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Starting next spring, a complete human-genome sequence can be ordered for just $5,000, thanks to a new sequencing service announced by Complete Genomics, a startup based in Mountain View, CA. The stunning price drop–sequencing currently costs approximately 20 times that amount–could completely change the way that human-genomics research is done and open up new possibilities in personalized medicine. Researchers say that a $5,000 genome would enable new studies to identify rare genetic variants linked to common diseases, and it could open up the sequencing market to diagnostic and pharmaceutical companies, making genome sequencing a routine part of clinical drug testing.

Complete Genomics, which has received $46 million in venture funding to date and has largely stayed under the radar, plans to launch with a bang and anticipates the capacity to sequence 1,000 genomes in 2009 and 20,000 in 2010. That would represent a massive jump: with a price tag of $100,000 to $1 million over the past two years, only a handful of human genomes have been sequenced to date.

“Suddenly, these guys are talking about sequencing hundreds to thousands of genomes in the next couple of years,” says Chad Nusbaum, codirector of the Genome Sequencing and Analysis program at the Broad Institute, in Cambridge, MA. “That opens up tremendous vistas for the kind of science we want to do. It’s really by generating hundreds of human-genome sequences that you can start to ask hard questions about human genetics.”

Complete Genomics says that it has already sequenced a human genome, although it has not yet released the data for independent review. “ ‘Stunning’ is not too strong a word, if they can do it in the very near term,” says Jeffrey Schloss, program director for technology development at the U.S. National Human Genome Research Institute, on the possibility of a $5,000 genome. “But I haven’t seen any data and I don’t know anyone who has, which is of course critical.”

J. Craig Venter, founder of the J. Craig Venter Institute, in Rockville, MD, is working with Complete Genomics to validate its technology, comparing the sequence that it generates with a reference sequence of his own genome.

Complete Genomics says that its cheap price tag comes thanks to two innovations: a way to densely pack DNA, developed by Rade Drmanac, the company’s chief scientific officer, and a method to randomly read DNA letters, based on sequencing technology developed at George Church’s lab at Harvard.

To start with, an 80-base-pair piece of DNA is inserted into a circular piece of synthetic DNA and replicated 1,000 times with a specialized enzyme. That large aggregate of DNA spontaneously compresses into a tightly packed ball, thanks to chemical characteristics engineered into the synthetic DNA. These DNA “nanoballs” are then packed onto specially fabricated arrays with unprecedented density–about a billion balls fit on a chip the size of a microscope slide. The high density of DNA allows large volumes to be sequenced quickly with few reagents, one of the most costly components of the process.

Next, as with other approaches, Complete Genomics determines the sequence of the target DNA using a series of fluorescently labeled DNA strands designed to bind to corresponding letters. But while advanced sequencing technologies currently in use–including those from Illumina, Applied Biosystems, and 454–read the sequence sequentially, letter by letter, Complete Genomics’s labels bind to the target DNA randomly. Both the labels and the DNA circle are designed to allow scientists to deduce the position of each highlighted base–information that is then used to computationally reconstruct the sequence of the target DNA. (With both Complete Genomics’s and other companies’ methods, the short strands are computationally stitched together to generate the entire genome sequence.)

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Credit: Technology Review

Tagged: Biomedicine, disease, gene-sequencing technology, $1000 genome

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