Gene device slashes the cost of decoding
- From: pluto <pluto@xxxxxxxxxxxx>
- Date: Tue, 02 Aug 2005 14:34:07 +0800
http://www.iht.com/articles/2005/08/01/business/dna.php
Gene device slashes the cost of decoding
By Nicholas Wade The New York Times
TUESDAY, AUGUST 2, 2005
A new kind of machine for decoding DNA may help bring costs so low that it
would be feasible to decode an individual's DNA for medical reasons.
The machine, developed by a U.S.-based company, 454 Life Sciences, was used
to resequence the genome of a small bacterium in four hours, its scientists
report in an article published online on Monday by the journal Nature.
In 1995, when the same bacterium was first sequenced, by Claire Fraser, it
required 24,000 separate operations spread over four to six months, she
said in an e-mail message.
The machine uses the chemistry of fireflies to generate a flash of light
each time a unit of DNA is correctly analyzed. The flashes from more than a
million DNA-containing wells, arrayed on a plate the size of a credit card,
are monitored by a light-detecting chip, the kind used in telescopes to
detect the faintest light from distant stars. Then they are sent to a
computer that reconstructs the sequence of the genome.
The decoding or sequencing of genomes has long depended on a chemical
process invented by Frederick Sanger in 1977. But genome centers based on
this technology are expensive to equip and operate.
For several years, biologists have been searching for a method that could
be miniaturized and made cheap enough to stimulate a range of new
applications.
Among several promising approaches, one called pyrosequencing has been
developed by Pal Nyren and Mostafa Ronaghi at the Royal Institute of
Technology in Stockholm.
The technique depends on separating the double helix of DNA into single
strands and building up new strands to complement the old ones. As each new
DNA base is added to a growing strand, a chemical component known as
pyrophosphate is discarded.
Nyren's team developed the chemistry to convert the discarded pyrophosphate
into a trigger for luciferase, the enzyme that fireflies use to generate
their light.
Because the chemists knew in each cycle which of the four DNA bases they
had added, a flash of light indicated the sequence at that point.
Ronaghi, who is now at Stanford University, said that he and Nyren had
developed the chemistry and showed it could be miniaturized and that 454
Life Sciences, having licensed their patents, had made the system
practical.
"What they have done here is very significant," Ronaghi said, noting that
the company had already sequenced 50 microbial genomes. "This is the first
step toward $1,000 human genome sequencing."
The Joint Genome Institute, a federal genome sequencing center in
California, has ordered one of the company's $500,000 sequencing machines
but has not yet installed it.
The machine's limitation is that at present it can only read DNA fragments
100 units or so in length, compared with the 800-unit reading length now
attained by the Sanger-based machines. That shorter span makes it harder to
reassemble all the fragments into a complete genome, said Paul Richardson
of the Joint Genome Institute, so that although microbial genomes can be
assembled, mammalian genomes may be beyond its reach at present.
Jonathan Rothberg, chairman of 454 Life Sciences, said the company was
already able to decode DNA 400 units at a time in test machines. It is
working toward sequencing a human genome for $100,000, he said, adding that
if costs could be further reduced to $20,000, the sequencing of individual
genomes would be medically worthwhile.
There would be little advantage at present in sequencing a patient's entire
genome, but in the medicine of the future, complete documentation about an
individual's genetic makeup could well provide a prognosis or indicate a
preferred treatment.
The new technology avoids a pitfall of the Sanger method, which is that the
fragments of DNA to be analyzed are first amplified by being cloned in
bacteria. But the bacteria cannot handle certain fragments, leaving gaps in
the genome sequence. In the new technique, each fragment of DNA is captured
in an individual drop of liquid and amplified to 10 million copies with a
well-established chemical method known as the polymerase chain reaction.
The 10 million copies from each droplet are then attached to an ultra-small
bead, and the beads are dropped into a credit-card-size grid of 1.6 million
wells, where the pyrosequencing takes place. Each time the correct base is
added to the fragments of DNA on a specific bead, a flash of 10,000 photons
is picked up through the bottom of the wells by the light-detecting chip
that sits under the small grid of wells.
A computer can reconstruct the sequence of bases composing the fragments
and from the overlaps between fragments it can reassemble the entire genome
from which they were derived.
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cheers
pluto
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