A fluorescent probe can spot the difference between the four DNA bases: adenine, thymine, cytosine and guanine.

Snorri Sigurdsson and Pavol Cekan from the Universty of Iceland, Reykjavik, have synthesised a highly fluorescent nucleoside (a base bound to a sugar) which can report the identity of its base-pair when placed in a DNA duplex. The fluorescence emitted by the duplex differs depending on which DNA base is paired with the probe.

The fluorescent nucleoside can report the identity of its base pair in duplex DNA

According to Sigurdsson and Cekan, the probe could find use in detecting single DNA base changes - single nucleotide polymorphisms (SNP) - at sites where variation can indicate disease. Changes within the gene apolipoprotein E, for example, are considered to be an indicator of predisposition to Alzheimer's. The researchers explain that detecting SNPs with their probe could make it possible to identify genetic diseases or recognise people who might be susceptible to them. Also, the probe would not only detect a SNP but could indicate which DNA base replaced the correct one.

David French from LGC, in Teddington, UK, who has recently studied SNP in the gene encoding sheep prion protein agrees that 'technology that can reliably discriminate between the four naturally occurring bases of DNA to analyse SNPs will be an useful tool for diagnostic tests.'

Sigurdsson plans to investigate the nucleoside's fluorescence under many different conditions. 'Better understanding of the nucleoside's properties will lay the groundwork to develop further compounds that may be better suited for routine-based fluorescence assays,' he says. 'One of the challenges is to find base-discriminating fluorescent nucleosides that emit light at the higher wavelengths detected by instruments currently used in laboratories around the world.'

Rachel Cooper