Mechanisms of complex chromosome structural abnormalities elucidated from transposons and three-dimensional structures

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07873
• 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: Tokyo Women's Medical University
• Principal Investigator: Yamamoto Toshiyuki 東京女子医科大学, 医学部, 教授 (20252851)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 染色体構造異常 / long-read sequencer / 全ゲノム解析 / 染色体サブテロメア / INV-DUP-DEL / DUP-TRP/INV-DUP

Outline of Final Research Achievements

The principal investigator has so far conducted genome copy number analysis of thousands of patients in order to clarify the causes of unknown neurodevelopmental disorders. As a result, we have reported many valuable chromosomal abnormalities that may lead to the identification of disease-causing genes. Since there are complex chromosomal structural abnormalities that cannot be explained by the mechanisms known so far, we conducted research to elucidate these mechanisms. Consequently, a previously unknown mechanism was revealed, such as that when deletions or duplications are adjacent to each other, they result in more complex structural abnormalities that are related to each other. They also found that the breakpoints are often associated with repeat sequences derived from retrotransposons.

Free Research Field

臨床遺伝学

Academic Significance and Societal Importance of the Research Achievements

染色体構造異常は先天性疾患、未診断難病の原因になるだけではなく、反復流産や不育症の原因にも関係している。染色体構造異常の発生メカニズムを明らかにすることはヒトを含む生物における染色体の安定やゲノム修復機構を理解することであり、将来的な疾患の予防や治療のための研究にとって欠かせない基本的な知見となる。本研究の成果がその１つとなることと考える。