INTERPRETING A SEQUENCED GENOME - TOWARD A COSMID TRANSGENIC LIBRARY OF CAENORHABDITIS-ELEGANS

We have generated a library of transgenic Caenorhabditis elegans strai ns that carry sequenced cosmids from the genome of the nematode. Each strain carries an extrachromosomal array containing a single cosmid, s equenced by the C. elegans Genome Sequencing Consortium, and a dominat e Rol-6 marker. More than 500 transgenic strains representing 250 cosm ids have been constructed. Collectively, these strains contain approxi mately 8 Mb of sequence data, or similar to 8% of the C. elegans genom e. The transgenic strains are being used to rescue mutant phenotypes, resulting in a high-resolution map alignment of the genetic, physical, and DNA sequence maps of the nematode. We have chosen the region of c hromosome III deleted by sDf127 and not covered by the duplication sDp 8(III;I) as a starting point for a systematic correlation of mutant ph enotypes with nucleotide sequence. In this defined region, we have ide ntified 10 new essential genes whose mutant phenotypes range From deve lopmental arrest at early larva, to maternal effect lethal. To date, 8 of these 10 essential genes have been rescued, In this region, these rescues represent similar to 10% of the genes predicted by GENEFINDER and considerably enhance the map alignment. Furthermore, this alignmen t facilitates future efforts to physically position and clone other ge nes in the region.