We describe a technique, genetically directed representational difference analysis (GDRDA), for specifically generating genetic markers linked to a trait of interest. GDRDA is applicable, in principle, to virtually any organism, because it requires neither prior knowledge of the chromosomal location of the gene controlling the trait nor the availability of a pre–existing genetic map. Based on a subtraction technique described recently called representational difference analysis, GDRDA uses the principles of transmission genetics to create appropriate Tester and Driver samples for subtraction. We demonstrate the usefulness of GDRDA by, for example, successfully targeting three polymorphisms to an interval of less than 1 cM of the mouse nude locus of chromosome 11.
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