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Human Genome News, May 1994; 6(1)

NCHGR Sequencing Branch States Goals

The philosophy and recent activities of the Sequencing Technology Branch, directed by Robert Strausberg and Carol Dahl, are highlighted in this article. Other NCHGR branches will be covered in future issues.

The NIH National Center for Human Genome Research (NCHGR) formed the Sequencing Technology Branch to support research toward several interrelated goals, including the following.

  • Determine the complete genomic DNA sequence of several nonmammalian model organisms including Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, and Escherichia coli.
  • Refine, fully automate, and integrate systems of current sequencing approaches to achieve tenfold improvements in sequencing capability.
  • Develop novel methods, technologies, and instruments for fully integrated, innovative approaches to rapid, low-cost determination of DNA sequence. These new approaches are expected to offer 20- to 30-fold improvements in speed and cost.
  • Serve as the NCHGR focal point for extramural technology transfer activities and promote collaborative multidisciplinary research with close integration among academic and industrial research laboratories.

Research Accomplishments and Challenges

Much effort and substantial resources will be needed to accomplish the ambitious sequencing technology goals of the Human Genome Project. However, encouraging progress and new ideas in sequencing technology development have come forth this year. Technological paths are now envisioned, say Dahl and Strausberg, for accomplishing and possibly exceeding the original sequencing goals of the project.

Recent advances in automating gel-based technology have resulted in significantly improved sequence throughput. These advances will require systems integration to match sample flow with data flow through all steps of the process. A particular need now is improved informatics, especially for the finishing stages of genomic sequencing. In addition, with the increase in DNA sequence throughput, better systems are needed to handle information output; these include improved data-management tools and analysis software.

Advances in capillary electrophoresis and ultrathin gel electrophoresis are projected to improve parallelization and speed of DNA analysis at least tenfold. In addition, new efforts are being undertaken to apply microfabrication and microelectromechanical systems technology to the sample preparation and separation steps and mass spectrometry to the separation step. These methods could afford a 100- to 1000-fold increase in speed and associated decreases in cost. Independent improvements must be made in methods for sample preparation, assay technology, detection systems, and data management and analysis. Ongoing efforts to develop fully automated and integrated modular systems based on current approaches are likely to benefit the development of newer miniaturized technologies under way in the NCHGR program and elsewhere.

The notion that new sequencing technologies would be an important product of the Human Genome Project was a common theme throughout the NIH-DOE planning process for the new 5-year plan (1994-98). Development of these technologies provides an unprecedented opportunity to interface technology development with biological research.

Sequencing Beyond the Reference Human Genome

The force driving sequencing-technology development for the Human Genome Project is the need for cost-effective methods to sequence the human and other genomes. Such technology should also serve as a platform for developing instrumentation for DNA sequence analysis in a wide variety of applications in the diagnostic, clinical, environmental, forensic, and agricultural markets. Successful implementation of these instruments will require substantial engineering design changes to address specialized needs. In medical diagnostic applications, for example, an ideal system might inject a biological sample into a cassette, automatically position the cassette in a reader, automatically and accurately determine the results, display them on a computer screen, and immediately transfer the results to the patient's record. For environmental or agricultural uses, readily transportable, miniaturized, handheld devices would be desirable. Others outside the Human Genome Project who are studying the effects of environmental mutagens will require sequencing instruments with a very high degree of sensitivity. Goals will include searching for rare genetic changes in cell populations.

Agencies Cooperating To Develop New Sequencing Technology Applications

NIH and DOE can interface effectively with other federal agencies to facilitate further development and application of genome technologies in the marketplace. Toward that end, Strausberg and Dahl have developed extensive collaborations with the staff of the Advanced Technology Program (ATP) of the National Institute of Standards and Technology (NIST) within the U.S. Department of Commerce.

The mission of ATP is to stimulate economic growth in the United States through technology development and deployment to the marketplace. Projects selected for support by ATP have the potential for broad-based economic impact but a relatively high technical risk and a long time horizon. Funding is through cooperative agreements with companies or industrial consortia. The ATP mission is well suited to advancing DNA sequence-based technologies to serve the needs of many markets. [See HGN 5(5), 5 (January 1994).]

NCHGR sequencing technology staff and Stanley Abramowitz, manager of the ATP Biotechnology Program, organized a workshop on ATP funding at "The Human Genome Project: Commercial Implications" meeting this spring in San Francisco. The workshop emphasized ATP interest in biotechnology and pointed to projects already supported by ATP for developing transgenic animals and oligonucleotide array hybridization.

Dahl and Strausberg, who are formally detailed part-time to NIST, will continue to work with ATP managers. Other federal agencies have also been identified as having technology-development programs that could interface well with the Human Genome Project. Through such interagency collaboration, products of the Human Genome Project will be positioned more effectively to impact biology, medicine, and many other areas of opportunity.

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Human Genome Program, U.S. Department of Energy, Human Genome News (v6n1).

Human Genome Project 1990–2003

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.

Human Genome News

Published from 1989 until 2002, this newsletter facilitated HGP communication, helped prevent duplication of research effort, and informed persons interested in genome research.