A selective microarray method to identify genetic variations has been developed by scientists in Germany.

Variations in our genetic make-up are responsible for some diseases and are known to be major players in an individual's predisposition to side effects of a drug. Convenient and rapid detection of these variations could help to adapt therapy to the individual or develop 'personalized medicine'. 

This has prompted Andreas Marx and colleagues at the University of Konstanz to devise a high-throughput technique for the selective detection of single nucleotide variations in a genetic sequence. Single nucleotide variations occur in human DNA at a frequency of approximately 1 in 1000 bases. 

'Conventional enzyme-based strategies for the detection of single nucleotide variations often lack sufficient selectivity,' said Marx. 'We found that the selectivity could be increased by chemically modifying the substrate of a particular enzyme, DNA polymerase.' 

Marx modified the 4' position of oligonucleotides on the end of immobilised primer probes on a microarray. This small change, the addition of a methoxymethylene group, resulted in the more precise identification of the single nucleotide variations. 

'These systems should allow analysis of several thousands of single nucleotide variations at different positions within the genome of a person in parallel,' said Marx. 'This is still a challenging task that none of the present systems is able to achieve reliably.' 

Marx hopes to develop the system to allow the analysis of single nucleotide variations from natural samples, without the need for prior amplification by polymerase chain reaction. 

Oliver Seitz, an expert in DNA diagnostics at Humboldt University, Berlin, believes that Marx's work could have a significant impact on the development of DNA diagnostic probes. 'The method brings high specificity to high-throughput format,' said Seitz. 'The challenge now is to combine multiplex analysis with specificity and signal amplification in a miniaturized format, to enable point-of-care diagnostics.' 

Alison Stoddart