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Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer’s disease neurons van den Bos, Hilda; Spierings, Diana C J; Taudt, Aaron; Bakker, Bjorn; Porubský, David; Falconer, Ester; Novoa, Carolina; Halsema, Nancy; Kazemier, Hinke G; Hoekstra-Wakker, Karina; et al.

Abstract

Background: Alzheimer’s disease (AD) is a neurodegenerative disease of the brain and the most common form of dementia in the elderly. Aneuploidy, a state in which cells have an abnormal number of chromosomes, has been proposed to play a role in neurodegeneration in AD patients. Several studies using fluorescence in situ hybridization have shown that the brains of AD patients contain an increased number of aneuploid cells. However, because the reported rate of aneuploidy in neurons ranges widely, a more sensitive method is needed to establish a possible role of aneuploidy in AD pathology. Results: In the current study, we used a novel single-cell whole genome sequencing (scWGS) approach to assess aneuploidy in isolated neurons from the frontal cortex of normal control individuals (n = 6) and patients with AD (n = 10). The sensitivity and specificity of our method was shown by the presence of three copies of chromosome 21 in all analyzed neuronal nuclei of a Down’s syndrome sample (n = 36). Very low levels of aneuploidy were found in the brains from control individuals (n = 589) and AD patients (n = 893). In contrast to other studies, we observe no selective gain of chromosomes 17 or 21 in neurons of AD patients. Conclusion: scWGS showed no evidence for common aneuploidy in normal and AD neurons. Therefore, our results do not support an important role for aneuploidy in neuronal cells in the pathogenesis of AD. This will need to be confirmed by future studies in larger cohorts.

Item Metadata

Title
Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer’s disease neurons
Creator
van den Bos, Hilda; Spierings, Diana C J; Taudt, Aaron; Bakker, Bjorn; Porubský, David; Falconer, Ester; Novoa, Carolina; Halsema, Nancy; Kazemier, Hinke G; Hoekstra-Wakker, Karina; Guryev, Victor; den Dunnen, Wilfred F A; Foijer, Floris; Colomé-Tatché, Maria; Boddeke, Hendrikus W G M; Lansdorp, Peter M
Publisher
BioMed Central
Date Issued
2016-05-31
Description
Background: Alzheimer’s disease (AD) is a neurodegenerative disease of the brain and the most common form of dementia in the elderly. Aneuploidy, a state in which cells have an abnormal number of chromosomes, has been proposed to play a role in neurodegeneration in AD patients. Several studies using fluorescence in situ hybridization have shown that the brains of AD patients contain an increased number of aneuploid cells. However, because the reported rate of aneuploidy in neurons ranges widely, a more sensitive method is needed to establish a possible role of aneuploidy in AD pathology. Results: In the current study, we used a novel single-cell whole genome sequencing (scWGS) approach to assess aneuploidy in isolated neurons from the frontal cortex of normal control individuals (n = 6) and patients with AD (n = 10). The sensitivity and specificity of our method was shown by the presence of three copies of chromosome 21 in all analyzed neuronal nuclei of a Down’s syndrome sample (n = 36). Very low levels of aneuploidy were found in the brains from control individuals (n = 589) and AD patients (n = 893). In contrast to other studies, we observe no selective gain of chromosomes 17 or 21 in neurons of AD patients. Conclusion: scWGS showed no evidence for common aneuploidy in normal and AD neurons. Therefore, our results do not support an important role for aneuploidy in neuronal cells in the pathogenesis of AD. This will need to be confirmed by future studies in larger cohorts.
Subject
Aneuploidy; Single-cell sequencing; Alzheimer’s disease; Brain; Neurons
Genre
Article
Type
Text
Language
eng
Date Available
2018-05-17
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0366932
URI
http://hdl.handle.net/2429/65986
Affiliation
Medicine, Faculty of; Non UBC; Hematology, Division of; Medicine, Department of
Citation
Genome Biology. 2016 May 31;17(1):116
Publisher DOI
10.1186/s13059-016-0976-2
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
van den Bos et al.
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)