Rescue of 21 trisomy in Down syndrome cells using spindle assembly checkpoint

• Project/Area Number: 15H04321
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical genome science
• Research Institution: Hiroshima University
• Principal Investigator: Matsuura Shinya 広島大学, 原爆放射線医科学研究所, 教授 (90274133)
• Co-Investigator(Kenkyū-buntansha): 宮本 達雄 広島大学, 原爆放射線医科学研究所, 講師 (40452627) ; 柳原 啓見 広島大学, 原爆放射線医科学研究所, 助教 (50719474)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2015: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: 染色体 / 細胞周期チェックポイント / 遺伝病

Outline of Final Research Achievements

The aim of this study was to normalize 21 trisomy in Down's syndrome cells by induction of chromosome instability. We transfected BubR1 siRNA into Down's syndrome cells and analyzed their karyotypes. Cellular phenotype of mosaic variegated aneuploidy was observed, but a cell clone in which excessive chromosome 21 was normalized was not yet obtained. We will establish such cell clones that lost only excessive chromosome 21 by increasing the number of isolated cell clones.

Research Products

• [Journal Article] Exploration of genetic basis underlying individual differences in radiosensitivity within human populations using genome editing technology. (2018)
  • Author(s): Miyamoto T, Akutsu SN, Tauchi H, Kudo Y, Tashiro S, Yamamoto T, Matsuura S.
  • Journal Title: J Radiat Res. Volume: Epub ahead of print Issue: suppl_2 Pages: 1-8
  • DOI: 10.1093/jrr/rry007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Updated summary of genome editing technology in human cultured cells linked to human genetics studies (2017)
  • Author(s): Miyamoto Tatsuo、Akutsu Silvia Natsuko、Matsuura Shinya
  • Journal Title: Journal of Human Genetics Volume: 63 Issue: 2 Pages: 133-143
  • DOI: 10.1038/s10038-017-0349-z
  • Peer Reviewed
• [Journal Article] PLK1-mediated phosphorylation of WDR62/MCPH2 ensures proper mitotic spindle orientation (2017)
  • Author(s): Miyamoto Tatsuo、Akutsu Silvia Natsuko、Fukumitsu Akihiro、Morino Hiroyuki、Masatsuna Yoshinori、Hosoba Kosuke、Kawakami Hideshi、Yamamoto Takashi、Shimizu Kenji、Ohashi Hirofumi、Matsuura Shinya
  • Journal Title: Human Molecular Genetics Volume: 26 Issue: 22 Pages: 4429-4440
  • DOI: 10.1093/hmg/ddx330
  • Peer Reviewed
• [Journal Article] Induction of somatic mutations by low-dose X-rays: the challenge in recognizing radiation-induced events (2017)
  • Author(s): Nagashima Haruki、Shiraishi Kumiko、Ohkawa Saori、Sakamoto Yuki、Komatsu Kenshi、Matsuura Shinya、Tachibana Akira、Tauchi Hiroshi
  • Journal Title: J Radiat Res Volume: 58 Issue: suppl_2 Pages: 1-7
  • DOI: 10.1093/jrr/rrx053
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of ATM heterozygous mutations underlying individual differences in radiosensitivity using genome editing in human cultured cells. (2017)
  • Author(s): Royba E, Miyamoto T, Natsuko Akutsu S, Hosoba K, Tauchi H, Kudo Y, Tashiro S, Yamamoto T, Matsuura S.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 5996-5996
  • DOI: 10.1038/s41598-017-06393-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Wilms tumor accompanied by premature chromatid separation (2017)
  • Author(s): Shimada K, Yanagisawa R, Kubota N, Hidaka E, Sakashita K, Ishii E, Matsuura S, Ogiso Y
  • Journal Title: Pediatr Blood Cancer Volume: 64 Issue: 3
  • DOI: 10.1002/pbc.26255
  • Peer Reviewed
• [Journal Article] Cilia play a role in breaking left-right symmetry of the sea urchin embryo. (2016)
  • Author(s): Takemoto A, Miyamoto T, Simono F, Kurogi N, Kurabayashi MS, Awazu A, Suzuki KT, Yamamoto T, Sakamoto N
  • Journal Title: Genes Cells Volume: in press Issue: 6 Pages: 568-578
  • DOI: 10.1111/gtc.12362
  • Peer Reviewed / Open Access
• [Journal Article] Functional consequence of fibulin-4 missense mutations associated with vascular and skeletal abnormalities and cutis laxa (2016)
  • Author(s): Sasaki T, Hanisch FG, Deutzmann R, Sakai LY, Sakuma T, Miyamoto T, Yamamoto T, Hannappel E, Chu ML, Lanig H, von der Mark K
  • Journal Title: Matrix Biol Volume: 56 Pages: 132-149
  • DOI: 10.1016/j.matbio.2016.06.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Analysis of individual differences in radio sensitivity using genome editing (2016)
  • Author(s): Matsuura S, Royba E, Akutsu SN, Yanagihara H, Ochiai H, Kudo Y, Tashiro H, Miyamoto T
  • Journal Title: Annals of the ICRP Volume: Published online before print Issue: 1_suppl Pages: 1-7
  • DOI: 10.1177/0146645316633941
  • Peer Reviewed / Open Access
• [Journal Article] Ciliopathy in PCS(MVA) syndrome (2015)
  • Author(s): Miyamoto T, Matsuura S
  • Journal Title: Oncotarget Volume: 6(28) Issue: 28 Pages: 24582-24583
  • DOI: 10.18632/oncotarget.5244
  • Peer Reviewed / Open Access
• [Presentation] Unravelling the pathological mechanisms of structure-chromosomal instability post IR in PCS(MVA) syndrome (2018)
  • Author(s): Silvia Natsuko Akutsu, Tatsuo Miyamoto, Shinya Matsuura
  • Organizer: The 7th International symposium of Phoenix Leader Education Program for Renaissance from Radiation Disaster
  • Int'l Joint Research
• [Presentation] 分裂期キナーゼPLK1による遺伝性小頭症原因遺伝子産物WDR62のリン酸化を介した細胞分裂軸安定化機構 (2017)
  • Author(s): 宮本達雄、細羽康介、Silvia Natsuko Akutsu、福満啓博、政綱宣規、森野豊之、川上秀史、山本卓、清水健司、大橋博文、松浦伸也
  • Organizer: 第60回日本放射線影響学会
• [Presentation] 真性小頭症原因遺伝子産物WDR62による星状体微小管重合を介した細胞分裂軸制御 (2017)
  • Author(s): 宮本達雄、福満啓博、Silvia Natsuko Akutsu、政綱宜規、細羽康介、山本卓、松浦伸也
  • Organizer: 第40回日本分子生物学会年会
• [Presentation] PLK1-mediated phosphorylation of WDR62/MCPH2 is required for proper mitotic spindle orientation (2017)
  • Author(s): Tatsuo Miyamoto, Kosuke Hosoba, Silvia Natsuko Akutsu, Hiroyuki Morino, Akihiro Fukumitsu, Yoshinori Masatsuna, Hideshi Kawakami, Takashi Yamamoto, Kenji Shimizu, Hirofumi Ohashi, Shinya Matsuura
  • Organizer: 第75回日本癌学会学術総会
• [Presentation] Identification of ATM heterozygous mutations underlying individual differences in radiosensitivity using genome editing technolog (2017)
  • Author(s): Tatsuo Miyamoto, Ekaterina Royba, Silvia Natsuko Akutsu, Kosuke Hosoba, Hiroshi Tauchi, Yoshiki Kudo, Satoshi Tashiro, Takashi Yamamoto and Shinya Matsuura
  • Organizer: 日本人類遺伝学会第62回大会
• [Presentation] Trial for correction of trisomy 21 in a Down syndrome patient-derived induced pluripotent stem cells (iPSc) (2017)
  • Author(s): Silvia Natsuko Akutsu, Tatsuo Miyamoto, Hiroshi Ochiai, Kenichi Suzuki, Akira Shimamoto, Takashi Yamamoto and Shinya Matsuura
  • Organizer: 日本人類遺伝学会第62回大会
• [Presentation] Genome editing technique as a useful tool for analysing individual differences of radiosensitivity (2017)
  • Author(s): Ekaterina Royba, Tatsuo Miyamoto, Silvia Natsuko Akutsu, Kosuke Hosoba, Yoshiki Kudo, Satoshi Tashiro, Shinya Matsuura;
  • Organizer: The 6th International symposium of Phoenix Leader Education Program for Renaissance from Radiation Disaster
  • Int'l Joint Research
• [Presentation] ATM heterozygous mutations underlying individual differences in radiosensitivity in human populations (2016)
  • Author(s): Shinya Matsuura, Ekaterina Royba, Tatsuo Miyamoto, Silvia Natsuko Akutsu, Takashi Yamamoto, Yoshiki Kudo, Satoshi Tashiro
  • Organizer: ASHG2016 (Vancouver)
  • Place of Presentation: Vancouver（カナダ）
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] Generation of PCS (MVA) syndrome mutation knock-in mice using CRISPR/Cas9-mediated genome editing technology (2016)
  • Author(s): Kosuke Hosoba, Tatsuo Miyamoto and Shinya Matsuura
  • Organizer: ASHG2016 (Vancouver)
  • Place of Presentation: Vancouver（カナダ）
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] A combined approach of exome sequencing and genome editing identified WDR62/MCPH2 mutations in patients with primary microcephaly (2016)
  • Author(s): Tatsuo Miyamoto, Yoshinori Masatsuna, Akihiro Fukumitsu, Silvia Natsuko Akustu, Kosuke Hosoba, Hiroyuki Morino, Hideshi Kawakami, Takashi Yamamoto, Kenji Shimizu, Hirofumi Ohashi, Shinya Matsuura
  • Organizer: ASHG2016 (Vancouver)
  • Place of Presentation: Vancouver（カナダ）
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] Molecular basis of human BUBR1 deficiency, a central protein of the spindle assembly checkpoint (2016)
  • Author(s): Shinya Matsuura, Tatsuo Miyamoto, Kosuke Hosoba, Hiroshi Ochiai, Takashi Yamamoto, Makoto Furutani-Seiki
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
  • Invited
• [Presentation] WDR62/MCPH2 mutations identified in patients with primary microcephaly by a combined approach of exome sequencing and genome editing technology (2016)
  • Author(s): Nobunori Masatsuna, Silvia Natsuko Akustu, Kosuke Hosoba, Hiroyuki Morino, Hideshi Kawakami, Takashi Yamamoto, Kenji Shimizu, Hirofumi Oohashi, Tatsuo Miyamoto, Shinya Matsuura
  • Organizer: ICHG2016 (Kyoto)
  • Place of Presentation: Kyoto
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Book] ゲノム編集入門 山本卓 編 (2016)
  • Author(s): 宮本 達雄
  • Total Pages: 226
  • Publisher: 裳華房