RNAi-Based Functional Genomics in Caenorhabditis elegans

Characterizing the functions of the many genes discovered by the sequencing projects is now the primary focus of genome-scale studies. Although sequence or structure-based comparisons are helping to generate hypotheses on the biochemical functions of many gene products, determining the in vivo role(s) for large sets of genes remains a critical objective. RNA interference (RNAi) offers a rapid way to gain a first look at loss-of-function phenotypes associated with specific genes. So far RNAi has been used to test the function of a third of the predicted genes in the Caenorhabditis elegans (C. elegans) genome, and it can be expected that a first pass survey of the entire genome will soon be completed. From the current body of work an initial estimate of the power and challenges of using RNAi for genome-wide analyses can be made. A comparison of results obtained from independent large-scale RNAi studies reveals that despite a high degree of congruence, no single study is likely to achieve a comprehensive RNAi-based phenotypic ”map“ of the C. elegans genome instead a more accurate picture will be assembled from a composite of independent results for the same genes. RNAi analysis, together with other functional genomic approaches such as expression profiling and protein interaction mapping, is transforming C. elegans into a premier model system for the development and integration of functional genomic approaches in a metazoan.