OE Human Genome Program Second Contractor-Grantee Workshop (1991)
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.. 1 II !I Acknowledgements I' I The. information for this report was compiled and prepared for publication by Laura Yust and other Human Genome Management Information System staff members. Charles Cantor contributed the I "Santa Fe Workshop Summary" with assistance from Elbert Branscomb, Anthony Carrano, Leroy Hood, Robert Moyzis, Robert Robbins, and DOE program staff. Sylvia Spengler (workshop organizer) and Eileen Mendez at the Lawrence Berkeley Laboratory Human Genome Center provided the abstracts. Most importantly, the contributions of grantees and contractors to the DOE Human Genome Program are gratefully acknowledged. For information or additional copies of this report contact: Laura Yust Human Genome Management Information System Oak Ridge National Laboratory P.O. Box 2008 Oak Ridge, TN 37831-6050 615/574-7582, FrS 624-7582; Fax: 615/574-9888, FTS 624-9888; Internet: "[email protected]"; BITNET: "[email protected]" I I I This report has been reproduced directly from the best available copy. Available from the National Technical Information Service, U.S. Department of Commerce, Springfield, Virginia 22161. I -I Price: Printed Copy A06 II Microfiche AOl l l ' Codes are used for pricing all publications. The code is determined by the number of pages in the publication. Information pertaining to the pricing codes can be found in the current issues of the following publications, which are generally available in most libraries. Energy Research Abstracts, (ERA); Government Reports Announcements and Index (GRA and I); Scientific and Technical Abstract Reports (STAR); and publication, NTIS-PR-360 available from (NTIS) at the above address. Conf-91 02129 Dist: Category UC-408 DOE uman enome Program Report of the Second Contractor-Grantee Workshop February 17-20, 1991 Santa Fe, New Mexico Date Published: August 1991 Prepared for the U.S. Department of Energy Office of Energy Research Office of Health and Environmental Research Washington, D.C. 20585 under budget and reporting code KP 0404000 Prepared by Human Genome Management Information System Oak Ridge National Laboratory Oak Ridge, TN 37831-6050 Managed by MARTIN MARIETTA ENERGY SYSTEMS, INC. for the U.S. DEPARTMENT OF ENERGY UNDER CONTRACT DE-AC05-840R21400 Preface For over four decades the Office of Health and Environmental Research of the Department of Energy (DOE) and its predecessor organizations have supported major research on the genetic effects of energy-related agents. Although knowledge and capabilities in this area have advanced in many ways, DOE realized in the early 1980s that more complete genetic resources would be required for tasks such as measuring mutations in descendants of the Hiroshima and Nagasaki survivors. These novel resources would include physical maps of the 24 different human chromosomes, a complete human genome DNA base sequence, and the computational tools to use this information. Partly because of the need for new and different approaches to modem challenges, DOE began the Human Genome Initiative in 1987. The number of genome-funded projects has increased rapidly, and the initiative has grown into a flourishing program, with a complementary counterpart at the National Institutes of Health. The impact of the Human Genome Project on science and society will be substantial as significant achievements become frequent occurrences. New physical mapping strategies have allowed our national laboratories and university grantees to move ahead in a timely manner, and development of innovative approaches to determining the base sequence of chromosomes is proceeding at an encouraging rate. Our computational capabilities are improving. New networking workstations and methods of inputting and analyzing mapping and sequencing data are being developed to allow investigators easy access to data from major databanks. Investigations are under way into the ethical, legal, and social implications of the use of data generated by this program. The first of many DOE Human Genome Distinguished Postdoctoral Fellowships have been awarded to train additional scientists in areas critical to the success of the Human Genome Program. Program management needs, such as project coordination and the desire to create an environment in which the program's investigators could interact, formed the basis for this workshop. We are indebted to Sylvia Spengler and the session chairs, but especially to all contributors. The 1991 workshop had many stimulating presentations, and numerous collaborative efforts have developed, but we anticipate that its successor, scheduled for the fall of 1992, will provide additional concepts, strategies, and technologies that are not yet imagined and that are based on multidisciplinary interactions. We await with excitement what lies ahead. Benjamin J. Barnhart Human Genome Program Office of Health and Environmental Research DOE Office of Energy Research Table of Contents Preface ................................................................................... 1 Workshop Agenda . iv Santa Fe Workshop Summary . • . • . 1 Speaker Abstracts* . • • . 8 Informatics: New Methods, Unresolved Problems . 10 aoning/Amplification . • . 15 Mapping: Progress and New Methods . 19 DNA Sequencing Instrumentation/Database Needs . 23 DNA Sequencing Methodology . 26 New Techniques and Instruments . 30 Poster Abstracts* .•..........................•....... 0 • • • 34 Informatics: New Methods, Unresolved Problems ...... 0 • • • • • • • • 38 aoning/Amplification ................................. 0 •• 0 52 Mapping: Progress and New Methods . 57 DNA Sequencing/Instrumentation Database Needs . 67 DNA Sequencing Methodology . 78 New Techniques and Instruments . 89 Author Index . 0 • • • • • • • • • • • • • • • • • 0 • • • • • • • • • • • • • • • • • • • 0 105 Workshop Participants . 109 *The abstracts were reproduced as closely as possible to the author's originaL iii Workshop Agenda Sunday, February 17 12 noon - 5:30 pm: Registration 5:00 - 7:30 pm: Mixer, video talk by Senator Domenici Monday, February 18 8:30 am - 12 noon: Chair, C. Cantor Introduction: B. Barnhart Human Genome Program in the Overall DOE Context: D. Galas Mapping: Progress and New Methods: G. Evans R. Stallings G. Sutherland T. Caskey M. Simon P. de Jong Lunch Talk on Ethical, Legal, and Social Issues: M. Y esley 2:00 - 5:30 pm: Chair, R. Moyzis Cloning/Amplification: V.Rao S. Antonarak:is M. McCormick P. Youderian D. Nelson G. Hermanson 5:30 - 7:00 pm: Poster Session Tuesday, February 19 8:30 am - 12 noon: Chair, R. Robbins Informatics: New Methods, Unresolved Problems: T. Slezak J. Fickett R. Douthart D. Searls T. Hunkapiller E. Lawler iv Tuesday, February 19 (continued) 3:30 - 6:00 pm: Chair, E. Branscomb Database Needs for Sequencing Projects: R. Gesteland C. Lawrence L Hood Public Databases: P. Pearson C. Burks 7:00 - 9:00 pm: Buffet and Poster Session Wednesday, February 20 8:30 am - 12 noon: Chair, A Carrano DNA Sequencing Methodology: L. Smith B. Karger D. Berg A Riggs R. Keller F. W. Studier 2:00 - 5:30 pm: Chair, L. Hood New Techniques and Instruments: B. Trask B. Jacobson J. C. Giddings R. Kopelman R. Foote R. Athwal J. Vas Meeting Summary and Perspective: C. Cantor v Santa Fe Workshop Summary* The Department of Energy (DOE) Human Genome Program held its Second Contractor-Grantee Workshop in Santa Fe, New Mexico, on February 17-20, 1991. Almost all the DOE-supported projects were represented, either by oral presentations or by posters. More than 200 DOE supported scientists attended the meeting, in addition to invited guests and representatives from a number of interested industries. Benjamin Barnhart, Manager, Human Genome Program, Office of Health and Environmental Research (OHER), welcomed the attendees and gave a brief overview of research that would be presented as platform and poster sessions throughout the 3-day workshop. Six platform sessions focused on database and computer algorithm needs for existing or projected genome research, large DNA fragment cloning, progress in physical mapping, DNA sequencing instrumentation, strategies for preparing samples for efficient DNA sequencing, and new methods for a variety of genome efforts. David Galas, Associate Director, OHER, spoke about the relationship between the Human Genome Program and other OHER research programs. He emphasized the importance of new strategies, resources, and technologies being developed in the Human Genome Program for research aimed at understanding genomic damage by radiation and chemicals. He also stated that DOE is uniquely positioned to make major advances in protein structure and function relationships, because DOE's extensive capabilities in structural biology at the national laboratories will be coordinated with those of the Human Genome Project. Michael Yesley [Los Alamos National Laboratory (LANL)] presented ethical, legal, and social issues pertaining to data produced in the genome project. The general impression conveyed by most presenters was that physical mapping efforts are going well; chromosomes 16, 19, and portions of 11 are now well covered with large numbers of assembled contigs. Fluorescence in situ hybridization (FISH) is emerging as an extremely effective method for ordering cloned probes. Automated DNA sequencing is becoming more efficient through approaches like capillary or thin gel electrophoresis. Informatics support for most current physical mapping efforts and for large scale DNA sequencing needs to be increased, and more focus is needed on ongoing biology projects. At present there