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Development of DNA microarray-based reseqeuncing system for neurological diseases.

Research Project

Project/Area Number 16209028
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, Professor, 医学部附属病院, 教授 (70150612)

Co-Investigator(Kenkyū-buntansha) GOTO Jun  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (10211252)
TAKAHASHI Yuji  The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (00372392)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥49,660,000 (Direct Cost: ¥38,200,000、Indirect Cost: ¥11,460,000)
Fiscal Year 2005: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2004: ¥31,070,000 (Direct Cost: ¥23,900,000、Indirect Cost: ¥7,170,000)
KeywordsParkinson disease / neurodegenerative diseases / DNA microarray / DNA chip / resequencing / disease-associated genes / PCR / molecular genetics / DNA microarray / DNA chip / 疾患関連遺伝子 / 分子遺伝学 / DNA micro array
Research Abstract

The purpose of this project is to develop a high throughput mutational analysis system for neurological diseases. The approach consists of 1.to develop microarray bases reseqeuncing of causative genes for neurological diseases. 2.application of comprehensive analysis of candidate genes for sporadic diseases. and 3.analysis of phenotypic variations bases on comprehensive mutational analysis. To accomplish, these aims, we have developed DNA microarrays for Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, adrenoleukodsytrophy, familial spastic paraplegia. We have confirmed that the sensitivity and specificity of DNA microarray-bases reseqeuncing are comparable to those based on dideoxynucleotide chain terminator method. We have applied DMA microarray-based reseqeuncing for comprehensive mutational analysis of causative genes for 43 patients with spastic paraplegia. We have identified 7 patients with SPG4 and a patient with SPG3A. Among the SPG4 patients, there are two sporadic cases, suggesting reduced penetrance of the mutations. Thus, we have demonstrated that the high throughput DNA microarray-based resegeuncing system is highly useful for molecular dissection of neurological diseases including Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, adrenoleukodsytrophy, familial spastic paraplegia

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (19 results)

All 2005 2004

All Journal Article (19 results)

  • [Journal Article] Polyglutamine represses cAMP-mediated transcription without aggregate formation.2005

    • Author(s)
      Takahashi T, Nozaki K, Tsuji S, Nishizawa M, Onodera O.
    • Journal Title

      Neuroreport 16(3)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interference with activity-dependent transcriptional activation of BDNF gene depending upon the expanded polyglutamines in neurons.2005

    • Author(s)
      Miyashita T, Tabuchi A, Fukuchi M, Hara D, Kisukeda T, Shimohata T, Tsuji S, Tsuda M
    • Journal Title

      Biochem Biophys Res Commun 333(4)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Spinocerebellar ataxia type 15.2005

    • Author(s)
      Gardner RJ, Knight MA, Hara K, Tsuji S, Forrest SM, Storey E.
    • Journal Title

      Cerebellum 4(1)

      Pages: 47-50

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family.2005

    • Author(s)
      Funayama M, Hasegawa K, Ohta E, Kawashima N, Komiyama M, Kowa H, Tsuji S, Obata F.
    • Journal Title

      Ann Neurol 57(6)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Interference of CREB-dependent transcriptional activation by expanded polyglutamine stretches - Augmentation of transcriptional Activation as a potential therapeutic strategy for polyglutamine disease/2005

    • Author(s)
      Shimohata M, Shimohata T, Igarashi S, Naruse S, Tsuji S
    • Journal Title

      J. Neurochem 93

      Pages: 654-663

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] O.Polyglutamine represses cAMP-responsive-element-mediated transcription without aggregate formation.2005

    • Author(s)
      Takahashi T, Nozaki K, Tsuji S, Nishizawa M, Onodera
    • Journal Title

      Neuroreport 16(3)

      Pages: 295-299

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interference with activity-dependent transcriptional activation of BDNF gene depending upon the expanded polyglutamines in neurons.2005

    • Author(s)
      Miyashita T, Tabuchi A, Fukuchi M, Hara D, Kisukeda T, Shimohata T, Tsuji S, Tsuda M.
    • Journal Title

      Biochem Biophys Res Commun 333(4)

      Pages: 1241-1248

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Spinocerebellar ataxia type 15.2005

    • Author(s)
      Gardner RJ, Knight MA, Hara K, Tsuji S, Forrest SM, Storey E.
    • Journal Title

      Cerebellum 5;4(1)

      Pages: 47-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interference of CREB-dependent transcriptional activation by expanded polyglutamine stretches-Augmentation of transcriptional activation as a potential therapeutic strategy for polyglutamine diseases/2005

    • Author(s)
      Shimohata, M, Shimohata, T, Igarashi, S, Naruse, S, Tsujil, S
    • Journal Title

      J.Neurochem 93

      Pages: 654-663

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polyglutamine represses cAMP-responsive-element-mediated transcription without aggregate formation.2005

    • Author(s)
      Takahashi T, Nozaki K, Tsuji S, Nishizawa M, Onodera O.
    • Journal Title

      Neuroreport 16(3)

      Pages: 295-299

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Interference of CREB-dependent transcriptional activation by expanded polyglutamine stretches - Augmentation of transcriptional activation as a potential therapeutic strategy for polyglutamine diseases2005

    • Author(s)
      Shimohata, M, Shimohata, T, Igarashi, S, Naruse, S, Tsuji, S.
    • Journal Title

      J.Neurochem 93

      Pages: 654-663

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Adult-onset leukocncephalopathy with vanishing whitte matter with a missense mutation in EIF2B5.2004

    • Author(s)
      Ohtake H, Shimohata, T, Terajima, K, Kimura, T, Jo, R, Kaseda, R, Iizuka, O, Takano, M, Akaiwa, Y, Goto, H, Kobayashi, H, Sugai, T, Muratake, T, Hosoki, T, Shioiri, T, Okamoto, K, Onodera, O, Tanaka, K, Someya, T, Nakada, T, Tsuji, S
    • Journal Title

      Neurology 62

      Pages: 1601-3

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adult-onset leukoencephalopathy with vanishing white matter with a missense mutation in EIF2B52004

    • Author(s)
      Ohtake H, Shimohata, T., Terajima, K., Kimura, T., Jo, R., Kaseda, R., Iizuka, O., Takano, M., Akaiwa, Y., Goto, H., Kobayashi, H., Sugai, T., Muratake, T., Hosoki, T., Shioiri, T., Okamoto, K., Onodera, O., Tanaka, K., Someya, T., Nakada, T., Tsuji, S.
    • Journal Title

      Neurology 62

      Pages: 1601-1603

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Five year follow up of a patient with spinal and bulbar muscular atrophy treated with leuprorelin.2004

    • Author(s)
      Shimohata T, Kimura T, Nishizawa M, Onodera O, Tsuji S.
    • Journal Title

      J Neurol Neurosurg Psychiatry 75

      Pages: 1206-1207

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Aprataxin, the causative protein for early-onset ataxia with ocular motor apraxia and hypoalbuminemia, is a nuclear protein with a potential role as a nucleotide repair protein.2004

    • Author(s)
      Sano, Y., Date, H, Igarashi, S, Onodera, O, Oyake, M, Takahashi, T, Hayashi, S, Morimatsu, M, Takahashi, H, Makifuchi, T, Fukuhara, N, Tsuji, S.
    • Journal Title

      Ann.Neurol. 55

      Pages: 241-249

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Japanese SCA families with a distinct phenotype linked to a locus overlapping with SCA15 locus2004

    • Author(s)
      Hara, K, Fukushima, T, Suzuki, T, Shimohata, T, Oyake, M, Ishiguro, H, Hirota, K, Miyashita, A, Kuwano, R, Kurisaki, H, Yomono, H, Goto, J, Kanazawa, I, Tsuji, S
    • Journal Title

      Neurol. 62

      Pages: 648-651

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Greenstein, P.Huntington's Disease-like 2 (HDL2) in North America and Japan.2004

    • Author(s)
      Margolis RL, Holmes, S E., Rosenblatt, A., Gourley, L., O'Hearn, E., Ross, C A., Seltzer, W K., Walker, RH., Ashizawa, T., Rasmussen, A., Hayden, M., Almqvist, E W., Harris, J., Fahn, S., MacDonald, M E., Mysore, J., Shimohata, T., Tsuji, S., Potter, N., Nakaso, K., Adachi, Y., Nakashima, K., Bird, T., Krause, A.
    • Journal Title

      Ann Neurol 56

      Pages: 670-674

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Beta-synuclein gene alterations in dementia with Lewy bodies.2004

    • Author(s)
      Ohtake H, Limprasert, P., Fan, Y., Onodera, O., Kakita, A., Takahashi, H., Bonner, L T., Tsuang, D W., Murray, I V., Lee, V M., Trojanowski, JQ., Ishikawa, A., Idezuka, J., Murata, M., Toda, T., Bird, T D., Leverenz, J B., Tsuii, S.
    • Journal Title

      Neurology 63

      Pages: 805-811

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adult-onset leukoencephalopathy with vanishing white matter with a missense mutation in EIF 2B5.2004

    • Author(s)
      Ohtake H, Shimohata, T., Terajima, K., Kimura, T., Jo, R., Kaseda, R., Iizuka, O., Takano, M., Akaiwa, Y., Goto, H., Kobayashi, H., Sugai, T., Muratake, T., Hosoki, T., Shioiri T., Okamoto, K., Onodera, O., Tanaka, K., Someya, T., Nakada, T., Tsuji, S.
    • Journal Title

      Neurology 62

      Pages: 1601-1603

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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