Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis
| Autor(a) principal: | |
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| Data de Publicação: | 2023 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/55900 |
Resumo: | © 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license. |
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Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosisAmyotrophic Lateral SclerosisGenetic modifiersPost-zygotic mutationsRepeat expansions© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license.Amyotrophic lateral sclerosis is a heterogeneous, fatal neurodegenerative disease, characterized by motor neuron loss and in 50% of cases also by cognitive and/or behavioral changes. Mendelian forms of ALS comprise approximately 10-15% of cases. The majority is however considered sporadic, but also with a high contribution of genetic risk factors. To explore the contribution of somatic mutations and/or epigenetic changes to disease risk, we performed whole genome sequencing and methylation analyses using samples from multiple tissues on a cohort of 26 monozygotic twins discordant for ALS, followed by in-depth validation and replication experiments. The results of these analyses implicate several mechanisms in ALS pathophysiology, which include a role for de novo mutations, defects in DNA damage repair and accelerated aging.This study was funded by the Thierry Latran Foundation and the Dutch ALS foundation. Project MinE Belgium was supported by a grant from IWT (n° 140935), the ALS Liga België, the National Lottery of Belgium and the KU Leuven Opening the Future Fund. M.A.v.E. is additionally supported by the Rudolf Magnus Brain Center Talent Fellowship. P.V.D. holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders, the ALS Liga België and the KU Leuven funds “Een Hart voor ALS,” “Laeversfonds voor ALS Onderzoek” and the “Valéry Perrier Race against ALS Fund.” Several authors of this publication are member of the European Reference Network for Rare Neuromuscular Diseases (ERN-NMD). A.A.-C. receives salary support from the National Institute for Health Research (NIHR) Dementia Biomedical Research Unit and Biomedical Research Centre in Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. O.H. is funded by the Health Research Board Clinician Scientist Programme and Science Foundation Ireland. R.L.M is also supported by the Thierry Latran Foundation (ALSIBD) and the ALS Association (2284). The Swedish Brain Foundation (grants nr. 2012-0262, 2012-0305, 2013-0279, 2016-0303), the Swedish Science Council (grants nr 2012-3167, 2017-03100), the Knut and Alice Wallenberg Foundation (grants nr. 2012.0091, 2014.0305), the Bertil Hållsten Foundation, the Ulla-Carin Lindquist Foundation, the Neuroförbundet Association, the Torsten and Ragnar Söderberg Foundation, Umeå University Insamlingsstiftelsen (223-2808-12, 223-1881-13, 2.1.12-1605-14), Västerbotten County Council, Swedish Brain Power, King Gustaf V:s and Queen Victoria's Freemason's Foundation.ElsevierRepositório da Universidade de LisboaTazelaar, Gijs H.P.Hop, Paul J.Seelen, Meinievan Vugt, Joke J.F.A.van Rheenen, WouterKool, Lindyvan Eijk, Kristel R.Gijzen, MarleenDooijes, DennisMoisse, MatthieuCalvo, AndreaMoglia, CristinaBrunetti, MauraCanosa, AntonioNordin, AngelicaPardina, Jesus S. MoraRavits, JohnAl-Chalabi, AmmarChio, AdrianoMcLaughlin, Russell L.Hardiman, OrlaVan Damme, PhilipCarvalho, MamedeNeuwirth, ChristophWeber, MarkusAndersen, Peter Mvan den Berg, Leonard H.Veldink, Jan H.van Es, Michael A.2023-01-17T14:20:26Z20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/55900engNeurobiol Aging. 2023 Feb;122:76-870197-458010.1016/j.neurobiolaging.2022.11.0101558-1497info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:03:07Zoai:repositorio.ul.pt:10451/55900Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:06:28.022439Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis |
| title |
Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis |
| spellingShingle |
Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis Tazelaar, Gijs H.P. Amyotrophic Lateral Sclerosis Genetic modifiers Post-zygotic mutations Repeat expansions |
| title_short |
Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis |
| title_full |
Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis |
| title_fullStr |
Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis |
| title_full_unstemmed |
Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis |
| title_sort |
Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis |
| author |
Tazelaar, Gijs H.P. |
| author_facet |
Tazelaar, Gijs H.P. Hop, Paul J. Seelen, Meinie van Vugt, Joke J.F.A. van Rheenen, Wouter Kool, Lindy van Eijk, Kristel R. Gijzen, Marleen Dooijes, Dennis Moisse, Matthieu Calvo, Andrea Moglia, Cristina Brunetti, Maura Canosa, Antonio Nordin, Angelica Pardina, Jesus S. Mora Ravits, John Al-Chalabi, Ammar Chio, Adriano McLaughlin, Russell L. Hardiman, Orla Van Damme, Philip Carvalho, Mamede Neuwirth, Christoph Weber, Markus Andersen, Peter M van den Berg, Leonard H. Veldink, Jan H. van Es, Michael A. |
| author_role |
author |
| author2 |
Hop, Paul J. Seelen, Meinie van Vugt, Joke J.F.A. van Rheenen, Wouter Kool, Lindy van Eijk, Kristel R. Gijzen, Marleen Dooijes, Dennis Moisse, Matthieu Calvo, Andrea Moglia, Cristina Brunetti, Maura Canosa, Antonio Nordin, Angelica Pardina, Jesus S. Mora Ravits, John Al-Chalabi, Ammar Chio, Adriano McLaughlin, Russell L. Hardiman, Orla Van Damme, Philip Carvalho, Mamede Neuwirth, Christoph Weber, Markus Andersen, Peter M van den Berg, Leonard H. Veldink, Jan H. van Es, Michael A. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Tazelaar, Gijs H.P. Hop, Paul J. Seelen, Meinie van Vugt, Joke J.F.A. van Rheenen, Wouter Kool, Lindy van Eijk, Kristel R. Gijzen, Marleen Dooijes, Dennis Moisse, Matthieu Calvo, Andrea Moglia, Cristina Brunetti, Maura Canosa, Antonio Nordin, Angelica Pardina, Jesus S. Mora Ravits, John Al-Chalabi, Ammar Chio, Adriano McLaughlin, Russell L. Hardiman, Orla Van Damme, Philip Carvalho, Mamede Neuwirth, Christoph Weber, Markus Andersen, Peter M van den Berg, Leonard H. Veldink, Jan H. van Es, Michael A. |
| dc.subject.por.fl_str_mv |
Amyotrophic Lateral Sclerosis Genetic modifiers Post-zygotic mutations Repeat expansions |
| topic |
Amyotrophic Lateral Sclerosis Genetic modifiers Post-zygotic mutations Repeat expansions |
| description |
© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-01-17T14:20:26Z 2023 2023-01-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/55900 |
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http://hdl.handle.net/10451/55900 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Neurobiol Aging. 2023 Feb;122:76-87 0197-4580 10.1016/j.neurobiolaging.2022.11.010 1558-1497 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Elsevier |
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Elsevier |
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