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J-GLOBAL ID：201802237224799200   整理番号：18A0618310

ゲノムワイド解析新しいALS遺伝子としてKIF5Aを同定する【Powered by NICT】

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

著者 (120件)： Nicolas Aude (Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  Kenna Kevin P. (Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA) ,  Renton Alan E. (Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  Renton Alan E. (Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Renton Alan E. (Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA) ,  Ticozzi Nicola (Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy) ,  Ticozzi Nicola (Department of Pathophysiology and Transplantation, “Dino Ferrari” Center - Universita degli Studi di Milano, Milan 20122, Italy) ,  Faghri Faraz (Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  Faghri Faraz (Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA) ,  Chia Ruth (Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  Dominov Janice A. (Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA) ,  Kenna Brendan J. (Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA) ,  Nalls Mike A. (Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  Nalls Mike A. (Data Tecnica International, Glen Echo, MD, USA) ,  Keagle Pamela (Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA) ,  Rivera Alberto M. (Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  van Rheenen Wouter (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands) ,  Murphy Natalie A. (Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  van Vugt Joke J.F.A. (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands) ,  Geiger Joshua T. (Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA) ,  Van der Spek Rick A. (Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands) ,  Pliner Hannah A. (Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  Shankaracharya (Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA) ,  Smith Bradley N. (Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King’s College London, London SE5 9RS, UK) ,  Marangi Giuseppe (Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  Marangi Giuseppe (Institute of Genomic Medicine, Catholic University, Roma, Italy) ,  Topp Simon D. (Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King’s College London, London SE5 9RS, UK) ,  Abramzon Yevgeniya (Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  Abramzon Yevgeniya (Sobell Department of Motor Neuroscience and Movement Disorders, University College London, Institute of Neurology, London, UK) ,  Gkazi Athina Soragia (Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King’s College London, London SE5 9RS, UK) ,  Eicher John D. (Genetics and Pharmacogenomics, MRL, Merck & Co., Inc., Boston, MA 02115, USA) ,  Kenna Aoife (Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA) ,  Mora Gabriele (ALS Center, Salvatore Maugeri Foundation, IRCCS, Mistretta, Messina, Italy) ,  Calvo Andrea (“Rita Levi Montalcini” Department of Neuroscience, University of Turin, Turin, Italy) ,  Mazzini Letizia (“Maggiore della Carita” University Hospital, Novara, Italy) ,  Riva Nilo (Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy) ,  Mandrioli Jessica (Department of Neuroscience, St. Agostino Estense Hospital, Azienda Ospedaliero Universitaria di Modena, Modena, Italy) ,  Caponnetto Claudia (Department of Neurosciences, Ophthalmology, Genetics, Rehabilitation, Maternal and Child Health, Ospedale Policlinico San Martino, Genoa, Italy) ,  Battistini Stefania (Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy) ,  Volanti Paolo (ALS Center, Salvatore Maugeri Foundation, IRCCS, Mistretta, Messina, Italy) ,  La Bella Vincenzo (ALS Clinical Research Center, University of Palermo, Palermo, Italy) ,  Conforti Francesca L. (Institute of Neurological Sciences, National Research Council, Mangone, Cosenza, Italy) ,  Borghero Giuseppe (Department of Neurology, Azienda Universitario Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy) ,  Messina Sonia (Department of Clinical and Experimental Medicine, University of Messina and Nemo Sud Clinical Center for Neuromuscular Diseases, Aurora Foundation, Messina, Italy) ,  Simone Isabella L. (Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy) ,  Trojsi Francesca (Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania “Luigi Vanvitelli,” Naples, Italy) ,  Salvi Fabrizio (“Il Bene” Center for Immunological and Rare Neurological Diseases at Bellaria Hospital, IRCCS, Istituto delle Scienze Neurologiche, Bologna, Italy) ,  Logullo Francesco O. (Neurological Clinic, Marche Polytechnic University, Ancona, Italy) ,  D’Alfonso Sandra (Department of Health Sciences, University of Eastern Piedmont, Novara, Italy) ,  Corrado Lucia (Department of Health Sciences, University of Eastern Piedmont, Novara, Italy) ,  Capasso Margherita (Department of Neurology, University of Chieti, Chieti, Italy) ,  Ferrucci Luigi (Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA) ,  Moreno Cristiane de Araujo Martins (Department of Neurology, Columbia University, New York, NY 10032, USA) ,  Kamalakaran Sitharthan (Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA) ,  Goldstein David B. (Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA) ,  Gitler Aaron D. (Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA) ,  Harris Tim (Bioverativ, 225 2nd Avenue, Waltham, MA 02145, USA) ,  Myers Richard M. (HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA) ,  Phatnani Hemali (Center for Genomics of Neurodegenerative Diseases (CGND), New York Genome Center, New York, NY, USA) ,  Musunuri Rajeeva Lochan (Computational Biology, New York Genome Center, New York, NY, USA) ,  Evani Uday Shankar (Computational Biology, New York Genome Center, New York, NY, USA) ,  Abhyankar Avinash (Computational Biology, New York Genome Center, New York, NY, USA) ,  Zody Michael C. (Computational Biology, New York Genome Center, New York, NY, USA) ,  Kaye Julia (Gladstone Institute of Neurological Disease, San Francisco, CA, USA) ,  Finkbeiner Steven (Gladstone Institute of Neurological Disease, San Francisco, CA, USA) ,  Finkbeiner Steven (Departments of Neurology and Physiology, University of California, San Francisco, San Francisco, CA, USA) ,  Wyman Stacia K. (Gladstone Institute of Neurological Disease, San Francisco, CA, USA) ,  LeNail Alex (Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA) ,  Lima Leandro (Gladstone Institute of Neurological Disease, San Francisco, CA, USA) ,  Fraenkel Ernest (Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA) ,  Fraenkel Ernest (Broad Institute, 415 Main Street, Cambridge, MA 02142, USA) ,  Svendsen Clive N. (Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA) ,  Svendsen Clive N. (Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA) ,  Thompson Leslie M. (Department of Neurobiology and Behavior, Institute of Memory Impairment and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA) ,  Thompson Leslie M. (Department of Psychiatry and Human Behavior, Institute of Memory Impairment and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA) ,  Van Eyk Jennifer E. (The Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA) ,  Berry James D. (Harvard Medical School, Department of Neurology, Massachusetts General Hospital (MGH), Boston, MA, USA) ,  Berry James D. (Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, USA) ,  Miller Timothy M. (Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA) ,  Kolb Stephen J. (Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA) ,  Cudkowicz Merit (Harvard Medical School, Department of Neurology, Massachusetts General Hospital (MGH), Boston, MA, USA) ,  Cudkowicz Merit (Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, USA) ,  Baxi Emily (Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA) ,  Benatar Michael (Department of Neurology, University of Miami, Miami, FL 33136, USA) ,  Taylor J. Paul (Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA) ,  Taylor J. Paul (Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA) ,  Rampersaud Evadnie (Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA) ,  Wu Gang (Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA) ,  Wuu Joanne (Department of Neurology, University of Miami, Miami, FL 33136, USA) ,  Lauria Giuseppe (3rd Neurology Unit, Motor Neuron Diseases Center, Fondazione IRCCS Istituto Neurologico “Carlo Besta,” and Department of Biomedical and Clinical Sciences “Luigi Sacco,” University of Milan, Milan, Italy) ,  Verde Federico (Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy) ,  Fogh Isabella (Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy) ,  Fogh Isabella (Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King’s College London, London SE5 9RS, UK) ,  Tiloca Cinzia (Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy) ,  Comi Giacomo P. (Neurology Unit, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) ,  Soraru Gianni ,  Cereda Cristina ,  Corcia Philippe ,  Laaksovirta Hannu ,  Myllykangas Liisa ,  Jansson Lilja ,  Valori Miko ,  Ealing John ,  Hamdalla Hisham ,  Rollinson Sara ,  Pickering-Brown Stuart ,  Orrell Richard W. ,  Sidle Katie C. ,  Malaspina Andrea ,  Hardy John ,  Singleton Andrew B. (Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  Johnson Janel O. (Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA) ,  Arepalli Sampath ,  Sapp Peter C. (Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA) ,  McKenna-Yasek Diane (Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA) ,  Polak Meraida ,  Asress Seneshaw ,  Al-Sarraj Safa (Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King’s College London, London SE5 9RS, UK) ,  King Andrew (Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King’s College London, London SE5 9RS, UK) ,  Troakes Claire (Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King’s College London, London SE5 9RS, UK)
資料名： Neuron  (Neuron)
巻： 97  号： 6  ページ： 1268-1283.e6  発行年： 2018年 
JST資料番号： T0649A  ISSN： 0896-6273  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： ALSに関連する新規遺伝子を同定するために,著者らは研究の二系統を行った。20,806ALS症例および59,804人の対照を比較ゲノムワイド関連研究を行った。独立,1,138指標家族性ALS症例と19,494の対照を比較した稀な変異型負荷解析を行った。両手法により,ALSに関連する新規遺伝子であるキネシンファミリーメンバー5A(KIF5A)を同定した。興味深いことに,主にKIF5AのN末端モータードメインにおける突然変異は二種類の神経変性疾患:遺伝性痙性対麻痺(SPG10)およびシャルコー・マリー・トゥース2型(CMT2)の原因。とは対照的に,ALS関連変異は主にC末端カーゴ結合尾部ドメインに位置していると機能喪失変異を有する患者は,典型的なALS症例と比較して拡張された生存率を示した。まとめると,これらの結果はKIF5Aの変異に起因する表現型スペクトルを広げ,ALSの病因における細胞骨格欠陥の役割を強化する。Copyright 2018 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【Powered by NICT】

シソーラス用語： 突然変異 ,  貨物 ,  表現型 ,  スペクトル ,  生存率 ,  変異 ,  *遺伝子 ,  患者 ,  病因 ,  細胞骨格
準シソーラス用語： C末端 ,  遺伝性痙性対麻痺 ,  神経変性疾患 ,  アミノ末端 ,  比較ゲノミクス , 【Automatic Indexing@JST】

著者キーワード (7件)： ALS ,  KIF5A ,  GWAS ,  WES ,  WGS ,  貨物 ,  軸索輸送

分類 (2件)： 末梢神経系  (EJ12020U) ,  神経の基礎医学  (GN01020W)

タイトルに関連する用語 (5件)： ゲノム ,  解析 ,  ALS ,  遺伝子 ,  同定