Endocrine Abstracts

One of the major current challenges in molecular genetics is the identification of genes underlying common, genetically complex diseases. The human genome sequence, and that of several model organisms, is now available and tools are available to measure in a single experiment the expression of every gene in these genomes. These resources offer unprecedented opportunities for disease gene identification. We have combined a classical genome screen approach, which localises disease genes, with DNA microarray analysis to measure gene expression, in order to identify genes that map to disease loci and show aberrant expression in disease states. In applying this strategy to the study of insulin resistance, we identified a defective gene, Cd36 or fatty acid translocase, that causes defective insulin action and fatty acid metabolism in the spontaneously hypertensive rat, a model of the human insulin resistance syndromes. We are now pursuing the combined linkage and microarray approach further for the study of other complex traits, and are using microarrays to define the mechanisms by which defective fatty acid metabolism can lead to defects in insulin action.