أعرض في EDS

Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis

التفاصيل البيبلوغرافية
العنوان: Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis
المؤلفون: Ahmad Al Khleifat, Alfredo Iacoangeli, Joke J. F. A. van Vugt, Harry Bowles, Matthieu Moisse, Ramona A. J. Zwamborn, Rick A. A. van der Spek, Aleksey Shatunov, Johnathan Cooper-Knock, Simon Topp, Ross Byrne, Cinzia Gellera, Victoria López, Ashley R. Jones, Sarah Opie-Martin, Atay Vural, Yolanda Campos, Wouter van Rheenen, Brendan Kenna, Kristel R. Van Eijk, Kevin Kenna, Markus Weber, Bradley Smith, Isabella Fogh, Vincenzo Silani, Karen E. Morrison, Richard Dobson, Michael A. van Es, Russell L. McLaughlin, Patrick Vourc’h, Adriano Chio, Philippe Corcia, Mamede de Carvalho, Marc Gotkine, Monica P. Panades, Jesus S. Mora, Pamela J. Shaw, John E. Landers, Jonathan D. Glass, Christopher E. Shaw, Nazli Basak, Orla Hardiman, Wim Robberecht, Philip Van Damme, Leonard H. van den Berg, Jan H. Veldink, Ammar Al-Chalabi
المساهمون: Wellcome Trust, Unión Europea. Comisión Europea. 7 Programa Marco, Unión Europea. Comisión Europea. H2020, Unión Europea. Fondo Social Europeo (ESF/FSE), Research Foundation - Flanders, KU Leuven (Bélgica), Science Foundation Ireland, Amyotrophic Lateral Sclerosis Association (Estados Unidos), NIH - National Institute of Neurological Disorders and Stroke (NINDS) (Estados Unidos), Repositório da Universidade de Lisboa, Vural, Atay (ORCID 0000-0003-3222-874X & YÖK ID 182369), Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), Ahmad Al, Khleifat, Alfredo, Iacoangeli, Joke J F A van, Vugt, Harry, Bowles, Matthieu, Moisse, Ramona A J, Zwamborn, Rick A A van, der Spek, Aleksey, Shatunov, Johnathan, Cooper-Knock, Simon, Topp, Ross, Byrne, Cinzia, Gellera, Victoria, Lopez, Ashley R, Jones, Sarah, Opie-Martin, Yolanda, Campos, Wouter van, Rheenen, Brendan, Kenna, Kristel R Van, Eijk, Kevin, Kenna, Markus, Weber, Bradley, Smith, Isabella, Fogh, Vincenzo, Silani, Karen E., Morrison, Richard, Dobson, Michael A van, Es, Russell L., McLaughlin, Patrick, Vourc’h, Adriano, Chio, Philippe, Corcia, Mamede, de Carvalho, Marc, Gotkine, Monica, P Panades, Jesus ,S Mora, Pamela, J Shaw, John, E Landers, Jonathan, D Glass, Christopher, E Shaw, Orla, Hardiman, Wim, Robberecht, Philip Van, Damme, Leonard H van, den Berg, Jan, H Veldink, Ammar, Al-Chalabi, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine
المصدر: npj Genomic Medicine, Vol 7, Iss 1, Pp 1-8 (2022)
npj Genomic Medicine
Al Khleifat, A, Iacoangeli, A, van Vugt, J J F A, Bowles, H, Moisse, M, Zwamborn, R A J, van der Spek, R A A, Shatunov, A, Cooper-Knock, J, Topp, S, Byrne, R, Gellera, C, López, V, Jones, A R, Opie-Martin, S, Vural, A, Campos, Y, van Rheenen, W, Kenna, B, Van Eijk, K R, Kenna, K, Weber, M, Smith, B, Fogh, I, Silani, V, Morrison, K E, Dobson, R, van Es, M A, McLaughlin, R L, Vourc'h, P, Chio, A, Corcia, P, de Carvalho, M, Gotkine, M, Panades, M P, Mora, J S, Shaw, P J, Landers, J E, Glass, J D, Shaw, C E, Basak, N, Hardiman, O, Robberecht, W, Van Damme, P, van den Berg, L H, Veldink, J H & Al-Chalabi, A 2022, ' Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis ', NPJ Genomic Medicine, vol. 7, no. 1, 8 . https://doi.org/10.1038/s41525-021-00267-9
Dipòsit Digital de la UB
Universidad de Barcelona
NPJ Genomic Medicine
بيانات النشر: Nature Portfolio, 2022.
سنة النشر: 2022
مصطلحات موضوعية: Genetics and heredity, C9ORF72, VARIANTS, QH426-470, Article, 03 medical and health sciences, 0302 clinical medicine, Human genetics, Genetics, INCLUSION-BODY MYOPATHY, Amyotrophic lateral sclerosis (ALS), Molecular Biology, Genetics (clinical), COPY NUMBER VARIATION, 030304 developmental biology, Genetics & Heredity, 0303 health sciences, Science & Technology, Genètica humana, HERITABILITY, Comparative genomics, Amyotrophic lateral sclerosis, Disease progression, Advanced launch system (STS), ASSOCIATION, HEXANUCLEOTIDE REPEAT EXPANSION, Genome sequences, PAGET-DISEASE, Medicine, BONE, Life Sciences & Biomedicine, FAMILIAL FRONTOTEMPORAL DEMENTIA, 030217 neurology & neurosurgery, Esclerosi lateral amiotròfica
الوصف: © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype.
This research was funded in whole, or in part, by the Wellcome Trust [Grant number]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The authors acknowledge use of the research computing facility at King’s College London, Rosalind (https://rosalind.kcl.ac.uk), which is delivered in partnership with the National Institute for Health Research (NIHR) Biomedical Research Centres at South London & Maudsley and Guy’s & St. Thomas’ NHS Foundation Trusts, and part-funded by capital equipment grants from the Maudsley Charity (award 980) and Guy’s & St. Thomas’ Charity (TR130505). The views expressed are those of the author (s) and not necessarily those of the NHS, the NIHR, King’s College London, or the Department of Health and Social Care. National. The authors acknowledge Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The authors acknowledge Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome Trust. A.A.K. is funded by The Motor Neurone Disease Association (MNDA), NIHR Maudsley Biomedical Research Centre and and ALS Association Milton Safenowitz Research Fellowship. This project was funded by the MND Association and the Wellcome Trust. This is an EU Joint Programme-Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organisations under the aegis of JPND - www.jpnd.eu (United Kingdom, Medical Research Council (MR/L501529/1 and MR/R024804/1) and Economic and Social Research Council (ES/L008238/1)). A.A.C. is an NIHR Senior Investigator. C.E.S. and A.A.C. receive salary support from the National Institute for Health Research (NIHR) Dementia Biomedical Research Unit 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. The work leading up to this publication was funded by the European Community’s Health Seventh Framework Program (FP7/2007–2013; grant agreement number 259867) and Horizon 2020 Program (H2020-PHC-2014-two-stage; grant agreement number 633413). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 772376 - EScORIAL. The collaboration project is co-funded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. Project MinE Belgium was supported by a grant from IWT, the Belgian ALS Liga and a grant from Opening the Future Fund (KU Leuven). PVD holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by 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”. R.L.McL. is supported by Science Foundation Ireland (17/CDA/4737). MinE USA is funded by the US ALS Association. We thank the patients and families from the Emory ALS Clinic participating in this research. Funding was provided by US National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) (R01NS073873, J.E.L.) and the American ALS Association (J.E.L.).
وصف الملف: application/pdf; fulltext; Electronic; pdf
اللغة: English
تدمد: 2056-7944
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5ed582d2f280d0aca61a78bfda7e338e
https://doaj.org/article/2c1accb04c5e475dbe0325f3e155c28c
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....5ed582d2f280d0aca61a78bfda7e338e
قاعدة البيانات: OpenAIRE
الوصف
تدمد:20567944