title: Genome-wide screen for modifiers of Parkinson's disease genes in Drosophila.
abstract: BACKGROUND
  Mutations in parkin and PTEN-induced kinase 1 (Pink1) lead to autosomal recessive forms of Parkinson's disease (PD). parkin and Pink1 encode a ubiquitin-protein ligase and a mitochondrially localized serine/threonine kinase, respectively. Recent studies have implicated Parkin and Pink1 in a common and evolutionarily conserved pathway for protecting mitochondrial integrity.
  
  
  RESULTS
  To systematically identify novel components of the PD pathways, we generated a genetic background that allowed us to perform a genome-wide F1 screen for modifiers of Drosophila parkin (park) and Pink1 mutant phenotype. From screening ~80% of the fly genome, we identified a number of cytological regions that interact with park and/or Pink1. Among them, four cytological regions were selected for identifying corresponding PD-interacting genes. By analyzing smaller deficiency chromosomes, available transgenic RNAi lines, and P-element insertions, we identified five PD-interacting genes. Among them, opa1 and drp1 have been previously implicated in the PD pathways, whereas debra (dbr), Pi3K21B and β4GalNAcTA are novel PD-interacting genes.
  
  
  CONCLUSIONS
  We took an unbiased genetic approach to systematically isolate modifiers of PD genes in Drosophila. Further study of novel PD-interacting genes will shed new light on the function of PD genes and help in the development of new therapeutic strategies for treating Parkinson's disease.
authors.affiliation: Department of Biology, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Fernandes
authors.forename: Yong
authors.initials: Y
authors.lastname: Rao
mesh_terms: D000375:Aging / Q000473:pathology; D000483:Alleles; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics; D055785:Gene Knockdown Techniques; D017344:Genes, Insect / Q000235:genetics; D005820:Genetic Testing; D049750:Genome, Insect / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D034622:RNA Interference; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D014921:Wings, Animal / Q000473:pathology; D000099202:PTEN-Induced Putative Kinase
chemical_list: D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D019204:GTP-Binding Proteins; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; C534484:PINK1 protein, Drosophila; D000099202:PTEN-Induced Putative Kinase; C504426:DRP1 protein, Drosophila; C487430:park protein, Drosophila