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Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways.
Cirulli, Elizabeth T; Lasseigne, Brittany N; Petrovski, Slavé; Sapp, Peter C; Dion, Patrick A; Leblond, Claire S; Couthouis, Julien; Lu, Yi-Fan; Wang, Quanli; Krueger, Brian J; Ren, Zhong; Keebler, Jonathan; Han, Yujun; Levy, Shawn E; Boone, Braden E; Wimbish, Jack R; Waite, Lindsay L; Jones, Angela L; Carulli, John P; Day-Williams, Aaron G; Staropoli, John F; Xin, Winnie W; Chesi, Alessandra; Raphael, Alya R; McKenna-Yasek, Diane; Cady, Janet; Vianney de Jong, J M B; Kenna, Kevin P; Smith, Bradley N; Topp, Simon; Miller, Jack; Gkazi, Athina; Al-Chalabi, Ammar; van den Berg, Leonard H; Veldink, Jan; Silani, Vincenzo; Ticozzi, Nicola; Shaw, Christopher E; Baloh, Robert H; Appel, Stanley; Simpson, Ericka; Lagier-Tourenne, Clotilde; Pulst, Stefan M; Gibson, Summer; Trojanowski, John Q; Elman, Lauren; McCluskey, Leo; Grossman, Murray; Shneider, Neil A; Chung, Wendy K.
Afiliação
  • Cirulli ET; Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC 27708, USA.
  • Lasseigne BN; HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
  • Petrovski S; Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
  • Sapp PC; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Dion PA; Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2B4, Canada.
  • Leblond CS; Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2B4, Canada.
  • Couthouis J; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Lu YF; Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
  • Wang Q; Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
  • Krueger BJ; Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
  • Ren Z; Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
  • Keebler J; Duke University School of Medicine, Durham, NC 27708, USA.
  • Han Y; Duke University School of Medicine, Durham, NC 27708, USA.
  • Levy SE; HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
  • Boone BE; HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
  • Wimbish JR; HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
  • Waite LL; HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
  • Jones AL; HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
  • Carulli JP; Biogen Idec, Cambridge, MA 02142, USA.
  • Day-Williams AG; Biogen Idec, Cambridge, MA 02142, USA.
  • Staropoli JF; Biogen Idec, Cambridge, MA 02142, USA.
  • Xin WW; Neurogenetics DNA Diagnostic Laboratory, Center for Human Genetics Research, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Chesi A; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Raphael AR; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • McKenna-Yasek D; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Cady J; Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Vianney de Jong JM; Department of Genome Analysis, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, Netherlands.
  • Kenna KP; Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Republic of Ireland.
  • Smith BN; Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London SE5 8AF, UK.
  • Topp S; Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London SE5 8AF, UK.
  • Miller J; Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London SE5 8AF, UK.
  • Gkazi A; Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London SE5 8AF, UK.
  • Al-Chalabi A; Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London SE5 8AF, UK.
  • van den Berg LH; Department of Neurology, Brain Center Rudolf Magnus, University Medical Centre Utrecht, 3508 GA Utrecht, Netherlands.
  • Veldink J; Department of Neurology, Brain Center Rudolf Magnus, University Medical Centre Utrecht, 3508 GA Utrecht, Netherlands.
  • Silani V; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan 20149, Italy, and Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan 20122, Italy.
  • Ticozzi N; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan 20149, Italy, and Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan 20122, Italy.
  • Shaw CE; Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London SE5 8AF, UK.
  • Baloh RH; Cedars Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Appel S; Houston Methodist Hospital, Houston, TX 77030, USA, and Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
  • Simpson E; Houston Methodist Hospital, Houston, TX 77030, USA, and Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
  • Lagier-Tourenne C; Ludwig Institute for Cancer Research and Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Pulst SM; Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
  • Gibson S; Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
  • Trojanowski JQ; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Elman L; Department of Neurology, Penn ALS Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • McCluskey L; Department of Neurology, Penn ALS Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Grossman M; Department of Neurology, Penn Frontotemporal Degeneration Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Shneider NA; Department of Neurology, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA.
  • Chung WK; Department of Pediatrics and Medicine, Columbia University, New York, NY 10032, USA.
Science ; 347(6229): 1436-41, 2015 Mar 27.
Article em En | MEDLINE | ID: mdl-25700176
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Autofagia / Proteínas Serina-Treonina Quinases / Predisposição Genética para Doença / Exoma / Esclerose Lateral Amiotrófica Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Autofagia / Proteínas Serina-Treonina Quinases / Predisposição Genética para Doença / Exoma / Esclerose Lateral Amiotrófica Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2015 Tipo de documento: Article