Feature: Next next generation sequencing

Technological advances in the field of genome sequencing are overcoming cost and speed limitations and opening the door to new applications, with the next third generation genome sequencers just around the corner

The Ion Personal Genome Machine from Ion Torrent uses third generation genome sequencing technology.

The Ion Personal Genome Machine from Ion Torrent uses third generation genome sequencing technology.

The third generation

The two non-fluorescing technologies operate via quite different methods, with detection systems based on tiny changes in electrical current or pH, thus removing the most expensive components, and associated costs, of sequencing instruments. Hence, in terms of achieving the $US1000 genome, it is likely to be one of these that will reach the goal first.

Both nanopore sequencing, from Oxford Nanopore Technologies (ONT), and Ion Torrent, from Mass Genomics (which was just acquired by Life Technologies), are based on silicon chips. The ONT chip contains hundreds of wells each covered by a lipid bilayer that contains a nanopore – which is a hole around one nanometre in diameter – with each pore an individual electrical channel.

Sequencing is based on exonuclease cleavage of the single DNA strand and detection occurs when the cleaved nucleotide falls through the pore, transiently disrupting the current. The change in current amplitude is unique for each base (A,G,C,T and 5-Methylcytosine - the direct reading of which is unique to nanopore technology). ONT plan to commercialise their nanopore sequencing system by the end of 2010.

Ion Torrent, while also relying on advances in semi-conductor technology, sequences by monitoring DNA synthesis. Single types of nucleotides are sequentially flooded across the chip. Nucleotide incorporation into the new DNA strand results in the release of a H+ ion, which is detected by the pH sensitive dielectric layer. These breadbox–sized benchtop instruments cost about $US45,000 (disposable chips with 1.5 million wells are about $US500) and even come with an iPod, of all things, pre-installed with an application to monitor runs and cycles in real time. How 2010 is that? The Ion Torrent Personal Genome Machine (PGM) sequencer is just making its way into American research labs now.

Whether these single molecule sequencing systems live up to their potential is yet to be demonstrated. “True comparisons with current platforms will only be possible when there has been enough customer access via independent purchase,” says Sydney geneticist, Dr Vanessa Hayes, who has just left Australia to join the J. Craig Venter Institute in San Diego.

Mark Crowe of the Australian Genome Research Facility agrees that it’s too early to tell whether these third generation sequencers will truly provide a breakthrough. “If the technology works, it could completely turn things around for genome sequencing,” he says. “But there are a lot of big ‘ifs’ there.”

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Tags genome sequencinggenomicsIlluminaPacific Biosciencesnext generation sequencing454third generation sequencing

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