Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi

Genome-wide analysis of gene function is essential for the post-genome era, and development of efficient and economical technology suitable for it has been in demand. Here we report a large-scale inactivation of the expressed genes in the nematode Caenorhabditis elegans, For this purpose, we have es tablished a high-throughput "RNAi-by-soaking" methodology by modifying the conventional RNAi method [1, 2], A set of tag-sequenced, nonredundant cDNAs corresponding to approximately 10,000 genes [3] (representing half of the predicted genes [4]) was used for the systematic RNAi analysis. We have pro cessed approximately 2500 genes to date. In development, 27% of them showed detectable phenotypes, such as embryonic lethality, postembryonic lethalit y, sterility, and morphological abnormality. Of these, we analyzed the phen otypes of Fl sterility in detail, and we have identified 24 genes that migh t play important roles in germline development. Combined with the ongoing a nalysis of expression patterns of these cDNAs [3, 5], the functional inform ation obtained in this work will provide a starting point for the further a nalysis of each gene. Another finding from this screening is that the incid ence of essential genes is significantly lower in the X chromosome than in the autosomes.