Mutation analysis of patients with neurodegenerative disorders using NeuroX array
- Autores
- Ghani, Mahdi; Lang, Anthony E.; Zinman, Lorne; Nacmias, Benedetta; Sorbi, Sandro; Bessi, Valentina; Tedde, Andrea; Tartaglia, Maria Carmela; Surace, Ezequiel Ignacio; Sato, Christine; Moreno, Danielle; Xi, Zhengrui; Hung, Rachel; Nalls, Mike A.; Singleton, Andrew; George Hyslop, Peter St.; Savchenko, Ekaterina
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Genetic analyses of patients with neurodegenerative disorders have identified multiple genes that need to be investigated for the presence of damaging variants. However, mutation analysis by Sanger sequencing is costly and time consuming. We tested the utility of a recently designed semi-custom genome-wide array (NeuroX; Illumina, Inc) tailored to study neurodegenerative diseases (e.g., mutation screening). We investigated 192 patients with 4 different neurodegenerative disorders for the presence of rare damaging variations in 77 genes implicated in these diseases. Several causative mutations were identified and confirmed by Sanger sequencing, including PSEN1 p.M233T responsible for Alzheimer's disease in a large Italian family, as well as SOD1 p.A4V and p.I113T in patients with amyotrophic lateral sclerosis. In total, we identified 78 potentially damaging rare variants (frequency <1%), including ABCA7 p.L400V in a family with Alzheimer's disease and LRRK2 p.R1514Q in 6 of 98 patients with Parkinson's disease (6.1%). In conclusion, NeuroX appears to be helpful for rapid and accurate mutation screening, although further development may be still required to improve some current caveats.
Fil: Ghani, Mahdi. University of Toronto; Canadá
Fil: Lang, Anthony E.. University of Toronto; Canadá. Toronto Western Hospital; Canadá
Fil: Zinman, Lorne. University of Toronto; Canadá. Sunnybrook Health Sciences Centre; Canadá
Fil: Nacmias, Benedetta. Università degli Studi di Firenze; Italia
Fil: Sorbi, Sandro. Università degli Studi di Firenze; Italia
Fil: Bessi, Valentina. Università degli Studi di Firenze; Italia
Fil: Tedde, Andrea. Università degli Studi di Firenze; Italia
Fil: Tartaglia, Maria Carmela. University of Toronto; Canadá
Fil: Surace, Ezequiel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina
Fil: Sato, Christine. University of Toronto; Canadá
Fil: Moreno, Danielle. University of Toronto; Canadá
Fil: Xi, Zhengrui. University of Toronto; Canadá
Fil: Hung, Rachel. University of Toronto; Canadá
Fil: Nalls, Mike A.. National Institute on Aging; Estados Unidos
Fil: Singleton, Andrew. National Institute on Aging; Estados Unidos
Fil: George Hyslop, Peter St.. University of Toronto; Canadá. University of Cambridge; Reino Unido
Fil: Savchenko, Ekaterina. University of Toronto; Canadá - Materia
-
MUTATION
NEURODEGENERATIVE DISORDER
NEUROX - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/85292
Ver los metadatos del registro completo
| id |
CONICETDig_ea7289bbc50f8c8908dc6a7c46cde768 |
|---|---|
| oai_identifier_str |
oai:ri.conicet.gov.ar:11336/85292 |
| network_acronym_str |
CONICETDig |
| repository_id_str |
3498 |
| network_name_str |
CONICET Digital (CONICET) |
| spelling |
Mutation analysis of patients with neurodegenerative disorders using NeuroX arrayGhani, MahdiLang, Anthony E.Zinman, LorneNacmias, BenedettaSorbi, SandroBessi, ValentinaTedde, AndreaTartaglia, Maria CarmelaSurace, Ezequiel IgnacioSato, ChristineMoreno, DanielleXi, ZhengruiHung, RachelNalls, Mike A.Singleton, AndrewGeorge Hyslop, Peter St.Savchenko, EkaterinaMUTATIONNEURODEGENERATIVE DISORDERNEUROXhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Genetic analyses of patients with neurodegenerative disorders have identified multiple genes that need to be investigated for the presence of damaging variants. However, mutation analysis by Sanger sequencing is costly and time consuming. We tested the utility of a recently designed semi-custom genome-wide array (NeuroX; Illumina, Inc) tailored to study neurodegenerative diseases (e.g., mutation screening). We investigated 192 patients with 4 different neurodegenerative disorders for the presence of rare damaging variations in 77 genes implicated in these diseases. Several causative mutations were identified and confirmed by Sanger sequencing, including PSEN1 p.M233T responsible for Alzheimer's disease in a large Italian family, as well as SOD1 p.A4V and p.I113T in patients with amyotrophic lateral sclerosis. In total, we identified 78 potentially damaging rare variants (frequency <1%), including ABCA7 p.L400V in a family with Alzheimer's disease and LRRK2 p.R1514Q in 6 of 98 patients with Parkinson's disease (6.1%). In conclusion, NeuroX appears to be helpful for rapid and accurate mutation screening, although further development may be still required to improve some current caveats.Fil: Ghani, Mahdi. University of Toronto; CanadáFil: Lang, Anthony E.. University of Toronto; Canadá. Toronto Western Hospital; CanadáFil: Zinman, Lorne. University of Toronto; Canadá. Sunnybrook Health Sciences Centre; CanadáFil: Nacmias, Benedetta. Università degli Studi di Firenze; ItaliaFil: Sorbi, Sandro. Università degli Studi di Firenze; ItaliaFil: Bessi, Valentina. Università degli Studi di Firenze; ItaliaFil: Tedde, Andrea. Università degli Studi di Firenze; ItaliaFil: Tartaglia, Maria Carmela. University of Toronto; CanadáFil: Surace, Ezequiel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; ArgentinaFil: Sato, Christine. University of Toronto; CanadáFil: Moreno, Danielle. University of Toronto; CanadáFil: Xi, Zhengrui. University of Toronto; CanadáFil: Hung, Rachel. University of Toronto; CanadáFil: Nalls, Mike A.. National Institute on Aging; Estados UnidosFil: Singleton, Andrew. National Institute on Aging; Estados UnidosFil: George Hyslop, Peter St.. University of Toronto; Canadá. University of Cambridge; Reino UnidoFil: Savchenko, Ekaterina. University of Toronto; CanadáElsevier Science Inc2015-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/85292Ghani, Mahdi; Lang, Anthony E.; Zinman, Lorne; Nacmias, Benedetta; Sorbi, Sandro; et al.; Mutation analysis of patients with neurodegenerative disorders using NeuroX array; Elsevier Science Inc; Neurobiology of Aging; 36; 1; 1-2015; 545.e9-545.e140197-4580CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.neurobiolaging.2014.07.038info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0197458014005077info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268030/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:17:26Zoai:ri.conicet.gov.ar:11336/85292instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:17:27.047CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Mutation analysis of patients with neurodegenerative disorders using NeuroX array |
| title |
Mutation analysis of patients with neurodegenerative disorders using NeuroX array |
| spellingShingle |
Mutation analysis of patients with neurodegenerative disorders using NeuroX array Ghani, Mahdi MUTATION NEURODEGENERATIVE DISORDER NEUROX |
| title_short |
Mutation analysis of patients with neurodegenerative disorders using NeuroX array |
| title_full |
Mutation analysis of patients with neurodegenerative disorders using NeuroX array |
| title_fullStr |
Mutation analysis of patients with neurodegenerative disorders using NeuroX array |
| title_full_unstemmed |
Mutation analysis of patients with neurodegenerative disorders using NeuroX array |
| title_sort |
Mutation analysis of patients with neurodegenerative disorders using NeuroX array |
| dc.creator.none.fl_str_mv |
Ghani, Mahdi Lang, Anthony E. Zinman, Lorne Nacmias, Benedetta Sorbi, Sandro Bessi, Valentina Tedde, Andrea Tartaglia, Maria Carmela Surace, Ezequiel Ignacio Sato, Christine Moreno, Danielle Xi, Zhengrui Hung, Rachel Nalls, Mike A. Singleton, Andrew George Hyslop, Peter St. Savchenko, Ekaterina |
| author |
Ghani, Mahdi |
| author_facet |
Ghani, Mahdi Lang, Anthony E. Zinman, Lorne Nacmias, Benedetta Sorbi, Sandro Bessi, Valentina Tedde, Andrea Tartaglia, Maria Carmela Surace, Ezequiel Ignacio Sato, Christine Moreno, Danielle Xi, Zhengrui Hung, Rachel Nalls, Mike A. Singleton, Andrew George Hyslop, Peter St. Savchenko, Ekaterina |
| author_role |
author |
| author2 |
Lang, Anthony E. Zinman, Lorne Nacmias, Benedetta Sorbi, Sandro Bessi, Valentina Tedde, Andrea Tartaglia, Maria Carmela Surace, Ezequiel Ignacio Sato, Christine Moreno, Danielle Xi, Zhengrui Hung, Rachel Nalls, Mike A. Singleton, Andrew George Hyslop, Peter St. Savchenko, Ekaterina |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
MUTATION NEURODEGENERATIVE DISORDER NEUROX |
| topic |
MUTATION NEURODEGENERATIVE DISORDER NEUROX |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Genetic analyses of patients with neurodegenerative disorders have identified multiple genes that need to be investigated for the presence of damaging variants. However, mutation analysis by Sanger sequencing is costly and time consuming. We tested the utility of a recently designed semi-custom genome-wide array (NeuroX; Illumina, Inc) tailored to study neurodegenerative diseases (e.g., mutation screening). We investigated 192 patients with 4 different neurodegenerative disorders for the presence of rare damaging variations in 77 genes implicated in these diseases. Several causative mutations were identified and confirmed by Sanger sequencing, including PSEN1 p.M233T responsible for Alzheimer's disease in a large Italian family, as well as SOD1 p.A4V and p.I113T in patients with amyotrophic lateral sclerosis. In total, we identified 78 potentially damaging rare variants (frequency <1%), including ABCA7 p.L400V in a family with Alzheimer's disease and LRRK2 p.R1514Q in 6 of 98 patients with Parkinson's disease (6.1%). In conclusion, NeuroX appears to be helpful for rapid and accurate mutation screening, although further development may be still required to improve some current caveats. Fil: Ghani, Mahdi. University of Toronto; Canadá Fil: Lang, Anthony E.. University of Toronto; Canadá. Toronto Western Hospital; Canadá Fil: Zinman, Lorne. University of Toronto; Canadá. Sunnybrook Health Sciences Centre; Canadá Fil: Nacmias, Benedetta. Università degli Studi di Firenze; Italia Fil: Sorbi, Sandro. Università degli Studi di Firenze; Italia Fil: Bessi, Valentina. Università degli Studi di Firenze; Italia Fil: Tedde, Andrea. Università degli Studi di Firenze; Italia Fil: Tartaglia, Maria Carmela. University of Toronto; Canadá Fil: Surace, Ezequiel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina Fil: Sato, Christine. University of Toronto; Canadá Fil: Moreno, Danielle. University of Toronto; Canadá Fil: Xi, Zhengrui. University of Toronto; Canadá Fil: Hung, Rachel. University of Toronto; Canadá Fil: Nalls, Mike A.. National Institute on Aging; Estados Unidos Fil: Singleton, Andrew. National Institute on Aging; Estados Unidos Fil: George Hyslop, Peter St.. University of Toronto; Canadá. University of Cambridge; Reino Unido Fil: Savchenko, Ekaterina. University of Toronto; Canadá |
| description |
Genetic analyses of patients with neurodegenerative disorders have identified multiple genes that need to be investigated for the presence of damaging variants. However, mutation analysis by Sanger sequencing is costly and time consuming. We tested the utility of a recently designed semi-custom genome-wide array (NeuroX; Illumina, Inc) tailored to study neurodegenerative diseases (e.g., mutation screening). We investigated 192 patients with 4 different neurodegenerative disorders for the presence of rare damaging variations in 77 genes implicated in these diseases. Several causative mutations were identified and confirmed by Sanger sequencing, including PSEN1 p.M233T responsible for Alzheimer's disease in a large Italian family, as well as SOD1 p.A4V and p.I113T in patients with amyotrophic lateral sclerosis. In total, we identified 78 potentially damaging rare variants (frequency <1%), including ABCA7 p.L400V in a family with Alzheimer's disease and LRRK2 p.R1514Q in 6 of 98 patients with Parkinson's disease (6.1%). In conclusion, NeuroX appears to be helpful for rapid and accurate mutation screening, although further development may be still required to improve some current caveats. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015-01 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/85292 Ghani, Mahdi; Lang, Anthony E.; Zinman, Lorne; Nacmias, Benedetta; Sorbi, Sandro; et al.; Mutation analysis of patients with neurodegenerative disorders using NeuroX array; Elsevier Science Inc; Neurobiology of Aging; 36; 1; 1-2015; 545.e9-545.e14 0197-4580 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/85292 |
| identifier_str_mv |
Ghani, Mahdi; Lang, Anthony E.; Zinman, Lorne; Nacmias, Benedetta; Sorbi, Sandro; et al.; Mutation analysis of patients with neurodegenerative disorders using NeuroX array; Elsevier Science Inc; Neurobiology of Aging; 36; 1; 1-2015; 545.e9-545.e14 0197-4580 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neurobiolaging.2014.07.038 info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0197458014005077 info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268030/ |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
| eu_rights_str_mv |
openAccess |
| rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
| dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier Science Inc |
| publisher.none.fl_str_mv |
Elsevier Science Inc |
| dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
| reponame_str |
CONICET Digital (CONICET) |
| collection |
CONICET Digital (CONICET) |
| instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
| _version_ |
1844614127318728704 |
| score |
13.069144 |