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Development of a comprehensive molecular diagnosis system for neurological diseases based on DNAmicroarrays.

Research Project

Project/Area Number 18209032
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionThe University of Tokyo

Principal Investigator

TSUJI Shoji  The University of Tokyo, Faculty of Medicine, Neurology, Professor (70150612)

Co-Investigator(Kenkyū-buntansha) GOTO Jun  The University of Tokyo, Faculty of Medicine, Neurology, Lecturer (10211252)
TAKAHASHI Yuji  The University of Tokyo, Faculty of Medicine, Neurology, Research Associate (00372392)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥47,580,000 (Direct Cost: ¥36,600,000、Indirect Cost: ¥10,980,000)
Fiscal Year 2007: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2006: ¥31,070,000 (Direct Cost: ¥23,900,000、Indirect Cost: ¥7,170,000)
KeywordsMicroarray / genome / nervous disease / gene / biotechnology
Research Abstract

This project focused on development of a comprehensive molecular diagnosis system for neurological diseases based on DNA microarrays. lb accomplish this aim, we have developed 1. DNA microarray-based comprehensive resequencing system, and 2. high density array-CGH system to accomplish detection of deletions/multiplications and identification of breakpoints We have developed DNA microarray-based resequencing system for amyotrophic lateral sclerosis, Parkinson disease, adrenoleukodystrophy, and familial spastic paraplegia. With this system, we have shown DNA microarray-based resequencing system is highly efficient to identify point mutations. Although DNA resequencing microarrays are quite effective for identification of point mutations, they are inefficient for detection of deletions or multiplication. To overcome this problem, we have newly developed high density array-CGH system to allow detection of deletions/multiplications of PARK2 gene with the resolution of 100-200bp. Since the resolution is extremely high, the junction segments can be easily amplified by PCR employing PCR primers flanking the deletions/multiplications, allowing identification of breakpoints of deletions/multiplications on nucleotide levels. We applied this system for investigation of the mechanisms of deletions/multiplications of PARK2 in patients with autosomal recessive juvenile Parkinsonism (AR JP). We have determined deletions/multiplications of 299 alleles. The breakpoints clustered in a narrow region of PARK2 that coincides with the center of FRA6E (common fragile site). Indeed analysis of 120 cancer cell lines allowed 31 deletions/multiplications and the distribution is quite similar to that found in ARJP Taken together these studies demonstrate that common mechanisms underlie the of deletions/multiplications in the germline mutations (AR-JP) as well as somatic mutations (cancer cell lines).

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (21 results)

All 2008 2007 Other

All Journal Article (9 results) (of which Peer Reviewed: 6 results) Presentation (12 results)

  • [Journal Article] Familial cases presenting very early onset autosomal dominant Alzheimer's disease with I143T in presenilin-1 gene: Implication for genotype-phenotype correlation.2008

    • Author(s)
      Arai, N, Kishino, A, Takahashi, Y, Morita1, D, Nakamura, K, Yokoyama, T, Watanabe, T, Ida, M., Goto, J, Tsuji, S.
    • Journal Title

      Neurogeneticcs 9

      Pages: 65-67

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Familial cases presenting very early onset autosomal dominant Alzheimer's disease with I143T in presenilin-1 gene : Implication for genotype-phenotype correlation2008

    • Author(s)
      Arai, N, Kishino, A, Takahashi, Y, Morital, D, Nakamura, K, Yokoyama, T, Watanabe, T, Ida, M., Goto, J, Tsuji, S.
    • Journal Title

      Neurogenetics 9

      Pages: 65-67

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Familial cases presenting very early onset autosomaldominant Aizheimer's disease with I143T in presenilin-1 gene: Implication for genotype-phenotype correlation2008

    • Author(s)
      Arai, N, Kishino, A, Takahashi, Y, Morital, D, Nakamura, K, Yokoyama, T, Watanabe, T, Ida, M., Goto, J, Tsuji, S.
    • Journal Title

      Neurogeneticcs

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of high-throughput microarray-based resequencing system for neurological disorders and its app-lication to molecular genetics of amyotrophic lateral sclerosis2008

    • Author(s)
      347. Takahashi, Y, Seki, N, Ishiura, H, Mitsui, J, Matsukawa, T, Kishino, A, Onodera, O, Aoki, M, Shimozawa, M, Murayama, S, Itoyama, Y, Suzuki, Y, Sobue, S, Nishizawa, M, Goto, J
    • Journal Title

      Archives of Neurology

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] otal deletion and a missensemutation of ITPRl inJapanese SCA15 families2008

    • Author(s)
      348. Hara, K, Shiga, A, Nozaki, H, Mitsui, J, Takahashi, Y, Ishiguro, H, Yomono, H, Kurisaki, H, GotomJ, Ikeuchi, T, Tsuji, S, Nishizawa, M, and Onodera, O.
    • Journal Title

      Neurology

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of high-throughput microarray-based resequencing system for neurological disorders and its application to molecular genetics of amyotrophic lateral sclerosis.

    • Author(s)
      Takahashi, Y, Seki, N, Ishiura, H, Mitsui, J, Matsukawa, T, Kishino, A, Onodera, O, Aoki, M, Shimozawa, M, Murayama, S, Itoyama, Y, Suzuki, Y, Sobue, S, Nishizawa, M, Goto, J
    • Journal Title

      Archives of Neurology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Total deletion and a missense mutatio of ITPR1 in Japanese SCA15 families.

    • Author(s)
      Hara, K, Shiga, A, Nozaki, H, Mitsui, J, Takahashi, Y, Ishiguro, H, Yomono, H, Kurisaki, H, Gotom J, Ikeuchi, T, Tsuji, S, Nishizawa, M, and Onodera, O.
    • Journal Title

      Neurology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Development of high-throughput microarray-based resequencing system for neurological disorders and its application to molecular genetics of amyotrophic lateral sclerosis

    • Author(s)
      Takahashi, Y, Seki, N, Ishiura, H, Mitsui, J, Matsukawa, T, Kishino, A, Onodera, O, Aoki, M, Shimozawa, M, Murayama, S, Itoyama, Y, Suzuki, Y, Sobue, S, Nishizawa, M, Goto, J., Tsuji, S.
    • Journal Title

      Archives of Neurology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 「研究成果報告書概要(欧文)」より

    • Author(s)
      Hara, K, Shiga, A, Nozaki, H, Mitsui, J, Takahashi, Y, Ishiguro, H, Yomono, H, Kurisaki, H, Gotom J, Ikeuchi, T, Tsuji, S, Nishizawa, M, Onodera, O.
    • Journal Title

      Neurology (in press)

    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Identification of novel heterozygous nonsynonymous variations of (ANG), VEGF and ALS2 in sporadic ALS (SALS) patients and its implication in the genetic risks of SALS.2007

    • Author(s)
      Y. Takahashi, J. Goto, S. Tsuji.
    • Organizer
      57th Annual Meeting of American Society of Human Genetics
    • Place of Presentation
      San Diego, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Comprehensive analysis of breakpoints of PARK2 rearrangements in patients with autosomal recessive juvenile parkinsonism (AR-JP)employing a high-density tiling array-based comparative genomic hybridization (array-CGH) system.2007

    • Author(s)
      J. Mitsui, Y. Takahashi1, H. Tomiyama, H. Yoshino, J. Goto, Y. Mizuno, N. Hattori, S. Tsuji1.
    • Organizer
      57th Annual Meeting of American Society of Human Genetics
    • Place of Presentation
      San Diego, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A comprehensive mutational analysis system using resequencing microarray delineates molecular epidemiology of hereditary spastic paraplegias in the Japanese population.2007

    • Author(s)
      H. Ishiura, Y. Takahashi, J. Goto, S. Tsuji.
    • Organizer
      57th Annual Meeting of American Society of Human Genetics
    • Place of Presentation
      San Diego, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Genome-wide association studies on Multiple system atrophy (MSA).2007

    • Author(s)
      Y. Nakahara1, Y. Momose Y. Takahashi, J. Goto1, S. Tsuji
    • Organizer
      57th Annual Meeting of American Society of Human Genetics
    • Place of Presentation
      San Diego, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Identification of novel heterozygous nonsynonymous variations of (ANG), VEGF and ALS2 in sporadic ALS (SALS) patients and its implication in the genetic risks of SALS2007

    • Author(s)
      Y. Takahashi, J. Goto, S. Tsuji
    • Organizer
      57th Annual Meeting of American Society of Human Genetics
    • Place of Presentation
      San Diego, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Tsujil. Comprehensive analysis of breakpoints of PARK2 rearrangements in patients with autosomal recessive juvenile parkinsonism (AR-JP) employing a high-density tiling array-based comparative genomic hybridization (array-CGH) system2007

    • Author(s)
      J. Mitsui, Y. Takahashil, H. Tomiyama, H. Yoshino, J. Goto, Y. Mizuno, N. Hattori, S.
    • Organizer
      57th Annual Meeting of American Society of Human Genetics
    • Place of Presentation
      San Diego, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] comprehensive mutational analysis system using resequencing microarray delineates molecular epidemiology of hereditary spastic paraplegias in the Japanese population2007

    • Author(s)
      H. Ishiura, Y. Takahashi, J. Goto, S. Tsuji. A.
    • Organizer
      57th Annual Meeting of American Society of Human Genetics
    • Place of Presentation
      San Diego, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Genome-wide association studies on Multiple system atrophy (MSA)2007

    • Author(s)
      Y. Nakaharal, Y. Momose Y. Takahashi, J. Gotol, S. Tsuji
    • Organizer
      57th Annual Meeting of American Society of Human Genetics
    • Place of Presentation
      San Diego, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Identification of novel heterozygous nonsynonymous variations of(ANG),VEGF and ALS2 in SporadicALS(SALS)patients and its imphcation in the genetic risks of SALS2007

    • Author(s)
      Y. Takahashi, J, Goto, S. Tsuji,
    • Organizer
      57th Annual Meeting of American Scoeity of Human Genetics
    • Place of Presentation
      San Diego,USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Genome-wide association stμdies on MUItiple system atrophy(MSA)2007

    • Author(s)
      Y. Nakaharal, Y. Momose Y. Takahashi, J. Gotol, S. Tsuji
    • Organizer
      57th Annual Meeting of American Scoeity of Human Genetics
    • Place of Presentation
      San Diego,USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Japan A comprehensive mutational analysis sysbem using resequencing microarray dekmeates molecular epidemiology of hererhtary spastic paraplegias hl the Japanese population2007

    • Author(s)
      H. lshiura, Y. Takahashi, J. Goto, S. Tsuji
    • Organizer
      57th Annual Meeting of American Scoeity of Human Genetics
    • Place of Presentation
      San Diego,USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Comprehensive analysis of breakpoints of PARK2 rearrangements in patients with autosomal recessive juvenile parkinsonism(AR-JP)employing a high-density tiling array-based comparative genomic hybri(lization(array-CGH)system2007

    • Author(s)
      J. Mitsui, Y. Takahashil, H. Tomiyama, H. Yoshino, J. Goto, Y. Mizuno, N. Hattori, S. Tsujil
    • Organizer
      57th Annual Meeting of American Scoeity of Human Genetics
    • Place of Presentation
      San Diego,USA
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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