Genomic analysis of Common marmosets and identification of primate models for psychiatric disorders

• Project/Area Number: 16K15559
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Nagoya University
• Principal Investigator: Ozaki Norio 名古屋大学, 医学系研究科, 教授 (40281480)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: コモンマーモセット / CNV / 精神疾患

Outline of Final Research Achievements

To elucidate the etiology of psychiatric disorders, it is critical to establish appropriate animal models reflecting their pathogenesis. Common marmosets (Callithrix jacchus) have advantages as animal models for psychiatric disorders because the higher function of their brain is similar to that of humans. In this study, we performed genomic analysis of marmosets and aimed to identify pathogenic copy number variations (CNVs) associated the risk of psychiatric disorders, and to examine phenotypes of individuals with these CNVs. As a result of the analysis of 47 marmoset individuals, we identified a very large deletion (8.4 Mb) at chromosome 16 in one individual. CNVs of this size may be associated with the risk of psychiatric disorders in humans. However, we could not do any further examination because phenotype data for this individual was not available.

Research Products

• [Journal Article] Rare loss of function mutations in N-methyl-d-aspartate glutamate receptors and their contributions to schizophrenia susceptibility (2018)
  • Author(s): Yu Yanjie、Lin Yingni、Takasaki Yuto、Wang Chenyao、Kimura Hiroki、Xing Jingrui、Ishizuka Kanako、Toyama Miho、Kushima Itaru、Mori Daisuke、Arioka Yuko、Uno Yota、Shiino Tomoko、Nakamura Yukako、Okada Takashi、Morikawa Mako、Ikeda Masashi、Iwata Nakao、Okahisa Yuko、Takaki Manabu、Sakamoto Shinji、et al.
  • Journal Title: Translational Psychiatry Volume: 8 Issue: 1 Pages: 12-20
  • DOI: 10.1038/s41398-017-0061-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders (2017)
  • Author(s): Ishizuka K、Fujita Y、Kawabata T、Kimura H、Iwayama Y、Inada T、Okahisa Y、Egawa J、Usami M、Kushima I、Uno Y、Okada T、Ikeda M、Aleksic B、Mori D、Someya To、Yoshikawa T、Iwata N、Nakamura H、Yamashita T、Ozaki N
  • Journal Title: Translational Psychiatry Volume: 7 Issue: 8 Pages: e1184-e1184
  • DOI: 10.1038/tp.2017.173
  • Peer Reviewed / Open Access
• [Journal Article] A novel rare variant R292H in RTN4R affects growth cone formation and possibly contributes to schizophrenia susceptibility (2017)
  • Author(s): Kimura H、Fujita Y、Kawabata T、Ishizuka K、Wang C、Iwayama Y、Okahisa Y、Kushima I、Morikawa M、Uno Y、Okada T、Ikeda M、Inada T、Branko A、Mori D、Yoshikawa T、Iwata N、Nakamura H、Yamashita T、Ozaki N
  • Journal Title: Translational Psychiatry Volume: 7 Issue: 8 Pages: e1214-e1214
  • DOI: 10.1038/tp.2017.170
  • Peer Reviewed / Open Access
• [Journal Article] Copy Number Variant in the Region of Adenosine Kinase (ADK) and Its Possible Contribution to Schizophrenia Susceptibility (2017)
  • Author(s): Kimura Hiroki、Kushima Itaru、Yohimi Akira、Aleksic Branko、Ozaki Norio
  • Journal Title: Int J Neuropsychopharmacol Volume: - Issue: 5 Pages: 1-5
  • DOI: 10.1093/ijnp/pyx103
  • Peer Reviewed
• [Journal Article] High-resolution copy number variation analysis of schizophrenia in Japan. (2017)
  • Author(s): Kushima I, Aleksic B, Nakatochi M, Shimamura T, Shiino T, Yoshimi A, Kimura H, Takasaki Y, Wang C, Xing J, Ishizuka K, Oya-Ito T, Nakamura Y, Arioka Y, Maeda T, Yamamoto M, Yoshida M, Noma H, Hamada S, Morikawa M, Uno Y, Okada T, Iidaka T, Iritani S, Yamamoto T,
  • Journal Title: Molecular Psychiatry Volume: 22 Issue: 3 Pages: 430-440
  • DOI: 10.1038/mp.2016.88
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Single-neuron and genetic correlates of autistic behavior in macaque (2016)
  • Author(s): K. Yoshida, Y. Go, I. Kushima, A. Toyoda, A. Fujiyama, H. Imai, N. Saito, A. Iriki, N. Ozaki, M. Isoda
  • Journal Title: Science Advances Volume: 2 Issue: 9
  • DOI: 10.1126/sciadv.1600558
  • NAID: 120006222007
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] やっぱり聞いちゃう遺伝医学 (2017)
  • Author(s): 尾崎紀夫
  • Organizer: 精神障害の遺伝学.人類遺伝学会
  • Invited
• [Presentation] 当事者・家族のニーズに答える研究成果を目指して (2017)
  • Author(s): 尾崎紀夫
  • Organizer: 精神医学研究・教育と精神医療を繋ぐ精神神経学会会長講演
  • Invited
• [Presentation] 統合失調症と自閉スペクトラム症発症に関わるrare variants探索から分子病態解明へ (2017)
  • Author(s): 尾崎紀夫
  • Organizer: 生物精神・神経精神薬理学会シンポジウム:遺伝子点変異による精神神経疾患の発症機構解明
  • Invited
• [Presentation] 統合失調症前駆状態と自閉スペクトラム症の関係性を考える：症候と病態 (2016)
  • Author(s): 尾崎紀夫
  • Organizer: 第20回日本精神保健・予防学会学術集会 ー特別シンポジウム「ARMSと発達障害の類似と相違」
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-11-12
• [Presentation] 自閉スペクトラム症の診断と病態 （教育シンポジウム 神経化学会会員のための精神疾患教育講座） (2016)
  • Author(s): 尾崎紀夫
  • 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（福岡県福岡市）
• [Presentation] The dysfunction of neurodevelopmental genes, NDE1 and RELN in schizophrenia revealed by the common disease-rare variant hypothesis (2016)
  • Author(s): 尾崎紀夫
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] 自閉スペクトラム症―診断上の留意点と発症メカニズムについて (2016)
  • Author(s): 尾崎紀夫
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸コンベンションセンター（神戸国際会議場・神戸国際展示場）（兵庫県神戸市）
• [Presentation] 自閉スペクトラム症ゲノム解析研究の現状と方向性 (2016)
  • Author(s): 尾崎紀夫
  • Organizer: 第112回日本精神神経学会（研究推進委員会シンポ；精神医学研究推進のために必要なこと）
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
• [Presentation] 全ゲノム解析時代の倫理的配慮：社会的及び学術的な意義を有する研究 (2016)
  • Author(s): 尾崎紀夫
  • Organizer: 第112回日本精神神経学会（研究倫理委員会シンポ；精神医学研究における個人情報保護と倫理指針ー画像・ゲノム・症例報告ー）
  • Place of Presentation: 幕張メッセ（千葉県千葉市）