Mouse Working Group Developing Strategies

The first meeting of the NIH-DOE Joint Working Group on the Mouse was held in Bethesda, Maryland, on May 6. Attendees were welcomed by Elke Jordan, Deputy Director, NIH National Center for Human Genome Research (NCHGR) and David Galas, Associate Director, DOE Office of Health and Environmental Research (OHER). Jordan indicated that the task of the working group is to help NIH and DOE determine the role of the mouse in the Human Genome Project and to develop a strategy for efficiently using the mouse to accomplish project goals [HGN 3(1) 10 (May 1991)] as outlined in the 5-year plan.

The meeting opened with a discussion of the value of model organisms in the genome project. Several features make the mouse an important model organism:

functional genes and other unique DNA probes can be efficiently analyzed and placed onto well-ordered genetic maps, which can be related to the genomes of humans and other species by exploiting conserved syntenic homologies;
mutants can be generated to study gene function; and
multigene traits, lethal mutations, and spontaneous mutations that may not be observed in humans can be studied more easily.

Strategies for completing the mouse genetic and physical maps are still evolving, but much progress has been made on the maps of simpler organisms. Physical maps of the intestinal bacterium Escherichia coli, the yeast Saccharomyces cerevisiae, and the nematode Caenorhabditis elegans are complete or nearly so, and sequencing of their genomes has begun. In addition, significant progress has been made in constructing a physical map of the fruit fly Drosophila melanogaster.

DOE and NIH agency representatives summarized research being conducted under the Human Genome Project.

Benjamin Barnhart, Manager, OHER Human Genome Program, stated that DOE has had a longstanding interest in studying model organisms through its Radiation Biology and Chemical Toxicology programs. Most recently, program emphasis has been on mechanistic studies (i.e., mechanisms of radiation and energy-related chemical damage causation). Currently, DOE annual support for the mouse is around $8 million; however, these projects, which include the large resources of mouse mutants at Oak Ridge National Laboratory and studies on mutagenesis, carcinogenesis, development, and reproduction, are not within the scope of the Human Genome Project.

Galas said that although NIH has more responsibility to support model organisms, DOE is exploring new ideas and examining how its national laboratories can respond to the overall effort. He indicated that DOE intends to maintain some flexibility in supporting such projects. Discussion followed about ways to make national laboratory resources available to the general mouse scientific community.

Bettie Graham (NCHGR) reported that NCHGR support for 12 mouse-related research projects totals $5.3 million in FY 1991:

ten investigator-initiated R01 research projects primarily to support genetic mapping,
one R01 project to develop software tools that permit access to diverse databases, and
one center grant to develop a complete physical map of the mouse genome.

To facilitate information exchange and to coordinate research findings, the mouse community has established 21 chromosome-specific committees, one for each of the 19 autosomes and the X and Y chromosomes [see HGN 3(1), 11 (May 1991)]. This varied representation was considered useful because several ideas would be allowed to flourish and, with time, a consensus could be reached on the best way to display map information. Committee reports will appear this year as a supplement to Mammalian Genome.

Verne Chapman (Roswell Park Cancer Center) summarized meetings in Princeton, New Jersey; the United Kingdom; and Annapolis, Maryland. He expressed pleasure that the mouse community has come together to agree on common research goals for the next 3 to 5 years and to cooperate with NIH and DOE in accomplishing genome project objectives. Mouse research goals:

Genetic Map - Establish 320 reference loci spaced 5 cM apart on each chromosome.
Physical Map - Develop a physical map of regions of particular genetic interest with the long-term goal of constructing 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 Database at Johns Hopkins University to provide users with integrated mouse and human genome data.
Sequencing - Sequence genome regions that are of biological interest (genes and other selected regions).

Joseph Nadeau (Jackson Laboratory) described several mouse mapping resources under development in the United States, Europe, and Japan, including

dinucleotide repeats for genetic mapping;
new methods and tools for analyzing data (such as a two-dimensional gel electrophoresis method being developed in Japan);
yeast artificial chromosome and P1 vectors for constructing physical maps; and
databases, including the object-oriented database being developed as part of the NCHGR mouse genome center led by Eric Lander at the Massachusetts Institute of Technology.

Working group members also discussed briefly what the mouse research community needs to do to make effective and efficient contributions to the Human Genome Project. These topics will be explored more fully in future meetings:

maintenance of existing databases and development of additional ones;
preservation and development of mouse resources (mapping panels, recombinant inbred strains, DNA, etc.);
research support for constructing genetic and physical maps and for studying conserved synteny and gene function between mouse and human; and
development and application of state-of-the-art technology.

Next Mouse Working Group Meeting: September 15,16

Topic: Mouse Genetic Map

Mouse Working Group Contact:

Bettie J. Graham, Chief
Research Grants Branch
NIH NCHGR
Bldg. 38A, Room 617
Bethesda, MD 20892
301/496-7531
Fax: 301/480-2770

Reported by Bettie J. Graham

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The electronic form of the newsletter may be cited in the following style:
Human Genome Program, U.S. Department of Energy, Human Genome News (v3n2).

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Human Genome Project Information Archive1990–2003

Mouse Working Group Developing Strategies

Human Genome Project Information Archive
1990–2003