Elucidation of molecular pathogenesis of amyotrophic lateral sclerosis based on genome analysis

• Project/Area Number: 23500433
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: IIDA ARITOSHI 独立行政法人理化学研究所, 統合生命医科学研究センター, 上級研究員 (10277585)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ゲノム解析 / 筋萎縮性側索硬化症 / 感受性遺伝子 / 国際情報交換 / ゲノムワイド関連解析 / ALS

Research Abstract

I employed several genetic approaches to understand the molecular pathogenesis of amyotrophic lateral sclerosis (ALS) more precisely. I identified two proteins (Z512BP-1 and Z512BP-2) as binding partners of ZNF512B. Case control association study showed that a SNP in Z512BP-1 is highly associated with susceptibility to ALS. In addition, I performed genome wide association studies (GWAS) and finally identified a total of 33 SNPs highly associated with ALS susceptibility. The associations between these SNPs and ALS require confirmation in further replication studies.

Research Products

• [Journal Article] ZNF512B gene is a prognostic factor in patients with amyotrophic lateral sclerosis (2013)
  • Author(s): Tetsuka S, Morita M, Iida A, Uehara R, Ikegawa S, and Nakano I
  • Journal Title: Journal of Neurological Sciences Volume: 324 Pages: 163-166
  • Peer Reviewed
• [Journal Article] ZNF512B gene is a prognostic factor in patients with amyotrophic lateral sclerosis. (2013)
  • Author(s): Tetsuka S, Morita M, Iida A, Uehara R, Ikegawa S, and Nakano I.
  • Journal Title: Journal of the Neurological Sciences Volume: 324 Issue: 1-2 Pages: 163-166
  • DOI: 10.1016/j.jns.2012.10.029
  • Peer Reviewed
• [Journal Article] Novel deletion mutations of OPTN in amyotrophic lateral sclerosis in Japanese. (2012)
  • Author(s): Iida A, Hosono N, Sano M, Kamei T, Oshima S, Tokuda T, Nakajima M, Kubo M, Nakamura Y, and Ikegawa S.
  • Journal Title: Neurobiology of Aging Volume: 33 Issue: 8 Pages: 1843.e19-1843.e24
  • DOI: 10.1016/j.neurobiolaging.2011.12.037
  • Peer Reviewed
• [Journal Article] Large-scale screening of TARDBP mutation in amyotrophic lateral sclerosis in Japanese (2012)
  • Author(s): Iida A, Kamei T, Sano M, Oshima S, Tokuda T, Nakamura Y, and Ikegawa S
  • Journal Title: Neurobiology of Aging Volume: 33 Pages: 786-790
  • Peer Reviewed
• [Journal Article] Optineurin mutations in Japanese amyotrophic lateral sclerosis (2012)
  • Author(s): Iida A, Hosono N, Sano M, Kamei T, Oshima S, Tokuda T, Kubo M, Nakamura Y, and Ikegawa S
  • Journal Title: Journal of Neurology, Neurosurgery & Psychiatry Volume: 83 Pages: 233-235
  • Peer Reviewed
• [Journal Article] Optineurin mutations in Japanese amyotrophic lateral sclerosis. (2012)
  • Author(s): Iida A, Hosono N, Sano M, Kamei T, Oshima S, Tokuda T, Kubo M, Nakamura Y, and Ikegawa S.
  • Journal Title: Journal of Neurology, Neurosurgery, and Psychiatry Volume: 83 Issue: 2 Pages: 233-235
  • DOI: 10.1136/jnnp.2010.234963
  • Peer Reviewed
• [Journal Article] A functional variant in ZNF512B is associated with susceptibility to amyotrophic lateral sclerosis in Japanese (2011)
  • Author(s): Iida A, Takahashi A, Kubo M, Saito S, Hosono N, Ohnishi Y, Kiyotani K, Mushiroda T, Nakajima M, Ozaki K, Tanaka T, Tsunoda T, Oshima S, Sano M, Kamei T, Tokuda T, Aoki M, Hasegawa K, Mizoguchi K, Morita M, Takahashi Y, Katsuno M, Atsuta N, Watanabe H, Tanaka F, Kaji R, Nakano I, Kamatani N, Tsuji S, Sobue G, Nakamura Y, and Ikegawa S
  • Journal Title: Human Molecular Genetics Volume: 20 Pages: 3684-3692
  • Peer Reviewed
• [Journal Article] Replication analysis of SNPs on 9p21.2 and 19p13.3 with amyotrophic lateral sclerosis in East Asians (2011)
  • Author(s): Iida A, Takahashi A, Deng M, Zhang Y, Wang J, Atsuta N, Tanaka F, Kamei T, Sano M, Oshima S, Tokuda T, Morita M, Akimoto C, Nakajima M, Kubo M, Kamatani N, Nakano I, Sobue G, Nakamura Y, Fan D, and Ikegawa S
  • Journal Title: Neurobiology of Aging Volume: 32 Issue: 4 Pages: 757.e13-757.e14
  • DOI: 10.1016/j.neurobiolaging.2010.12.011
  • Peer Reviewed
• [Journal Article] A functional variant in ZNF512B is associated with susceptibility to amyotrophic lateral sclerosis in Japanese. (2011)
  • Author(s): Iida A
  • Journal Title: Hum Mol Genet Volume: 20 Issue: 18 Pages: 3684-3692
  • DOI: 10.1093/hmg/ddr268
  • Peer Reviewed
• [Presentation] ZNF512B gene serves as prognostic factor in patients with amyotrophic lateral sclerosis (2012)
  • Author(s): Tetsuka S, Morita M, Iida A, Ikegawa S, and Nakano I
  • Organizer: 23rd International Symposium on ALS/MND
  • Place of Presentation: Chicago, USA
  • Year and Date: 2012-12-06
• [Presentation] 筋萎縮性側索硬化症におけるoptineurin遺伝子の欠失 (2012)
  • Author(s): 飯田有俊, 細野直哉, 佐野元規, 亀井徹正, 大嶋秀一, 徳田虎雄, 中島正宏, 久保充明, 中村祐輔, 池川志郎
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 新宿, 日本
  • Year and Date: 2012-10-27
• [Presentation] 当院におけるZNF512B 遺伝子を持つALS 患者についての検討 (2012)
  • Author(s): 手塚修一, 森田光哉, 飯田有俊, 池川志郎, 中村祐輔, 中野今冶
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京, 日本
  • Year and Date: 2012-05-25
• [Presentation] 新規ALS 感受性遺伝子ALSC1 は, TGF-β シグナルのポジティブレギュレーターである (2011)
  • Author(s): 飯田有俊, 田中章景, 中村祐輔, 祖父江元, 池川志郎
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都, 日本
  • Year and Date: 2011-09-23
• [Presentation] 大規模ゲノム関連解析を用いた新規ALS感受性遺伝子の同定 (2011)
  • Author(s): 飯田有俊, 高橋篤, 久保充明, 亀井徹正, 佐野元規, 大嶋秀一, 徳田虎雄, 青木正志, 梶龍兒, 中野今治, 辻省次, 祖父江元, 中村祐輔, 池川志郎
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋, 日本
  • Year and Date: 2011-05-18
• [Presentation] 大規模ゲノム関連解析による新規ALS易罹 患性遺伝子ZNF512Bの 同定 (2011)
  • Author(s): 飯田有俊、中村祐輔, 池川志郎
  • Organizer: 「病態に根ざしたALSの新規治療法開発班」平成23年度ワークショップ(招待講演)
  • Place of Presentation: JA共済ビル（東京）
• [Presentation] 新規ALS感受性遺伝子ALSC1は、TGF-βシグナルのポジティブレギュレーターである (2011)
  • Author(s): 飯田有俊、田中章景、中村祐輔、祖父江元、池川志郎
  • Organizer: 第84回 日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] 大規模ゲノム関連解析を用いた 新規ALS 感受性遺伝子の同定 (2011)
  • Author(s): 飯田有俊、高橋篤、久保充明、亀井徹正、佐野元規、大嶋秀一、徳田虎雄、青木正志、梶龍兒、中野今治、辻省次、祖父江元、中村祐輔、池川志郎
  • Organizer: 第52回 日本神経学会学術大会
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Presentation] 筋萎縮性側索硬化症におけるoptineurin遺伝子の欠失
  • Author(s): 飯田有俊、細野直哉、佐野元規、亀井徹正、大嶋秀一、徳田虎雄、中島正宏、久保充明、中村祐輔、池川志郎
  • Organizer: 日本人類遺伝学会 第57回大会
  • Place of Presentation: 京王プラザホテル (東京）
• [Presentation] ZNF512B genen serves as a prognostic factor in patients with amyotrophic lateral sclerosis
  • Author(s): Tetsuka S, Morita M, Iida A, Ikegawa S, and Nakano I.
  • Organizer: 23rd International Symposium on ALS/MND
  • Place of Presentation: シェラトン ホテル シカゴ （米国）
• [Presentation] 当院におけるZNF512B遺伝子を持つALS患者についての検討
  • Author(s): 手塚修一、森田光哉、飯田有俊、池川志郎、中村祐輔、中野今冶
  • Organizer: 第53回 日本神経学会学術大会
  • Place of Presentation: 東京国際フォーラム（東京）
• [Patent(Industrial Property Rights)] ZNF512B 遺伝子の一塩基多型に基づく筋萎縮性側索硬化症の検査方法 (2009)
  • Inventor(s): 飯田有俊, 池川志郎, 中村祐輔, 祖父江元
  • Industrial Property Rights Holder: 理化学研究所, 国立大学法人名古屋大学, 有限責任中間法人徳洲会
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2009-206279
  • Filing Date: 2009-09-07