Jones, A.R., Troakes, C., King, A. et al. (13 more authors) (2015) Stratified gene expression analysis identifies major amyotrophic lateral sclerosis genes. Neurobiology of Aging, 36 (5). 2006.e1-2006.e9. ISSN 0197-4580
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 Elsevier Inc. All rights reserved. |
Keywords: | Gene expression; Amyotrophic lateral sclerosis; Spinal cord; Disease spread; C9ORF72; RNA processing |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Feb 2016 16:22 |
Last Modified: | 14 Jun 2016 09:52 |
Published Version: | http://dx.doi.org/10.1016/j.neurobiolaging.2015.02... |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.neurobiolaging.2015.02.017 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:93678 |