Study on aberrant splicings in dominant non-coding repeat expansion disorders

• Project/Area Number: 19590988
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Nagoya University
• Principal Investigator: MATSUURA Tohru Nagoya University, 大学院・医歯薬学総合研究科, 准教授 (90402560)
• Co-Investigator(Kenkyū-buntansha): OHNO Kinji 名古屋大学, 大学院・医学系研究科, 教授 (80397455)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 優性遺伝性非翻訳領域リピート病 / DM1 / スプライシング / RNA / 非翻訳リピート病 / myotonic dystrophy type 1(DM1) / 筋強直性ジストロフィー1型(DM1) / 遺伝子スプライシング異常 / Exonアレイ / 薬剤スクリーニング

Research Abstract

優性遺伝性非翻訳リピート病の主要な疾患である筋強直性ジストロフィー1型(DM1)の主な病態メカニズムは、伸長CUGを介した標的遺伝子スプライシング異常にある。Exonアレイを用いてDM1神経筋組織における、スプライシング異常遺伝子の網羅的な解析を行った。この中で抽出された3つのエクソンのスプライシング異常メカニズムと、その病態メカニズムを解析した。

Research Products

• [Journal Article] Spinocerebellar ataxia type 10 (2010)
  • Author(s): 松浦徹, 阿部康二
  • Journal Title: 神経内科 72 Pages: 159-164
• [Journal Article] SCA10. Clinical Neuroscience月刊 (2009)
  • Author(s): 松浦徹, 大野欽司
  • Journal Title: 臨床神経科学 27 Pages: 66-68
• [Journal Article] Alu-mediated acquisition of unstable ATTCT pentanucleotide repeats in the human ATXN10 gene. (2009)
  • Author(s): Kurosaki T, Matsuura T, Ohno K, Ueda S
  • Journal Title: Mol Biol Evol 26 Pages: 2573-2579
  • Peer Reviewed
• [Journal Article] Spinocerebellar ataxia type 31 is associated with "inserted" penta-nucleotide repeats containing (TGGAA)n. (2009)
  • Author(s): Sato N, Amino T, Kobayashi K, Asakawa S, Ishiguro T, Tsunemi T, Takahashi M, Matsuura T, et. al.
  • Journal Title: Am J Hum Genet 85 Pages: 544-557
  • Peer Reviewed
• [Journal Article] Ancestral Origin of the ATTCT Repeat Expansion in Spinocerebellar Ataxia Type 10 (SCA10). (2009)
  • Author(s): Almeida T, Alonso I, Martins S, Ramos EM, Azevedo L, Ohno K, Amorim A, Saraiva-Pereira ML, Jardim LB, Matsuura T, et. al.
  • Journal Title: PLoS One 4
  • Peer Reviewed
• [Journal Article] Tannic acid facilitates expression of the polypyrimidine tract binding protein and alleviates deleterious inclusion of CHRNA1 exon P3A due to an hnRNP H-disrupting mutation in congenital myasthenic syndrome. (2009)
  • Author(s): Bian Y, Masuda A, Matsuura T, Ito M, Okushin K, Engel AG, Ohno K
  • Journal Title: Hum Mol Genet 18 Pages: 1229-1237
  • Peer Reviewed
• [Journal Article] The ATTCT repeats of spinocerebellar ataxia type 10 display strong nucleosome assemblywhich is enhanced by repeat interruptions. (2009)
  • Author(s): Hagerman KA, Ruan H, Edamura KN, Matsuura T, et. al.
  • Journal Title: Gene 434 Pages: 29-34
  • Peer Reviewed
• [Journal Article] Tannic acid facilitates expression of the polypyrimidine tract binding protein and alleviates deleterious inclusion of CHRNA1 exon P3A due to an hnRNP H-disrupting mutation in congenital myasthenic syndrome (2009)
  • Author(s): Bian Y, Masuda A, Matsuura T, Ito M, Okushin K, Engel AG, Ohno K.
  • Journal Title: Human Molecular Genetics 18 Pages: 1229-1237
  • Peer Reviewed
• [Journal Article] 遺伝性脊髄小脳変性症 (2008)
  • Author(s): 松浦徹
  • Journal Title: Modern Physician 28 Pages: 1798-1802
• [Journal Article] 脊髄小脳失調症10型の分遺伝学的解析 (2008)
  • Author(s): 松浦徹
  • Journal Title: 臨床神経学 48 Pages: 1-10
• [Journal Article] Long-range PCR for the diagnosis of spinocerebellar ataxia type 10. (2008)
  • Author(s): Kurosaki T, *Matsuura T, Ohno K, Ueda S
  • Journal Title: Neurogenetics 9 Pages: 151-152
  • Peer Reviewed
• [Journal Article] Myotonic dystrophy type 2 in Japan: ancestral origin distinct from Caucasian families (2008)
  • Author(s): Saito T, Amakusa, Y, Kimura T, Yahara O, Aizawa H, Ikeda Y, Day JW, Ranum LPW, Ohno K, Matsuura T
  • Journal Title: Neurogenetics 9 Pages: 61-63
  • Peer Reviewed
• [Journal Article] HnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation disrupmyasthenic syndrome. (2008)
  • Author(s): Masuda A, Shen XM, Ito M, Matsuura T, Engel AG, Ohno K
  • Journal Title: Hum Mol Genet 17 Pages: 4022-4035
  • Peer Reviewed
• [Journal Article] HnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation disrupting its binding causes congenital myasthenic syndromes (2008)
  • Author(s): Masuda A, Shen XM, Ito M, Matsuura T, Engel AG, Ohno K.
  • Journal Title: Human Molecular Genetics 17 Pages: 4022-4035
  • Peer Reviewed
• [Journal Article] Human branch point consensus sequence is yUnAy (2008)
  • Author(s): Gao R, Masuda A, Matsuura T, Ohno K.
  • Journal Title: Nucleic Acids Research 36 Pages: 2257-2267
  • Peer Reviewed
• [Journal Article] Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities. (2007)
  • Author(s): Ichihara M, Murakumo Y, Masuda A, Matsuura T, Asai N, Jijiwa M, Ishida M, Shinmi J, Yatsuya H, Qiao S, Takahashi M, Ohno K
  • Journal Title: Nucleic Acids Res 35
  • Peer Reviewed
• [Journal Article] In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5' splice sites. (2007)
  • Author(s): Sahashi K, Masuda A, Matsuura T, Shinmi J, Zhang Z, Takeshima Y, Matsuo M, Sobue G, Ohno K
  • Journal Title: Nucleic Acids Res 35 Pages: 5995-6003
  • Peer Reviewed
• [Journal Article] In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5' splice sites (2007)
  • Author(s): Sahashi K, Masuda A, Matsuura T, et al.
  • Journal Title: Nucleic Acids Res 35 Pages: 5995-6003
  • Peer Reviewed
• [Journal Article] Thermodynamic instability of siRNA duplex is a prerequisite for depe ndable prediction of siRNA activities (2007)
  • Author(s): Ichihara M, Murakumo Y, Masuda A, Matsuura T, et al.
  • Journal Title: Nucleic Acids Res 35
  • Peer Reviewed
• [Journal Article] Instability of expanded CAG/CAA repeats in spinocerebellar ataxia type 17.
  • Author(s): Gao R, Matsuura T, Coolbaugh M, Zuhlke C, Nakamura K, Rasmussen A, SicilianMJ, et. al.
  • Journal Title: Eur J 16 Pages: 215-222
  • Peer Reviewed
• [Journal Article] Human branch point consensus sequeis yUnAy.
  • Author(s): Gao R, Masuda A, Matsuura T, Ohno K
  • Journal Title: Nucleic Acids 36 Pages: 2257-2267
  • Peer Reviewed
• [Presentation] Misregulation of diacylglycerol kinase eta (DGKη) splicing as a potential cause of neuropsychiatric symptoms in myotonic dystrophy type 1 (2009)
  • Author(s): Matsuura T
  • Organizer: 7thInternational Myotonic Dystrophy Consortium Meeting
  • Place of Presentation: Wurzburg, Germany
• [Presentation] 筋強直性ジストロフィー1型スプライシング異常の既認可薬による制御 (2009)
  • Author(s): 松浦徹
  • Organizer: 第18回日本人類遺伝学会総会
  • Place of Presentation: 東京
• [Presentation] 筋強直性ジストロフィー1型(DM1)の脳特異的スプライシング異常解析 (2009)
  • Author(s): 松浦徹
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
• [Presentation] Misregulation of diacylglycerol kinase et a(DGKη)splicing as a potential cause of neuropsychiatric symptoms in myotonic dystrophy type 1 (2009)
  • Author(s): Matsuura T, et al.
  • Organizer: 7th International Myotonic Dystrophy Consortium Meeting
  • Place of Presentation: Wurzburg, Germany
• [Presentation] 脊髄小脳失調症10型の分子遺伝学的解析 (2008)
  • Author(s): 松浦徹
  • Organizer: 第49回日本神経学会総会2007年度学会賞招待講演
  • Place of Presentation: 横浜
• [Presentation] Myotonic dystrophy type 2 in Japan: distinct ancestral origin from Caucasian families (2007)
  • Author(s): Matsuura T
  • Organizer: 6th international Myotonic Dystrophy Consortium Meeting
  • Place of Presentation: Milan, Italy
• [Presentation] 筋強直性ジストロフィー1型(DM1)の網羅的pre-mRNAスプライシング異常解析 (2007)
  • Author(s): 松浦徹
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋
• [Presentation] Comprehensive analysis of aberrantly spliced exons in myotonic dystrophy type 1 using Affymetrix Exon Array (2007)
  • Author(s): Yamashita Y, Matsuura T, Shinmi J, et al.
  • Organizer: American Society of Human Genetics
  • Place of Presentation: San Diego, CA
• [Remarks]
  • URL: http://www.okayama-u.ac.jp/user/med/shinkeinaika/index.htm
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/neurogenetics/
• [Remarks]
  • URL: http://www.okayama-u.ac.jp/user/med/shinkeinaika/index.htm
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/neurogenetics/