DNA chips detect disease

A DNA chip that can identify genetic mutations has been synthesised by Japanese scientists.

The most common form of genetic variation between individuals is caused by single-nucleotide differences in our DNA code. These are called single nucleotide polymorphisms (SNPs). SNPs can be used to identify disease genes and can highlight when a person is likely to develop a disease.

Kenzo Fujimoto and colleagues at the Japan Advanced Institute of Science and Technology have developed a simple and rapid method for identifying SNPs. The method could be the basis for automated, high-throughput diagnosis, they claim.

The method uses a short strand of DNA, known as an oligodeoxynucleotide probe, attached to a glass chip. The probe contains DNA bases complementary to those in the DNA strand containing the SNP of interest, except that one base is replaced by a vinyl-containing nucleoside known as cvP. When Fujimoto placed the target DNA onto the chip and shone ultraviolet light on it, the cvP reacted with an adenine base on the target DNA, in a reaction known as photocrosslinking. Fujimoto detected the photocrosslinked product using fluorescence imaging.

Because photocrosslinking only occurs when all the bases on the probe are complementary to those on the target DNA, if there is a mismatch in the strands the chip does not fluoresce.

'This method is an efficient reaction and proceeds with high sequence specificity,' said Fujimoto. 'Photochemical DNA manipulation is a highly original research theme.'
Hans-Achim Wagenknecht, an expert in molecular diagnostics at the University of Regensburg, Germany, believes the work represents a significant improvement for SNP detection. 'Such cheap, sensitive and reliable screening tools are clearly needed for the clinical diagnostics of genetic variations, infectious diseases and pharmacology,' he said.