Elucidation of genetic factors and molecular pathology of neurodevelopmental disorders by a multifaceted approach

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03641
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Saitsu Hirotomo 浜松医科大学, 医学部, 教授 (40402838)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: マルチオミクス解析 / インフォマティクス解析 / 尿細胞 / ゲノム編集マウス

Outline of Final Research Achievements

By reanalyzing exome data using state-of-the-art informatics analysis and by performing a multi-omics analysis combining RNA-seq and whole genome analysis using urinary cells, we succeeded in identifying causative genetic abnormalities in 50% of the cases. The analysis was particularly useful in identifying variants in intronic regions, and the prediction of splice aberrations and the evaluation of splice aberrations by RNA-seq are highly complementary to each other. The multi-omics analysis using urine cells, which can be collected noninvasively, are expected to improve the gene diagnosis rate. In addition, we reported four reports on the elucidation of molecular pathophysiology using genome-edited mice.

Free Research Field

分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

尿細胞は、皮膚線維芽細胞の代替細胞として非侵襲的に取得可能である点が優れており、今後採取方法に更なる改良を加えることで、マルチオミクス解析を用いた遺伝子解析研究におけるパラダイムシフトを起こすことが期待される。実際に尿細胞用いたRNA-seq解析で原因未同定であった3症例の原因同定に成功しており、疾患原因が不明で苦しむ患者の助けになる臨床的意義の高い研究成果である。