Exploration of psoriasis-susceptibility variants in germline and somatic cells by exome sequencing

• Project/Area Number: 15K09785
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tokai University
• Principal Investigator: OKA Akira 東海大学, 総合医学研究所, 講師 (80384866)
• Co-Investigator(Kenkyū-buntansha): 池田 志斈 順天堂大学, 医学部, 教授 (40193198) ; 照井 正 日本大学, 医学部, 教授 (30172109) ; 佐野 栄紀 高知大学, 教育研究部医療学系臨床医学部門, 教授 (80273621) ; 馬渕 智生 東海大学, 医学部, 教授 (30408059)
• 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 乾癬 / Superimposed linear / 体細胞変異 / 全ゲノムシークエンシング / エクソーム / シークエンシング / 遺伝子 / ゲノム / 家族症例

Outline of Final Research Achievements

Any somatic mutations in psoriasis have never been investigated, though variants in the germline have been analyzed around the world. However, there should be disease-causing variants in not only germline but also somatic cells. Thus, cutaneous mosaicism may contribute to the psoriasis pathogenesis. Therefore, we investigated variants of affected and unaffected skin in superimposed linear psoriasis showing manifestations along Blaschko’s line by whole genome sequencing. We obtain the massive data from sequencing and are exploring DNA substitutions, LOH (loss of heterozygosity), CNV (copy number variant), and structural variant now.

Research Products

• [Journal Article] RXRB Is an MHC-Encoded Susceptibility Gene Associated with Anti-Topoisomerase I?Antibody-Positive Systemic Sclerosis (2017)
  • Author(s): Oka Akira、Asano Yoshihide、Hasegawa Minoru、Fujimoto Manabu、Kawaguchi Yasushi、Takahashi Hiroki、Goto Daisuke、Endo Hirahito、Jinnin Masatoshi、Mano Shuhei、Hosomichi Kazuyoshi、Mabuchi Tomotaka、Ueda Mahoko Takahashi、Nakagawa So、 SBahram Seiamak、Takehara Kazuhiko、Sato Shinichi、Ihn Hironobu
  • Journal Title: Journal of Investigative Dermatology Volume: 137 Issue: 9 Pages: 1878-1886
  • DOI: 10.1016/j.jid.2017.04.028
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis. (2017)
  • Author(s): Terao C, Kawaguchi T, Dieude P, Varga J, Kuwana M, Hudson M, Kawaguchi Y, Matucci-Cerinic M, Ohmura K, Riemekasten G, Kawasaki A, Airo P, Horita T, Oka A, Hachulla E, Yoshifuji H, Caramaschi P, Hunzelmann N, Baron M, Atsumi T, Hassoun P, Torii T, Takahashi M, et al.
  • Journal Title: Ann Rheum Dis. Volume: 印刷中 Issue: 6 Pages: 1150-1158
  • DOI: 10.1136/annrheumdis-2016-210645
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] RXRB is a MHC-encoded susceptibility gene associated with anti-topoisomerase I antibody-positive systemic sclerosis (2017)
  • Author(s): Akira Oka, Yoshihide Asano, Minoru Hasegawa, Manabu Fujimoto, Osamu Ishikawa, Masataka Kuwana, Yasushi Kawaguchi, Toshiyuki Yamamoto et al.
  • Journal Title: Journal of Investigative Dermatology Volume: -
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Recessive Inheritance of Population-Specific Intronic LINE-1 Insertion Causes a Rotor Syndrome Phenotype (2015)
  • Author(s): Tatehiro Kagawa, Akira Oka, Yoshinao Kobayashi, Yoichi Hiasa, Tsuneo Kitamura, Hiroshi Sakugawa, Yukihiko Adachi, Kazuya Anzai, Kota Tsuruya, Yoshitaka Arase, Shunji Hirose, Koichi Shiraishi, Takashi Shiina, Tadayuki Sato, Ting Wang, Masayuki Tanaka, Hideki Hayashi et al.
  • Journal Title: Human Mutation Volume: 36 Issue: 3 Pages: 327-332
  • DOI: 10.1002/humu.22745
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Relationship between Human Evolution and Neurally Mediated Syncope Disclosed by the Polymorphic Sites of the Adrenergic Receptor Gene α2B-AR (2015)
  • Author(s): Komiyama T, Hirokawa T, Sato K, Oka A, Kamiguchi H, Nagata E, Sakura H, Otsuka K, Kobayashi H.
  • Journal Title: PLoS One. Volume: 10 Issue: 4 Pages: e0120788-e0120788
  • DOI: 10.1371/journal.pone.0120788
  • Peer Reviewed / Open Access / Int'l Joint Research