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