NHGRI Funds Large-Scale Sequencing Centers
New Era of Sequencing for Cancer and Other Medical Purposes
Begins
Bethesda, Md. — The National Human Genome
Research Institute (NHGRI) today announced the results of the recent
competition for support of its three large-scale sequencing centers,
strengthening efforts to use the power of DNA sequencing to unlock
the genomic secrets of human diseases. Also today, NHGRI and the
National Cancer Institute (NCI), both part of the National Institutes
of Health (NIH), announced that all three sequencing centers will
devote a significant part of their efforts to The Cancer Genome
Atlas (TCGA) Pilot Project, which is testing the feasibility of
a large-scale, systematic approach to identify important genomic
changes involved in cancer.
"Genomic sequencing has already made a substantial impact on both
biological and medical research. A major focus of the next phase
will be medical sequencing, which involves using sequencing technologies
to identify genes that contribute to common human diseases, most
of which have so far eluded gene hunters,” said NHGRI Director
Francis S. Collins, M.D., Ph.D. “These discoveries will shed new
light on the biological pathways involved in human health and disease,
which in turn will lead to better strategies for diagnosis, treatment
and prevention. It is gratifying that our sequencing centers are
going to play a major role in bringing the promise of personalized
health care closer to reality.”
The sequencing centers were selected through a competitive, peer-reviewed
process based on scientific merit of each center’s application,
as well as costs and efficiency. The three NHGRI-supported, large-scale
sequencing centers, their principal investigators and their approximate
Fiscal Year (FY) 2007 funding levels are:
- Broad Institute Sequencing Platform, The Eli & Edythe L. Broad
Institute of the Massachusetts Institute of Technology and Harvard
University; Eric S. Lander, Ph.D.; Cambridge, Mass., $48 million
- Washington University Genome Sequencing Center, Washington
University School of Medicine, Saint Louis; Richard K. Wilson,
Ph.D.; $41 million.
- Human Genome Sequencing Center, Baylor College of Medicine,
Houston; Richard Gibbs, Ph.D.; $27.6 million
The sequencing centers will be funded under cooperative agreements
in which substantial programmatic involvement is anticipated among
NHGRI and the recipients during performance of the scientific activities.
The cooperative agreements also require each sequencing center
to participate in the NHGRI’s Minority Action Plan by developing
and implementing a training and education program to increase the
number of under-represented minorities in genomic sciences.
Over the next four years, the centers in NHGRI’s Large-Scale Sequencing
Research Network will utilize existing technology to continue large-scale
sequencing of important targets. Almost half of the sequencing
capacity will be dedicated to medical sequencing. The sequencing
centers will also pursue new ways to increase the speed and lower
the cost of DNA sequencing by testing and implementing several
new technologies which could potentially revolutionize large-scale
sequencing and expand the use of genomics in medical research and
health care. The combined sequence output from the centers, using
current technologies, is expected to be about 12 billion DNA base
pairs per month — the equivalent of four human genomes.
A significant portion of NHGRI’s medical sequencing program will
be used for The Cancer Genome Atlas (TCGA), which was launched
in December 2005 as a $100 million collaborative three-year pilot
project between NHGRI and NCI. TCGA consists of four integrated
components: the Genome Sequencing Centers announced today, plus
seven Cancer Genome Characterization Centers, a Data Collection
Center, and the Biospecimen Core Resource. In the pilot phase of
TCGA , the Genome Sequencing Centers will sequence a substantial
number of selected gene targets to identify genomic changes, such
as single base mutations and small insertion/deletions, in three
types of tumors: brain (glioblastoma), lung (squamous cell), and
ovarian.
“Cancer is an extremely complex disease. The Genome Sequencing
Centers will play a pivotal role in our systematic effort to assess
the range of genomic changes associated with malignancy,” said
Mark S. Guyer, Ph.D., director of NHGRI's Division of Extramural
Research. “This genomic information will provide the research community
with a powerful tool for uncovering new therapeutic targets and
developing better strategies for diagnosing, treating and preventing
cancer.”
Other medical sequencing projects will use DNA sequencing to:
discover new genes that are involved in common diseases; identify
the genes responsible for dozens of relatively rare, single-gene
(autosomal Mendelian) diseases; sequence all of the genes on the
X chromosome from affected individuals to identify those involved
in sex-linked diseases; and survey the range of variants in genes
known to contribute to certain common diseases. The start of each
project will depend on a number of factors, including the strategic
selection of specific diseases and the availability of patient
samples with appropriate informed consent.
“The availability of the human genome sequence, as well as other
genomic resources produced by our sequencing centers, has transformed
biomedical research everywhere,” said NHGRI’s Associate Director
of Extramural Research Jane Peterson, Ph.D., who is also a program
director for NHGRI’s Large-Scale Sequencing Research Network. “The
addition of medical sequencing projects is challenging and quite
exciting. Making these data publicly available to researchers will
build upon the past success of NHGRI’s rapid data access model,
and will continue to expand our knowledge of human health and disease.”
The sequencing centers also will focus increased attention on
sequencing the genomes of organisms, such as bacteria, fungi, parasites,
and insects, which cause or transmit human diseases. In addition,
they will pursue promising new areas of health-related research.
For example, the large-scale sequencing program has already started
to sequence the genomes of 100 microorganisms found in the human
gut, and will build on this by using genomic sequencing to characterize
the complex microbial communities found at many sites in and on
the human body. Microbes have a profound effect on many human physiological
processes, such as digestion and drug metabolism, and play a vital
role in disease susceptibility. It is hoped new information about
these organisms will lead to improved methods for monitoring and
maintaining human health.
In addition to medical sequencing and technology development efforts,
the sequencing research network will continue its groundbreaking
work in comparative genomics, which involves sequencing and comparing
the genomes of various organisms. This has proven to be one of
the most powerful ways of identifying the parts of the human genome
that are most functionally important, and therefore most likely
to be relevant for an understanding of disease. In addition to
the large-scale sequencing centers, other important comparative
sequencing data will be contributed by the NIH Intramural Sequencing
Center (NISC) in Rockville, Md. NISC conducts sequencing projects
for NIH investigators and also generates sequence data to support
various NHGRI sequencing program activities. NISC funding will
be around $7 million, with half of this coming from intramural
funds.
Since the completion of the human genome sequence in 2003, the
sequencing centers have sequenced and published analyses of the
genomes of a wide range of animals, including the mouse, chimpanzee,
chicken, dog, rat, honey bee and sea urchin. This has provided
researchers with a powerful tool for understanding the structure
and function of the human genome. For instance, DNA sequences that
are shared, or conserved, between humans and another species may
be essential for turning genes on and off during development.
NHGRI's process for selecting sequencing targets to enter the
pipeline for the sequencing centers begins with three working groups
comprised of experts from across the research community. Each of
the working groups is responsible for developing a proposal for
a set of genomes to sequence that would advance knowledge in one
of three important scientific areas: to identify areas in genetic
research where the application of high-throughput sequencing resources
would rapidly lead to significant medical advances; understanding
of the human genome; and understanding the evolutionary biology
of genomes.
A coordinating committee then reviews the working groups' proposals,
helping to fine-tune the suggestions and integrate them into an
overarching set of scientific priorities. The intent of the target
selection process is to maintain flexibility so the focus of the
sequencing program can be adjusted as the state of knowledge improves
over the next four years in order to pursue the most biomedically
compelling sequencing targets. The recommendations of the coordinating
committee are reviewed and approved by the National Advisory Council
for Human Genome Research, which in turn forwards its recommendations
to NHGRI leadership. For more on the selection process, go to: www.genome.gov/Sequencing/OrganismSelection.
In addition, each sequencing center may use up to 10 percent of
its capacity to work on targets of its own choosing. This will
afford the sequencing centers some flexibility to demonstrate innovative
uses of sequence information.
A complete list of organisms and their sequencing status can be
viewed at www.genome.gov/10002154.
High-resolution photos of many of the organisms being sequenced
in NHGRI’s Large-Scale Sequencing Program are available at: www.genome.gov/10005141.
NHGRI is one of the 27 institutes and centers at the National
Institutes of Health, an agency of the Department of Health and
Human Services (DHHS). Additional information about NHGRI can
be found at its Web site, www.genome.gov.
For more information about cancer and the National Cancer
Institute, please visit the NCI Web site at www.cancer.gov or
call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
More information about The Cancer Genome Atlas Pilot Project is
available at http://cancergenome.nih.gov/.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov. |