Mutation Screening of Genome Instability Syndromes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19844
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 63:Environmental analyses and evaluation and related fields
• Research Institution: Nagoya University
• Principal Investigator: NAKAZAWA Yuka 名古屋大学, 環境医学研究所, 講師 (00533902)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: ゲノム不安定性疾患 / VUS

Outline of Final Research Achievements

With the widespread adoption of next-generation sequencing technologies, the identification of gene mutations responsible for various diseases has rapidly advanced. However, a large amount of data on variants of uncertain significance (VUSs) has also accumulated. In this study, we targeted genetic disorders characterized by genomic instability and utilized a multi-omics approach to evaluate the pathogenicity of VUSs, identify causative mutations, and explore potential therapeutic candidates. As a result, we identified novel intronic mutations and proposed therapeutic candidates using antisense oligonucleotides (ASOs).

Free Research Field

人類遺伝学、ゲノム生物学、分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

一般的に、全エクソーム解析で疾患原因変異が同定されるのは、両親のゲノム情報も併せて解析したうえで、およそ30-40%程度と言われている。残りの60-70%の解決には、イントロン領域も含めた全ゲノム解析とVUSの適切な評価が重要と考えられる。本研究の成果は、今後の遺伝性疾患の原因変異特定および創薬・個別化医療に役立つものと期待される。