Race for $1,000 Genome Heats
Up
Millions in grant money drive genome sequencing.
By Nina Flanagan
Running neck and neck, Solexa and 454 have announced
their second-generation sequencers in the race for
better understanding of the human genome. Both companies
have shipped early copies of instruments that promise to
sequence more DNA in less time than previously possible.
The announcements follow the National Human Genome
Research Institute (NHGRI) initiative to award $13
million in grants to speed development of these
technologies in order to reduce costs and expand genomic
applications. The goal is to be able to sequence a
mammalian-size genome for $1,000 or less, enabling the
sequencing of an individual’s genome during routine
medical care. In addition, the X Prize Foundation
recently announced a $10 million prize for the creation
of technology that can map 100 human genomes in ten
days.
Single-Molecule Sequencing
Helicos BioSciences received a $2 million grant from
NHGRI to fund research of its proprietary
single-molecule (RNA and DNA) sequencing technology (tSMS)
for resequencing applications and de novo sequencing of
large genomes. Advantages of the technology include: no
PCR bias, no amplification errors, and 1,000-times less
reagent costs than Sanger sequencing. "A key part
of this grant is to investigate novel ways of using our
single-molecule detection technology to sequence DNA in
a way that allows the 20% with repeat sequences,
amplifications, etc. to be more easily aligned and gets
to the truth of what the actual sequence of that
individual’s DNA is," states Steve Lombardi,
Helicos’ senior VP of marketing.
Chromosome Sequencing
Researchers at Solexa recently announced successful
sequencing of the human X chromosome using its Genome
Analysis System. "This platform analyzes one
gigabase per run," says Tony Smith, vice president
and chief scientific officer. The company’s sequencing
method involves randomly fragmenting DNA into short
pieces (a few hundred bases long) and adding a special
adapter to the end of each fragment, so they can bind to
an eight-channel flow cell. Single DNA molecules are
amplified into clonal clusters of up to 1,000 identical
copies of each molecule. Each channel of the flow cell
can yield up to 5 million distinct clusters and generate
more than 125 megabases of sequence data. The 1G Genome
Analyzer images the clusters through a series of digital
photographs.
"Our data showed we had sequenced 2.6 billion
bases, which means we had an average of 16-fold coverage
of the human X chromosome. The over-sampling gives you
much higher confidence," explains Smith. He says
customers are looking for high-accuracy sequencing that’s
faster and less expensive. "Our system delivers
about 100-times the throughput of conventional
sequencing at about 1/100th of the cost," he says.
The Genome Sequencer FLX system from 454 serves as an
upgrade to the two-year old Genome Sequencer 20 that was
used by scientists at Cold Spring Harbor Laboratory to
reveal the dual role of the Argonaute 4 (AGO4) protein
in RNA-directed DNA methylation.
"Feedback from early adopter sites has been very
positive due to longer read lengths, increased
throughput per run and very high single read accuracy
over 200 bases," says Christopher McLeod, president
and CEO of 454 Life Sciences. "The GS FLX offers
high-throughput sequencing with single read accuracy
equivalent to traditional Sanger sequencing."
In a single run, the GS FLX system can read 100
megabases in less than eight hours.
Focus on Resequencing
Jonathan Witonsky, an industry analyst for Frost
& Sullivan, says there is an increased demand for
resequencing. "Information from the human genome
database is driving research to look at genes associated
with certain diseases, in order to do targeted
resequencing for comparative genomic studies," he
says. Costs have been driven down by large-scale
sequencing efforts. "Over the past three years,
there has been a 30-40% drop in costs," Witonsky
adds, "and by 2012, costs per reaction will drop
from the current $8 per reaction to $5."
Applied Biosystems (ABI) has introduced the
VariantSEQr Resequencing System for mutation detection.
With ready-to-use PCR primer sets (for resequencing up
to 500 DNA samples) and suggested protocols for PCR and
sequencing, this system is designed to work with ABI’s
instruments, reagents, and software. Proprietary
software, SeqScape Software v2.1.1, provides mutation
profiling with detailed result reports. The initial
product offering includes resequencing sets for 280
genes, and the company says it welcomes suggestions from
researchers to help prioritize genes that are currently
in development.
Allison Proffitt contributed to this report.
