New Sequencing Resources Aid Effort
In September, international leaders of Human Genome Project (HGP) sequencing
confirmed a plan to complete a rough draft of the human genome by next spring,
a year ahead of schedule. This accelerated pace is made possible by the commercialization
of a new generation of automated capillary DNA sequencing machines and by
BAC mapping resources generated from DOE-sponsored clone projects.
The rough draft will provide a scaffold of sequence across about 90% of the
human genome. Remaining gaps will be closed and accuracy improved over the
following 3 years to achieve a complete, high-quality human DNA reference
sequence by 2003 [see HGN 10(1-2), 1 (www.ornl.gov/hgmis/publicat/hgn/v10n1/01goals.shtml)].
So far, about 13% of human sequence has been finished, and another 12% is
available in draft form (genome.ornl.gov/GCat;
www.ncbi.nlm.nih.gov/genome/seq).
Sequencing Allocation
About 60% of the draft sequence will be produced by six major NIH-funded
sequencing centers, including those previously established at Washington University,
St. Louis; MIT-Whitehead Institute; and Baylor College of Medicine. In July,
laboratories at the University of Washington, Seattle; Genome Therapeutics
Corp.; and Stanford University joined the NIH production sequencing effort.
The DOE-funded Joint Genome Institute (JGI) and the Sanger Center (United
Kingdom) will generate about 10% and 30%, respectively, of the draft sequence.
(See box, below right, for details on JGI sequencing.) France, Germany, and
Japan are contributing significant amounts of human sequence, and China recently
joined the worldwide project. To avoid duplicated work, each laboratory focuses
on particular genomic regions.
Sequencing group members reaffirmed the policy of placing all sequence in
publicly accessible databases within 24 hours of obtaining a continuous 1000-
to 2000-base assembly. They also agreed that sequencing should continue to
be based on a proven strategy using BAC clones containing DNA from known genomic
locations.
BAC-End Sequences: Prime Resource
Data from the DOE-funded BAC-end sequencing projects at The Institute for
Genome Research (TIGR) and the University of Washington, Seattle (UWS), are
critical for achieving the new HGP goals. These projects are generating single-sequence
reads from both ends of the human DNA insert in 450,000 BAC clones [HGN
10(1-2), 4 (www.ornl.gov/hgmis/publicat/hgn/v10n1/04bacend.shtml)
and BAC Web page (www.ornl.gov/meetings/bacpac/)].
In March, DOE increased its support of BAC-end sequencing projects to accelerate
their completion and usefulness for guiding production sequencing. The BAC-end
sequences, called sequence tag connectors (STCs), are valuable tools for eliminating
redundant sequencing. They can direct researchers to particular BAC clones
needed for extending a sequenced region along the chromosome and can identify
clones representing genomic regions still not sequenced. STCs also can provide
quality checks on sequence assemblies and are useful for spanning regions
resisting standard sequencing biochemistry.
STC data will furnish researchers with markers spaced on average every 3000
to 4000 bases across the entire human genome, a 100-fold improvement over
other current human genome maps. Detailed data on BACs are available at TIGR
(www.tigr.org/tdb/humgen/bac_end_search/bac_end_intro.html)
and UWS (www.genome.washington.edu).
The STC data resource is complemented by several other types of mapping information,
including FISH mapping of BAC clones.
FY1999 HGP Budgets
- DOE: $89.8M
- NIH: $225.7M
- Total: $315.5M
For more information, contact:
Department of Energy, Jeff Sherwood, 202-586-5806
NHGRI, 301-402-0911
Whitehead Institute, Eve Nichols or Seema Kumar, 617-258-5183
Washington University School of Medicine in St. Louis, Linda Sage, 314-286-0119
Baylor College of Medicine, B.J. Almond, 713-798-7971
Wellcome Trust, Noorece Ahmed, 44 171 611-8540 (United Kingdom)
Sanger Centre, Jane Rogers, 44 122 383-4244 (United Kingdom)
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