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Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson’s Disease
Genetic studies of the familial forms of Parkinson’s disease (PD) have identified a number of causative genes with an established role in its pathogenesis. These genes only explain a fraction of the diagnosed cases. The emergence of Next Generation Sequencing (NGS) expanded the scope of rare variant...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399448/ https://www.ncbi.nlm.nih.gov/pubmed/30833663 http://dx.doi.org/10.1038/s41598-019-40102-x |
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author | Yemni, Eman Al Monies, Dorota Alkhairallah, Thamer Bohlega, Saeed Abouelhoda, Mohamed Magrashi, Amna Mustafa, Abeer AlAbdulaziz, Basma Alhamed, Mohamed Baz, Batoul Goljan, Ewa Albar, Renad Jabaan, Amjad Faquih, Tariq Subhani, Shazia Ali, Wafa Shinwari, Jameela Al-Mubarak, Bashayer Al-Tassan, Nada |
author_facet | Yemni, Eman Al Monies, Dorota Alkhairallah, Thamer Bohlega, Saeed Abouelhoda, Mohamed Magrashi, Amna Mustafa, Abeer AlAbdulaziz, Basma Alhamed, Mohamed Baz, Batoul Goljan, Ewa Albar, Renad Jabaan, Amjad Faquih, Tariq Subhani, Shazia Ali, Wafa Shinwari, Jameela Al-Mubarak, Bashayer Al-Tassan, Nada |
author_sort | Yemni, Eman Al |
collection | PubMed |
description | Genetic studies of the familial forms of Parkinson’s disease (PD) have identified a number of causative genes with an established role in its pathogenesis. These genes only explain a fraction of the diagnosed cases. The emergence of Next Generation Sequencing (NGS) expanded the scope of rare variants identification in novel PD related genes. In this study we describe whole exome sequencing (WES) genetic findings of 60 PD patients with 125 variants validated in 51 of these cases. We used strict criteria for variant categorization that generated a list of variants in 20 genes. These variants included loss of function and missense changes in 18 genes that were never previously linked to PD (NOTCH4, BCOR, ITM2B, HRH4, CELSR1, SNAP91, FAM174A, BSN, SPG7, MAGI2, HEPHL1, EPRS, PUM1, CLSTN1, PLCB3, CLSTN3, DNAJB9 and NEFH) and 2 genes that were previously associated with PD (EIF4G1 and ATP13A2). These genes either play a critical role in neuronal function and/or have mouse models with disease related phenotypes. We highlight NOTCH4 as an interesting candidate in which we identified a deleterious truncating and a splice variant in 2 patients. Our combined molecular approach provides a comprehensive strategy applicable for complex genetic disorders. |
format | Online Article Text |
id | pubmed-6399448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63994482019-03-07 Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson’s Disease Yemni, Eman Al Monies, Dorota Alkhairallah, Thamer Bohlega, Saeed Abouelhoda, Mohamed Magrashi, Amna Mustafa, Abeer AlAbdulaziz, Basma Alhamed, Mohamed Baz, Batoul Goljan, Ewa Albar, Renad Jabaan, Amjad Faquih, Tariq Subhani, Shazia Ali, Wafa Shinwari, Jameela Al-Mubarak, Bashayer Al-Tassan, Nada Sci Rep Article Genetic studies of the familial forms of Parkinson’s disease (PD) have identified a number of causative genes with an established role in its pathogenesis. These genes only explain a fraction of the diagnosed cases. The emergence of Next Generation Sequencing (NGS) expanded the scope of rare variants identification in novel PD related genes. In this study we describe whole exome sequencing (WES) genetic findings of 60 PD patients with 125 variants validated in 51 of these cases. We used strict criteria for variant categorization that generated a list of variants in 20 genes. These variants included loss of function and missense changes in 18 genes that were never previously linked to PD (NOTCH4, BCOR, ITM2B, HRH4, CELSR1, SNAP91, FAM174A, BSN, SPG7, MAGI2, HEPHL1, EPRS, PUM1, CLSTN1, PLCB3, CLSTN3, DNAJB9 and NEFH) and 2 genes that were previously associated with PD (EIF4G1 and ATP13A2). These genes either play a critical role in neuronal function and/or have mouse models with disease related phenotypes. We highlight NOTCH4 as an interesting candidate in which we identified a deleterious truncating and a splice variant in 2 patients. Our combined molecular approach provides a comprehensive strategy applicable for complex genetic disorders. Nature Publishing Group UK 2019-03-04 /pmc/articles/PMC6399448/ /pubmed/30833663 http://dx.doi.org/10.1038/s41598-019-40102-x Text en © The Author(s) 2019 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/. |
spellingShingle | Article Yemni, Eman Al Monies, Dorota Alkhairallah, Thamer Bohlega, Saeed Abouelhoda, Mohamed Magrashi, Amna Mustafa, Abeer AlAbdulaziz, Basma Alhamed, Mohamed Baz, Batoul Goljan, Ewa Albar, Renad Jabaan, Amjad Faquih, Tariq Subhani, Shazia Ali, Wafa Shinwari, Jameela Al-Mubarak, Bashayer Al-Tassan, Nada Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson’s Disease |
title | Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson’s Disease |
title_full | Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson’s Disease |
title_fullStr | Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson’s Disease |
title_full_unstemmed | Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson’s Disease |
title_short | Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson’s Disease |
title_sort | integrated analysis of whole exome sequencing and copy number evaluation in parkinson’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399448/ https://www.ncbi.nlm.nih.gov/pubmed/30833663 http://dx.doi.org/10.1038/s41598-019-40102-x |
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