A comprehensive assessment of benign genetic variability for neurodegenerative disorders

Over the last few years, as more and more sequencing studies have been performed, it has become apparent that the identification of pathogenic mutations is, more often than not, a complex issue. Here, with a focus on neurodegenerative diseases, we have performed a survey of coding genetic variabilit...

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Main Authors: Guerreiro, Rita, Sassi, Celeste, Gibbs, Jesse, Edsall, Connor, Hernandez, Dena, Brown, Kristelle, Lupton, Michelle, Parkinnen, Laura, Ansorge, Olaf, Hodges, Angela, Ryten, Mina, Tienari, Pentti, Van Deerlin, Vivanna, Trojanowski, John, Morgan, Kevin, Powell, John, Singleton, Andrew, Hardy, John, Bras, Jose
Format: Article
Language:English
Published: 2018
Online Access:https://eprints.nottingham.ac.uk/50595/
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author Guerreiro, Rita
Sassi, Celeste
Gibbs, Jesse
Edsall, Connor
Hernandez, Dena
Brown, Kristelle
Lupton, Michelle
Parkinnen, Laura
Ansorge, Olaf
Hodges, Angela
Ryten, Mina
Tienari, Pentti
Van Deerlin, Vivanna
Trojanowski, John
Morgan, Kevin
Powell, John
Singleton, Andrew
Hardy, John
Bras, Jose
author_facet Guerreiro, Rita
Sassi, Celeste
Gibbs, Jesse
Edsall, Connor
Hernandez, Dena
Brown, Kristelle
Lupton, Michelle
Parkinnen, Laura
Ansorge, Olaf
Hodges, Angela
Ryten, Mina
Tienari, Pentti
Van Deerlin, Vivanna
Trojanowski, John
Morgan, Kevin
Powell, John
Singleton, Andrew
Hardy, John
Bras, Jose
author_sort Guerreiro, Rita
building Nottingham Research Data Repository
collection Online Access
description Over the last few years, as more and more sequencing studies have been performed, it has become apparent that the identification of pathogenic mutations is, more often than not, a complex issue. Here, with a focus on neurodegenerative diseases, we have performed a survey of coding genetic variability that is unlikely to be pathogenic. We have performed whole-exome sequencing in 478 samples derived from several brain banks in the United Kingdom and the United States of America. Samples were included when subjects were, at death, over 60 years of age, had no signs of neurological disease and were subjected to a neuropathological examination, which revealed no evidence of neurodegeneration. This information will be valuable to studies of genetic variability as a causal factor for neurodegenerative syndromes. We envisage it will be particularly relevant for diagnostic laboratories as a filter step to the results being produced by either genome-wide or gene-panel sequencing. We have made this data publicly available at www.alzforum.org/exomes/hex.
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spelling nottingham-505952018-03-22T12:19:38Z https://eprints.nottingham.ac.uk/50595/ A comprehensive assessment of benign genetic variability for neurodegenerative disorders Guerreiro, Rita Sassi, Celeste Gibbs, Jesse Edsall, Connor Hernandez, Dena Brown, Kristelle Lupton, Michelle Parkinnen, Laura Ansorge, Olaf Hodges, Angela Ryten, Mina Tienari, Pentti Van Deerlin, Vivanna Trojanowski, John Morgan, Kevin Powell, John Singleton, Andrew Hardy, John Bras, Jose Over the last few years, as more and more sequencing studies have been performed, it has become apparent that the identification of pathogenic mutations is, more often than not, a complex issue. Here, with a focus on neurodegenerative diseases, we have performed a survey of coding genetic variability that is unlikely to be pathogenic. We have performed whole-exome sequencing in 478 samples derived from several brain banks in the United Kingdom and the United States of America. Samples were included when subjects were, at death, over 60 years of age, had no signs of neurological disease and were subjected to a neuropathological examination, which revealed no evidence of neurodegeneration. This information will be valuable to studies of genetic variability as a causal factor for neurodegenerative syndromes. We envisage it will be particularly relevant for diagnostic laboratories as a filter step to the results being produced by either genome-wide or gene-panel sequencing. We have made this data publicly available at www.alzforum.org/exomes/hex. 2018-02-23 Article NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/50595/1/270686.full.pdf Guerreiro, Rita, Sassi, Celeste, Gibbs, Jesse, Edsall, Connor, Hernandez, Dena, Brown, Kristelle, Lupton, Michelle, Parkinnen, Laura, Ansorge, Olaf, Hodges, Angela, Ryten, Mina, Tienari, Pentti, Van Deerlin, Vivanna, Trojanowski, John, Morgan, Kevin, Powell, John, Singleton, Andrew, Hardy, John and Bras, Jose (2018) A comprehensive assessment of benign genetic variability for neurodegenerative disorders. BioRxiv . https://doi.org/10.1101/270686 doi:10.1101/270686 doi:10.1101/270686
spellingShingle Guerreiro, Rita
Sassi, Celeste
Gibbs, Jesse
Edsall, Connor
Hernandez, Dena
Brown, Kristelle
Lupton, Michelle
Parkinnen, Laura
Ansorge, Olaf
Hodges, Angela
Ryten, Mina
Tienari, Pentti
Van Deerlin, Vivanna
Trojanowski, John
Morgan, Kevin
Powell, John
Singleton, Andrew
Hardy, John
Bras, Jose
A comprehensive assessment of benign genetic variability for neurodegenerative disorders
title A comprehensive assessment of benign genetic variability for neurodegenerative disorders
title_full A comprehensive assessment of benign genetic variability for neurodegenerative disorders
title_fullStr A comprehensive assessment of benign genetic variability for neurodegenerative disorders
title_full_unstemmed A comprehensive assessment of benign genetic variability for neurodegenerative disorders
title_short A comprehensive assessment of benign genetic variability for neurodegenerative disorders
title_sort comprehensive assessment of benign genetic variability for neurodegenerative disorders
url https://eprints.nottingham.ac.uk/50595/
https://eprints.nottingham.ac.uk/50595/
https://eprints.nottingham.ac.uk/50595/