Hunting with traps: Genome-wide strategies for gene discovery and functional analysis

With sequence analysis of the human genome well underway, there is an incre asingly urgent challenge to understand the fundamental function and interpl ay of genes that build and maintain an organism. Several approaches will be critical For interpreting gene function, including random cDNA sequencing, expression profiling in different tissues, genetic analysis of human or mo del organism phenotypes, and creation of transgenic or "knockout" animals. Traditional gene-trapping approaches, in which genes are randomly disrupted with DNA elements inserted throughout the genome, have been used to genera te large numbers of mutant organisms for genetic analysis. Recent modificat ions of gene-trapping methods and their increased use in mammalian systems are likely to result in a wealth of new information on gene function. Vario us trapping strategies allow genes to be segregated based on criteria like the specific subcellular location of an encoded protein, the tissue express ion profile, or responsiveness to specific stimuli. Genome-wide gene-trappi ng strategies, which integrate gene discovery and expression profiling, can be applied in a massively parallel Format to produce living assays for dru g discovery.