title: Impact of gene copy number variation on anesthesia in Drosophila melanogaster.
abstract: BACKGROUND
  Chromosomal deletions and duplications, which result in halving or doubling of copy number in a block of genes, are an important source of variation between individuals. Phenotypic effects of copy number variation are commonly observed, but effects on sensitivity to volatile anesthetics have not been assessed in any organism.
  
  
  METHODS
  The potency with which halothane depresses the righting reflex of fruit flies was measured in congenic Drosophila strains, each of which was heterozygous for a deletion of average size 400 kb. Over 200 strains were examined, thereby scanning approximately half of the fly genome.
  
  
  RESULTS
  Although the vast majority of deletion heterozygotes were indistinguishable from the control, eight had significantly altered sensitivity to halothane. Genetic tests supported the hypothesis that the change in anesthetic sensitivity was the result of reduction in copy number and not adventitious mutations in the strains. Among the eight outliers, the difference in halothane potency ranged from a 25% increase to a 15% decrease. Changes of similar magnitude but distinctive patterns were found when these lines were tested with enflurane, isoflurane, and sevoflurane.
  
  
  CONCLUSIONS
  Variation in gene copy number has a significant impact on anesthetic sensitivity in Drosophila melanogaster. The level of transcription of a few genes must thus be limiting for a normal response to volatiles. Coupling between gene copy and gene expression is universal, and the components of the fly's nervous system are highly conserved; therefore, this work provides a rationale for investigating the clinical impact of copy number variation.
authors: Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892-3736, USA.
authors: Debasmita P
authors: DP
authors: Alone
authors: Jason C
authors: JC
authors: Rodriguez
authors: Cameron L
authors: CL
authors: Noland
authors: Howard A
authors: HA
authors: Nash
mesh_terms: D000758:Anesthesia / Q000379:methods; D000818:Animals; D030801:Animals, Genetically Modified; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster; D005260:Female; D018628:Gene Dosage / Q000187:drug effects / Q000235:genetics*; D014644:Genetic Variation / Q000187:drug effects / Q000235:genetics*; D006221:Halothane / Q000494:pharmacology; D008297:Male
chemical_list: D029721:Drosophila Proteins; D006221:Halothane