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Human Genome News Archive Edition

Human Genome News, May 1991; 3(1)

Workshop on Mouse Genome Mapping

The Fourth International Workshop on Mouse Genome Mapping, held November 4-8, 1990, in Annapolis, Maryland, brought together a community of scientists interested in mapping the mouse genome. The work of chromosome committees began in Annapolis, and their reports are being prepared for publication in Mammalian Genome in 1991.

Workshop participants defined common research goals for mapping the mouse genome that reflect the unique strengths and value of the mouse as an experimental genetic system. These goals include development and dissemination of the following:

  • saturated genetic maps based on well-spaced reference loci,
  • physical maps of selected chromosome segments, and
  • mouse genomics databases.

Genetic Mapping

Goals: Establishment of about 160 to 320 reference loci spaced 5 to 10 cM apart on each chromosome. Ideal reference loci have the following characteristics:

  • inexpensive and easy to type,
  • highly variable among laboratory strains as well as diverse Mus species,
  • universally available as markers typed by polymerase chain reaction (PCR) assays as well as Southern blotting,
  • derived from expressed genes, and
  • conserved between humans and mice.

Such sets of reference loci will provide universal cross-reference points for mapping specific genes of interest and a framework for high-resolution mapping of specific chromosomal regions.

Results: Unambiguously ordered multilocus maps of extended linkage groups, with adjacent markers spaced no more than 20 cM apart, for all chromosomes. The maps are composed largely of named genes identified by recombinant DNA probes in Southern blotting assays. Hundreds of genes are being placed each year. Saturated maps now exist for most segments of the X chromosome, estimated to be 80 cM in length; over 50 ordered DNA markers are spaced no more than 5 cM apart. Extended regions of chromosomes 1, 2, 3, 16, and 17 are similarly well mapped. Physical mapping studies have already confirmed the accuracy of some maps.

Several crucial gaps in these maps are now being addressed. Strategies for identifying centromeres and telomeres are being developed, and new approaches for identifying polymorphic anonymous DNA segments should yield large numbers of widely distributed new markers. DNA variants associated with several telomeres have been identified, and a satellite probe, specific for the centromeres of laboratory-strain mouse chromosomes, seems likely to provide a genetic tag for centromeres as genetic loci in interspecies backcrosses.

Novel uses of oligonucleotides as probes or as PCR primers have dramatically increased the number of polymorphic loci available while reducing the time and genomic DNA consumed in doing the assays. Some combination of strategies seems likely to provide the markers needed to fill the remaining gaps in the genetic map. Other strategies exploit cross hybridization of mouse genomic DNA with human variable number tandem repeat probes and with randomly chosen oligomer sequences. Other methods appear likely to define numerous useful polymorphisms throughout the mouse genome.

Elegant in situ hybridization experiments suggest that many repeated sequence classes that are widely distributed over the genome may tend to concentrate in regions corresponding to Giemsa bands. This biased distribution raises the intriguing possibility that in the course of pushing genetic maps to closure, much will be learned about the physical organization of mammalian chromosomes and perhaps about the evolution of the organization as well.

Physical Mapping

Goals: Physical analysis of regions of particular genetic interest, with the long-term goal of an ordered set of recombinant clones spanning the whole genome.

Results: Availability of physical maps spanning megabase regions near loci of interest. These data, together with the growing number of yeast artificial chromosome (YAC) clones centered on genes of interest, suggest that resources already available for large-scale cloning and mapping may be sufficient to assemble large parts of the desired long-range DNA map of the mouse genome. Use of YACs to attack genomic regions of special interest is rapidly becoming routine.

Simultaneously, significant technology development is taking place. Improved methods were reviewed for screening high-density filters of YAC libraries and for generating and interpreting fingerprinting data for YAC clones.

A particular advantage of using the mouse as an experimental system is a series of deletion mutations centered on several genes known to play crucial roles in early development and in neural function. These deletion resources will be useful in the long-range physical mapping of several regions of the mouse genome.

Databases

Goals: Collection, integration, analysis, display, and dissemination of mouse genomic information.

Results: An impressive collection of databases recording gene mapping results, molecular clones and probes, and physical mapping data. Specific modifications were discussed to ensure that each database can continue to accommodate data flow and store increasing amounts of raw data (e.g., recombination fractions and haplotypes) as well as derived interpretations (e.g., linkage maps). Work is under way to create methods for integrating and displaying these data in interactive systems that draw simultaneously on several data sources. Also, efforts are being made in conjunction with the Genome Data Base project to provide users with ready access to integrated mouse and human genomic information.

Conclusion

Elaboration of a mouse genome map based on DNA markers is well under way. Based on visible mutations and biochemical markers, numerous points of cross reference to the classical map have been established. The use of several mouse species and genetically defined inbred strains has yielded highly informative genetic mapping resources that have been especially valuable in mapping functional genes.

Thus, the usefulness of comparing mouse with human genetic and physical maps has increased as more mouse genes have been mapped and as experimental models of human hereditary disease have been identified. The ability to define, map, and manipulate mouse genes makes the species a unique laboratory resource for studying the genetics of biologically and medically important traits.


Mouse Chromosome Committees

Chromosome Number, Chair and Cochairs

  • 1:
    Michael Seldin
    , Duke University Medical School
    Beverly Paigen, Jackson Laboratory
  • 2:
    Linda Siracusa
    , Thomas Jefferson University
    Catherine Abbott, University College, London
  • 3:
    Miriam Meisler
    , University of Michigan, Ann Arbor
    Michael Seldin, Duke University Medical School
  • 4:
    Jeffrey Friedman
    , Rockefeller University
    Konrad Huppi, NIH National Cancer Institute (NCI)
  • 5:
    Christine Kozak
    , NIH National Institute of Allergy and Infectious Diseases
    Dennis Stephenson, Roswell Park Cancer Institute
  • 6:
    Rosemary Elliott
    , Roswell Park Cancer Institute
    Nathan Bahary, Rockefeller University
  • 7:
    Eugene Rinchik
    , Oak Ridge National Laboratory
    Steve Brown, St. Mary's Hospital Medical School, London
  • 8:
    Jeffrey Ceci
    , Frederick Cancer Research and Development Center, NCI
    Jo Peters, Medical Research Council
  • 9:
    David Kingsley
    , Frederick Cancer Research and Development Center, NCI
  • 10:
    Ben Taylor
    , Jackson Laboratory
    Monica Justice, Frederick Cancer Research and Development Center, NCI
  • 11:
    Arthur Buchberg
    , Thomas Jefferson University
    Sally Camper, University of Michigan, Ann Arbor
  • 12:
    Peter D'Eustachio
    , New York University Medical Center
  • 13:
    Monica Justice
    , Frederick Cancer Research and Development Center, NCI
    Dennis Stephenson, Roswell Park Cancer Institute
  • 14:
    Joseph Nadeau
    , Jackson Laboratory
  • 15:
    Beverly Mock
    , NIH National Cancer Institute
  • 16:
    Roger Reeves
    , Johns Hopkins School of Medicine
    Muriel Davisson, Jackson Laboratory
  • 17:
    Lee Silver
    , Princeton University
  • 18:
    Muriel Davisson
    , Jackson Laboratory
  • 19:
    Jean-Louis Guenet
    , Institut Pasteur
  • X:
    Steve Brown
    , St. Mary's Hospital Medical School, London
    Philip Avner, Institut Pasteur
  • Y:
    Eva Eicher
    , Jackson Laboratory

Copies of the workshop program and abstracts are available from:

  • Verne Chapman
    Department of Molecular and Cellular Biology
    Roswell Park Cancer Institute
    Elm and Carlton Streets
    Buffalo, NY 14263
    716/845-5840
    Fax: 716/845-8169

Reported by Verne Chapman (Roswell Park Cancer Institute) Peter D'Eustachio (New York University Medical Center) and Joseph Nadeau (Jackson Laboratory)

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Human Genome Project 1990–2003

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