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Identifying susceptible genes for Parkinson disease employing next-generation sequencer

Research Project

Project/Area Number 22890041
Research Category

Grant-in-Aid for Research Activity Start-up

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

Principal Investigator

MITSUI Jun  The University of Tokyo, 医学部附属病院, 特任助教 (70579862)

Project Period (FY) 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
Fiscal Year 2010: ¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
Keywordsゲノム / 神経内科学 / パーキンソン病 / 関連解析 / 次世代シーケンサー
Research Abstract

To identify susceptible genes for Parkinson disease, comprehensive resequencing analysis of candidate genes (responsible genes for lysosomal storage disease) employing a next-generation sequencer was conducted. We arranged 64 DNA samples of patients with Parkinson disease in an 8x8 rectangular array, and formed the pooled DNA sample sets by each row and column (8 rows and 8 columns). Each pooled DNA sample set was subjected to PCR amplifications of candidate genes (approximately 24 kb in total) and every amplicons for each set were mixed. The mixed amplicons for each set was subjected to an analysis of single lane of Illumina GAIIx, single-end, 100bp, according to manufactures' instructions.
Reads were aligned to the reference sequences (hg19) of candidate genes by BWA with default parameters, and approximately 1,000-2,000 coverage per allele was obtained. Only 50 bp of reads with more than 20 of QV were used to screen variants. We specifically focused on rare variants not registered in dbSNP, and searching for such variants employing an integer programming algorithm. The results were that 3 variants not registered in dbSNP were obtained; each variant was identified in three different samples in the heterozygous state. All of them were nonsynonymous single nucleotide substitutions. One was reported to be pathogenic for a lysosomal storage disease, and two were unknown variants. All variants were confirmed by an additional direct nucleotide sequence analysis (Sanger method).
Based on these results, it was suggested that the matrix pooling approach is an accurate and cost effective testing algorithm for detection of rare variants.

Report

(2 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (14 results)

All 2011 2010 Other

All Journal Article (7 results) (of which Peer Reviewed: 3 results) Presentation (6 results) Remarks (1 results)

  • [Journal Article] Adult-onset leukoencephalopathies with vanishing white matter with novel missense mutations in EIF2B2, EIF2B3, and EIF2B5.2011

    • Author(s)
      Matsukawa T, Wang X, Liu R, Wortham NC, Onuki Y, Kubota A, Hida A, Kowa H, Fukuda Y, Ishiura H, Mitsui J, Takahashi Y, Aoki S, Takizawa S, Shimizu J, Goto J, Proud CG, Tsuji S
    • Journal Title

      Neurogenetics

    • Related Report
      2010 Final Research Report
  • [Journal Article] Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1.2011

    • Author(s)
      Ishiura H, Fukuda Y, Mitsui J, Nakahara Y, Ahsan B, Takahashi Y, Ichikawa Y, Goto J, Sakai T, Tsuji S.
    • Journal Title

      Neurogenetics. 12(2)

      Pages: 117-21

    • Related Report
      2010 Final Research Report
  • [Journal Article] Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1.2011

    • Author(s)
      Ishiura H, Fukuda Y, Mitsui J, et. al.
    • Journal Title

      Neurogenetics.

      Volume: 12 Pages: 117-121

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of genomic instabilities underlying two common fragile-site-associated loci, PARK2 and DMD, in germ cell and cancer cell lines.2010

    • Author(s)
      Mitsui J, Takahashi Y, Goto J, Tomiyama H, Ishikawa S, Yoshino H, Minami N, Smith DI, Lesage S, Aburatani H, Nishino I, Brice A, Hattori N, Tsuji S.
    • Journal Title

      Am J Hum Genet. 87(1)

      Pages: 75-89

    • Related Report
      2010 Final Research Report
  • [Journal Article] Multiplexed resequencing analysis to identify rare variants in pooled DNA with barcode indexing using next-generation sequencer.2010

    • Author(s)
      Mitsui J, Fukuda Y, Azuma K, Tozaki H, Ishiura H, Takahashi Y, Goto J, Tsuji S.
    • Journal Title

      J Hum Genet. 55(7)

      Pages: 448-55

    • NAID

      10030735916

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mechanisms of genomic instabilities underlying two common fragile-site-associated loci, PARK2 and DMD, in germ cell and cancer cell lines.2010

    • Author(s)
      Mitsui J, et. al.
    • Journal Title

      Am J Hum Genet.

      Volume: 87 Pages: 75-89

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multiplexed resequencing analysis to identify rare variants in pooled DNA with barcode indexing using next-generation sequencer.2010

    • Author(s)
      Mitsui J, et. al.
    • Journal Title

      J Hum Genet.

      Volume: 55 Pages: 448-455

    • NAID

      10030735916

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 疾患と関連する稀で多様な変異の検出を目的としたpooled DNA解析2011

    • Author(s)
      三井純,土井晃一郎,石浦浩之,高橋祐二,後藤順,森下真一,辻省次
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-20
    • Related Report
      2010 Final Research Report
  • [Presentation] 孤発性疾患の研究 ~パーキンソン病~2011

    • Author(s)
      三井純
    • Organizer
      第52回日本神経学会学術大会,シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-19
    • Related Report
      2010 Final Research Report
  • [Presentation] Case-control association study of PARK2 exon rearrangements in Parkinson disease using an array comparative genomic hybridization analysis.2010

    • Author(s)
      Mitsui J, et al.
    • Organizer
      American Society of Human Genetics.
    • Place of Presentation
      Washington D.C., U.S.A.
    • Year and Date
      2010-11-04
    • Related Report
      2010 Final Research Report
  • [Presentation] Case-control association study of PARK2 exon rearrangements in Parkinson disease using an array comparative genomic hybridization analysis.2010

    • Author(s)
      Mitsui J, et. al.
    • Organizer
      American Society of Human Genetics
    • Place of Presentation
      Washington D.C., U.S.A
    • Year and Date
      2010-11-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] 孤発性パーキンソン病の遺伝子:common disease-multiple rare variants2010

    • Author(s)
      三井純
    • Organizer
      第51回日本神経学会総会,シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] アレイCGHを用いたPARK2欠失・重複変異検出によるパーキンソン病の関連解析2010

    • Author(s)
      三井純,高橋祐二,後藤順,齊藤祐子,村山繁雄,辻省次
    • Organizer
      第51回神経学会総会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2010-08-27   Modified: 2016-04-21  

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