Exome sequencing of schizophrenia using families with multiple affected members

• Project/Area Number: 15K09804
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Nagoya University
• Principal Investigator: Aleksic Branko 名古屋大学, 医学系研究科(国際), 特任准教授 (60547511)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2016: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
• Keywords: exome sequecing / Exome sequecing / whole exome sequecing / Schizophrenia / 臨床精神分子遺伝学 / 次世代シークエンサー

Outline of Final Research Achievements

In this research we dissected genetic architecture of schizophrenia using families with multiple affected members. Until now most family based exome sequencing used trio based design and research was focused mainly on de novo variants (i.e. variants that are not present in parents but exist in affected children). In the current research besides de novo variants we focused on inherited variants. These are variants that are present in all affected member in one pedigree. In addition we investigated variants that are rare and of high impact (i.e. splice site mutation and/or nonsense variants), which may be family specific but exhibit incomplete penetrance (i.e. present in both affected and non affected members of the same family.

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] Mutation screening of GRIN2B in schizophrenia and autism spectrum disorder in a Japanese population. (2016)
  • Author(s): Takasaki Y, Koide T, Wang C, Kimura H, Xing J, Kushima I, Ishizuka K, Mori D, Sekiguchi M, Ikeda M, Aizawa M, Tsurumaru N, Iwayama Y, Yoshimi A, Arioka Y, Yoshida M, Noma H, Oya-Ito T, Nakamura Y, Kunimoto S, Aleksic B, Uno Y, Okada T, Ujike H, Egawa J, Kuwabara H, Someya T, Yoshikawa T, Iwata N, Ozaki N
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 33311-33311
  • DOI: 10.1038/srep33311
  • Peer Reviewed / Open Access
• [Journal Article] Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders (2016)
  • Author(s): Xing J, Kimura H, Wang C, Ishizuka K, Kushima I, Arioka Y, Yoshimi A, Nakamura Y, Shiino T, Oya-Ito T, Takasaki Y, Uno Y, Okada T, Iidaka T, Aleksic B, Mori D, Ozaki N.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 27491-27491
  • DOI: 10.1038/srep27491
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serbian Language version of the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up: Cross-Cultural Adaptation and Assessment of Reliability. (2016)
  • Author(s): Carakovac M, Jovanovic J, Kalanj M, Rudic N, Aleksic-Hil O, Aleksic B, Villalobos IB, Kasuya H, Ozaki N, Lecic-Tosevski D, Pejovic-Milovancevic M.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 38222-38222
  • DOI: 10.1038/srep38222
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant