{"id":"hum0512","version":1,"url":"https://humandbs.dbcls.jp/research/hum0512/v1","datePublished":"2025-07-30","versions":[{"version":1,"datePublished":"2025-07-30"}],"title":{"ja":"自己免疫疾患のリスク多型の同定と機能解析","en":"Identification and functional analysis of risk polymorphisms in autoimmune diseases"},"summary":{"aims":{"ja":"自己免疫疾患は免疫システムが自己組織を障害する疾患群であり、人口の1％以上が罹患する難病である。自己免疫疾患の発症リスクにはゲノム配列の個人差（多型）が強く関与している。大規模ゲノム解析によって自己免疫疾患の発症等に関与する「リスク多型」が数多く同定されてきた。リスク多型の多くは免疫機能に関わる細胞の遺伝子発現制御領域に集積しているため、リスク多型の機能を正確に理解するためには、免疫機能に関わる細胞におけるリスク多型と遺伝子発現制御との関連を評価する必要がある。本研究では、自然多型を用いる従来の研究手法に加えて、ゲノム編集により導入した人工多型も活用することで、リスク多型の機能を解明することを目指す。具体的には、広範囲の細胞のマルチオミックスデータを詳細に解析し、網羅的・統合的ゲノム解析を駆使することで自己免疫疾患のリスク多型の局在を同定し、それらの機能を解明することを目指す。","en":"Autoimmune diseases occur when the immune system damages the body's tissues, affecting over 1% of the population. Genomic polymorphisms strongly influence autoimmune disease risk, with many identified through large-scale genomic analyses. Since these risk polymorphisms often cluster in gene expression regulatory regions of immune cells, evaluating their relationship with gene regulation in these cells is essential for understanding their functions. This research aims to elucidate risk polymorphism functions using both natural polymorphisms and artificial ones introduced through genome editing. We will analyze multi-omics data from various cells and employ comprehensive genomic analysis to precisely identify risk polymorphism locations and understand their functions."},"methods":{"ja":"bulk RNA-seq、bulk ATAC-seq、single cell CITE-seq","en":"bulk RNA-seq, bulk ATAC-seq, single cell CITE-seq (RNA-seq)"},"targets":{"ja":"健常者3名","en":"3 healthy donors"},"url":{"ja":[{"url":"https://immunogenetics.med.keio.ac.jp/","text":"https://immunogenetics.med.keio.ac.jp/"}],"en":[{"url":"https://immunogenetics.med.keio.ac.jp/en","text":"https://immunogenetics.med.keio.ac.jp/en"}]}},"listingSummary":{"methods":{"ja":"発現\nクロマチン構造","en":"Expression profiling and chromatin structure analysis"},"targets":{"ja":"健常者：3名\n（日本人）","en":"3 healthy donors\n(Japanese)"},"typeOfData":{"ja":"NGS\n（RNA-seq、ATAC-seq、scCITE-seq）","en":"NGS\n(RNA-seq, ATAC-seq, scCITE-seq)"}},"releaseNote":{"ja":"健常ドナー3名から単離したCD4+ T細胞およびCD3+ T細胞をノックダウン後24時間後、48時間後、72時間後に回収した細胞から抽出したRNA/DNAを対象としたbulk RNA-seq、bulk ATAC-seq、scCITE-seqを行った結果をfastq、tab、otherファイルにて提供する。","en":"CD4+ T cells and CD3+ T cells isolated from three healthy individuals were collected at 24, 48, and 72 hours after knockdown with LEF1 siRNA or control siRNA. RNA/DNA extracted from the CD4+ T cells and CD3+ T cells were used for bulk RNA-seq, bulk ATAC-seq and single-cell CITE-seq analyses. Fastq, tab and other files are provided."},"dataProviders":[{"name":{"ja":"石垣 和慶","en":"Kazuyoshi Ishigaki"},"organization":{"name":{"ja":"理化学研究所 生命医科学研究センター ヒト免疫遺伝研究チーム","en":"Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences"}}}],"researchProjects":[],"grants":[{"title":{"ja":"自己免疫疾患のリスク多型機能解析による個別化抗サイトカイン療法の確立","en":"Establishment of personalized anti-cytokine therapy through functional analysis of autoimmune disease risk polymorphisms"},"agency":{"ja":"科学研究費助成事業 基盤研究（B）","en":"KAKENHI Grant-in-Aid for Scientific Research (B)"},"grantIds":["22H03114"]},{"title":{"ja":"自己免疫疾患のリスク多型の機能を制御する転写因子の探索","en":"Identification of transcription factor controlling autoimmunity risk allele's pathogenic function"},"agency":{"ja":"科学研究費助成事業 研究活動スタート支援","en":"KAKENHI Grant-in-Aid for Research Activity Start-up"},"grantIds":["21K20647"]},{"title":{"ja":"ゲノム編集技術とターゲット解析を駆使した関節リウマチリスク多型機能解析","en":"Functional analysis of rheumatoid arthritis risk polymorphisms using genome editing technology and targeted analysis"},"agency":{"ja":"科学研究費助成事業 若手研究","en":"KAKENHI Grant-in-Aid for Early-Career Scientists"},"grantIds":["25K19621"]},{"title":{"ja":"Polygenic risk scoreが生体に与える影響の評価に関する技術開発","en":"Development of technology for evaluating the impact of polygenic risk scores on biological systems"},"agency":{"ja":"日本医療研究開発機構（AMED） ゲノム医療実現バイオバンク利活用プログラム","en":"Biobank - Construction and Utilization biobank for genomic medicine REalization (B-Cure), Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP22tm0424223"]},{"title":{"ja":"ゲノム編集技術を併用したリスク多型機能解析による関節リウマチの病態解明","en":"Elucidation of rheumatoid arthritis pathogenesis through functional analysis of risk polymorphisms combined with genome editing technology"},"agency":{"ja":"日本医療研究開発機構（AMED） 免疫アレルギー疾患実用化研究事業","en":"Practical Research Project for Allergic Diseases and Immunology, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP22ek0410099"]},{"title":{"ja":"バイオバンクを活用したT細胞受容体配列情報に基づく関節リウマチの新規診断マーカーの同定","en":"Identification of novel diagnostic markers for rheumatoid arthritis based on T cell receptor sequence information using biobanks"},"agency":{"ja":"日本医療研究開発機構（AMED） ゲノム研究を創薬等出口に繋げる研究開発プログラム","en":"Research and Development Program for Translating Genomic Research into Drug Discovery and Other Applications, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP23tm0524005"]},{"title":{"ja":"関節リウマチにおけるHLA遺伝子多型と喫煙の相互作用によるT細胞レベルの免疫寛容破綻の全容解明","en":"Comprehensive elucidation of T cell-level immune tolerance breakdown through interaction between HLA gene polymorphisms and smoking in rheumatoid arthritis"},"agency":{"ja":"日本医療研究開発機構（AMED） 免疫アレルギー疾患実用化研究事業","en":"Practical Research Project for Allergic Diseases and Immunology, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP25ek0410139"]},{"title":{"ja":"生体試料を用いた大規模機能ゲノミクス解析支援及びヒト免疫機能評価基盤の高度化","en":"Support for large-scale functional genomics analysis using biological samples and advancement of human immune function evaluation platform"},"agency":{"ja":"日本医療研究開発機構（AMED） 生命科学・創薬研究支援基盤事業","en":"Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS), Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP22ama121015"]},{"title":{"ja":"遺伝的多様性と機能に関するマルチオミックスを中心としたヒト免疫評価法の確立と支援の為のサポート機関","en":"Support organization for establishment and implementation of human immune evaluation methods centered on multi-omics of genetic diversity and function"},"agency":{"ja":"日本医療研究開発機構（AMED） ワクチン開発のための世界トップレベル研究開発拠点の形成事業","en":"Japan Initiative for World-leading Vaccine Research and Development Centers, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP223fa627010"]}],"relatedPublications":[{"title":"Accurate, sensitive, and efficient chromatin accessibility quantification at target loci using UNIChro-seq","doi":"https://doi.org/10.1038/s41467-026-75767-2","datasets":["JGAD000960"]}],"datasets":["JGAD000960"],"controlledAccessUsers":[{"principalInvestigator":{"ja":"浜田 道昭","en":"Michiaki Hamada"},"affiliation":{"ja":"浜田研究室, 理工学術院, 早稲田大学","en":"Hamada Laboratory, Faculty of Science and Engineering, Waseda University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"RNA標的創薬データベースの構築","en":"Construction of RNA-targeted Drug Discovery Database"},"periodStart":"2023-01-05","periodEnd":"2027-10-31","datasets":["JGAD000960"]}]}