Lawrence Livermore National
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Production DNA Sequencing Begun
The year 1996 marked a transition
to the final and most challenging phase of the U.S. Human Genome Project,
as pilot programs aimed at refining largescale sequencing strategies and
resources were funded by DOE and NIH (see Research
Highlights, DNA Sequencing). Internationally, large-scale human genome
sequencing was kicked off in late 1995 when The Wellcome Trust announced
a 7-year, $75-million grant to the private Sanger Centre to scale up its
sequencing capabilities. French investigators also have announced intentions
to begin production sequencing.
Funding agencies worldwide agree
that rapid and free release of data is critical. Other issues include sequence
accuracy, types of annotation that will be most useful to biologists, and
how to sustain the reference sequence.
The international Human
Genome Organisation maintains a Web page to provide information on
current and future sequencing projects and links to sites of participating
groups. The site also links to reports and resources developed at the February
1996 and 1997 Bermuda meetings on largescale human genome sequencing, which
were sponsored by The Wellcome Trust.
a major restructuring of its Human Genome Program, on October 23, 1996,
the DOE Office of Biological and Environmental Research established the
Joint Genome Institute (JGI) to integrate
work based at its three major human genome centers.
With easy access to both LBNL and LLNL, a building in Walnut Creek,
California, is being modified. Here, starting in late FY 1998, production
DNA sequencing will be carried out for JGI. Until that time, large-scale
sequencing will continue at LANL, LBNL, and LLNL. Expectations are that
within 3 to 4 years the Production Sequencing Facility will house some
200 researchers and technicians working on highthroughput DNA sequencing
using state-of-the-art robotics.
Initial plans are to target gene-rich regions of around 1 to 10 megabases
for sequencing. Considerations include gene density, gene families (especially
clustered families), correlations to model organism results, technical
capabilities, and relevance to the DOE mission (e.g., DNA repair, cancer
susceptibility, and impact of genotoxins). The JGI program is subject to
regular peer review.
Sequence data will be posted daily on the Web; as the information progresses
to finished quality, it will be submitted to public databases.
As JGI and other investigators involved in the Human Genome Project
are beginning to reveal the DNA sequence of the 3 billion base pairs in
a reference human genome, the data already are becoming valuable reagents
for explorations of DNA sequence function in the body, sometimes called
"functional genomics." Although largescale sequencing is JGI's major focus,
another important goal will be to enrich the sequence data with information
about its biological function. One measure of JGI's progress will be its
success at working with other DOE laboratories, genome centers, and non-DOE
academic and industrial collaborators. In this way, JGI's evolving capabilities
can both serve and benefit from the widest array of partners.