Evolution of Yaponesians based on the diversity of HLA haplotypes

2022 Fiscal Year Annual Research Report

• Project Area: Deciphering Origin and Establishment of Japonesians mainly based on genome sequence data
• Project/Area Number: 21H00342
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: 細道 一善 東京薬科大学, 生命科学部, 教授 (50420948)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: ヤポネシア / HLA遺伝子 / HLAハプロタイプ

Outline of Annual Research Achievements

ヒトの主要組織適合遺伝子複合体(Human leukocyte antigen; HLA)は免疫応答の入り口として自己と非自己の認識を担うとともに、ヒトにおける機能的遺伝子と しては最も高度な多型を示す。この多型は自己免疫性疾患や感染症、さらには薬剤副作用と関連する遺伝要因として研究が進んでいる。さらに、その高度な多型 性は個人識別、人類集団の起源や形成過程を探る遺伝マーカーとしても有益である。本研究では古代人のHLA領域のハプロタイプ構造を明らかにし、免疫学的な視 点からもヤポネシア人の歴史を探ることを目的としており、これまでに、古代人のHLA遺伝子型ならびにHLAハプロタイプの決定を進めた。11のHLA遺伝子(HLA-A、 HLA-B、HLA-C、HLA-DPA1、HLA-DPB1、HLA-DQA1、HLA-DQB1、HLA-DRB1、HLA-DRB3、HLA-DRB4、HLA-DRB5、)についてプローブとのハイブリダイゼーションによって HLA遺伝子由来のDNA断片を濃縮した。ハイブリダイゼーションによって得られたDNAライブラリをNextSeq2000 (illumina)にて解析し、IPD- IMGT/HLADatabaserelease3.21.0.をリファレンスとしてHLA型を決定した。解析した29サンプルのうち、14サンプルにおいてHLAハプロタイプを決定した。特に北海道縄文晩期の有珠モシリ遺跡出土人骨11体は全てのHLAハプロタイプを決定することが可能であった。14サンプルから13種類のHLAハプロタイプを決定し、現代日本人集団における頻度を求めたところ、いずれも1%以下の低頻度であった。それぞれのHLAハプロタイプは頻度の特徴が異なり、多数の地域で低頻度で認められるものと特定の地域で比較的高い頻度を示すタイプが存在していた。

Research Progress Status

令和4年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和4年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] Universidad San Francisco de Quito(エクアドル)
  • Country Name: ECUADOR
  • Counterpart Institution: Universidad San Francisco de Quito
• [Journal Article] Genetic factors associated with serum amylase in a Japanese population: combined analysis of copy-number and single-nucleotide variants (2023)
  • Author(s): Zannatun Nayema, Takehiro Sato, Takayuki Kannon, Hiromasa Tsujiguchi, Kazuyoshi Hosomichi, Hiroyuki Nakamura, Atsushi Tajima
  • Journal Title: Journal of Human Genetics Volume: 68 Pages: 313～319
  • DOI: 10.1038/s10038-022-01111-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel SRY-box transcription factor 9 variant in campomelic dysplasia and the location of missense and nonsense variants along the protein domains: A case report (2022)
  • Author(s): Carlos A. Calvache, Estefania C. Vasquez, Vanessa I. Romero, Kazuyoshi Hosomichi, Juan C. Pozo
  • Journal Title: Frontiers in Pediatrics Volume: 10 Pages: 975947
  • DOI: 10.3389/fped.2022.975947
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Visualization of clonal expansion after massive depletion of cells carrying the bovine leukemia virus (BLV) integration sites during the course of disease progression in a BLV naturally-infected cow: a case report (2022)
  • Author(s): Susumu Saito, Kazuyoshi Hosomichi, Meripet Polat Yamanaka, Tetsuya Mizutani, Shin-nosuke Takeshima, Yoko Aida
  • Journal Title: Retrovirology Volume: 19 Pages: 24
  • DOI: 10.1186/s12977-022-00609-0
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive Genetic Exploration of Fused Teeth by Whole Exome Sequencing (2022)
  • Author(s): Heetae Park, Kazuyoshi Hosomichi, Yong-Il Kim, Yu Hikita, Atsushi Tajima, Tetsutaro Yamaguchi
  • Journal Title: Applied Sciences Volume: 12 Pages: 11899～11899
  • DOI: 10.3390/app122311899
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Isolation of ferret astrocytes reveals their morphological, transcriptional, and functional differences from mouse astrocytes (2022)
  • Author(s): Jureepon Roboon, Tsuyoshi Hattori, Dinh Thi Nguyen, Hiroshi Ishii, Mika Takarada-Iemata, Takayuki Kannon, Kazuyoshi Hosomichi, Takashi Maejima, Kengo Saito, Yohei Shinmyo, Michihiro Mieda, Atsushi Tajima, Hiroshi Kawasaki, Osamu Hori
  • Journal Title: Frontiers in Cellular Neuroscience Volume: 16 Pages: 877131
  • DOI: 10.3389/fncel.2022.877131
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] AMBRA1 p.Gln30Arg Mutation, Identified in a Cowden Syndrome Family, Exhibits Hyperproliferative Potential in hTERT-RPE1 Cells (2022)
  • Author(s): Sundaramoorthy Revathidevi, Kazuyoshi Hosomichi, Toyoaki Natsume, Hirofumi Nakaoka, Naoko T. Fujito, Hisako Akatsuka, Takehito Sato, Arasambattu Kannan Munirajan, Ituro Inoue
  • Journal Title: International Journal of Molecular Sciences Volume: 23 Pages: 11124～11124
  • DOI: 10.3390/ijms231911124
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Exploring the Genetic Basis of Dens Evaginatus Using Whole-Exome Sequencing (2022)
  • Author(s): Heetae Park, Kazuyoshi Hosomichi, Yong-Il Kim, Atsushi Tajima, Tetsutaro Yamaguchi
  • Journal Title: Applied Sciences Volume: 12 Pages: 8962～8962
  • DOI: 10.3390/app12188962
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Gallus gallus RJF reference genome reveals an MHCY haplotype organized in gene blocks that contain 107 loci including 45 specialized, polymorphic MHC class I loci, 41 C-type lectin-like loci, and other loci amid hundreds of transposable elements (2022)
  • Author(s): Ronald M Goto, Charles D Warden, Takashi Shiina, Kazuyoshi Hosomichi, Jibin Zhang, Tae Hyuk Kang, Xiwei Wu, Marla C Glass, Mary E Delany, Marcia M Miller
  • Journal Title: G3 Genes|Genomes|Genetics Volume: 12 Pages: jkac218
  • DOI: 10.1093/g3journal/jkac218
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Familial Pseudohypoparathyroidism Type IB Associated with an SVA Retrotransposon Insertion in the GNAS Locus (2022)
  • Author(s): Sayaka Kawashima, Akiko Yuno, Shinichiro Sano, Akie Nakamura, Keisuke Ishiwata, Tomoyuki Kawasaki, Kazuyoshi Hosomichi, Kazuhiko Nakabayashi, Hidenori Akustu, Hirotomo Saitsu, Maki Fukami, Takeshi Usui, Tsutomu Ogata, Masayo Kagami
  • Journal Title: Journal of Bone and Mineral Research Volume: 37 Pages: 1850～1859
  • DOI: 10.1002/jbmr.4652
  • Peer Reviewed / Open Access
• [Journal Article] RHEB is a potential therapeutic target in T cell acute lymphoblastic leukemia (2022)
  • Author(s): Loc Thi Pham, Hui Peng, Masaya Ueno, Susumu Kohno, Atuso Kasada, Kazuyoshi Hosomichi, Takehiro Sato, Kenta Kurayoshi, Masahiko Kobayashi, Yuko Tadokoro, Atsuko Kasahara, Mahmoud I Shoulkamy, Bo Xiao, Paul F Worley, Chiaki Takahashi, Atsushi Tajima, Atsushi Hirao
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 621 Pages: 74～79
  • DOI: 10.1016/j.bbrc.2022.06.089
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel Variation in Acyl-CoA Synthetase Long Chain Family Member 6 (ACSL6) Results in Protein Structural Modification and Multiple Non-Related Neoplasia in a 46-Year-Old: Case Report (2022)
  • Author(s): Maria Isabel Castillo, Erick Freire, Vanessa I. Romero, Benjamin Arias-Almeida, Carlos Reyes, Kazuyoshi Hosomichi
  • Journal Title: Frontiers in Oncology Volume: 12 Pages: 899579
  • DOI: 10.3389/fonc.2022.899579
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive Comparison of Novel Bovine Leukemia Virus (BLV) Integration Sites between B-Cell Lymphoma Lines BLSC-KU1 and BLSC-KU17 Using the Viral DNA Capture High-Throughput Sequencing Method (2022)
  • Author(s): Meripet Polat Yamanaka, Susumu Saito, Kazuyoshi Hosomichi, Yoko Aida
  • Journal Title: Viruses Volume: 14 Pages: 995～995
  • DOI: 10.3390/v14050995
  • Peer Reviewed / Open Access
• [Journal Article] No evidence of bovine leukemia virus proviral DNA and antibodies in human specimens from Japan (2022)
  • Author(s): Meripet Polat Yamanaka, Susumu Saito, Yukiko Hara, Ryosuke Matsuura, Shin-Nosuke Takeshima, Kazuyoshi Hosomichi, Yasunobu Matsumoto, Rika A Furuta, Masami Takei, Yoko Aida
  • Journal Title: Retrovirology Volume: 19 Pages: 995
  • DOI: 10.1186/s12977-022-00592-6
  • Peer Reviewed / Open Access
• [Journal Article] Deficiency of the splicing factor RBM10 limits EGFR inhibitor response in EGFR-mutant lung cancer (2022)
  • Author(s): Shigeki Nanjo, Kazuyoshi Hosomichi, Trever G Bivona et al.
  • Journal Title: Journal of Clinical Investigation Volume: 132 Pages: e145099
  • DOI: 10.1172/JCI145099
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Familial idiopathic basal ganglia calcification with a heterozygous missense variant (c.902C>T/p.P307L) in SLC20A2 showing widespread cerebrovascular lesions. (2022)
  • Author(s): Kenji Sakai, Chiho Ishida, Koji Hayashi, Naotaka Tsuji, Takayuki Kannon, Kazuyoshi Hosomichi, Nobuyuki Takei, Akiyoshi Kakita, Atsushi Tajima, Masahito Yamada
  • Journal Title: Neuropathology Volume: 42 Pages: 126～133
  • DOI: 10.1111/neup.12781
  • Peer Reviewed / Open Access
• [Journal Article] Biased expression of mutant alleles in cancer-related genes in esophageal squamous cell carcinoma (2022)
  • Author(s): Masahiko Takahashi, Kazuyoshi Hosomichi, Hirofumi Nakaoka, Haruhito Sakata, Naoya Uesato, Kentaro Murakami, Masayuki Kano, Takeshi Toyozumi, Yasunori Matsumoto, Tetsuro Isozaki, Nobufumi Sekino, Ryota Otsuka, Itsuro Inoue, Hisahiro Matsubara
  • Journal Title: Esophagus Volume: 19 Pages: 294～302
  • DOI: 10.1007/s10388-021-00900-7
  • Peer Reviewed / Open Access
• [Journal Article] Glucokinase-maturity onset diabetes mellitus in the young suggested by factory-calibrated glucose monitoring data: a case report (2022)
  • Author(s): Nao Nomura, Katsumi Iizuka, Eiichi Goshima, Kazuyoshi Hosomichi, Atsushi Tajima, Sodai Kubota, Yanyan Liu, Ken Takao, Takehiro Kato, Masami Mizuno, Takuo Hirota, Tetsuya Suwa, Yukio Horikawa, Daisuke Yabe
  • Journal Title: Endocrine Journal Volume: 69 Pages: 473～477
  • DOI: 10.1507/endocrj.EJ21-0526
  • Peer Reviewed / Open Access
• [Presentation] ヒトゲノムの解読困難領域の解析 (2022)
  • Author(s): 細道 一善
  • Organizer: 日本人類遺伝学会第67回大会
• [Presentation] 現代に受け継がれる古代人HLAハプロタイプ (2022)
  • Author(s): 細道 一善
  • Organizer: 第76回 日本人類学会大会・ 第38回 日本霊類学会大会 連合大会
• [Presentation] 微量および断片化DNAにおけるキャプチャー法によるHLAタイピング (2022)
  • Author(s): 5.岩内 陽子, 奥平 裕子, 桝屋 安里, 朝治 桜子, 葉畑 美和, 法花津 匠, 福島 香織, 中島 文明, 細道 一善
  • Organizer: 第30回日本組織適合性学会大会
• [Presentation] 繰り返し配列の違いを伴う新規HLAアレル配列の精度の検証 (2022)
  • Author(s): 6.奥平 裕子, 朝治 桜子, 桝屋 安里, 葉畑 美和, 法花津 匠, 岩内 陽子, 中島 文明, 野口 博司, Nuntana Kasitanon, Worawit Louthrenoo, 細道 一善, 竹内 二士夫, 猪子 英俊
  • Organizer: 第30回日本組織適合性学会大会
• [Presentation] NGSリードデータの繰り返し配列は新たなambiguityを生じ判定結果に影響する (2022)
  • Author(s): 8.桝屋 安里, 奥平 裕子, 岩内 陽子, 朝治 桜子, 葉畑 美和, 法花津 匠, 福島 香織, 細道 一善, 中島 文明
  • Organizer: 第30回日本組織適合性学会大会
• [Presentation] NGS法によるイラン人集団のHLA 11Lociタイピングおよびハプロタイプ調査 (2022)
  • Author(s): 9.葉畑 美和, 奥平 裕子, 桝屋 安里, 朝治 桜子, 法花津 匠, 岩内 陽子, 福島 香織, 細道 一善, 中島 文明
  • Organizer: 第30回日本組織適合性学会大会