Revised 5-Year Research Goals of the U.S. Human Genome
Human Genome News 5(4) (November 1993). Adapted
from: F. Collins and D. Galas, "A new five-year plan for the
U.S. Human Genome Project," Science 262: 43-46
(October 1, 1993).
October 1, 1993, to September 30, 1998 (FY 1994-98)
Mapping and Sequencing the Human Genome
- Genetic Mapping
- Complete the 2- to 5-cM map by 1995. (Goals for map
resolution remain unchanged.)
- Develop technology for rapid genotyping.
- Develop markers that are easier to use.
- Develop new mapping technologies.
- Physical Mapping
- Complete a sequence tagged site (STS) map of the human
genome at a resolution of 100 kb. (Goals for map
resolution remain unchanged.)
- DNA Sequencing
- Develop efficient approaches to sequencing one- to
several megabase regions of DNA of high biological
- Develop technology for high-throughput sequencing,
focusing on systems integration of all steps from
template preparation to data analysis.
- Build up a sequencing capacity to allow sequencing at a
collective rate of 50 Mb per year by the end of the
period. This rate should result in an aggregate of 80 Mb
of DNA sequence completed by the end of FY 1998.
- Gene Identification
- Develop efficient methods for identifying genes and for
placement of known genes on physical maps or sequenced
- Technology Development
- Substantially expand support of innovative technological
developments as well as improvements in current
technology for DNA sequencing and for meeting the needs
of the Human Genome Project as a whole.
- Model Organisms
- Finish an STS map of the mouse genome at a 300-kb
- Finish the sequence of the Escherichia coli and Saccharomyces
cerevisiae genomes by 1998 or earlier.
- Continue sequencing Caenorhabditis elegans and Drosophila
melanogaster genomes with the aim of bringing C.
elegans to near completion by 1998.
- Sequence selected segments of mouse DNA side by side with
corresponding human DNA in areas of high biological
- Continue to create, develop, and operate databases and
database tools for easy access to data, including
effective tools and standards for data exchange and links
- Consolidate, distribute, and continue to develop
effective software for large-scale genome projects.
- Continue to develop tools for comparing and interpreting
- Ethical, Legal, and Social Implications (ELSI)
- Continue to identify and define issues and develop policy
options to address them.
- Develop and disseminate policy options regarding genetic
testing services with potential widespread use.
- Foster greater acceptance of human genetic variation.
- Enhance and expand public and professional education that
is sensitive to sociocultural and psychological issues.
- Continue to encourage training of scientists in
interdisciplinary sciences related to genome research.
- Technology Transfer
- Encourage and enhance technology transfer both into and
out of centers of genome research.
- Cooperate with those who would establish distribution
centers for genome materials.
- Share all information and materials within 6 months of
their development. This should be accomplished by
submission of information to public databases or
repositories, or both, where appropriate.
U.S. Human Genome Project Updates Goals
Unexpected advances in genome research and more-sophisticated
understanding of how to achieve long-term objectives have led
genome project planners at NIH and DOE to update their initial 5-year goals. The new 5-year plan
appeared in the October 1 issue of Science in an article
coauthored by Francis Collins, Director of the National Center
for Human Genome Research, and David Galas, formerly head of the
DOE Human Genome Program and Associate Director of the DOE Office
of Health and Environmental Research.
The new plan extends research goals in already established
categories and adds specific new goals for developing technology
for gene identification and mapping. It also provides for
outreach programs to distribute genome materials to the
scientific community. Although the plan covers the next 5 years
of the project (through September 1998), the goals were designed
to address both long- and short-term needs.
Obtaining the complete human DNA sequence is still the
ultimate goal of the project. Although debate continues over the
value of sequencing the whole genome, researchers recognize the
importance of DNA sequence information in revealing genes and
other biological information that could not be obtained by
The new goals again assume a funding level for the whole
genome program of $200 million annually, adjusted for inflation
after 1990. Although this amount was also assumed when the
initial goals were developed and implemented, appropriations have
never reached that level. U.S. genome project funding for FY 1994
(which began October 1) is about $170 million.
A New Plan Needed Progress over the last 3 years has
put the initial goals well within reach with detailed human
genetic maps; improved physical maps of human and model organism
genomes; development of DNA sequencing and informatics
technology; and identification of major ethical, legal, and
social issues (ELSI) concerning the increased availability of
genetic information. Although the first 5-year plan was not due
to expire until September 1995, "Advances in genome research
have already changed the way research is being done,"
Collins said. "We need to incorporate these advances into
our present research goals to ensure that the program continues
to be ambitious and cutting edge."
The genome project has already had a profound impact on
biomedical research. In just the past few years, maps generated
by project researchers have helped in finding genes associated
with dozens of genetic conditions, including Menkes syndrome, the
X-linked immune disorder ammaglobulinemia, Huntington's disease,
myotonic dystrophy, fragile X syndrome, neurofibromatosis types 1
and 2, and others. In addition to the identification of many more
disease genes, other future developments will enable researchers
to explore gene mutations and health effects caused by
Developing New Goals In developing the new goals, an
NIH-DOE working group sought advice from scientists, other
interested scholars, and public representatives, including many
outside the Human Genome Project. (Reports of these meetings are
available from HGMIS and the NCHGR Office of Communications;
HGMIS, ORNL, 1060 Commerce Park, MS6480, Oak Ridge, TN 37831;
NCHGR, Bethesda, MD 20892; 301/402-0911, Fax: -4570)
The plan was presented to and approved by the NIH National
Advisory Council for Human Genome Research and the DOE Health and
Environmental Research Advisory Committee.
The following are some general observations underlying
specific new goals.
Technology Development. This will continue to be
crucial to future program success, particularly in the area of
large-scale DNA sequencing. Accomplishments that influence
research strategies include new types of genetic markers (i.e.,
microsatellites) assayable by the polymerase chain reaction
(PCR); improved vector systems for cloning large DNA fragments
and methods for assembling clones into physical maps; use of
sequence tagged sites (STSs) as common physical mapping entities;
and improved DNA sequencing technology and automation.
Future Mapping Efforts. These efforts should focus on
regions both larger and smaller than a single chromosome, the
basic unit of genome analysis to date. (An "average"
human chromosome contains about 150 Mb.) Production of
whole-genome low-resolution maps is now feasible due to PCR and
robotic developments. Increasing attention needs to be paid to
fine-detail mapping of smaller DNA regions (one to a few
megabases) as well. One million bases is an ambitious dimension
for detailed analysis, the plan says, and will provide a
"useful bridge" between conventional genetics and
larger-scale genomics research as well as a "foundation for
innovation" to develop methods with applicability to larger
regions. Planners note that progress already achieved allows
greater focus on gene information to enrich the maps produced.
Specific goals covering the period between October 1, 1993,
and September 30, 1998, appear in an additional article in HGN
5(4):2 called "Five-Year Goals". More details
pertaining to these goals are given below.
Genetic Map. Researchers expect that the genetic map
specified in the first 5-year plan will be completed on time, but
technological improvements are needed to allow rapid typing of
families by nonexperts and simultaneous multimarker testing of
large numbers of individuals by researchers studying complex
genetic diseases. Also needed are methods for automated
polymorphic marker screening and new gene mapping strategies not
based on a standard set of polymorphic markers.
Physical Map. An STS-based physical map of the human
genome with an average resolution of about 300 kb will be
completed within 2 to 3 years. Because this level of detail is
not sufficiently useful to either gene mappers or sequencers, the
plan calls for markers placed at 100-kb intervals. Such a map
would be useful to researchers using conventional methods to
isolate genes localized within 100 kb of a mapped marker or in
To facilitate gene finding and DNA sequencing, new approaches
are needed for constructing higher-resolution maps and for
cloning systems closely tied to development of sequencing
technology. The plan also recommends improving clone libraries
with regard to stability and chimerism and increasing their
DNA Sequencing. Although sequencing costs will meet
the original 1996 goal of $0.50/bp, planners estimate that $100
million per year will be needed to develop sequencing technology
of sufficient sequencing rate to permit the entire human genome
to be sequenced by 2005. Further cost reduction and increased
ability to assess sequence accuracy are also critical. The plan
recommends expanding the number of groups working on large-scale
sequencing, improving conventional gel-based approaches, and
developing revolutionary new methods.
Gene Identification. Mapping progress and
technological improvements have now enabled project planners to
specify the development of gene identification technology as a
new goal. Incorporating genes into the rapidly growing body of
maps and sequences of both human and model organism genomes will
make these resources more useful to researchers exploring their
effects on human health.
Technology Development. Cooperation is encouraged in
developing vital new technologies, especially automation and
robotics, that are expandable and exportable to basic science
laboratories sequencing genomes not being studied in the Human
Model Organisms. Original goals will probably be
exceeded for the mouse genetic map, Drosophila melanogaster
physical map, and DNA sequencing of Escherichia coli, Sacharomyces
cerevisiae, and Caenorhabditis elegans. Priorities
include completion of the mouse map and sequencing of specified
Informatics. Although much progress has been made,
further development of accessible, user-friendly tools to
collect, organize, and interpret vast amounts of data continues
to be crucial to the success of the project. Major future goals
are data management, analysis, and distribution.
ELSI. ELSI discussions are tied to both genomic
research and use of the data it produces. Initial policy options
regarding this use are being developed for four areas identified
as having the greatest immediate potential impact on society:
privacy, fairness, clinical applications, and professional and
public education. Reports on the full range of issues will
continue to be presented during the next 2 years.
Policymakers must consider cultural and other social
influences as they prepare policies that anticipate the
increasing impact on the public of widespread genetic testing for
common conditions. Also recommended and encouraged are the active
involvement of concerned individuals and groups in developing
policy options as well as increased public and professional
education at all levels to prevent stigmatization and
Training. Because of the increased number of genome
centers, more high-quality training programs are expected to be
established to meet the need for interdisciplinary training of
scientists for genome research.
Technology Transfer. Many new companies have already
been established to develop applications of genome research, and
collaborations between government-funded genome scientists and
the private sector have increased. The plan encourages further
cooperation with industry but cautions that care must be taken to
avoid conflicts of interest. Technology transfer from other
fields to genome centers must also occur.
Outreach. The private sector is encouraged (with seed
funding in some cases) to establish distribution centers for
genome materials and respond quickly to the evolving needs of the
scientific community. The policy on data and material sharing
(within 6 months of creation) has been well accepted.
Article adapted from Science, 262, 43-46 (October 1, 1993).
Reprints are available from HGMIS and the NCHGR Office of
Communications (Contact: HGMIS, ORNL, P.O. Box 2008, Oak Ridge,
TN 37831-6050, 423/576-6669, Fax: /574-9888 or NCHGR, Bethesda,
MD 20892, 301/402-0911, Fax: -4570).
The new DOE-NIH 5-year plan credits the "spirit of
international cooperation and sharing" that has
characterized the Human Genome Project and played a major role in
The Human Genome Organization was commended for coordinating
international research efforts by organizing chromosome workshops
to encourage collaboration and expedite chromosome map
- Notable international collaborations:
- Caenorhabditis elegans sequencing project (United
States and United Kingdom).
- Chromosome 16 physical mapping project (Los Alamos
National Laboratory and Australia).
- Chromosome 21 high-resolution physical map (Lawrence
Livermore National Laboratory and Japan).
- Human genetic map (NIH and Centre d'Etude du
- Whole-genome approach to a human physical map (Whitehead
Institute and Genethon).