Detection of novel LINE-1 insertion in prefrontal cortex of patients with schizophrenia

• Project/Area Number: 15K09801
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kumamoto University (2016-2017); The University of Tokyo (2015)
• Principal Investigator: Bundo Miki 熊本大学, 大学院生命科学研究部(医), 准教授 (00597221)
• Co-Investigator(Renkei-kenkyūsha): IWAMOTO Kazuya 熊本大学, 大学院生命科学研究部, 教授 (40342753) ; KASAI Kiyoto 東京大学, 医学部付属病院, 教授 (80322056) ; KATO Tadafumi 理化学研究所, 脳科学研究センター, チームリーダー (30214381)
• Research Collaborator: UEDA Junko ; KIYOTA Emi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 統合失調症 / 死後脳 / LINE-1 / レトロトランスポゾン / 精神疾患 / 体細胞変異

Outline of Final Research Achievements

We recently reported that the copy number of long interspersed nucleotide element (LINE-1) retrotransposon was higher in the neurons of patients with schizophrenia than in the neurons of healthy controls. The purpose of this study is to detect the somatic insertion sites of LINE-1 using human postmortem brains. We developed a new method to identify the brain-specific LINE-1 insertion genomic site. Using this method, we detected 83.8% (720/859) of LINE-1 found in the reference human genome sequence (hg38) and 30-80 of unknown non-reference somatic LINE-1 insertions in single neuronal nuclei from prefrontal cortex of a human without any psychiatric diseases. We have been conducting a case-control study using postmortem brain samples from patients with schizophrenia and controls to clarify the role of somatic LINE-1 insertions in the pathogenesis of schizophrenia.

Research Products

• [Journal Article] Identification of somatic mutations in postmortem human brains by whole genome sequencing and their implications for psychiatric disorders. (2018)
  • Author(s): Nishioka M, Bundo M, Ueda J, Katsuoka F, Sato Y, Kuroki Y, Ishii T, Ukai W, Murayama S, Hashimoto E, Nagasaki M, Yasuda J, Kasai K, Kato T, Iwamoto K.
  • Journal Title: Psychiatry Clin Neurosci. Volume: 72 Issue: 4 Pages: 280-294
  • DOI: 10.1111/pcn.12632
  • Peer Reviewed / Open Access
• [Presentation] ヒト前頭葉神経細胞における体細胞ゲノム変異の検出 (2018)
  • Author(s): 文東美紀、加藤忠史、岩本和也
  • Organizer: 第123回日本解剖学会総会
  • Invited
• [Presentation] ヒト死後脳を用いたシングルセルレベルのLINE-1新規挿入同定の試み (2017)
  • Author(s): 文東美紀、上田順子、西岡将基、清田恵美、石井貴男、鵜飼渉、橋本恵理、笠井清登、加藤忠史、岩本和也
  • Organizer: 第39回日本生物学的精神医学会・第47回日本神経精神薬理学会合同年会
• [Presentation] Detection of retrotransposon by next generation sequencing and its application to single brain cells (2017)
  • Author(s): Miki Bundo, Junko Ueda-Hayashi, Masaki Nishioka, Emi Kiyota, Kiyoto Kasai, Tadafumi Kato, Kazuya Iwamoto
  • Organizer: 第40回日本神経科学大会
• [Presentation] LINE-1 copy number analysis of schizophrenic patients (2017)
  • Author(s): Miki Bundo, Tadafumi Kato, Kazuya Iwamoto
  • Organizer: More Epigenetics in Clinical Medicine
  • Int'l Joint Research / Invited
• [Presentation] ヒト死後脳由来のニューロン・オリゴデンドロサイトを使用したシングルセルゲノム解析 (2016)
  • Author(s): 文東美紀
  • Organizer: 第38回日本生物学的精神医学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2016-09-08
• [Presentation] Comprehensive DNA methylation analysis of neuron and oligodendrocyte from human postmortem brains. (2016)
  • Author(s): 文東美紀
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-07-20
• [Presentation] Somatic mutations in human brains and monozygotic twins discordant for psychiatric disorders. (2016)
  • Author(s): 西岡将基
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-07-20
• [Presentation] Brain genome and epigenome analyses in psychiatric disorders. (2015)
  • Author(s): Bundo M
  • Organizer: 第38回日本神経科学会
  • Place of Presentation: 神戸国際会議場・兵庫
  • Year and Date: 2015-07-28
  • Invited
• [Book] Genomic Mosaicism in Neurons and Other Cell Types (Chapter 11: Estimation of LINE-1 Copy Number in the Brain Tissueand Isolated Neuronal Nuclei) (2017)
  • Author(s): Miki Bundo, Tadafumi Kato, Kazuya Iwamoto
  • Total Pages: 382
  • Publisher: Springer
  • ISBN: 9781493972807
• [Book] Genomic mosaicism in neurons and other cell types (book chapter:Estimation of LINE-1 copy number in the brain tissue and isolated neuronal nuclei.) (2017)
  • Author(s): Bundo M, Kato T, Iwamoto K
  • Publisher: Springer
• [Book] Epigenetic Methods in Neuroscience Research (2015)
  • Author(s): Bundo M, Kato T, Iwamoto K
  • Total Pages: 9
  • Publisher: Springer
• [Remarks] 熊本大学大学院 生命科学研究部 分子脳科学分野
  • URL: https://www.molbrain.com/
• [Remarks] 熊本大学大学院生命科学研究部先端生命医療科学部門分子脳科学分野
  • URL: https://www.molbrain.com/
• [Remarks] 東京大学大学院医学系研究科 分子精神医学講座
  • URL: http://www.molpsy.com/index.html