{"id":"hum0312","version":2,"url":"https://humandbs.dbcls.jp/research/hum0312/v2","datePublished":"2024-06-20","versions":[{"version":1,"datePublished":"2024-06-17"},{"version":2,"datePublished":"2024-06-20"}],"title":{"ja":"機能性遺伝子多型の網羅的解析を介した多因子疾患の病態解明","en":"Genetic study of complex diseases through comprehensive analysis of functional variants"},"summary":{"aims":{"ja":"自己免疫疾患を含む多因子疾患においてゲノムワイド関連解析（Genome-wide association study：GWAS）が行われ、1000を超える疾患感受性遺伝子領域が同定されてきた。しかしGWASは、疾患に関連する遺伝子多型が連鎖不平衡ブロック内に存在することを示すにすぎず、病態の理解のためには、1. 原因遺伝子多型の同定、2. 原因遺伝子多型が周辺の遺伝子の機能に与える影響の解明、3. これらの遺伝子多型の積み重なりが病態に関わる細胞・組織の機能に与える影響の解明、が必要である。本研究では、既存の疾患GWASデータと、expression quantitative trait loci（eQTL）やsplicing QTL（sQTL）解析などを統合したオミックス解析により、機能性遺伝子多型の網羅的解析を通じて様々な多因子疾患の病態解明を目指す。","en":"Genome-wide association studies (GWAS) have been conducted in multifactorial diseases such as autoimmune diseases, and more than 1000 disease susceptibility variants have been identified. However, GWAS only indicates the presence of disease-causing variants within a region. The effects of the accumulation of these variants on the functions of cells and tissues involved in disease states must be clarified. This study aims to integrate public GWAS data and expression quantitative trait loci (eQTL) and splicing QTL (sQTL) analyses to elucidate the pathogenesis of various multifactorial diseases through a comprehensive analysis of functional variants."},"methods":{"ja":"【DRA016393/DRA016394/DRA016395/DRA018714】ヒトリンパ芽球様細胞株（Lymphoblastoid Cell Line：LCL）の total RNA を使用した Iso-seq ならびに RNA-seq\n【DRA016285】末梢血単核細胞（PBMC）から29の免疫細胞サブセットを14-color cell sorter BD FACSAria Fusionを用いて分離し、total RNAを抽出した後、ポリA選択、SMART-seq v4 Ultra Low Input RNA Kitと SQK-LSK109を用いたcDNAライブラリーの調製を行った。フローサイトメトリー染色パネルについては、Human Immunology Projectの定義に従った。好中球は、EasySep Direct Human Neutrophil Isolation KitsまたはMACSxpress Neutrophil Isolation Kits humanで回収した。生成されたcDNAはFlongle Flow Cell（ロングリード）により塩基配列を決定した。","en":"[DRA016393 / DRA016394 / DDRA016395 / RA018714] Total RNAs from Lymphoblastoid Cell line (LCL) samples were used for Iso-seq and RNA-seq analyses\n[DRA016285] Twenty-nine immune cell subsets were isolated from peripheral blood mononuclear cells using the 14-color cell sorter BD FACSAria Fusion. Total RNA was extracted, followed by polyA selection and cDNA library preparation using the SMART-seq v4 Ultra Low Input RNA Kit and SQK-LSK109 for cDNA library preparation. For flow cytometry staining panels, the definitions of the Human Immunology Project were followed. Neutrophils were recovered with EasySep Direct Human Neutrophil Isolation Kits or MACSxpress Neutrophil Isolation Kits human. The generated cDNA was sequenced by Flongle Flow Cell (long-read system)."},"targets":{"ja":"【DRA016393/DRA016394/DRA016395/DRA018714】1000 Genomes Registryの日本人LCLにインターフェロン（IFNa2）刺激有/無条件下で培養した細胞\n【DRA016285】健常人末梢血から分離した29種類の免疫細胞種","en":"[DRA016393 / DRA016394 / DDRA016395 / RA018714] Samples with and without interferon (IFNa2) stimulation were obtained from LCL samples derived from the 1000 Genomes Registry.\n[DRA016285] 29 immune cell types isolated from peripheral blood cells collected from a 42-year-old healthy individual"},"url":{"ja":[{"url":"https://www.tmd.ac.jp/press-release/20240528-3/","text":"https://www.tmd.ac.jp/press-release/20240528-3/"}],"en":[{"url":"https://www.tmd.ac.jp/english/press-release/20240528-3/","text":"https://www.tmd.ac.jp/english/press-release/20240528-3/"}]}},"listingSummary":{"methods":{"ja":"発現","en":"Expression profiling"},"targets":{"ja":"日本人健常者不死化B細胞株：95検体\n（細胞株）\n健常人：1名\n（日本人）","en":"immortalized B cell lines from healthy Japanese volunteers: 95 samples\n(Cell-line)\n1 healthy subject\n(Japanese)"},"typeOfData":{"ja":"NGS\n（RNA-seq、Iso-seq）","en":"NGS\n(RNA-seq, Iso-seq)"}},"releaseNote":{"ja":"健常人1名の末梢血から分離した免疫細胞29画分を用いたロングリードRNA-seq解析データをfastqファイルにて提供する。","en":"29 immune cell subsets were isolated from peripheral blood mononuclear cells collected from a healthy individual. Long-read RNA sequencing was performed with each immune cell subset sample. Fastq files are provided."},"dataProviders":[{"name":{"ja":"高地 雄太","en":"Yuta Kochi"},"organization":{"name":{"ja":"東京医科歯科大学 難治疾患研究所 ゲノム機能多様性分野","en":"Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University"}}}],"researchProjects":[{"name":{"ja":"TRAnscriptomic resource of Immune cells using Long-read Sequencing (TRAILS)","en":"TRAnscriptomic resource of Immune cells using Long-read Sequencing (TRAILS)"},"url":{"ja":[{"url":"https://www.tmd.ac.jp/press-release/20240528-3/","text":"https://www.tmd.ac.jp/press-release/20240528-3/"}],"en":[{"url":"https://www.tmd.ac.jp/english/press-release/20240528-3/","text":"https://www.tmd.ac.jp/english/press-release/20240528-3/"}]}}],"grants":[{"title":{"ja":"免疫細胞におけるsplicing QTLを介した自己免疫疾患病因メカニズムの解明","en":"Mechanisms of autoimmune disease pathogenesis through splicing QTLs in immune cells"},"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":["18H02849"]},{"title":{"ja":"トランスオミックス解析によるNMD標的転写産物の生理病理学的意義の解明","en":"Investigating the physiological and pathological significance of NMD target transcripts through transomics analysis"},"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":["22H02597"]},{"title":{"ja":"自己免疫疾患におけるレトロエレメントおよびその多型の役割の解明","en":"Exploring the role of retroelements and their polymorphisms in autoimmune diseases"},"agency":{"ja":"科学研究費助成事業 挑戦的萌芽研究","en":"KAKENHI Grant-in-Aid for challenging Exploratory Research"},"grantIds":["21K19501"]},{"title":{"ja":"レトロトランスポゾン領域を介したシェーグレン症候群の病態機序の解明","en":"Elucidation of Sjögren's syndrome pathogenesis through retrotransposon sequences"},"agency":{"ja":"科学研究費助成事業 特別研究員奨励費","en":"KAKENHI Grant-in-Aid for JSPS Fellows"},"grantIds":["21J00596"]},{"title":{"ja":"超高深度アイソフォミクス手法の構築および時空間プロテインアトラスの作成","en":"Development of high-depth Isoformics techniques and creation of a spatiotemporal protein atlas"},"agency":{"ja":"科学研究費助成事業 特別研究員奨励費","en":"KAKENHI Grant-in-Aid for JSPS Fellows"},"grantIds":["21J15131"]},{"title":{"ja":"大規模プロテオフォーム解析法の開発とその全体像の理解","en":"Large-scale proteoform analysis for unveiling the entire view"},"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":["21H02459"]}],"relatedPublications":[{"title":"Long-read sequencing for 29 immune cell subsets reveals disease-linked isoforms","doi":"https://doi.org/10.1038/s41467-024-48615-4","datasets":["DRA016285"]}],"datasets":["DRA016394","DRA018714","DRA016393","DRA016395","DRA016285"],"controlledAccessUsers":[]}