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Using Fluorescence In Situ Hybridization (FISH) Analysis to Measure Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative Diseases

  • Julbert Caneus
  • Antoneta Granic
  • Heidi J. Chial
  • Huntington PotterEmail author
Protocol
Part of the Neuromethods book series (NM, volume 131)

Abstract

Chromosome instability is a form of genomic instability that leads to cells with an abnormal number of chromosomes, defined as aneuploidy. Aneuploidy that results from chromosome instability can be complete or mosaic, depending on whether all or only some of the cells that make up an organism have an abnormal number of chromosomes. Aneuploidy is associated with many human conditions, such as cancer and Down syndrome (DS, trisomy 21), and it has more recently become a focus of investigation in neurodegenerative diseases, including Alzheimer’s disease (AD), Niemann-Pick C1 (NPC), and frontotemporal lobar degeneration (FTLD). In these disorders, aneuploid cells in affected brain regions appear to contribute significantly to apoptosis and neurodegeneration, and may thus underlie the associated cognitive deficits. Herein, we describe the methods that our laboratory has developed to analyze the frequency of chromosome instability (i.e., mosaic aneuploidy) in AD, NPC, and FTLD and associated cell death. Our goal is to provide the reader with guidelines for using these methods and to offer insights into their utility and potential limitations.

Key words

Neurodegenerative disease Alzheimer’s disease (AD) Frontotemporal lobar degeneration (FTLD) Frontotemporal dementia (FTD) Niemann-Pick C1 (NPC) Mosaic aneuploidy Sporadic disease Fluorescent in situ hybridization (FISH) Metaphase chromosome spread Apoptosis Single-cell sequencing 

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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Julbert Caneus
    • 1
    • 2
  • Antoneta Granic
    • 1
    • 3
    • 4
    • 5
  • Heidi J. Chial
    • 1
  • Huntington Potter
    • 1
    • 2
    Email author
  1. 1.Department of Neurology, Rocky Mountain Alzheimer’s Disease Center, and Linda Crnic Institute for Down SyndromeUniversity of Colorado School of MedicineAuroraUSA
  2. 2.Neuroscience ProgramUniversity of Colorado, Anschutz Medical CampusAuroraUSA
  3. 3.Institute of Neuroscience, Newcastle Institute for AgeingNewcastle UniversityNewcastle upon TyneUK
  4. 4.NIHR Newcastle Biomedical Research Centre in Ageing and Chronic DiseaseNewcastle UniversityNewcastle upon TyneUK
  5. 5.Newcastle upon Tyne NHS Foundation Trust, Campus for Ageing and VitalityNewcastle UniversityNewcastle upon TyneUK

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