Drosophila as a Model for Human Diseases

Abstract

The fruit fly Drosophila melanogaster is a powerful genetic model organism that can be easily manipulated. Advanced tools have been constructed in Drosophila for disruption of genes (both somatic and germ line) as well as misexpression of endogenous and foreign transgenes. A high degree of similarity between these two proteomes suggests that as many as 74% of human diseaseā€causing genes could be studied in a Drosophila model.

Keywords: genetic model organism; drosophila melanogaster; disease; etiology; transgenics

References

Adams MD, Celniker SE, Holt RA, et al. (2000) The genome sequence of Drosophila melanogaster. Science 287: 2185–2195.

Altschul SF, Madden TL, Schäffer AA, et al. (1997) Gapped BLAST and PSI‐BLAST: a new generation of protein database search programs. Nucleic Acids Research 25: 3389–3402.

Auluck P, Chan HY, Trojanowski J, Lee V and Bonini NM (2002) Chaperone suppression of α‐synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295: 865–867.

Berger J, Suzuki T, Senti KA, et al. (2001) Genetic mapping with SNP markers in Drosophila. Nature Genetics 29: 475–481.

Brand AH and Perrimon N (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118: 401–415.

Chan HY, Warrick JM, Gray‐Board GL, Paulson HL and Bonini NM (2000) Mechanisms of chaperone suppression of polyglutamine disease: selectivity, synergy and modulation of protein solubility in Drosophila. Human Molecular Genetics 9: 2811–2820.

Feany MB and Bender WW (2000) A Drosophila model of Parkinson's disease. Nature 404: 394–398.

Fernandez‐Funez P, Rosales MLN, de Gouyon B, et al. (2000) Identification of genes that modify ataxin‐1‐induced neurodegeneration. Nature 408: 101–106.

Hunter CP (1999) Genetics: a touch of elegance with RNAi. Current Biology 9: R440–R442.

Jackson GR, Salecker I, Dong X, et al. (1998) Polyglutamine‐expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron 21: 633–642.

Jiang YH, Armstrong D, Albrecht U, et al. (1998) Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long‐term potentiation [see comments]. Neuron 21: 799–811.

Kazemi‐Esfarjani P and Benzer S (2000) Genetic suppression of polyglutamine toxicity in Drosophila. Science 287: 1837–1840.

Kishino T, Lalande M and Wagstaff J (1997) UBE3A/E6‐AP mutations cause Angelman syndrome. Nature Genetics 15: 70–73; erratum Nature Genetics 15: 411.

Reiter LT, Potocki L, Chien S, Gribskov M and Bier EA (2001) Systematic analysis of human disease‐associated gene sequences in Drosophila melanogaster. Genome Research 11: 1114–1125.

Rubin GM and Spradling AC (1982) Genetic transformation of Drosophila with transposable element vectors. Science 218: 348–353.

Salzberg A and Bellen HJ (1996) Invertebrate versus vertebrate neurogenesis: variations on the same theme? Developmental Genetics 18: 1–10.

Theodosiou NA and Xu T (1998) Use of FLP/FRT system to study Drosophila development. Methods 14: 355–365.

Veraksa A, Del Campo M and McGinnis W (2000) Developmental patterning genes and their conserved functions: from model organisms to humans. Molecular Genetics and Metabolism 69: 85–100.

Warrick JM, Chan HY, Gray‐Board GL, et al. (1999) Suppression of polyglutamine‐mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nature Genetics 23: 425–428.

Warrick JM, Paulson HL, Gray‐Board GL, et al. (1998) Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila. Cell 93: 939–949.

Wittmann CW, Wszolek MF, Shulman JM, et al. (2001) Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science 293: 711–714.

Further Reading

Duffy JB (2002) GAL4 System in Drosophila: A fly Geneticist's Swiss Army Knife. Genesis 34: 1–15.

Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W and Tuschl T (2001) Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. The EMBO Journal 20: 6877–6888.

Fortini M and Bonini N (2000) Modeling human neurodegenerative diseases in Drosophila: on a wing and a prayer. Trends in Genetics 16: 161–167.

Sullivan W, Ashburner M and Hawley RS (2000) Drosophila Protocols. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Wu MN and Bellen HJ (1997) Genetic dissection of synaptic transmission in Drosophila. Current Opinion in Neurobiology 7: 624–630.

Web Links

Homophila. Human disease to Drosophila gene database http://homophila.sdsc.edu

Online Mendelian Inheritance in Man (OMIM) http://www.ncbi.nlm.nih.gov/omim/

Flybase. The FlyBase database of the Drosophila Genome Projects and community literature. The FlyBase Consortium http://flybase.bio.indiana.edu/

The Drosophila p‐screen database http://flypush.imgen.bcm.tmc.edu/pscreen/

The Homophila human disease gene to fly gene database http://homophila.sdsc.edu

Ubiquitin protein ligase E3A (human papilloma virus E6‐associated protein, Angelman syndrome) (UBE3A); Locus ID: 7337. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7337

Ubiquitin protein ligase E3A (human papilloma virus E6‐associated protein, Angelman syndrome) (UBE3A); MIM number: 601623. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?601623

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Reiter, Lawrence T(Jan 2006) Drosophila as a Model for Human Diseases. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005578]