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Human Genome News Archive Edition

Human Genome News, March 1992; 3(6)

Second NIH-DOE Joint Mouse Working Group

The second meeting of the NIH-DOE Joint Mouse Working Group was held September 15-16, 1991, in Boston. Different topics were the focus of each of four sessions:

  • Mouse Genome Center at the Massachusetts Institute of Technology (MIT);
  • U.K. Mouse Genome Project;
  • status of the mouse genetic map; and
  • requirements for completing a 1-cM genetic map of the mouse.

For a list of working group members, see HGN 3(1), 10 (May 1991).

MIT Mouse Genome Center

Eric Lander (MIT Mouse Genome Center) discussed progress at the center, which is sponsored by the NIH National Center for Human Genome Research, in constructing

  • a genetic map consisting of 2000 ordered polymorphic markers that are maximally useful (i.e., highly variable, typable by polymerase chain reaction, and easy to distribute) and
  • a physical map of genetically ordered 1- to 2-Mb contigs. Closure is not one of the goals, so the map will have gaps.

Lander indicated good progress during the first 12 months, with about 400 markers having been isolated and 338 mapped. He plans to supply data periodically to the Encyclopedia of the Mouse Genome (EMG) after the information has been shown to be error free. EMG integrates data from a variety of mouse genome databases with software that generates graphical displays of cytogenetic or linkage maps.

U.K. Mouse Genome Project

Steve Brown (St. Mary's Hospital Medical School, London) indicated that the U.K. Mouse Genome Project is linked to the European mouse genome program through the European Collaborative Interspecific Backcross (EUCIB) project, which includes the Pasteur Institute in Paris, the Medical Research Council Resource Center in London, and Freie Universitaet, Berlin. The goal of EUCIB is to provide a resource for genetic typing rather than to generate a complete map. The EUCIB database will be used to store mouse probe and mapping data; provide interlocus recombination data and LOD scores; derive gene order from haplotype data; and ultimately store yeast artificial chromosome (YAC) clone reference data. The resource-a 1000-animal backcross between C57BL/6 and Mus spretus, planned to provide a genetic resolution of 0.3 cM at a confidence level of 95%-is expected to be available later this year with about 5 to 10 mg of DNA available from each backcross mouse.

Another component of the U.K. Mouse Genome Program is the generation of cDNAs, primarily to find genes. The cDNAs will be isolated from mouse testes and 8.5-day-old embryos; highly abundant cDNA species will be eliminated through hybridization; random cDNAs will be sequenced from each end of the insert; and cDNAs will be mapped onto somatic cell hybrid panels and the EUCIB DNA panels.

Status of the Mouse Genetic Map

Neal Copeland (NCI-Frederick Cancer Resource and Development Center) summarized the progress of several laboratories using the genomic approach to mapping the mouse. Joe Nadeau (Jackson Laboratory) reported on the Genomic Database of the Mouse (GBASE), which consists of published mouse genetic map data. Nadeau stated that GBASE contains information on 3375 loci (3191 with genetic locations) and about 2100 probes and clones; not all are mapped. Many databases are available on diskette through the EMG Project, a key goal of which is to consolidate databases on the genetics and biology of the laboratory mouse and to present these data in a standardized, readily learned, easy-to-use format.

Future mouse database needs include (1) physical mapping data structure to handle incoming data, (2) one central database that includes all information about the mouse, (3) tools for analyzing map data, (4) integration of information from various mouse crosses, (5) methods for integrating the genetic and physical maps, (6) maps of telomeres and centromeres, (7) more-precise ways of identifying candidate genes, and (8) methods for transferring information from map-rich species such as human and mouse to map-poor species such as cow and dog.

Requirements for Completing the Mouse Genetic Map

The group agreed that the original goal to construct a 1-cM mouse genetic map is still appropriate and feasible and that the map should include genes and anonymous DNA sequences. The project is about one-third accomplished, with some 1000 markers (genes and anonymous DNA sequences surrounding CA repeats) established in well-ordered genetic maps; the markers are largely derived from the interspecific backcrosses. An additional 500 to 1000 loci have been linked to chromosomes and subchromosomal regions using recombinant inbred strain analyses and other mapping methods.

Acknowledging the contribution of anonymous DNA markers in the completion of a genetic map with evenly spaced markers, the working group made the following recommendations:

  • Fill in existing gaps by mapping additional functional genes and anonymous loci;
  • Continue development of both genome-wide and chromosome-specific genetic mapping efforts. The chromosome-by-chromosome approach will promote the production of more-dense genetic maps and allow for the elaboration of physical maps from genetic maps;
  • Develop widely accessible mouse genetic mapping resources to accelerate the mapping of genes by making available responsive and timely YAC screening services;
  • Encourage development of new technology to facilitate genetic and physical mapping efforts, more-efficient mapping strategies, and sequence-based methods of analysis;
  • Develop a centralized public database and database tools that provide easy access to map data;
  • Simplify access to DOE facilities and other large laboratories and genome centers that routinely perform techniques such as chromosome sorting and library construction to accelerate the mapping efforts of individual laboratories.

Other Considerations

The working group recognized the need for international cooperation to pursue the mapping project in a cohesive manner (see related article, Fifth Mouse Genome Mapping Workshop) and felt that a future meeting of the working group could be devoted to a discussion on sharing resources and databases.

Members will prepare a paper on using the mouse map to facilitate construction of the human map and on the value of the mouse map to basic biology. They suggested that such a document should be widely disseminated and published in Human Genome News.


Mouse database contacts:

  • EMG
    Janice Ormsby
    Jackson Laboratory
    207/288-3371, ext. 1227
    Fax: 207/288-5079
    Internet: davidnaman@jax.org
  • EUCIB
    Stephen Brown
    (Int.) 44/71-723-1252, ext. 5484
    Fax: (Int.) 44/71-706-3272
  • GBASE
    Thomas Roderick
    Jackson Laboratory
    207/288-3371
    Fax: 207/288-5079
    Internet: thr@morgan.jax.org

A complete meeting report is available from the 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
NIH NCHGR

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Human Genome Project 1990–2003

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