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Detecting and Validating MAPT Mutations in Neurodegeneration Patients and Analysis of Exon Splicing Consequences

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Tau Protein

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2754))

Abstract

Mutation of MAPT has been observed in patients with parkinsonism, progressive supranuclear palsy, and corticobasal degeneration and is a significant cause of frontotemporal dementia. In this chapter, we discuss considerations for next-generation sequencing analysis to identify MAPT mutations in patient genomic DNA and describe the validation of these mutations by Sanger sequencing. One of the most common effects of MAPT mutations is differential splicing of exon 10, which leads to an imbalance in the proportion of 3-repeat and 4-repeat tau isoforms. We describe how to investigate the effect of novel DNA variants on the splicing efficiency of this exon in vitro using the exon-trapping technique, also known as the splicing reporter minigene assay.

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Disclaimer

B.G. is a director of the Pacific Analytics PTY LTD & SMRTR PTY LTD, Australia, a founding member of the International Cerebral Palsy Genetics Consortium, and a member of the Australian Genomics Health Alliance. These bodies had no role in the design, execution, analysis, or preparation of the manuscript. The authors declare that they have no conflicts of interest with the contents of this article.

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Authors and Affiliations

  1. Brain and Mind Centre and School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia

    Carol Dobson-Stone, Boris Guennewig & John B. Kwok

  2. New South Wales Brain Tissue Resource Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia

    Hamish Mundell

Authors
  1. Carol Dobson-Stone
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  2. Boris Guennewig
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  3. Hamish Mundell
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  4. John B. Kwok
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Corresponding author

Correspondence to Carol Dobson-Stone .

Editor information

Editors and Affiliations

  1. Inserm U1167, University of Lille, Villeneuve d’Ascq Cedex, France

    Caroline Smet-Nocca

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© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Dobson-Stone, C., Guennewig, B., Mundell, H., Kwok, J.B. (2024). Detecting and Validating MAPT Mutations in Neurodegeneration Patients and Analysis of Exon Splicing Consequences. In: Smet-Nocca, C. (eds) Tau Protein. Methods in Molecular Biology, vol 2754. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3629-9_22

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  • DOI: https://doi.org/10.1007/978-1-0716-3629-9_22

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3628-2

  • Online ISBN: 978-1-0716-3629-9

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