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Modeling and Analysis of Repeat RNA Toxicity in Drosophila

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Tandem Repeats in Genes, Proteins, and Disease

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1017))

Abstract

Expansion of repeat sequences beyond a pathogenic threshold is the cause of a series of dominantly inherited neurodegenerative diseases that includes Huntington’s disease, several spinocerebellar ataxias, and myotonic dystrophy types 1 and 2. Expansion of repeat sequences occurring in coding regions of various genes frequently produces an expanded polyglutamine tract that is thought to result in a toxic protein. However, in a number of diseases that present with similar clinical symptoms, the expansions occur in untranslated regions of the gene that cannot encode toxic peptide products. As expanded repeat-containing RNA is common to both translated and untranslated repeat expansion diseases, this repeat RNA is hypothesized as a potential common toxic agent.

We have established Drosophila models for expanded repeat diseases in order to investigate the role of multiple candidate toxic agents and the potential molecular pathways that lead to pathogenesis. In this chapter we describe methods to identify candidate pathogenic pathways and their constituent steps. This includes establishing novel phenotypes using Drosophila and developing methods for using this system to screen for possible modifiers of pathology. Additionally, we describe a method for quantifying progressive neurodegeneration using a motor functional assay as well as small RNA profiling techniques, which are useful in identifying RNA intermediates of pathogenesis that can then be used to validate potential pathogenic pathways in humans.

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Author information

Authors and Affiliations

  1. ARC Special Research Centre for the Molecular Genetics of Development and Discipline of Genetics, School of Molecular and Biomedical Sciences, The University of Adelaide, Adelaide, SA, Australia

    S. E. Samaraweera, L. V. O’Keefe, C. L. van Eyk, K. T. Lawlor & R. I. Richards

  2. The Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia

    D. T. Humphreys & C. M. Suter

  3. Faculty of Medicine, University of New South Wales, Kensington, Australia

    D. T. Humphreys & C. M. Suter

Authors
  1. S. E. Samaraweera
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  2. L. V. O’Keefe
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  3. C. L. van Eyk
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  4. K. T. Lawlor
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  5. D. T. Humphreys
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  6. C. M. Suter
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  7. R. I. Richards
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Editor information

Editors and Affiliations

  1. , Dept. of Biochemistry and Molecular Biol, The University of Melbourne, Flemington Road 30, Parkville, 3010, Victoria, Australia

    Danny M. Hatters

  2. Florey Neuroscience Institutes, and Mental Health, The University of Melbourne, Royal Parade, Parkville, 3010, Victoria, Australia

    Anthony J. Hannan

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Samaraweera, S.E. et al. (2013). Modeling and Analysis of Repeat RNA Toxicity in Drosophila . In: Hatters, D., Hannan, A. (eds) Tandem Repeats in Genes, Proteins, and Disease. Methods in Molecular Biology, vol 1017. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-438-8_13

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  • DOI: https://doi.org/10.1007/978-1-62703-438-8_13

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-437-1

  • Online ISBN: 978-1-62703-438-8

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