The Whitehead/MIT Center for Genome Research has had a longstanding commitment to developing maps of the mouse genome. This proposal is aimed at the construction of a gene-based radiation hybrid (RH) map of the mouse genome, consisting of approximately 15,000 loci. A gene-based map, showing the location of a large fraction of an organism's genes, is a tremendously powerful tool for genetic studies. Such a map is especially useful for the identification of genes known only by their phenotype, by positional cloning and positional candidate approaches. In addition, the availability of gene-based maps in multiple organisms provides the foundation for detailed synteny maps showing the correspondence between conserved genomic segments. Such synteny maps make it possible to exploit cross-species information in gene hunts, as well as revealing much about evolutionary forces molding the genome. Gene-based maps provide candidate genes for modifier genes and a crucial scaffold for sequencing the mouse genome. The first step in building the mouse gene map will be to create a mouse UniGene collection, in which available mouse ESTs are clustered into sets (named """"""""UniGenes"""""""") likely to represent the same gene. Sequence Tagged Site (STS) assays will be derived from the gene sequences. STS assays will be screened on the T31 RH panel DNAs using a high throughput robotic system called the Genomatron. A framework map will be generated using RH data from approximately 2,000 well-spaced genetically-mapped markers. We will map 13,000 UniGene clusters relative to this framework map. The selection of UniGene clusters will be coordinated with the European consortium to minimize overlap. All data will be regularly released into the public domain without patents or other restrictions.
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