ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization

Increasingly, repeat expansions are being identified as part of the complex genetic architecture of amyotrophic lateral sclerosis. To date, several repeat expansions have been genetically associated with the disease: intronic repeat expansions in C9orf72, polyglutamine expansions in ATXN2 and polyal...

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Autores: Tazelaar, Gijs H. P., Boeynaems, Steven, Decker, Mathias De, Povedano, Mònica, Assialioui, Abdelilah, Project MinE ALS Sequencing Consortium
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/174313
Acceso en línea:https://hdl.handle.net/2445/174313
Access Level:acceso abierto
Palabra clave:Esclerosi lateral amiotròfica
Genètica
Amyotrophic lateral sclerosis
Genetics
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spelling ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalizationTazelaar, Gijs H. P.Boeynaems, StevenDecker, Mathias DePovedano, MònicaAssialioui, AbdelilahProject MinE ALS Sequencing ConsortiumEsclerosi lateral amiotròficaGenèticaAmyotrophic lateral sclerosisGeneticsIncreasingly, repeat expansions are being identified as part of the complex genetic architecture of amyotrophic lateral sclerosis. To date, several repeat expansions have been genetically associated with the disease: intronic repeat expansions in C9orf72, polyglutamine expansions in ATXN2 and polyalanine expansions in NIPA1. Together with previously published data, the identification of an amyotrophic lateral sclerosis patient with a family history of spinocerebellar ataxia type 1, caused by polyglutamine expansions in ATXN1, suggested a similar disease association for the repeat expansion in ATXN1. We, therefore, performed a large-scale international study in 11 700 individuals, in which we showed a significant association between intermediate ATXN1 repeat expansions and amyotrophic lateral sclerosis (P = 3.33 × 10-7). Subsequent functional experiments have shown that ATXN1 reduces the nucleocytoplasmic ratio of TDP-43 and enhances amyotrophic lateral sclerosis phenotypes in Drosophila, further emphasizing the role of polyglutamine repeat expansions in the pathophysiology of amyotrophic lateral sclerosis.Oxford University Press (OUP)2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/174313Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1093/braincomms/fcaa064Brain Communications, 2020, vol. 2, num.. 2https://doi.org/10.1093/braincomms/fcaa064cc by-nc (c) Tazelaar, Gijs H. P. et al., 2020http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1743132026-05-29T05:05:01Z
dc.title.none.fl_str_mv ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
title ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
spellingShingle ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
Tazelaar, Gijs H. P.
Esclerosi lateral amiotròfica
Genètica
Amyotrophic lateral sclerosis
Genetics
title_short ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
title_full ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
title_fullStr ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
title_full_unstemmed ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
title_sort ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
dc.creator.none.fl_str_mv Tazelaar, Gijs H. P.
Boeynaems, Steven
Decker, Mathias De
Povedano, Mònica
Assialioui, Abdelilah
Project MinE ALS Sequencing Consortium
author Tazelaar, Gijs H. P.
author_facet Tazelaar, Gijs H. P.
Boeynaems, Steven
Decker, Mathias De
Povedano, Mònica
Assialioui, Abdelilah
Project MinE ALS Sequencing Consortium
author_role author
author2 Boeynaems, Steven
Decker, Mathias De
Povedano, Mònica
Assialioui, Abdelilah
Project MinE ALS Sequencing Consortium
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Esclerosi lateral amiotròfica
Genètica
Amyotrophic lateral sclerosis
Genetics
topic Esclerosi lateral amiotròfica
Genètica
Amyotrophic lateral sclerosis
Genetics
description Increasingly, repeat expansions are being identified as part of the complex genetic architecture of amyotrophic lateral sclerosis. To date, several repeat expansions have been genetically associated with the disease: intronic repeat expansions in C9orf72, polyglutamine expansions in ATXN2 and polyalanine expansions in NIPA1. Together with previously published data, the identification of an amyotrophic lateral sclerosis patient with a family history of spinocerebellar ataxia type 1, caused by polyglutamine expansions in ATXN1, suggested a similar disease association for the repeat expansion in ATXN1. We, therefore, performed a large-scale international study in 11 700 individuals, in which we showed a significant association between intermediate ATXN1 repeat expansions and amyotrophic lateral sclerosis (P = 3.33 × 10-7). Subsequent functional experiments have shown that ATXN1 reduces the nucleocytoplasmic ratio of TDP-43 and enhances amyotrophic lateral sclerosis phenotypes in Drosophila, further emphasizing the role of polyglutamine repeat expansions in the pathophysiology of amyotrophic lateral sclerosis.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/174313
url https://hdl.handle.net/2445/174313
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1093/braincomms/fcaa064
Brain Communications, 2020, vol. 2, num.. 2
https://doi.org/10.1093/braincomms/fcaa064
dc.rights.none.fl_str_mv cc by-nc (c) Tazelaar, Gijs H. P. et al., 2020
http://creativecommons.org/licenses/by-nc/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc (c) Tazelaar, Gijs H. P. et al., 2020
http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press (OUP)
publisher.none.fl_str_mv Oxford University Press (OUP)
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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