2023 Fiscal Year Final Research Report

Epigenetics studies of human diseases whose phenotypes do not follow Mendelian inheritance rules.

Research Project

PDF

Project/Area Number	20H03443
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 48040:Medical biochemistry-related
Research Institution	National Institute of Advanced Industrial Science and Technology
Principal Investigator	Kobayashi Shin 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (10397664)
Co-Investigator(Kenkyū-buntansha)	三浦史仁九州大学, 医学研究院, 准教授 (50447348) 廣瀬伸一福岡大学, 医学部, 教授 (60248515) 石野史敏東京医科歯科大学, 難治疾患研究所, 教授 (60159754)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	エピジェネティクス / 性差を示す遺伝性疾患 / X染色体不活性化
Outline of Final Research Achievements	PCDH19 clustering epilepsy is caused by mutations in the PCDH19 gene on the X chromosome. However, the mechanism explaining why only girls are affected remains unclear and there is no treatment available. We hypothesized that the disease is caused by abnormalities in X-chromosome inactivation (XCI), an epigenetic regulatory process. To test this, we collected blood samples from affected families and performed methylome analysis. The results showed no obvious methylation abnormalities across the entire X chromosome. Future analyses will focus on more specific regions for detailed methylation analysis. In addition, the analysis of Ftx KO mice, a disease model, led to the successful elucidation of the Xist expression control mechanism. Increasing the number of patient samples in the future is expected to contribute to the understanding of the disease mechanism.
Free Research Field	エピジェネティクス
Academic Significance and Societal Importance of the Research Achievements	これまで不明であった非メンデル遺伝の疾患発症メカニズム解明へ、従来見過ごされてきたXCI異常の検出に焦点を当て全く新しいアプローチで取り組んだ。本課題では、ヒト疾患解析において、ゲノム配列を基盤とする遺伝学に新たにエピジェネティクスを組み合わせた解析の基盤を整えた。今後患者の検体を揃えることにより、エピジェネティクスがヒト遺伝性疾患で果たす重要な役割を明らかにできると期待される。その成果は患者の治療法の確立に結び付く社会的意義のほか、他の非メンデル遺伝を示す疾患の発症理解にも新しい視点を提供できる点で学術的意義がある。