title: Drosophila models of early onset cognitive disorders and their clinical applications.
abstract: The number of genes known to cause human monogenic diseases is increasing rapidly. For the extremely large, genetically and phenotypically heterogeneous group of intellectual disability (ID) disorders, more than 600 causative genes have been identified to date. However, knowledge about the molecular mechanisms and networks disrupted by these genetic aberrations is lagging behind. The fruit fly Drosophila has emerged as a powerful model organism to close this knowledge gap. This review summarizes recent achievements that have been made in this model and envisions its future contribution to our understanding of ID genetics and neuropathology. The available resources and efficiency of Drosophila place it in a position to tackle the main challenges in the field: mapping functional modules of ID genes to provide conceptually novel insights into the genetic control of cognition, tailored functional studies to improve 'next-generation' diagnostics, and identification of reversible ID phenotypes and medication. Drosophila's behavioral repertoire and powerful genetics also open up perspectives for modeling genetically complex forms of ID and neuropsychiatric disorders, which overlap in their genetic etiologies. In conclusion, Drosophila provides many opportunities to advance future medical genomics of early onset cognitive disorders.
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: van der Voet
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Nijhof
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Merel A W
authors.initials: MA
authors.lastname: Oortveld
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: Annette.Schenck@radboudumc.nl.
authors.forename: Annette
authors.initials: A
authors.lastname: Schenck
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D058990:Molecular Targeted Therapy / Q000379:methods; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D029721:Drosophila Proteins
keywords: Cognitive disorders; Dendrites; Diagnostics; Drosophila melanogaster; Intellectual disability; Learning and memory; Mental retardation; Model organism; Neuropsychiatric disorders; Next-generation sequencing; Reversible cognitive defects; Synapse; Therapy; Treatment; Whole-exome sequencing