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Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.14/343716
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- Title
- Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS
- Related
- Neuron, Vol. 84, Issue 2, (2014), p.324-331
- DOI
- 10.1016/j.neuron.2014.09.027
- Publisher
- Cell Press
- Date
- 2014
- Author/Creator
- Smith, Bradley N
- Author/Creator
- Ticozzi, Nicola
- Author/Creator
- Calini, Daniela
- Author/Creator
- Vance, Caroline
- Author/Creator
- Danielson, Eric W
- Author/Creator
- Troakes, Claire
- Author/Creator
- Tiloca, Cinzia
- Author/Creator
- Al-Sarraj, Safa
- Author/Creator
- Lewis, Elizabeth A
- Author/Creator
- King, Andrew
- Author/Creator
- Colombrita, Claudia
- Author/Creator
- Pensato, Viviana
- Author/Creator
- Fallini, Claudia
- Author/Creator
- Castellotti, Barbara
- Author/Creator
- de Belleroche, Jacqueline
- Author/Creator
- Baas, Frank
- Author/Creator
- ten Asbroek, Anneloor L. M. A
- Author/Creator
- Sapp, Peter C
- Author/Creator
- McKenna-Yasek, Diane
- Author/Creator
- McLaughlin, Russell L
- Author/Creator
- Polak, Meraida
- Author/Creator
- Asress, Seneshaw
- Author/Creator
- Esteban-Peréz, Jesús
- Author/Creator
- Gkazi, Athina Soragia
- Author/Creator
- Munoz-Blanco, Jose Luis
- Author/Creator
- Simpson, Michael
- Author/Creator
- van Rheenen, Wouter
- Author/Creator
- Diekstra, Frank P
- Author/Creator
- Lauria, Giuseppe
- Author/Creator
- Duga, Stefano
- Author/Creator
- Corti, Stefania
- Author/Creator
- Cereda, Cristina
- Author/Creator
- Corrado, Lucia
- Author/Creator
- Sorarù, Gianni
- Author/Creator
- Topp, Simon
- Author/Creator
- Morrison, Karen E
- Author/Creator
- Williams, Kelly L
- Author/Creator
- Nicholson, Garth A
- Author/Creator
- Blair, Ian P
- Author/Creator
- Dion, Patrick A
- Author/Creator
- Leblond, Claire S
- Author/Creator
- Rouleau, Guy A
- Author/Creator
- Hardiman, Orla
- Author/Creator
- Veldink, Jan H
- Author/Creator
- van den Berg, Leonard H
- Author/Creator
- Kenna, Kevin P
- Author/Creator
- Al-Chalabi, Ammar
- Author/Creator
- Pall, Hardev
- Author/Creator
- Shaw, Pamela J
- Author/Creator
- Turner, Martin R
- Author/Creator
- Talbot, Kevin
- Author/Creator
- Taroni, Franco
- Author/Creator
- Garcia-Redondo, Alberto
- Author/Creator
- Wu, Zheyang
- Author/Creator
- Glass, Jonathan D
- Author/Creator
- Gellera, Cinzia
- Author/Creator
- Scotter, Emma L
- Author/Creator
- Ratti, Antonia
- Author/Creator
- Brown Jr., Robert H
- Author/Creator
- Silani, Vincenzo
- Author/Creator
- Shaw, Christopher E
- Author/Creator
- Landers, John E
- Author/Creator
- D'Alfonso, Sandra
- Author/Creator
- Mazzini, Letizia
- Author/Creator
- Comi, Giacomo P
- Author/Creator
- Del Bo, Roberto
- Author/Creator
- Ceroni, Mauro
- Author/Creator
- Kost, Jason
- Author/Creator
- Gagliardi, Stella
- Author/Creator
- Querin, Giorgia
- Author/Creator
- Bertolin, Cinzia
- Author/Creator
- Keagle, Pamela
- Author/Creator
- Miller, Jack W
- Description
- Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis.
- Description
- 8 page(s)
- Resource Type
- journal article
- Organisation
- Macquarie University. Australian School of Advanced Medicine
- Identifier
- http://hdl.handle.net/1959.14/343716
- Identifier
- mq:38221
- Identifier
- ISSN:0896-6273
- Identifier
- mq-rm-2013011162
- Identifier
- mq_res-ext-wos344167900011
- Language
- eng
- Reviewed
Macquarie University ResearchOnline
