SPELL - Nematode

Citation	Dybbs M, Ngai J, Kaplan JM. Using microarrays to facilitate positional cloning: identification of tomosyn as an inhibitor of neurosecretion. PLoS Genet, 2005.
PubMed ID	16103915
Short Description	Using microarrays to facilitate positional cloning: identification of tomosyn as an inhibitor of neurosecretion. GEO Record: GSE2210 Platform: GPL200 Download gene-centric, log2 transformed data: WBPaper00026714.ce.mr.csv
# of Conditions	9
Full Description	Forward genetic screens have been used as a powerful strategy to dissect complex biological pathways in many model systems. A significant limitation of this approach has been the time-consuming and costly process of positional cloning and molecular characterization of the mutations isolated in these screens. Here, the authors describe a strategy using microarray hybridizations to facilitate positional cloning. This method relies on the fact that premature stop codons (i.e., nonsense mutations) constitute a frequent class of mutations isolated in screens and that nonsense mutant messenger RNAs are efficiently degraded by the conserved nonsense-mediated decay pathway. They validate this strategy by identifying two previously uncharacterized mutations: (1) tom-1, a mutation found in a forward genetic screen for enhanced acetylcholine secretion in Caenorhabditis elegans, and (2) an apparently spontaneous mutation in the hif-1 transcription factor gene. They further demonstrate the broad applicability of this strategy using other known mutants in C. elegans, Arabidopsis, and mouse. Characterization of tom-1 mutants suggests that TOM-1, the C. elegans ortholog of mammalian tomosyn, functions as an endogenous inhibitor of neurotransmitter secretion. These results also suggest that microarray hybridizations have the potential to significantly reduce the time and effort required for positional cloning. Experimental Details: WBPaper00026714:tom-1(nu468)_1 WBPaper00026714:tom-1(nu468)_2 WBPaper00026714:unc-43(n1186)_1 WBPaper00026714:unc-43(n1186)_2 WBPaper00026714:unc-43(n1186)_3 WBPaper00026714:wt_1 WBPaper00026714:wt_2 WBPaper00026714:wt_3 WBPaper00026714:wt_4.
Tags	Method: microarray, Species: Caenorhabditis elegans, Topic: WT vs. mutant