Gregory SG, Sekhon M, Schein J, Zhao S, Osoegawa K, Scott CE, Evans RS, Burridge PW, Cox TV, Fox CA, Hutton RD, Mullenger IR, Phillips KJ, Smith J, Stalker J, Threadgold GJ, Birney E, Wylie K, Chinwalla A, Wallis J, Hillier L, Carter J, Gaige T, Jaeger S, Kremitzki C, Layman D, Maas J, McGrane R, Mead K, Walker R, Jones S, Smith M, Asano J, Bosdet I, Chan S, Chittaranjan S, Chiu R, Fjell C, Fuhrmann D, Girn N, Gray C, Guin R, Hsiao L, Krzywinski M, Kutsche R, Lee SS, Mathewson C, McLeavy C, Messervier S, Ness S, Pandoh P, Prabhu AL, Saeedi P, Smailus D, Spence L, Stott J, Taylor S, Terpstra W, Tsai M, Vardy J, Wye N, Yang G, Shatsman S, Ayodeji B, Geer K, Tsegaye G, Shvartsbeyn A, Gebregeorgis E, Krol M, Russell D, Overton L, Malek JA, Holmes M, Heaney M, Shetty J, Feldblyum T, Nierman WC, Catanese JJ, Hubbard T, Waterston RH, Rogers J, de Jong PJ, Fraser CM, Marra M, McPherson JD, Bentley DR. A physical map of the mouse genome. Nature. 2002 Aug 15;418(6899):743-50. PubMed.

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Comments

  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.

    View all comments by Judith Blake

  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:

    Copeland NG, Jenkins NA, Court DL. Recombineering: a powerful new tool for mouse functional genomics. Nat Rev Genet. 2001 Oct;2(10):769-79. PubMed.

    Ertekin-Taner N, Graff-Radford N, Younkin LH, Eckman C, Baker M, Adamson J, Ronald J, Blangero J, Hutton M, Younkin SG. 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.

    Bertram L, Blacker D, Mullin K, Keeney D, Jones J, Basu S, Yhu S, McInnis MG, Go RC, Vekrellis K, Selkoe DJ, Saunders AJ, Tanzi RE. Evidence for genetic linkage of Alzheimer's disease to chromosome 10q. Science. 2000 Dec 22;290(5500):2302-3. PubMed.

    Myers A, Holmans P, Marshall H, Kwon J, Meyer D, Ramic D, Shears S, Booth J, DeVrieze FW, Crook R, Hamshere M, Abraham R, Tunstall N, Rice F, Carty S, Lillystone S, Kehoe P, Rudrasingham V, Jones L, Lovestone S, Perez-Tur J, Williams J, Owen MJ, Hardy J, Goate AM. Susceptibility locus for Alzheimer's disease on chromosome 10. Science. 2000 Dec 22;290(5500):2304-5. PubMed.

    Dawson E, Abecasis GR, Bumpstead S, Chen Y, Hunt S, Beare DM, Pabial J, Dibling T, Tinsley E, Kirby S, Carter D, Papaspyridonos M, Livingstone S, Ganske R, Lõhmussaar E, Zernant J, Tõnisson N, Remm M, Mägi R, Puurand T, Vilo J, Kurg A, Rice K, Deloukas P, Mott R, Metspalu A, Bentley DR, Cardon LR, Dunham I. A first-generation linkage disequilibrium map of human chromosome 22. Nature. 2002 Aug 1;418(6897):544-8. Epub 2002 Jul 10 PubMed.

    View all comments by George Carlson

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