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The companies still have a long road to the $100 genome. BioNanomatrix has already shown that long pieces of DNA–two million letters in length–can be threaded into the channels of existing chips. But now researchers need to develop chips with many more channels, so that multiple genomes’ worth of DNA can be sequenced simultaneously.

The main hurdle for Complete Genomics will be to generate fluorescent labels that can be easily and accurately detected. Most current methods get over this problem by making many copies of the same DNA molecule and sequencing them simultaneously, thus boosting the signal to noise ration. But that approach limits the length of the piece of DNA that can be sequenced, and it increases cost by increasing the amount of chemicals needed for the reaction.

The project is part of the Advanced Technology Program, funded by the National Institute of Standards and Technology to spur development of novel, high-risk technologies. This year, Complete Genomics is releasing a commercial product based on similar chemistry, but the company has declined to give details on its status.

The technology necessary to achieve a $100 genome is still at least five years away, says George Church, a geneticist at Harvard Medical School, in Boston, and a member of Complete Genomics’ scientific advisory board. “But [it’s] coming from a company that has an almost-as-good technology coming out this year.”

Both Drmanac and Boyce-Jacino say that one of the biggest advantages of their technology will be the ability to sequence very long strands of DNA. The newest sequencing technologies in use today read DNA in fairly short spurts, from about 30 to 200 letters, which are then stitched together by a computer. This approach works well for some applications, such as resequencing a known genome. But a growing number of studies suggest that the small structural changes in DNA, such as deletions or inversions of short sequences, play a significant role in human variability, says Jeff Schloss, program director for technology development at the National Human Genome Research Center, in Bethesda, MD. “Those are much harder to pick up with short reads.”

Longer reads will also allow scientists to look at collections of genetic variations that have been inherited together, known as haplotypes. This kind of analysis can determine if a particular genetic variation has been passed down from the individual’s mother or father. Recent research suggests that in some cases, maternal or paternal inheritance can impact the severity of the disease. With new tools to better track inheritance patterns, scientists may discover that this phenomenon is more common than previously thought. “That’s one reason we’re hoping that several of the emerging methods will allow long reads,” says Schloss.

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Credit: BioNanomatrix

Tagged: Biomedicine, genome, sequencing

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