Human DNA Sequencing
- Generate a working draft of 90% of the genome (2001).
- Obtain a complete, high-quality genomic sequence (2003).
- Make all data publicly available.
HGP planners at DOE and NIH emphasized that the highest priority of the
Human Genome Project remains the same: to obtain and make publicly available
a complete and highly accurate reference sequence. The new projected completion
date was credited to recent advances achieved in technology and experience
with pilot large-scale efforts as well as to the contributions of international
partners in the sequencing effort, notably those of the Sanger Centre
in the U.K., and research centers in Germany, Japan, and France.
NIH and DOE sequencing centers expect to generate about 60-70% of the
human DNA sequence, which will be made available broadly and rapidly via
the web to stimulate future research.
A new sequencing milestone expected by 2001 as a result of the scale-up
is the generation of a "working draft" of 90% the genome that comprises
shotgun sequence data from mapped clones, with gaps and ambiguities unresolved.
If the data sets can be merged, private-sector sequencing efforts may
help increase the depth of the mapped draft, which scientists expect will
contain about half of the genes.
The continued emphasis on obtaining highly accurate sequence (1 error
in 10,000 bases) that is largely continuous (few gaps) across each human
chromosome, and the development of sustainable sequencing capacity underscores
the critical importance of these resources for understanding human biology
and for applications to other fields.
Achieving the HGP goal will require current sequencing capacity to be expanded
2-3 times, demanding further incremental advances in standard sequencing
technologies and improvements in efficiency and cost. For future sequencing
applications, planners emphasize the importance of supporting novel technologies
that may be 5-10 years in development.
- Create a long-term, sustainable sequencing capacity by improving current
technology and developing highly efficient novel technologies.
- Develop technologies for rapid identification of DNA sequence variants.
A new priority for the HGP is examining regions of natural variation
that occur among genomes (except those of identical twins). Goals specify
development of methods to detect different types of variation, particularly
the most common type called single nucleotide polymorphisms (SNPs) that
occur about once every 1000 bases. Scientists believe SNP maps will help
them identify genes associated with complex diseases such as cancer, diabetes,
vascular disease, and some forms of mental illness. These associations
are difficult to make using conventional gene hunting methods because
any individual gene may make only a small contribution to disease risk.
DNA sequence variations also underlie many individual differences in responses
to the environment and treatments.
- Expand support for current approaches and innovative technologies.
Efficient interpretation of the functions of human genes and other DNA
sequences requires developing the resources and strategies to enable large-scale
investigations across whole genomes. A technically challenging first priority
is to generate complete sets of full-length cDNA clones and sequences
for human and model organism genes. Other functional genomics goals include
studies into gene expression and control, creation of mutations that cause
loss or alteration of function in nonhuman organisms, and development
of experimental and computational methods for protein analyses.
- Obtain complete genomic sequences for C. elegans (1998), Drosophila
(2002), and mouse (2008).
first clue toward identifying and understanding the functions of human
genes or other DNA regions is often obtained by studying their parallels
in nonhuman genomes. To enable efficient comparisons, complete genomic
sequences already have been obtained for the bacterium E. coli
and the yeast S. cerevisiae, and work continues on sequencing
the genomes of the roundworm, fruit fly, and mouse. Planners note that
other genomes will need to be sequenced to realize the full promise of
comparative genomics, stressing the need to build a sustainable sequencing
Ethical, Legal, and Social Implications (ELSI)
- Analyze and address implications of identifying DNA sequence information
for individuals, families, and communities.
- Facilitate safe and effective integration of genetic technologies.
- Facilitate education about genomics in nonclinical and research settings.
Rapid advances in genetics and applications present new and complex ethical
and policy issues for individuals and society. ELSI programs that identify
and address these implications have been an integral part of the US HGP
since its inception. These programs have resulted in a body of work that
promotes education and helps guide the conduct of genetic research and
the development of related health professional and public policies.
Continuing and new challenges include safeguarding the privacy of individuals
and groups who contribute samples for large-scale sequence variation studies;
anticipating how resulting data may affect concepts of race and ethnicity;
identifying how genetic data could potentially be used in workplaces,
schools, and courts; commercial uses; and the impact of genetic advances
on concepts of humanity and personal responsibility.
Bioinformatics and Computational Biology
- Improve current databases and develop new databases and better tools
for data generation and capture and comprehensive functional studies.
Continued investment in current and new databases and analytical tools
is critical to the success of the Human Genome Project and to the future
usefulness of the data. Databases must be structured
to adapt to the evolving needs of the scientific community and allow queries
to be answered easily. Planners suggest developing a human genome database
analogous to model organism databases with links to phenotypic information.
Also needed are databases and analytical tools for the expanding body
of gene expression and function data, for modeling complex biological
networks and interactions, and for collecting and analyzing sequence variation
- Nurture the training of genomic scientists and establish career paths.
- Increase the number of scholars knowledgeable in genomics and ethics,
law, or the social sciences.
Planners note that future genomics scientists will require training in
interdisciplinary areas that include biology, computer science, engineering,
mathematics, physics, and chemistry. Additionally, scientists with management
skills will be needed for leading large data-production efforts.