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Title: | Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis |
Author: | Al Khleifat, Ahmad Iacoangeli, Alfredo Vugt, Joke J. F. A. van Bowles, Harry Moisse, Matthieu Zwamborn, Ramona A. J. Spek, Rick A. A. van der Shatunov, Aleksey Cooper-Knock, Johnathan Topp, Simon Byrne, Ross Gellera, Cinzia López, Victoria Jones, Ashley R. Opie-Martin, Sarah Vural, Atay Campos, Yolanda Rheenen, Wouter van Kenna, Brendan Eijk, Kristel R. van Kenna, Kevin Weber, Markus Smith, Bradley Fogh, Isabella Silani, Vincenzo Morrison, Karen E. Dobson, Richard Es, Michael A. van Mclaughlin, Russell L. Vourc’h, Patrick Chio, Adriano Corcia, Philippe Carvalho, Mamede de Gotkine, Marc Panades, Monica P. Mora, Jesus S. Shaw, Pamela J. Landers, John E. Glass, Jonathan D. Shaw, Christopher E. Basak, Nazli Hardiman, Orla Robberecht, Wim Damme, Philip van Berg, Leonard H. van der Veldink, Jan H. Al Chalabi, Ammar |
Keywords: | Esclerosi lateral amiotròfica Genètica humana Amyotrophic lateral sclerosis Human genetics |
Issue Date: | 28-Jan-2022 |
Publisher: | Springer Science and Business Media LLC |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41525-021-00267-9 |
It is part of: | npj Genomic Medicine, 2022, vol 7, num 1 |
URI: | http://hdl.handle.net/2445/183102 |
Related resource: | https://doi.org/10.1038/s41525-021-00267-9 |
ISSN: | 2056-7944 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE |
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