Hello there,
I have a question related to alleles and SNPs (Single Nucleotide Polymorphisms) in genetics. I have some trouble understanding the boundaries between these two. I understand a SNP is a variation in a single nucleotide pair somewhere in the genome and it can occur anywhere (intron, exon or coding part of a gene), while an allele is a different version of a gene. SNPs can be mapped and individuals can be regrouped by the SNPs they have in common (from what I understood at least). And SNPs also have important functions, for example in resisting diseases or so. But then, if different individuals can bear the same SNPs, why aren't the genes bearing these SNPs considered as different alleles altogether, specially if they happen to have an important metabolic role? Thanks a lot! Best regards, MS.
Dear Mario,
You are right, a single nucleotide polymorphism (SNP) can occur at any place in a gene, in the regulatory region, in exons or introns, or in functionally unrelated flanking or intervening sequences.
What do SNPs actually do?
In most cases, such SNPs have not been linked to a functional alteration of the gene, but occur in regions of which we do not know anything related to gene function. Indeed, it is thought that most SNPs do not affect the gene's function. However, such a SNP might have occurred on a chromosome on which a disease-related alteration is also present. Although the SNP does not alter gene function itself, it might in different members of a large family be indicative of the presence of the disease-related alteration (and co-segregate with it), in particular if it is very near the lesion point. In fact, very few SNPs have been directly linked to a disease state.
Alleles and SNPs: what is the difference?
"Allele" is an older term for a "copy of a gene". In the molecular age, we talk about different alleles if their DNA sequence varies between two copies, which is almost all the time the case: hardly any two unrelated individuals carry identical alleles of a given gene. In most cases, the two alleles of any given gene we carry in our body harbor numerous SNPs when compared to each other: yet, they represent just two different alleles.
When function matters
I think one confusion comes from when we start to talk about the function of an allele. Here, we might regroup different alleles with similar functions together, for example as loss-of-function alleles or gain-of-function alleles. Upon sequencing the entire gene, we might then find out that indeed, similar loss-of-function alleles might have some SNPs in common (or larger deletions, inversions, etc), but might vary in other, non-functional sequence alterations. So these would all classify as different alleles of a gene, but some are more closely related than others, resulting in similar functional defects.
One final thought
According to new sequence technologies, it will most likely turn out that there are as many versions (alleles) of a gene as there are individuals on our planet.
Please get back to me if you have further questions.