Caribbeans, compared with UK Caucasians. As all of the primates examined were GG homozygotes, it is likely that this allele is ancestral and that the C allele represents a relatively recent change in the IL-6 5' flanking sequence.

This assessment seems to have become generally accepted. The rather even distribution of G and C variants in the table you show is likely due to the subjects being of European ancestry, as suggested by this from SNPedia:

It [IL6 -174] tends to be quite polymorphic in Caucasians, but Asian and African populations are almost monomorphic (for the (G) allele).

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

[..] G is the default and C is the polymorphism

An allele (or just a nucleotide variant) cannot be "the polymorphism". There is polymorphism, if a given locus (or just a given nucleotide position) is polymorphic, that is, if as this position, there are different variants existing in the population. Therefore, an allele cannot be called polymorphism, only a locus can be called to be polymorphic and if a locus is polymorphic, then there is some polymorphism in the population.

I have never of people talking about the main or default variant. Do they use this word in the article you link? If yes, can you please indicate where?

Commonly, people talk about the wildtype versus the mutant variants. In this case, the wildtype variant is just the most common variant. Rarely I have seen people referring to wildtype variant when talking about variants that are at low frequency because the mutant is increasing in frequency and slowly reaching fixation. In such case, the wildtype mutant would correspond to the original variant at an arbitrary time point in the past but would not depend on the frequencies observed today.

|improve this answer|||||
$\endgroup$
  • $\begingroup$ I am not sure whether I answered your question or whether I missed the point you were trying to make. Let me know! $\endgroup$ – Remi.b Feb 13 '15 at 19:02
2
$\begingroup$

In this case, G is the genotype used for comparison because that's what's in the reference sequence for humans. Of course, this raises the question of why that's the reference. The answer is that it's because that's the sequence from the sample used to create the BAC that was sequenced and used to create that portion of the reference sequence.

Of course, it's not always like that. For example, when we discovered KCNJ18 and I submitted it for inclusion in the genome, I specifically submitted a sequence that represented the most likely haplotype given all of the samples we had sequenced. Of course, "most likely" may be population dependent.

As an aside, this is actually a bigger issue with some regions of the genome, where polymorphisms describe whole regions rather than just single bases. In the reference genome, these are the _hap_ chromosomes, which will often contain things like common structural rearrangements. These present a problem currently because they lead to biased mapping and variant calling. The first program known to make proper use of these was only released within the last month, in fact. One of the goals for the next human reference genome is to come up with a convenient graph representation of the genome that can include common polymorphic regions. This should lead to better quality genotyping of patients and study subjects.

|improve this answer|||||
$\endgroup$

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.