日本人に多い癒合歯の原因遺伝子を全エクソンシーケンスで網羅的に探索する

• Project/Area Number: 21K10173
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Kanagawa Dental College
• Principal Investigator: 山口 徹太郎 神奈川歯科大学, 歯学部, 教授 (40384193)
• Co-Investigator(Kenkyū-buntansha): 高橋 正皓 神奈川歯科大学, 歯学部, 講師 (10736713)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 過剰歯 / ヒトゲノム / 遺伝子 / 家族性 / 癒合歯 / 全エクソンシーケンス

Outline of Research at the Start

癒合歯はヒトの顎が進化の過程で短縮してきたことにより、歯胚同士の間隔が狭くなったために隣り合う歯胚が癒合するとする人類の歯の退化の1つの現象とする考え方もあることからその遺伝因子の解明は歯科にとどまらない人類学・人類遺伝学、人類進化学、分子生物学においても大きな学術的波及効果が期待できる。日本人での発症率・出現頻度が高い疾患であれば、本研究成果が国民に還元できるところは大きく、その解明は急務である。

Outline of Annual Research Achievements

過剰歯を好発する鎖骨頭蓋異形成症が、染色体6p21に存在する runt-related transcription factor 2 遺伝子変異に起因することが報告されている。さらに、過剰歯を合併する頭蓋縫合早期癒合症家系で9p13.3の Interleukin 11 Receptor Subunit Alpha 遺伝子のホモ接合体変異が原因であることが明らかになっている。また、非症候群においても家族性を呈する家系が報告されている。本申請課題研究代表者所属機関における過剰歯の家系内罹患について調査した。その結果、家族性を呈する4家系を見出した。これら非症候群の過剰歯、特に上顎正中埋伏過剰歯の罹患者について原因遺伝子変異を探索した結果、複数の候補遺伝子変異を同定することに成功した。

Research Products

• [Int'l Joint Research] 釜山大学(韓国)
• [Journal Article] Identification of candidate genes of familial multiple idiopathic cervical root resorption. Journal of endodontics (2023)
  • Author(s): Muromachi K, Hosomichi K, Park H, Yamaguchi T, Tani-Ishii N.
  • Journal Title: Journal of endodontics Volume: 22 Issue: 11 Pages: 1537-1547
  • DOI: 10.1016/j.joen.2023.09.008
  • Peer Reviewed
• [Journal Article] An Observational Study on Changes in the Oral and Gut Microbiota through Professional Mechanical Tooth Cleaning, including Tooth-Brushing Instructions in Patients with Multi-Bracket Appliances. (2023)
  • Author(s): Okuwaki S, Hosomichi K, Tajima A, Yamaguchi T.
  • Journal Title: Applied Sciences Volume: 13 Pages: 10843-10843
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of Mandibular Volume and Linear Measurements in Patients with Mandibular Asymmetry (2023)
  • Author(s): Hikosaka Y, Koizumi S, Kim Y-I, Adel M, Nadim M, Hikita Y, Yamaguchi T
  • Journal Title: Diagnostics (Basel) Volume: 13 Issue: 7 Pages: 1331-1331
  • DOI: 10.3390/diagnostics13071331
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Factors Associated with the Proximity of the Incisive Canal to the Maxillary Central Incisor (2023)
  • Author(s): Ishii T, Koizumi S, Yamaguchi T
  • Journal Title: Applied Sciences Volume: 13 Pages: 6899-6899
  • Peer Reviewed / Open Access
• [Journal Article] Validation of Machine Learning Models for Craniofacial Growth Prediction (2023)
  • Author(s): Kim E, Kuroda Y, Soeda Y, Koizumi S, Yamaguchi T
  • Journal Title: Diagnostics (Basel) Volume: 13 Pages: 3369-3369
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of the maxillary sinus size of adult Korean individuals with different skeletal patterns using cone-beam computed tomography. (2023)
  • Author(s): Mitsuda C, Takahashi M, Kim Y-I, Takeda M, Hatanaka R, Sambe T, Yamaguchi T
  • Journal Title: 神奈川歯科大学学会雑誌 Volume: 58 Pages: 99-104
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effects of root contact length on the failure rate of anchor screw. (2022)
  • Author(s): Ikenaka R, Koizumi S, Otsuka T, Yamaguchi T
  • Journal Title: Journal of Oral Science Volume: 64(3) Pages: 232-235
  • Peer Reviewed
• [Journal Article] Condylar asymmetry in patients with mandibular asymmetry assessed by cone-beam computed tomography. (2022)
  • Author(s): Yuasa K, Otsuka T, Suginouchi Y, Adel M, Kim Y-I, Hikita Y, Koizumi S, Hatanaka R, Maki K, Yamaguchi T
  • Journal Title: 神奈川歯学 Volume: 57(1) Pages: 24-30
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Exploring the Genetic Basis of Dens Evaginatus Using Whole-Exome Sequencing. (2022)
  • Author(s): Park H, Hosomichi K, Kim Y-I, Tajima A, Yamaguchi T
  • Journal Title: Applied Sciences Volume: 12(18) Issue: 18 Pages: 8962-8962
  • DOI: 10.3390/app12188962
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prevalence of saliva immunoglobulin A antibodies reactive with severe acute respiratory syndrome coronavirus 2 among Japanese people unexposed to the virus. (2022)
  • Author(s): Tsukinoki K, Yamamoto T, Saito J, Sakaguchi W, Iguchi K, Inoue Y, Ishii S, Sato C, Yokoyama M, Shiraishi Y, Kato N, Shimada H, Makabe A, Saito A, Tanji M, Nagaoka I, Saruta J, Yamaguchi T, Kimoto S, Yamaguchi H
  • Journal Title: Microbiol Immunol Volume: 66 Issue: 8 Pages: 403-410
  • DOI: 10.1111/1348-0421.13011
  • Peer Reviewed / Open Access
• [Journal Article] Factors influencing the differences between three-dimensional measurement with cephalometric analysis and cone-beam computed tomography. (2022)
  • Author(s): Ariwa M, Koizumi S, Yamaguchi T
  • Journal Title: 神奈川歯学 Volume: 57(2) Pages: 98-103
  • Peer Reviewed
• [Journal Article] Comprehensive Genetic Exploration of Fused Teeth by Whole Exome Sequencing. (2022)
  • Author(s): Park H, Hosomichi K, Kim Y-I, Hikita Y, Tajima A, Yamaguchi T
  • Journal Title: Applied Sciences Volume: 12(23) Issue: 23 Pages: 11899-11899
  • DOI: 10.3390/app122311899
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of Mandibular Posterior Anatomic Limit with Skeletal Patterns and Root Morphology Using Three-Dimensional Cone Beam Computed Tomography Comprehensive Analysis. (2022)
  • Author(s): Iguchi K, Kim Y-I, Adel M, Nadim M, Hatanaka R, Koizumi S, Yamaguchi T
  • Journal Title: Diagnostics Volume: 12(12) Issue: 12 Pages: 3019-3019
  • DOI: 10.3390/diagnostics12123019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chin Morphology in Relation to the Skeletal Pattern, Age, Gender, and Ethnicity. (2022)
  • Author(s): Okumura Y, Koizumi S, Suginouchi Y, Hikita Y, Kim Y-I, Adel M, Nadim M, Yamaguchi T
  • Journal Title: Applied Sciences Volume: 12(24) Issue: 24 Pages: 12717-12717
  • DOI: 10.3390/app122412717
  • Peer Reviewed / Open Access / Int'l Joint Research