DIRECT ISOLATION OF POLYMORPHIC MARKERS LINKED TO A TRAIT BY GENETICALLY DIRECTED REPRESENTATIONAL DIFFERENCE ANALYSIS

We describe a technique, genetically directed representational differe nce analysis (GDRDA), for specifically generating genetic markers link ed to a trait of interest. GDRDA is applicable, in principle, to virtu ally any organism, because it requires neither prior knowledge of the chromosomal location of the gene controlling the trait nor the availab ility 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 Tes ter and Driver samples for subtraction. We demonstrate the usefullness 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.