Sponsored by the U.S. Department of Energy Human Genome Program
Human Genome News Archive Edition
Human Genome News, July 1993; 5(2)
The National Center for Human Genome Research (NCHGR) sponsored a workshop on April 20-21 in Washington, D.C., to evaluate progress toward DNA sequencing goals established in the first 5-year plan and to begin planning for the next 5 years. Information from the workshop will be considered in developing future goals. The meeting was attended by NIH and DOE genome program staff, genome scientists, and representatives from the commercial sector, national laboratories, and universities.
Participants discussed the likelihood of meeting current 5-year goals for sequencing; the interface between mapping and sequencing within the overall program; programmatic balance among evolutionary technology development, revolutionary technology research, and production sequencing; development, implementation, and exportation of new technology; balance of genomic and cDNA sequencing and mapping; and training related to sequencing.
Below is a brief summary of discussion points and attendees' recommendations toward the 1998 sequencing and technology-development goals for the Human Genome Project. The next 5-year plan will span fiscal years 1994-98.
Sequencing. The project is expected to meet the 1995 goal of 20 Mb of model-organism sequence but probably not the goal of 10 Mb of human sequence. Attendees felt that the greatest impact of the genome project will come from sequence, sequence-derived information, and associated new technologies. Basic biological research will be the greatest beneficiary of these products. Where possible, sequencing efforts should be closely coordinated for human DNA and syntenic regions in the mouse. By 1998 (the 15-year project's midpoint), 175 Mb of model-organism DNA and 100 Mb of combined mouse and human DNA should have been sequenced, participants said. The combined capacity of all large-scale sequencing centers should be 100 Mb per year of documented high-quality finished sequence, with projected cost-efficiency of $0.25 per base pair.
To achieve the goals of sequencing the human genome and the genomes of selected model organisms, attendees suggested that funding for DNA sequencing and technology development should shift to more than $100 million per year. Commitment to long- and short-term training is also needed for future staffing and to encourage new scientists to enter production-sequencing projects. Although the information derived from sequencing full-length cDNAs is considered valuable, this approach is currently too expensive because of several problems, including normalization and the quality of cDNA libraries. In addition, large-scale cDNA mapping technology is not yet considered to be cost-effective.
Mapping-Sequencing Interface. The shift of funds from a mapping emphasis to a sequencing emphasis should begin now, according to participants. "Sequence-ready maps" or sequence substrates should be generated in production-sequencing groups to ensure maximum usefulness of the product. Because of concern over map quality, some attendees felt that two colinear maps within any region are needed to validate accuracy. The construction of a 100-kb-resolution map based on sequence tagged sites (STSs) is recommended for preparing state-of-the-art, sequence-ready substrates in conjunction with large-scale sequencing efforts.
Technology Development. The NCHGR program should continue to invest moderate levels of funds in high-risk, high-payoff technologies that seem a long way from large-scale implementation. Parallel development and testing of multiple approaches and strategies is critical. Each large-scale sequencing program should have both technology development and production sequencing, although the balance between these elements may vary. Emphasis was placed on integrated modular systems that can afford complete automation of the sequencing process. Identifying the most costly steps and targeting them for technology development is crucial.
Transfer and Exportability. Grant applications for technology development should include plans for transfer and exportability. An infrastructure may need to be established to facilitate distribution of information and technology transfer among laboratories. To prevent overlap and make better use of information obtained by each individual group, more coordination is needed among centers and individuals who are developing technology. The project needs to connect with the users of genome information to ensure development of the most-useful products, such as repositories of materials or user software. NCHGR may be able to facilitate coordination through meetings or a newsletter.
Systems Integration. Systems integration and sequencing informatics are critical areas in which technology must be advanced to drive down costs and improve production within tasks such as mapping or sequencing. Planned improvements in ABI 373 hardware are projected to increase sequencing throughput in the gel electrophoresis and raw-sequence-acquisition steps of the overall process by 32-fold within the next 5 years.
From this discussion, participants achieved consensus on multiple critical points, which they suggested should be considered as 1998 goals for the Human Genome Project:
The electronic form of the newsletter may be cited in the following style:
Human Genome Program, U.S. Department of Energy, Human Genome News (v5n2).
The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.
Published from 1989 until 2002, this newsletter facilitated HGP communication, helped prevent duplication of research effort, and informed persons interested in genome research.