Identification of tissue-specific somatic mosaicism in cleft lip and palate using whole exome sequencing

• Project/Area Number: 17K11863
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Aichi Gakuin University
• Principal Investigator: SUZUKI Satoshi 愛知学院大学, 歯学部, 非常勤講師 (30468996)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: エクソーム / 口唇口蓋裂 / モザイク / 遺伝子

Outline of Final Research Achievements

Exome analysis was performed using leucocyte-derived DNA from 20 patients with cleft lip and palate stored in our institutional gene banking. We also performed exome sequence on the both lip skin tissue obtained by surgery. The reading depth of the analysis was set to 150-200 depth, and the sequence used the pairwise method. The analysis accuracy was more than 98% and the results were reliable. The average SNPs were found in the analysis was 434928.05 from leukocytes and 438651.55 from tissues. Therefore, 3723.5 somatic mosaic mutations were confirmed per sample in the lip soft tissue.

Academic Significance and Societal Importance of the Research Achievements

この発見は多因子遺伝子疾患におけるmissing heritability解明の突破口になる可能性を秘めている。病変組織における約3700箇所あまりの変異が意味するところは研究試料の種類に関しても十分な考慮が必要であることを示唆している。

Research Products

• [Journal Article] SPECC1L regulates palate development downstream of IRF6 (2020)
  • Author(s): Hall Everett G、Wenger Luke W、Wilson Nathan R、Natsume Nagato、Ito Masaaki、Mori Akihiro、Imura Hideto、Kroc Sarah A、Adeyemo Wasiu L、Eshete Mekonen A、Bjork Bryan C、Suzuki Satoshi、Murray Jeffrey C、Schutte Brian C、Butali Azeez、Saadi Irfan
  • Journal Title: Human Molecular Genetics Volume: 29 Issue: 5 Pages: 845-858
  • DOI: 10.1093/hmg/ddaa002
  • Peer Reviewed
• [Journal Article] Patients with SATB2-sassociated syndrome exhibiting multiple odontomas (2018)
  • Author(s): Takashi Kikuiri, Hiroyuki Mishima, Hideto Imura, Satoshi Suzuki, Yusuke Matsuzawa, Takashi Nakamura, Satoshi Fukumoto, Yoshitaka Yoshimura, Satoshi Watanabe, Akira Kinoshita, Takahiro Yamada, Masanobu Shindoh, Yoshihiko Sugita, Hatsuhiko Maeda, Yasutaka Yawaka, Tadashi Mikoya, Nagato Natsume, Koh-ichiro Yoshiura
  • Journal Title: Am J Med Genet Volume: 176（12） Pages: 2614-2622
  • Peer Reviewed
• [Journal Article] Identification of 16q21 as a modifier of nonsyndromic orofacial cleft phenotypes (2017)
  • Author(s): Carlson Jenna C.、Standley Jennifer、Christensen Kaare、Hecht Jacqueline T.、Garidkhuu Ariuntuul、Moreno Uribe Lina M.、Nagato Natsume、Orioli Ieda M.、Suzuki Satoshi、Beaty Terri H.、Feingold Eleanor、Murray Jeffrey C.、Marazita Mary L.、Leslie Elizabeth J , et all.
  • Journal Title: Genetic Epidemiology Volume: 41 Issue: 8 Pages: 887-897
  • DOI: 10.1002/gepi.22090
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A case of Tetrasomy 15q with left cleft lip and alveolus (2017)
  • Author(s): Imura Hideto、Suzuki Satoshi、Mizuno Seiji、Sakuma Chisato、Natsume Nagato
  • Journal Title: ournal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 29 Issue: 5 Pages: 427-429
  • DOI: 10.1016/j.ajoms.2017.03.005
  • Peer Reviewed / Open Access
• [Journal Article] Association of MEOX2 polymorphism with nonsyndromic cleft palate only in a Vietnamese population (2017)
  • Author(s): Tran Duy L.、Imura Hideto、Mori Akihiro、Suzuki Satoshi、Niimi Teruyuki、Ono Maya、Sakuma Chisato、Nakahara Shinichi、Nguyen Tham T.H.、Pham Phuong T.、Hoang Viet、Tran Van T.T.、Nguyen Minh D.、Natsume Nagato
  • Journal Title: Congenital Anomalies Volume: - Issue: 4 Pages: 124-129
  • DOI: 10.1111/cga.12259
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Replication of GWAS Candidate Genes in non-syndromic Cleft lip and / or Cleft palate in Vietnamese population (2019)
  • Author(s): Suzuki S, Ono M, Niimi T, Yamamoto M, Imura H, NGUYEN C, Leslie E , Cooper M.E, Natsume N, NGUYEN M, Marazita M.L, Murray J.C
  • Organizer: The 59Th Annual Meeting of The Japanese Teratology Society The 13th World Congress of The International Cleft Lip and Palate Foundation(Nagoya)
  • Int'l Joint Research
• [Presentation] Replication of genome wide association findings for Cleft Lip and Palate a role for variants in MAFB, VAX1 and PAX7 in Asian populations. (2019)
  • Author(s): S. Suzuki, ML. Marazita, ME. Cooper,E. Dragan, A. Butali, M. Mansila, N. Natsume, Y. Suzuki, T. Niimi, M. Yamamoto, G. Ayanga, T. Erkhembaatar, H. Furukawa, K. Minami, H. Imura, K. Fujiwara, J. L’Heureux J, K. Durda,AC. Lidral, JC. Murray
  • Organizer: The 59Th Annual Meeting of The Japanese Teratology Society The 13th World Congress of The International Cleft Lip and Palate Foundation(Nagoya)
  • Int'l Joint Research
• [Presentation] ASSOCIATION OF MEOX2 POLYMORPHISM WITHNONSYNDROMIC CLEFT PALATE ONLY IN A COMPARISON BETWEEN A JAPANESE POPULATION AND A VIETNAMESE POPULATION (2019)
  • Author(s): Duy Le Tran,Hideto Imura, Akihiro Mori, Satoshi Suzuki, Teruyuki Niimi, Toko Hayakawa, Tham Thi Hong Nguyen, Phuong Thi Pham, Ut Cong Nguyen, Viet Hoang, Hiep Minh Trinh, Minh Duc Nguyen, Tan Van Ngo, Mai Van Phan, Nagato Natsume
  • Organizer: The 59Th Annual Meeting of The Japanese Teratology Society The 13th World Congress of The International Cleft Lip and Palate Foundation(Nagoya)
  • Int'l Joint Research
• [Presentation] エチオピア連邦民主共和国における先天異常に関する研究(第5報) (2018)
  • Author(s): 吉田 磨弥, 古川 博雄, 鈴木 聡, 山内 楓子, 井村 英人, 新美 照幸, 夏目 長門
  • Organizer: 第30回日本小児口腔外科学会総会・学術大会
• [Presentation] 日本人非症候性口唇口蓋裂におけるBMP4遺伝子の一塩基多型(rs4444235)遺伝子多型解析 (2018)
  • Author(s): 森 明弘, 井村 英人, 鈴木 聡, 吉田 磨弥, 古川 博雄, 新美 照幸, 佐久間 千里, 伊東 雅哲, 南 克浩, 秋山 泰範, 早川 統子, 夏目 長門
  • Organizer: 第42回日本口蓋裂学会総会・学術集会（大阪）
• [Presentation] Identfication of 16q21 as a modifier locus for orofacial cleft phenotypes (2017)
  • Author(s): E.J. Lesile, J.C.Standley, A.Petrin, J.R.Shaffer, A. Butali, C. J. Buxo, E. Castilla, K. Christensen, F.W.D. Deleyiannis, J.T.Hecht, L.L.Field, A.Garidkhuu, L.M. Moreno-Uribe, N. Nagato, L.M.Orioli, C, Poietta, S.Suzuki, A.R. Vieira, G.L. Wehby, S.M. Weingold, J.C. Murray, M.L. Marazazita
  • Organizer: The American Society of Human Genetics 2017 Annual Meeting
  • Int'l Joint Research