24-hour genome dawns

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    Speedy techniques herald overnight sequences

    Medicine could soon be tailor-made to patients' own genetic sequence. Credit: © Getty Images

    Sequencing the first human genome took more than ten years. Yours may take only 24 hours. Budding biotech firms are poised to make instant genomes a reality.

    In future, researchers hope to offer tailor-made medicine based on patients' own genetic sequence. To do this, "Existing technologies don't really cut it," says Eugene Chan of US Genomics in Woburn, Massachusetts.

    Chan's is one of several companies hoping to bring about personal genomes with methods that could hugely accelerate the process by which DNA letters are read. The techniques are to be tested at a next-generation sequencing facility in Rockville, Maryland, for which plans were announced last month.

    "The goal is to do a genome in minutes or seconds for a $1,000," says sequencing pioneer Craig Venter. Intrigued by the technologies, Venter will discuss them at University College London today, and at a last-minute session at the 14th International Genome Sequencing and Analysis Conference in Boston in October.

    Disentangling DNA

    Since its invention in 1977, the principles of chemical sequencing remain largely unchanged ? though automation has drastically speeded things up. Current machines, which sort through fluorescent-tagged lengths of DNA, can read only around 1,000 letters at a time, and samples need lengthy preparation and analysis, with associated cost.

    "We're reaching the limits [of current methods]," says Venter. "To sequence billions of bases in seconds we need something very different." Developments in nanotechnology and computing power are now making this possible.

    Rather than chopping DNA into fragments, then piecing the sequences back together on a computer, researchers hope to read straight through a long string of DNA ? like reading chapters rather than words of a book.

    Chan has developed a way to spool out the tangle of DNA in a chromosome using a 'nanofluidic' chip smaller than a computer key.

    “The goal is to do a genome in minutes or seconds for a $1,000 Craig Venter ”

    Fluidflowing through the chip draws the DNA through an array of pegs like bowling pins. One end works loose and is drawn into a funnel at the end.

    Rather than sequencing every letter, Chan and his team spot the differences between individuals ? and use the reference genome to fill in the rest. Fluorescent tags stick to variable spots; a detector reads their order as they flow past. The speed-reading technique gets through around 200,000 letters a minute, he claims.

    Others are turning to the cell itself for inspiration ? which copies its entire genome in a matter of hours when it divides. "The problem is already solved for you," says Daniel Densham of Mobious Genomics, a biotech company based in Exeter, UK.

    Densham uses an enzyme called polymerase, which copies DNA in the cell. As polymerase adds chemical letters A, C, G or T, to the strand, it changes shape in a characteristic way. Densham detects this change by directing a beam of electromagnetic radiation onto the surface of the enzyme and measuring the way it is scattered.

    Densham hopes to put multiple polymerases on a chip and analyse them simultaneously; his company has just been granted a European patent. But like other super-fast sequencing outfits, their biggest bottleneck is finding the computer power to process huge volumes of genomic information at high speed.

    At this stage, which of the emerging technologies is likely to become the standard is unclear. "Maybe in due course one will win out," says Tony Smith of Solexa, another UK biotech developing a chip-based genome reader," or maybe they'll be used in different ways."

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    24-hour genome dawns. Nature (2002) doi:10.1038/news020923-1

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