Elucidation of the mechanism for neurodevelopmental disorder derived from chromosomal microstructural abnormalities

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07803
• 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): 2018-04-01 – 2021-03-31
• Keywords: ゲノム構造異常 / 次世代シーケンス / ゲノムコピー数変化 / 神経発達障害

Outline of Final Research Achievements

Advanced technologies in genomic analysis have revealed that previously unknown complex genomic structural abnormalities are responsible for patients with neurodevelopmental disorders. The purpose of this study was to clarify the mechanism of complex structural abnormalities revealed by microarray chromosomal examination. For this purpose, nanopore sequence technology was used for a long sequencing. Consequently, some of the complex structural abnormalities consisted with multiple deletions and duplications were caused by chromothripsis or chromanasynthesis. Furthermore, we analyzed two cases showing complicated abnormalities associated with triplications in both ends of the duplication, and clarified for the first time in the world that it is composed of only two breakpoint-junctions.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

現在の発達したゲノム解析技術により、神経発達障害患者の３割程度は原因を明らかにすることができるようになってきている。しかしながら、半数以上の患者においては未だに原因が明らかでない。このような患者の発症原因の１つとしてコピー数変化のないゲノム構造異常が考えられる。本研究で明らかになったゲノム構造異常の発生メカニズムの理解は、今後ゲノム解析技術の進歩を臨床面に応用する際に大いに参考になると考える。