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Development of association analysis method for rare diseases based on comprehensive HLA typing with multiple risk factors

Research Project

Project/Area Number 16K18474
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical genome science
Research InstitutionKyoto University

Principal Investigator

Kawaguchi Shuji  京都大学, 医学研究科, 助教 (00525404)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
KeywordsHLA / 次世代シークエンサー / タイピング / アルゴリズム / 遺伝統計学 / マルチプレックスPCR / ジェノタイピング / ソフトウェア / 関連解析 / HTLV-1 / ゲノム / 免疫学 / バイオインフォマティクス
Outline of Final Research Achievements

We have established novel sequencing and typing technologies for HLA genes that can type more comprehensive HLA alleles with high resolution than conventional typing method. We have also developed a method for association analysis that can derive susceptible or protective amino acid residues on HLA protein with considering various risk factors of disease development. By using the developed methods, we carried out HLA typing of 928 patients of HTLV-1 associated myelopathy (HAM), 2,398 asymptomatic HTLV-1 carriers and 2,553 uninfected controls, and conducted association study between HLA genes and HAM development. As a result, we could identify susceptible and protective amino acid residues for HAM development that have different effect with proviral load.

Academic Significance and Societal Importance of the Research Achievements

従来のHLAアレルのタイピング方法は、高コストでありながら得られる精度や情報が少ないため、解析を行うためのサンプル数の不足や、得られたHLAアレルやアミノ酸残基の頻度に歪みが生じるといった問題が存在した。本研究で確立したHLA解析技術を用いることで、高精度でありながら低コストにHLA遺伝子解析を行うことが可能であり、様々な難治性疾患における発症リスクや診断に有用となるバイオマーカーの発見が期待できる。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Products Report
  • Research Products

    (16 results)

All 2021 2020 2019 2018 2017 2016 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 2 results) Book (3 results) Remarks (2 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 2 results)

  • [Journal Article] Genome wide association study of HTLV-1 associated myelopathy/tropical spastic paraparesis in the Japanese population2021

    • Author(s)
      Penova Marina et al.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 11

    • DOI

      10.1073/pnas.2004199118

    • Related Report
      Products Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HLA-HD: An accurate HLA typing algorithm for next-generation sequencing data2017

    • Author(s)
      Kawaguchi Shuji, Higasa Koichiro, Shimizu Masakazu, Yamada Ryo, Matsuda Fumihiko
    • Journal Title

      Human Mutation

      Volume: 38 Issue: 7 Pages: 788-797

    • DOI

      10.1002/humu.23230

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] HTLV-1 高浸淫地域における大規模HLA解析による感染およびHAM/TSP発症リスクの関連解析2018

    • Author(s)
      川口 修治、ペノヴァ マリナ、川口 喬久、清水 正和、高橋 めい子、日笠 幸一郎、松田 文彦
    • Organizer
      第五回日本HTLV-1学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 次世代シークエンサーと国際データベースを用いた高効率・高精度なHLA遺伝子群の包括的タイピング技術の確立2018

    • Author(s)
      川口 修治、日笠 幸一郎、清水 正和、山田 亮、松田 文彦
    • Organizer
      日本人類遺伝学会第63回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of an AI-assisted algorithm for the prediction of novel causal genes and variants for mendelian disorders2018

    • Author(s)
      Shuji Kawaguchi, Reitaro Tokumasu, Koichiro Higasa, Fumihiko Matsuda
    • Organizer
      From Molecules and Cells to Human Health : Ideas and concepts
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] HLA-HD: a high performance HLA typing algorithm using next generation sequencing results to create a reliable catalog of HLA alleles2016

    • Author(s)
      Kawaguchi S, Higasa K, Yamada R, Matsuda F
    • Organizer
      ICHG 2016
    • Place of Presentation
      Kyoto
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] 次世代シークエンスデータと国際データベースを用いたHLA遺伝子型の決定、最新醫學74巻2号、214-2192019

    • Author(s)
      川口 修治、日笠 幸一郎、山田 亮、松田 文彦
    • Total Pages
      6
    • Publisher
      最新医学社
    • Related Report
      2018 Annual Research Report
  • [Book] Comprehensive HLA Typing from a Current Allele Database Using Next-Generation Sequencing Data, in Methods Mol Biol., 1802, Sebastian Boegel (Eds): HLA Typing, 225-233.2018

    • Author(s)
      Kawaguchi Shuji、Higasa Koichiro、Yamada Ryo、Matsuda Fumihiko
    • Total Pages
      9
    • Publisher
      Humana Press, New York, NY
    • ISBN
      9781493985456
    • Related Report
      2018 Annual Research Report
  • [Book] Comprehensive HLA Typing from a Current Allele Database Using Next-Generation Sequencing Data., Methods Mol. Biol., Vol. 1802, Sebastian Boegel (Eds): HLA Typing, doi:10.1007/978-1-4939-8546-3_162018

    • Author(s)
      Shuji Kawaguchi, Koichiro Higasa, Ryo Yamada, Fumihiko Matsuda
    • Publisher
      Springer-Verlag New York
    • ISBN
      9781493985456
    • Related Report
      2017 Research-status Report
  • [Remarks] HLA-HD ホームページ

    • URL

      http://www.genome.med.kyoto-u.ac.jp/HLA-HD/

    • Related Report
      2018 Annual Research Report 2016 Research-status Report
  • [Remarks] HLA-HD

    • URL

      https://www.genome.med.kyoto-u.ac.jp/HLA-HD/

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 被験者のHLA遺伝子のアレルペアを判定する方法2021

    • Inventor(s)
      松田 文彦, 川口 修治, 日笠 幸一郎, 山田 亮
    • Industrial Property Rights Holder
      京都大学
    • Industrial Property Rights Type
      特許
    • Acquisition Date
      2021
    • Related Report
      Products Report
    • Overseas
  • [Patent(Industrial Property Rights)] HLA遺伝子のPCRプライマーセット及びそれを用いたシークエンス法2020

    • Inventor(s)
      松田 文彦, 川口 修治, 清水 正和, 日笠 幸一郎
    • Industrial Property Rights Holder
      京都大学
    • Industrial Property Rights Type
      特許
    • Acquisition Date
      2020
    • Related Report
      Products Report
  • [Patent(Industrial Property Rights)] HLA遺伝子のPCRプライマーセット及びそれを用いたシークエンス法2018

    • Inventor(s)
      松田文彦、川口修治、清水正和、日笠幸一郎
    • Industrial Property Rights Holder
      松田文彦、川口修治、清水正和、日笠幸一郎
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2017 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] HLA遺伝子のPCRプライマーセット及びそれを用いたシークエンス法2017

    • Inventor(s)
      松田 文彦, 川口 修治, 清水 正和, 日笠 幸一郎
    • Industrial Property Rights Holder
      松田 文彦, 川口 修治, 清水 正和, 日笠 幸一郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-024397
    • Filing Date
      2017-02-13
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 被験者のHLA遺伝子のアレルペアを判定する方法2016

    • Inventor(s)
      松田 文彦, 川口 修治, 日笠 幸一郎, 山田 亮
    • Industrial Property Rights Holder
      松田 文彦, 川口 修治, 日笠 幸一郎, 山田 亮
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-257041
    • Filing Date
      2016-12-28
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2023-03-30  

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