Naming genetic variants

Single nucleotide polymorphisms are generally referred to using a combination of numbers and letters.

The number indicates how far along the gene the polymorphism is found, while the letters refer to the type of nucleotide that is found at that point on the gene. For example, replacement of the wild-type guanine with thymine at the 516th base along the gene for cytochrome P-450 2B6 is a well-studied polymorphism linked to the rate of clearance of efavirenz (Sustiva) from the body. The wild-type allele is therefore referred to as 516G, while the less common allele is 516T. To signify the change from guanine to thymidine, the polymorphism may also be written as G516T or 516G>T.

Since everyone has two copies of each gene, it is possible to be homozygous either for the wild-type allele at this position (GG) or for the alternative allele (TT), or to be heterozygous, having inherited one of each allele (GT).

Polymorphisms can also occur outside a coding region of a gene, particularly in the promoter regions that usually lie before the start of the coding region. These are usually given negative values. For example, a polymorphism that involves replacement of adenine with cytosine in the 234th base before the start of the coding region can be written as –A234G or –234A>G.

Genetic researchers often refer to ‘haplotypes’ when discussing the effects of single nucleotide polymorphisms. Haplotypes are sets of more than one polymorphism that are found close to one another within a gene. These are referred to as 'linked’ and are usually passed on as a functional unit. An example is the HLA-B*5701 haplotype that is associated with abacavir hypersensitivity. This stretch of DNA within the HLA-B gene contains a number of polymorphisms. As haplotypes are larger pieces of DNA containing more than one linked polymorphism, they are often better predictors of an outcome than individual polymorphisms.