Dissecting the role of retroelements and their variations in autoimmune diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19501
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Kochi Yuta 東京医科歯科大学, 難治疾患研究所, 教授 (60415156)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 自己免疫疾患 / ゲノムワイド関連解析 / ロングリードシークエンシング / レトロエレメント

Outline of Final Research Achievements

We aimed to clarify the role of retroelements in autoimmune diseases. First, we catalogued retroelement variations by long-read whole genome sequencing of Japanese B cell lines (n=27). We also performed Long-read RNA-seq of IFN-α-stimulated B cell lines and generated a catalog of 163,747 RNAs. Approximately 80% were novel RNAs, some of which were transcribed from unannotated loci including retroelements. We also identified genetic variations affecting the expression of these RNAs. We then integrated these data with genome-wide association study data and comprehensively identified those involved in autoimmune diseases.

Free Research Field

ゲノム医学

Academic Significance and Societal Importance of the Research Achievements

本研究は、いまだ全貌が明らかになっていない自己免疫疾患の病因メカニズムについて、ゲノム上の未開拓領域であるレトロエレメントから迫るものである。本研究では、自己免疫疾患に関わるレトロエレメント由来のRNAを網羅的に明らかにしたが、これらの解析によって整備されたRNAカタログは、自己免疫疾患以外の様々な疾患の病因解明につながる貴重なリソースになると考えられる。