Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson’s Disease
| Autor: | Abeer E. Mustafa, Batoul Baz, Amna Magrashi, Tariq Faquih, Eman A.A. Al Yemni, Jameela Shinwari, Dorota Monies, Shazia Subhani, Nada Al-Tassan, Amjad Jabaan, Basma S. AlAbdulaziz, Wafa Ali, Mohamed Abouelhoda, Ewa Goljan, Bashayer R. Al-Mubarak, Thamer Alkhairallah, Mohamed H Al-Hamed, Renad Albar, Saeed Bohlega |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male DNA Copy Number Variations Ubiquitin-Protein Ligases lcsh:Medicine Computational biology Disease Biology DNA sequencing Article 03 medical and health sciences 0302 clinical medicine Exome Sequencing Missense mutation Humans Genetic Predisposition to Disease lcsh:Science Gene Exome sequencing Loss function Sequence Deletion Multidisciplinary lcsh:R Parkinson Disease Exons EPRS Phenotype 030104 developmental biology lcsh:Q Female 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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