A YAC-based physical map of the mouse genome

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A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project1. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map2 provides a comprehensive framework for mouse genomic studies.

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We thank D. Henriques, S. Jackson, Y.Y. Lau, S. Greenaway, P. Middlehurst, P. Weston, P. Avner, I. Poras, C. Mundy, B. Gorick, H. Blair, Y. Boyd, J. Crabtree, B. Roe, L. Rogers and J. King for their help in the X chromosome project. T.J.H. is a recipient of a Clinician-Scientist award from the Medical Research Council of Canada. This work was supported in part by grants from the National Institute for Human Genome Research (to E.S.L.), the Medical Research Council, UK, and the Wellcome Trust.

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Correspondence to Thomas J. Hudson or Eric S. Lander.

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