The humble mouse is often used as a model to unravel the mysteries of mammalian, particularly human, biology. However, members of the International Mouse Genome Consortium reported this week that they have succeeded in making a physical map of this rodent’s genome using, ironically, the sequence of the human genome as a template.

David Bentley, of The Wellcome Trust Sanger Institute, and colleagues from around the globe, describe the map in today’s advanced online publication of Nature. It can also be accessed online at http://www.ncbi.nlm.nih.gov/genome/guide/mouse or at http://www.ensembl.org/Mus_musculus/cytoview.

The mapping effort was facilitated by the high degree of chromosomal conservation between human and mouse genomes. A 1.6 million base pair section of human chromosome 6, for example, has extensive homology to a section of mouse chromosome 4. The authors found that in many cases the precise chromosomal order of genes is highly conserved between mice and humans, while in many other cases, al though the exact order has been lost, the gene is still found in the right neighborhood.

The new map is essential for researchers working to sequence all 2.8 billion base pairs of the mouse genome, providing a scaffold upon which randomly sequenced sections of the puzzle can be pieced together. It will also allow researchers to focus on regions of special interest in the genome, and presumably help the development of mouse models of human diseases.—Tom Fagan

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  1. The recent paper in Nature on the physical mapping of the mouse genome provides a powerful resource in the public domain for the investigation of genetic components of human biology and disease. With this resource, scientists who have mapped the general location of genetic components of interest will be able to quickly extend their investigations by obtaining biological reagents (clones) mapped to cover the region of interest. Access to these reagents will facilitate evaluation of genes in the selected region to ascertain the involvement of these genes and their products in diseases such as Alzheimer Disease.

  2. The completion of a physical map for the mouse genome, in addition to being a major achievement of the Human Genome Project, will accelerate identification of genes involved in susceptibility to human diseases. The key strategy, which underlines the utility of the mouse map, was aligning mouse BAC clones to the human genome sequence based on homology matches. The physical map provides the framework to assign mouse nucleotide sequence to chromosomal region and provides conserved segments and synteny between mouse and human. More importantly for human disease modeling in mice, the high resolution alignment allows identification of mouse clones corresponding to almost any chromosomal location in the human.

    Application of “recombineering” to rapidly modify BAC clones speeds the process of transgenesis and targeting specific mutations in the mouse towards development of disease models (Copeland et al., 2001). In Alzheimer’s disease, for example, there is general agreement that a gene (or genes) on Chromosome 10 is involved in susceptibility (Ertekin-Taner et al., 2000; Bertram et al., 2000; Myers et al., 2000). Creation of mouse models can test the relevance of regulatory or coding polymorphisms in the human, assuming appropriate phenotypes relevant to disease can be established. An even more powerful approach towards dissecting complex or polygenic traits is presaged by the recent publication of a linkage disequilibrium map for human chromosome 22 (Dawson et al., 2002). Genome-wide linkage disequilibrium maps will undoubtedly facilitate identification of chromosomal regions harboring alleles involved in complex diseases. The availability of the mouse physical map and complete genome sequence provide powerful tools for experimental dissection of disease processes.

    References:

    . Recombineering: a powerful new tool for mouse functional genomics. Nat Rev Genet. 2001 Oct;2(10):769-79. PubMed.

    . Linkage of plasma Abeta42 to a quantitative locus on chromosome 10 in late-onset Alzheimer's disease pedigrees. Science. 2000 Dec 22;290(5500):2303-4. PubMed.

    . Evidence for genetic linkage of Alzheimer's disease to chromosome 10q. Science. 2000 Dec 22;290(5500):2302-3. PubMed.

    . Susceptibility locus for Alzheimer's disease on chromosome 10. Science. 2000 Dec 22;290(5500):2304-5. PubMed.

    . A first-generation linkage disequilibrium map of human chromosome 22. Nature. 2002 Aug 1;418(6897):544-8. Epub 2002 Jul 10 PubMed.

References

External Citations

  1. http://www.ncbi.nlm.nih.gov/genome/guide/mouse
  2. http://www.ensembl.org/Mus_musculus/cytoview

Further Reading

No Available Further Reading

Primary Papers

  1. . A physical map of the mouse genome. Nature. 2002 Aug 15;418(6899):743-50. PubMed.