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See Inside December 2006

DNA Sequencing on the Cheap

Optical technology advances toward the $1,000 genome

The exorbitant cost of deciphering a person's genome dropped sharply in 2005, from $20 million to roughly a tenth of that amount. DNA-sequencing technology using off-the-shelf equipment devised by George M. Church of Harvard Medical School and his collaborators both at Harvard and Washington University in St. Louis may help realize the federal goal of reducing that price to $1,000 by 2015, which experts say would make it practical to decode a person's genes for routine medical purposes. The build-it-yourself method (right) the Church group developed is based on combining widely available and relatively inexpensive microscopes with high-speed digital cameras.

A related technique from 454 Life Sciences in Branford, Conn., also employs cameras coupled with microscopes to sequence DNA, except this method uses a different light-emitting technology than Church. Sequencing also usually relies on bacteria to multiply copies of the DNA target; both new methods instead use a combination of beads to grab the DNA and enzymes to reproduce it. The Church group's version works roughly 20 times faster than conventional sequencing, at a cost of $140,000. 454's system has a roughly 100 times higher throughput than conventional sequencing, at a cost of about $500,000 a machine.

In contrast to these optical technologies, current gene sequencing relies on electrophoresis, in which electric fields separate molecules based on their size and charge. H. Kumar Wickramasinghe of the IBM Almaden Research Center and his colleagues have devised a technique that combines electrophoresis with an atomic force microscope, which scans a surface by running extraordinarily sharp probes across it. The invention can sort DNA fragments roughly 100,000 times faster than conventional electrophoresis, albeit only with snippets up to 40 nucleotides long. The researchers note that their work could not only help accelerate DNA sequencing but also deliver molecules onto surfaces with unprecedented control.

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