The Berkeley Drosophila Genome Project Gene Disruption Project: Single P-Element Insertions Mutating 25% of Vital Drosophila Genes

Corresponding author: Allan C. Spradling, Howard Hughes Medical Institute Research Laboratories, Department of Embryology, Carnegie Institution of Washington, 115 W. University Pkwy., Baltimore, MD 21210., spradling{at}mail1.ciwemb.edu (E-mail)

Communicating editor: R. S. HAWLEY

A fundamental goal of genetics and functional genomics is to identify and mutate every gene in model organisms such as Drosophila melanogaster. The Berkeley Drosophila Genome Project (BDGP) gene disruption project generates single P-element insertion strains that each mutate unique genomic open reading frames. Such strains strongly facilitate further genetic and molecular studies of the disrupted loci, but it has remained unclear if P elements can be used to mutate all Drosophila genes. We now report that the primary collection has grown to contain 1045 strains that disrupt more than 25% of the estimated 3600 Drosophila genes that are essential for adult viability. Of these P insertions, 67% have been verified by genetic tests to cause the associated recessive mutant phenotypes, and the validity of most of the remaining lines is predicted on statistical grounds. Sequences flanking >920 insertions have been determined to exactly position them in the genome and to identify 376 potentially affected transcripts from collections of EST sequences. Strains in the BDGP collection are available from the Bloomington Stock Center and have already assisted the research community in characterizing >250 Drosophila genes. The likely identity of 131 additional genes in the collection is reported here. Our results show that Drosophila genes have a wide range of sensitivity to inactivation by P elements, and provide a rationale for greatly expanding the BDGP primary collection based entirely on insertion site sequencing. We predict that this approach can bring >85% of all Drosophila open reading frames under experimental control.

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				J. A. Fraser, P. Kansagra, C. Kotecki, R. D. C. Saunders, and L. I. McLellan The Modifier Subunit of Drosophila Glutamate-Cysteine Ligase Regulates Catalytic Activity by Covalent and Noncovalent Interactions and Influences Glutathione Homeostasis in Vivo J. Biol. Chem., November 21, 2003; 278(47): 46369 - 46377. [Abstract] [Full Text] [PDF]

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				J. Serano and G. M. Rubin The Drosophila synaptotagmin-like protein bitesize is required for growth and has mRNA localization sequences within its open reading frame PNAS, November 11, 2003; 100(23): 13368 - 13373. [Abstract] [Full Text] [PDF]

				J. M. Shulman and M. B. Feany Genetic Modifiers of Tauopathy in Drosophila Genetics, November 1, 2003; 165(3): 1233 - 1242. [Abstract] [Full Text] [PDF]

				P. J. Clyne, J. S. Brotman, S. T. Sweeney, and G. Davis Green Fluorescent Protein Tagging Drosophila Proteins at Their Native Genomic Loci With Small P Elements Genetics, November 1, 2003; 165(3): 1433 - 1441. [Abstract] [Full Text] [PDF]

				P. Deak, M. Donaldson, and D. M. Glover Mutations in makos, a Drosophila gene encoding the Cdc27 subunit of the anaphase promoting complex, enhance centrosomal defects in polo and are suppressed by mutations in twins/aar, which encodes a regulatory subunit of PP2A J. Cell Sci., October 15, 2003; 116(20): 4147 - 4158. [Abstract] [Full Text] [PDF]

				D. R. Dorer, J. A. Rudnick, E. N. Moriyama, and A. C. Christensen A Family of Genes Clustered at the Triplo-lethal Locus of Drosophila melanogaster Has an Unusual Evolutionary History and Significant Synteny With Anopheles gambiae Genetics, October 1, 2003; 165(2): 613 - 621. [Abstract] [Full Text] [PDF]