The art and design of genetic screens: Caenorhabditis elegans

The advantages of the nematode Caenorhabditis elegans for genetics studies are its short generation time, and that it is easy and inexpensive to maintain. Mutant strains can be frozen and maintained indefinitely. Because strains can be propagated as self-fertilizing hermaphrodites, screens for recessive mutations are easy — the F2 generation of mutagenized animals can be inspected for interesting phenotypes. Labour-intensive crosses are not required. Suppressor screens have been widely used to identify components of signal-transduction pathways. The ease with which mutants can be obtained is useful for saturation screening and for the analysis of structure–function relationships of a protein. Some screens are labour intensive, but are nevertheless fruitful if there are no other ways to generate mutants in a specific biological process. These have included screens for cell-death mutants, which have required screening on a compound microscope. Lethal mutations can be identified and maintained in heterozygous animals that segregate 1 in 4 dead embryos. This led to the development of maternal-effect lethal screens, which identified proteins that are required for early cell-fate decisions in the developing embryo. Sensitized screens can be used to identify genes that have a role in a process but are mutated to lethality. The advantage is that the screens can be carried out in the F1 generation and are identified as haploinsufficient loss-of-function loci. Synthetic-lethal screens can identify loci that act redundantly in a process.