High-throughput sequencing method of the KIR haplotype for clinical applications

• Project/Area Number: 26430195
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical genome science
• Research Institution: Kanazawa University
• Principal Investigator: Hosomichi Kazuyoshi 金沢大学, 医学系, 准教授 (50420948)
• Co-Investigator(Kenkyū-buntansha): 井ノ上 逸朗 国立遺伝学研究所, 総合遺伝研究系, 教授 (00192500) ; 椎名 隆 東海大学, 医学部, 准教授 (00317744)
• Research Collaborator: YABE Toshio 日本赤十字社, 関東甲信越ブロック血液センター, 検査開発二係長
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: NGS / KIR / HLA / 造血幹細胞移植 / 同種造血幹細胞移植 / 次世代シーケンサー / キラー細胞免疫グロブリン様受容体 / 組織適合性抗原

Outline of Final Research Achievements

Killer-cell immunoglobulin-like receptors (KIRs) expressing on natural killer (NK) cells are ligands of human leukocyte antigen (HLA) class I molecules. The number of KIR genes is different among KIR haplotypes, therefore each individual has a different number of inhibitory and activating KIR genes. Here, we established high-throughput sequencing method to identify the haplotype structure of HLA and KIR genes. The method for KIR and HLA typing was based on sequence capture method with custom oligo probes and MiSeq. Sequence reads from seventeen KIR genes could be aligned. The alignment result of KIR genes has distinct depth indicating copy number variation (CNV). The single nucleotide variants were used to estimate KIR allele sequence. Combination of CNV and SNVs as KIR allele could be available to estimate KIR haplotype structure.

Research Products

• [Journal Article] Identification of an HLA class I allele closely involved in the auto-antigen presentation in acquired aplastic anemia (2017)
  • Author(s): Zaimoku Y, Takamatsu H, Hosomichi K, Ozawa T, Nakagawa N, Imi T, Maruyama H, Katagiri T, Kishi H, Tajima A, Muraguchi A, Kashiwase K, Nakao S
  • Journal Title: Blood Volume: 印刷中 Issue: 21 Pages: 2908-2916
  • DOI: 10.1182/blood-2016-11-752378
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive genetic exploration of selective tooth agenesis of mandibular incisors by exome sequencing (2017)
  • Author(s): Yamaguchi T, Hosomichi K, Yano K, Kim Y, Nakaoka H, Kimura R, Otsuka H, Nonaka N, Haga S, Takahashi M, Shirota T, Kikkawa Y, Yamada A, Kamijo R, Park SB, Nakamura M, Maki K, Inoue I
  • Journal Title: Hum Genome Variation Volume: 印刷中 Issue: 1 Pages: 17005-17005
  • DOI: 10.1038/hgv.2017.5
  • NAID: 120006891152
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Rapid and cost-effective high-throughput sequencing for identification of germline mutations of BRCA1 and BRCA2 (2017)
  • Author(s): Ahmadloo S, Nakaoka H, Hayano T, Hosomichi K, You H, Utsuno E, Sangai T, Nishimura M, Matsushita K, Hata A, Nomura F, Inoue I
  • Journal Title: J Hum Genetics Volume: 印刷中 Issue: 5 Pages: 561-567
  • DOI: 10.1038/jhg.2017.5
  • NAID: 40021210379
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Whole-exome sequencing analysis of supernumerary teeth occurrence in Japanese individuals (2017)
  • Author(s): Takahashi M, Hosomichi K, Yamaguchi T, Yano K, Funatsu T, Adel M, Haga S, Maki K, Tajima A
  • Journal Title: Hum Genome Variation Volume: 印刷中 Issue: 1 Pages: 16046-16046
  • DOI: 10.1038/hgv.2016.46
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structure and evolution of the filaggrin gene repeated region in primates (2017)
  • Author(s): Romero V, Hosomichi K, Nakaoka H, Shibata H, Inoue I
  • Journal Title: BMC Evol Biol. Volume: 印刷中 Issue: 1 Pages: 10-10
  • DOI: 10.1186/s12862-016-0851-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Germline Variants of Prostate Cancer in Japanese Families (2017)
  • Author(s): Hayano T, Matsui H, Nakaoka H, Ohtake N, Hosomichi K, Suzuki K, Inoue I
  • Journal Title: PLoS One Volume: 印刷中 Issue: 10 Pages: e0164233-e0164233
  • DOI: 10.1371/journal.pone.0164233
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive microbiome analysis of tonsillar crypts in IgA nephropathy. (2017)
  • Author(s): Watanabe H, Goto S, Mori H, Higashi K, Hosomichi K, Aizawa N, Takahashi N, Tsuchida M, Suzuki Y, Yamada T, Horii A, Inoue I, Kurokawa K, Narita I.
  • Journal Title: Nephrol Dial Transplant. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] A partial nuclear genome of the Jomons who lived 3000 years ago in Fukushima, Japan. (2017)
  • Author(s): Kanzawa-Kiriyama H, Kryukov K, Jinam TA, Hosomichi K, Saso A, Suwa G, Ueda S, Yoneda M, Tajima A, Shinoda KI, Inoue I, Saitou N. A partial nuclear genome of the Jomons who lived 3000 years ago in Fukushima, Japan
  • Journal Title: J Hum Genetics Volume: 印刷中 Issue: 2 Pages: 213-221
  • DOI: 10.1038/jhg.2016.110
  • NAID: 40021064864
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive genetic testing approach for major inherited kidney diseases, using next-generation sequencing with a custom panel (2017)
  • Author(s): Mori T, Hosomichi K, Chiga M, Mandai S, Nakaoka H, Sohara E, Okado T, Rai T, Sasaki S, Inoue I, Uchida S.
  • Journal Title: Clin Exp Nephrol. Volume: 印刷中 Issue: 1 Pages: 63-75
  • DOI: 10.1007/s10157-016-1252-1
  • Peer Reviewed / Open Access
• [Presentation] New NGS HLA Typing By Targeted Enrichment Procedure -Capture Method- (2016)
  • Author(s): Hidetoshi Inoko, Yuko Okudaira, Anri Masuya, Astushi Tajima, Kazuyoshi Hosomichi.
  • Organizer: American Society for Histocompatibility and Immunogenetics 42nd Annual Meeting
  • Place of Presentation: Hyatt Regency St. Louis at the Arch (St. Louis, Missouri)
  • Int'l Joint Research
• [Presentation] HLA遺伝子群の網羅的タイピング法の臨床検査に向けた自動化システム開発 (2016)
  • Author(s): 細道一善, 副田憲司, 江畑明彦, 藤村興輝, 尾畑浩司, 猪子英俊, 田嶋敦
  • Organizer: 第25回日本組織適合性学会大会
  • Place of Presentation: 北海道大学 (北海道札幌市)
• [Presentation] PCRを用いないHLAのDNAタイピング開発 ―NGSキャプチャー法― (2016)
  • Author(s): 猪子英俊, 桝屋安里, 奥平裕子, 朝治桜子, 田嶋敦, 細道一善
  • Organizer: 第25回日本組織適合性学会大会
  • Place of Presentation: 北海道大学 (北海道札幌市)
• [Presentation] 日本在来牛と黒毛和種のウシ MHC 領域のリシークエンスによる比較解析 (2016)
  • Author(s): 竹嶋伸之輔, 細道一善, 万年英之, 国枝哲夫, 印牧美佐夫, 下桐猛, 間陽子
  • Organizer: 第25回日本組織適合性学会大会
  • Place of Presentation: 北海道大学 (北海道札幌市)
• [Presentation] 臍帯血を用いた次世代シークエンシングによる HLA 遺伝子の RNA 発現解析 (2016)
  • Author(s): 椎名隆, Yamamoto Fiona, 鈴木進悟, 森島聡子, 細道一善, 伊藤さやか, 重成敦子, 加藤俊一, 森島泰雄
  • Organizer: 第25回日本組織適合性学会大会
  • Place of Presentation: 北海道大学 (北海道札幌市)
• [Presentation] A pipeline for HLA typing from targeted Next Generation's Sequencing (NGS) data (2016)
  • Author(s): Waleed H. Omer, 中岡博史, 細道一善, 井ノ上逸朗
  • Organizer: 第25回日本組織適合性学会大会
  • Place of Presentation: 北海道大学 (北海道札幌市)
• [Presentation] 日本人集団には 0.9% の頻度で HLA-C*08:22が存在する (2016)
  • Author(s): 奥平裕子, 鈴木進悟, 桝屋安里, 朝治桜子, 安藤麻子, 光永滋樹, 細道一善, 猪子英俊
  • Organizer: 第25回日本組織適合性学会大会
  • Place of Presentation: 北海道大学 (北海道札幌市)
• [Presentation] HLA個別化医療の実現に向けて (2016)
  • Author(s): 細道一善
  • Organizer: 日本遺伝学会第88回大会シンポジウム
  • Place of Presentation: 日本大学国際関係学部 (静岡県三島市)
  • Invited
• [Presentation] HLA-based precision medicine can be a clinical reality (2016)
  • Author(s): Kazuyoshi Hosomichi
  • Organizer: 医学セミナー・第 13 回分子遺伝疫学セミナー
  • Place of Presentation: 筑波大学 (茨城県つくば市)
  • Invited
• [Presentation] ゲノム解析技術の革新と医学・医療へのインパクト (2016)
  • Author(s): 細道一善
  • Organizer: 第28回中央血液研究所学術講演会
  • Place of Presentation: 日本赤十字社中央血液研究所 (東京都江東区)
  • Invited
• [Presentation] 新世代ゲノム解析技術とゲノム医科学のイノベーション (2016)
  • Author(s): 細道一善
  • Organizer: 京滋血液研究会
  • Place of Presentation: HLA研究所 (京都府京都市)
  • Invited
• [Presentation] 同種造血幹細胞移植成績向上を目指した KIR ハプロタイプ解析手法の確立 (2015)
  • Author(s): 細道一善、屋部登志雄、椎名隆、田嶋敦、井ノ上逸朗
  • Organizer: 第60回日本人類遺伝学会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2015-11-19
• [Presentation] 同種造血幹細胞移植成績向上を目指した KIR ハプロタイプ解析手法の確立 (2015)
  • Author(s): 細道一善、屋部登志雄、椎名隆、田嶋敦、井ノ上逸朗
  • Organizer: 第24回日本組織適合性学会大会
  • Place of Presentation: ホテルレイクビュー水戸(茨城)
  • Year and Date: 2015-09-10
• [Presentation] The impact of NGS on HLA research. (2015)
  • Author(s): Kazuyoshi Hosomichi
  • Organizer: YARSI GENOMIC MEDICINE CONFERENCE 2015
  • Place of Presentation: Universitas YARSI (Jakarta, Indonesia)
  • Year and Date: 2015-05-06
  • Int'l Joint Research / Invited
• [Patent(Industrial Property Rights)] PCRを用いないキャプチャー法によるHLA遺伝子タイピング用プロー ブセット及びそれを用いたタイピング方法 (2016)
  • Inventor(s): 細道一善、猪子英俊、田嶋敦、井ノ上逸朗
  • Industrial Property Rights Holder: 細道一善、猪子英俊、田嶋敦、井ノ上逸朗
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-02-03