Elucidation of genetic factors for Parkinson disease employing next-generation sequencer

• Project/Area Number: 23790384
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human genetics
• Research Institution: The University of Tokyo
• Principal Investigator: MITSUI Jun 東京大学, 医学部附属病院, 助教 (70579862)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 関連解析 / ゲノム / 疾患感受性遺伝子

Research Abstract

We applied resequencing of pooled DNA using a next-generation sequencer to identification of disease associations with rare variants. Sixteen sets of pooled DNAs from eight pooled DNA samples were prepared. Each set of pooled DNAs was subjected to polymerase chain reaction to amplify the target gene, pooled into one tube with barcode indexing, and then subjected to extensive sequence analysis using theIllumina GAIIx. With the optimization of data processing to solve integer programming problems, we were able to extract novel variants from 64 samples.

Research Products

• [Journal Article] Present efforts in the medical genome center at the university of Tokyo hospital. (2013)
  • Author(s): Mitsui J, Ishiura H, Tsuji S.
  • Journal Title: Brain Nerve. Volume: 65(3) Pages: 247-55
  • NAID: 40019613433
• [Journal Article] Identification of ATP1A3 mutations by exome sequencing as the cause of alternating hemiplegia of childhood in Japanese patients. (2013)
  • Author(s): Ishii A, Saito Y, Mitsui J, Ishiura H, Yoshimura J, Arai H, Yamashita S, Kimura S, Oguni H, Morishita S, Tsuji S, Sasaki M, Hirose S.
  • Journal Title: PLoS One Volume: 8 Issue: 2 Pages: e56120-e56120
  • DOI: 10.1371/journal.pone.0056120
  • Peer Reviewed
• [Journal Article] CSF1R mutations identified in three families with autosomal dominantly inherited leukoencephalopathy. (2012)
  • Author(s): Mitsui J, Matsukawa T, Ishiura H, Higasa K, Yoshimura J, Saito TL, Ahsan B, Takahashi Y, Goto J, Iwata A, Niimi Y, Riku Y, Goto Y, Mano K, Yoshida M, Morishita S, Tsuji S.
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet. Volume: 159B(8) Issue: 8 Pages: 951-7
  • DOI: 10.1002/ajmg.b.32100
  • Peer Reviewed
• [Journal Article] The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement. (2012)
  • Author(s): Ishiura H
  • Journal Title: Am J Hum Genet. Volume: 91(2) Issue: 2 Pages: 320-9
  • DOI: 10.1016/j.ajhg.2012.07.014
  • Peer Reviewed
• [Journal Article] C9ORF72 repeat expansion in amyotrophic lateral sclerosis in the Kii peninsula of Japan. (2012)
  • Author(s): Ishiura H, Kokubo Y.
  • Journal Title: Arch Neurol. Volume: 69(9) Issue: 9 Pages: 1154-1158
  • DOI: 10.1001/archneurol.2012.1219
  • Peer Reviewed
• [Journal Article] Clinical features and haplotype analysis of newly identified Japanese patients with gelsolin-related familial amyloidosis of Finnish type. (2012)
  • Author(s): Taira M, Ishiura H, Mitsui J, Takahashi Y, Hayashi T, Shimizu J, Matsukawa T, Saito N, Okada K, Tsuji S, Sawamura H, Amano S, Goto J, Tsuji S.
  • Journal Title: Neurogenetics. Volume: 13(3) Issue: 3 Pages: 237-43
  • DOI: 10.1007/s10048-012-0330-0
  • Peer Reviewed
• [Journal Article] Increased gene dosage of myelin protein zero causes Charcot-Marie-Tooth disease. (2012)
  • Author(s): Maeda MH, Mitsui J, Soong BW, Takahashi Y, Ishiura H, Hayashi S, Shirota Y, Ichikawa Y, Matsumoto H, Arai M, Okamoto T, Miyama S, Shimizu J, Inazawa J, Goto J, Tsuji S.
  • Journal Title: Ann Neurol. Volume: 71(1) Pages: 84-92
  • Peer Reviewed
• [Journal Article] Increased gene dosage of myelin protein zero causes Charcot-Marie-Tooth disease (2012)
  • Author(s): Maeda MH, Ishiura H, et al
  • Journal Title: Ann Neurol Volume: 71 Issue: 1 Pages: 84-92
  • DOI: 10.1002/ana.22658
  • Peer Reviewed
• [Journal Article] Genetics of sporadic disease: insights fromhigh-throughput sequencing--Parkinson disease. (2011)
  • Author(s): Mitsui J.
  • Journal Title: RinshoShinkeigaku. Volume: 51(11) Pages: 973-4
• [Journal Article] Therapeutic trial design issues for future disease-modifying therapy of multiple system atrophy. (2011)
  • Author(s): Ichikawa Y, Goto J, Nakahara Y, Mitsui J, Tsuji S.
  • Journal Title: Rinsho Shinkeigaku. Volume: 51(11) Pages: 910-3
  • NAID: 130004504910
• [Journal Article] Adult-onset leukoencephalopathies with vanishing white matter with novel missense mutations in EIF2B2, EIF2B3, and EIF2B5 (2011)
  • Author(s): Matsukawa T, Ishiura H, et al
  • Journal Title: Neurogenetics Volume: 12 Issue: 3 Pages: 259-261
  • DOI: 10.1007/s10048-011-0284-7
  • Peer Reviewed
• [Journal Article] Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1 (2011)
  • Author(s): Ishiura H, et al
  • Journal Title: Neurogenetics Volume: 12 Issue: 2 Pages: 117-121
  • DOI: 10.1007/s10048-010-0271-4
  • Peer Reviewed
• [Journal Article] Genetic basis of sponadic Parkinson disease common disease-multiple rare variants. (2010)
  • Author(s): Mitsui J.
  • Journal Title: Rinsho Shinkeigaku. Volume: 50(11) Pages: 865-6
  • NAID: 130004504662
• [Presentation] ファブリー病の診断における問題点～E66Q に関連して～ (2012)
  • Author(s): 三井純.
  • Organizer: 第8回日本ファブリー病フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2012-07-22
• [Presentation] ファブリー病の診断における問題点～E66Qに関連して～ (2012)
  • Author(s): 三井 純
  • Organizer: 第8回日本ファブリー病フォーラム
  • Place of Presentation: 東京
• [Presentation] パーキンソン病における GLA解析 (2011)
  • Author(s): 三井純.
  • Organizer: 第7回日本ファブリー病フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2011-07-10
• [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回日本神経学会総会(招待講演)
  • Place of Presentation: 名古屋
• [Presentation] パーキンソン病の遺伝因子について (2011)
  • Author(s): 三井 純
  • Organizer: 第16回パーキンソン病フォーラム
  • Place of Presentation: 京都
• [Presentation] パーキンソン病におけるGLA遺伝子解析 (2011)
  • Author(s): 三井 純
  • Organizer: 第7回日本ファブリ―病フォーラム
  • Place of Presentation: 東京
• [Presentation] Whole genome解析による神経疾患へのアプローチ (2011)
  • Author(s): 三井 純，石浦 浩之，高橋 祐二，辻 省次
  • Organizer: 平成23年度第1回 パーソナルゲノム情報班 班会議
  • Place of Presentation: 東京
• [Presentation] パーキンソン病感受性遺伝子探索 ～ライソゾーム病関連遺伝子からのアプローチ～ (2011)
  • Author(s): 三井 純，辻省次
  • Organizer: 平成23年度厚生労働省難治性疾患克服研究事業ライソゾーム病（ファブリー病含む）に関する調査研究班会議
  • Place of Presentation: 東京