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Genomic Mosaicism in Neurons and Other Cell Types pp 361–378Cite as

Identification of Low Allele Frequency Mosaic Mutations in Alzheimer Disease

Part of the Neuromethods book series (NM,volume 131)

Abstract

Germline mutations ofAPP,PSEN1, andPSEN2 genes cause autosomal dominant Alzheimer disease (AD). Somatic variants of the same genes may underlie pathogenesis in sporadic AD, which is the most prevalent form of the disease. Importantly, such somatic variants may be present at very low allelic frequency, confined to the brain, and are thus very difficult or impossible to detect in blood-derived DNA. Ever-refined methodologies to identify mutations present in a fraction of the DNA of the original tissue are rapidly transforming our understanding of DNA mutation and their role in complex pathologies such as tumors. These methods stand poised to test to what extend somatic variants may play a role in AD and other neurodegenerative diseases.

Key words

  • Single- cell sequencing
  • Mosaicism
  • Somatic variant
  • Alzheimer’s disease
  • Parkinson’s disease

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Author information

Authors and Affiliations

  1. VIB Center for Brain & Disease Research, Leuven, Belgium

    Carlo Sala Frigerio, Mark Fiers & Bart De Strooper

  2. Center for Human Genetics, Universitaire ziekenhuizen and LIND, KU Leuven, Leuven, Belgium

    Carlo Sala Frigerio, Mark Fiers & Bart De Strooper

  3. Department of Human Genetics, University of Leuven, KU Leuven, Leuven, Belgium

    Thierry Voet

  4. Wellcome Trust Sanger Institute, Hinxton, UK

    Thierry Voet

  5. Dementia Research Institute(UK-DRI), University College London, Queen Square, WC1N 3BG, London, UK

    Bart De Strooper

Authors
  1. Carlo Sala Frigerio
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  2. Mark Fiers
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  3. Thierry Voet
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  4. Bart De Strooper
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Corresponding authors

Correspondence to Carlo Sala Frigerio or Bart De Strooper .

Editor information

Editors and Affiliations

  1. Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute (IC-CSIC), Madrid, Spain

    Dr. José María Frade

  2. Biological Studies and Laboratory of Genetics, The Salk Institute, La Jolla, California, USA

    Prof. Fred H. Gage

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Frigerio, C.S., Fiers, M., Voet, T., De Strooper, B. (2017). Identification of Low Allele Frequency Mosaic Mutations in Alzheimer Disease. In: Frade, J., Gage, F. (eds) Genomic Mosaicism in Neurons and Other Cell Types. Neuromethods, vol 131. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7280-7_17

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  • DOI: https://doi.org/10.1007/978-1-4939-7280-7_17

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