A colourful approach to detecting DNA variations can take the heat. A team led by Changill Ban from Pohang University of Science and Technology and Min Su Han from Chuang-Ang University, Seoul, in South Korea, has tested a technique that reveals mismatched DNA base pairs by a temperature change. 

The team's method detects DNA in which one base is paired with any base that is not its complementary partner. Mismatch detection can be used to find single base differences called single nucleotide polymorphisms (SNPs). Rapid SNP detection is essential, says Ban, as these DNA variations can be a marker for genetic disease. 

When gold-bound DNA strands unpair the system changes from purple (top) to red (bottom) as the gold de-aggregates

The team bound gold nanoparticles to single stranded DNA which then pairs to form duplex DNA containing mismatches. As the DNA pairs, the system turns from red to purple as the nanoparticles aggregate. On heating, the system reverts to red as the strands unpair or 'melt'. The researchers observed that the colour change occurs at a higher temperature when the system is treated with MutS, a protein that binds selectively to mismatched pairs. They also found that complexes containing different DNA mismatches melt at different temperatures, so it is also possible to identify which bases are mismatched.

Ban says that, as a colorimetric assay, the detection method is 'simpler and more convenient than other methods, allowing mutation detection with the naked eye.' Most current colorimetric detection methods rely on enzyme activity, requiring carefully controlled physiological reaction conditions to work. By using MutS, the team avoids these limitations, as the protein maintains its activity under a range of pHs and at high temperatures. 

The next stage will be to adapt the method for microarray technology, says Ban, allowing high throughput screening of DNA samples.

Harriet Brewerton