Guerreiro, RJ;
Schymick, JC;
Crews, C;
Singleton, A;
Hardy, J;
Traynor, BJ;
(2008)
TDP-43 Is Not a Common Cause of Sporadic Amyotrophic Lateral Sclerosis.
PLOS ONE
, 3
(6)
, Article e2450. 10.1371/journal.pone.0002450.
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Abstract
Background: TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS.Methodology/Principal Findings: To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus.Conclusions: Our data indicate that genetic variation in TARDBP is not a common cause of sporadic ALS in North American.
| Type: | Article |
|---|---|
| Title: | TDP-43 Is Not a Common Cause of Sporadic Amyotrophic Lateral Sclerosis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0002450 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0002450 |
| Language: | English |
| Additional information: | This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. This study was supported by grants from the ALS Association, the Packard Center for ALS Research at Hopkins, the intramural programs of NIA (1 Z01 AG000951-06) and NINDS and grant #SFRH/BD/27442/2006 from Fundacao para a Ciencia e Tecnologia, Portugal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/741330 |
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