Application of long-read sequencing technologies to investigate epilepsy-associated genes

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08164
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Yokohama City University
• Principal Investigator: MIZUGUCHI Takeshi 横浜市立大学, 医学部, 准教授 (90404996)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ロングリードシークエンサー / てんかん / Structural variant / リピート病

Outline of Final Research Achievements

To investigate the presence of a variant that remained unrecognized by standard genetic testing, we developed an analysis pipeline for long-read sequencing data. Using this pipeline, causal variants were newly identified in a difficult-to-sequence region characterized by GC-rich and repetitive sequences, suggesting the utility of this methodology for medical research. We also revealed previously unrecognized variability in the repeat size, configuration and composition of repeat expansion mutations that cause certain type of epilepsy.

Free Research Field

分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

てんかんは頻回の発作により脳機能に障害をきたす可能性が高く、遺伝子検査により早期に正確な診断をつけることは治療や医療情報提供、予後予測などの点で患者にもたらす利益が大きい。ロングリード解析により未解決症例の少なくとも一部の原因を同定できたこと、臨床症状とリピート内構造について塩基配列レベルの比較検討 (genotype-phenotype association) を行うための情報基盤を提供できたことは、遺伝情報を用いたてんかん診療の実現に資する成果である。