KV4@CU.NIH.GOV (05/23/91)
MEETING SUMMARY NIH-DOE JOINT WORKING GROUP ON THE MOUSE May 6, 1991 Bethesda, Maryland The first meeting of the NIH-DOE Joint Working Group on the Mouse was held in Bethesda, Maryland on Monday, May 6, 1991. The Joint Working Group on the Mouse is one of several official working groups of the Joint NIH-DOE Program Subcommittee. This subcommittee reports to each agency's program advisory committee. The attendees included all the members of the Joint Working Group and federal representatives (see Appendix). The members were welcomed by Dr. Elke Jordan, Deputy Director, National Center for Human Genome Research, NIH and Dr. David Galas, Director, Office of Health and Environmental Research (OHER), DOE. Dr. Jordan opened the discussion by describing the role model organisms can play in the Human Genome Project: much is known about their biology and genetics; their genomes are usually less complex than the human genome; and they are manipulatable and thus, can help interpret the human genome. Much progress has been made toward completing the genetic and physical maps of simpler organisms. The physical maps of E. coli, S. cerevisiae and C. elegans are complete or nearly so and sequencing of these genomes has begun. Significant progress has been made in constructing a physical map of D. melanogaster. Strategies for completing the genetic and physical maps of the mouse are still evolving. Dr. Jordan indicated that the charge to the Joint Working Group on the Mouse is to help the NIH and the DOE determine the role of the mouse in the Human Genome Project and to develop a strategy for efficiently using the mouse to accomplish the goals of the Project. Representatives of the DOE and the NIH agencies summarized research currently being conducted under the Human Genome Project. Dr. Benjamin Barnhart (OHER) stated that the DOE has had a long-standing interest in studying model organisms in its Radiation Biology and Chemical Toxicology Programs. Most recently, emphasis in these programs has been on mechanistic studies, i.e., mechanisms of action of radiation and energy- related chemicals. Currently DOE's support for the mouse is approximately $8 million; however, these projects, which include the large resource of mouse mutants at the Oak Ridge National Laboratory and studies on mutagenesis, carcinogenesis, development and reproduction, are not within the scope of the Human Genome Project. Dr. Galas stated that although NIH has more responsibility to support model organisms, the DOE is currently interested in new ideas and is examining how the National Laboratories can respond to the overall effort of the Human Genome Project. He indicated that many ideas are evolving and that DOE intends to maintain some flexibility in supporting such projects. There was some discussion by the mouse working group about how the resources of the National Laboratories could be made available to the general scientific community of mouse researchers. Dr. Bettie Graham, NCHGR, reported that in fiscal year 1991, the NIH is supporting 12 mouse-related research projects at the level of $5.3 million; 10 are investigator-initiated research (R01) projects to support genetic mapping, primarily; one is a program project to develop software tools that permit access to diverse databases; and one is a center grant to develop a complete physical map of the mouse genome. Over the past several years, scientists in the mouse community have taken the initiative to discuss how the mouse can contribute to the Human Genome Project. Dr. Verne Chapman (Roswell Park Cancer Center) summarized the reports from three meetings held in Princeton in November 1989, in the United Kingdom in April 1990, and in Annapolis in November 1990. He expressed pleasure that the mouse community has been able to come together independently to agree to common research goals for the next 3-5 years which include the following: Genetic Map-Establish 320 reference loci spaced 5 centimorgans apart on each chromosome. Physical Map-Develop a physical map of regions of particular genetic interest with the long-term goal of an ordered set of recombinant clones spanning the whole genome. Databases-Collect, integrate, analyze, display and disseminate mouse genomic information. Efforts will be made to work with the Genome Data Base project at Johns Hopkins University to provide users with integrated mouse and human genome information Sequencing-Sequence regions of the genome that are of biological interest (genes and other selected regions). In an effort to facilitate the exchange of information and coordinate research findings, the mouse community has established chromosome-specific committees. Their reports will appear as a supplement to Mammalian Genome in 1991. Since there are 21 different committees (one for each of the 19 autosomes and the X and Y chromosomes), there may well be 21 different ways that information is represented. Such an "experiment" was considered useful, because it will allow several ideas to flourish and, with time, a consensus would be reached about the best way to display map information. Dr. Joseph Nadeau (Jackson Laboratory) discussed resources currently available to mouse geneticists and techniques for constructing genetic and physical maps. He described the mouse mapping resources available in the United States and Europe, use of dinucleotide repeats for genetic mapping, new methods of analyzing data, such as the 2D gel method being developed in Japan, the tools to analyze data, use of YAC and P1 vectors for constructing physical maps, and databases that are available including the object-oriented database being developed as part of the NCHGR mouse genome center at MIT. The remainder of the meeting was given to an open discussion in which the members had an opportunity to express how they see the mouse contributing to the Human Genome Project. In summary, the mouse has several features as a model organism that make it important to the Human Genome Program: the ability to efficiently analyze functional genes and other unique DNA probes into well ordered genetic maps; the ability to relate these maps to the genome of humans and other species in conserved syntenic homologies; the ability to generate mutants to study gene function, its usefulness in studying multi-gene traits, and the ability to study lethal mutations or spontaneous mutations which may not be observed in humans. The members also discussed briefly what the mouse research community needs in order to contribute effectively and efficiently to the Human Genome Project. This includes maintenance of existing and development of additional databases, preservation of existing mouse resources (mapping panels/ recombinant inbred strains/DNA, etc.) and development of new ones; support of research for constructing genetic and physical maps and studying conserved synteny and gene function between mouse and humans, and development and applica tion of state-of- the-art technology. These will be discussed more fully in future meetings. The next meeting will be held in the fall of 1991. The discussion will focus on the state of the mouse genetic map in the United States and Europe and on a plan for obtaining the genetic map of the mouse. The Joint Working Group on the Mouse is planning to address physical mapping at a meeting in the spring of 1992. APPENDIX NIH-DOE JOINT WORKING GROUP ON THE MOUSE Roster Verne M. Chapman, Ph.D. Chairman, Molecular and Cellular Biology Department Roswell Park Cancer Institute Neal G. Copeland, Ph.D. Director of Mammalian Genetics Laboratory NCI-Frederick Cancer Research and Development Center Franklin D. Costantini, Ph.D. Associate Professor of Genetics and Development College of Physicians and Surgeons Columbia University William F. Dove, Ph.D. Professor of Oncology and Medical Genetics Streisinger Professor of Experimental Biology McArdle Laboratory for Cancer Research Joseph H. Nadeau, Ph.D. Staff Scientist The Jackson Laboratory Roger H. Reeves, Ph.D. Assistant Professor of Developmental Genetics The Johns Hopkins University School of Medicine Janet Rossant, Ph.D. Professor Department of Molecular and Medical Genetics Senior Scientist of the Samuel Lunenfeld Research Institute, Mt. Sinai Hospital Oliver Smithies, Ph.D. Excellence Professor of Pathology Department of Pathology, CB 7525 Brinkhous-Bullitt Building University of North Carolina at Chapel Hill Richard P. Woychik, Ph.D. Staff Scientist Mammalian Genetics, Biology Division Oak Ridge National Laboratory Government Representatives Benjamin J. Barnhart, Ph.D. Program Manager Human Genome Program OHER, DOE Daniel Drell, Ph.D. Biologist Human Genome Program OHER, DOE David Galas, Ph.D. Director, OHER DOE Bettie J. Graham, Ph.D. Chief, Research Grants Branch National Center for Human Genome Research NIH Elke Jordan, Ph.D. Deputy Director National Center for Human Genome Research NIH Jane Peterson, Ph.D. Chief, Research Centers Branch National Center for Human Genome Research NIH Marvin Stodolsky, Ph.D. Health Effects Research Division Human Genome Program OHER, DOE Robert L. Strausberg, Ph.D. Assistant to the Director for Technology Development National Center for Human Genome Research NIH