Physiological genomics: strategies in the hunt for gene function

摘要

With the completion of the sequencing of the human genome approaching, the current challenge facing life scientists has become the definition of the function of the nearly 100,000 human genes. Several strategies have been proposed for linking gene identification with function which involve high throughput screening methods. We have developed a strategy for gene identification in inbred rat strains which combines the use of genetic linkage analysis, and cDNA expression profiling, with thedevelopment of unique consomic and congenic rat strains. Central to this strategy is the use of high throughput physiological assessment of phenotype coupled to accurate genotypic characterization with the use of bioinformatics. As a proof of concept, weperformed a genome wide scan of 105 male F2 rats of a Dahl S×BN intercross with extensive phenotyping which included traits that are part of the major pathways regulating blood pressure. We have identified a total of 107 quantitative trait loci for atotal of 202 traits with a LOD score> 2.8 that is suggestive for linkage. Using a series of consomic and congenic rat strains derived from the Dahl S and BN background we have been able to isolate these regions and fix them into unique rat strains forfurther characterization and study.