Elucidation of the pathogenesis of intellectual disability/developmental delay by multi-omics analysis using a novel analytical method

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20852
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Hiraide Takuya 浜松医科大学, 医学部附属病院, 助教 (70783447)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: ゲノム解析 / RNA解析

Outline of Final Research Achievements

A multi-omics analysis was performed on a case of intellectual disability/developmental delay using genomic analysis of the patient's peripheral blood DNA and RNA analysis using urine-derived cells. The genomic analysis utilized an AI-based splicing prediction program. The multi-omics analysis identified cases with retrotransposon insertions in introns in patients with intellectual disability and brain dysplasia, which could be considered as possible cases of splicing abnormalities. Short-read sequencing was unable to reveal the entire insertion area, and genomic analysis was performed using long-read sequencing. As a result, we were able to elucidate that retrotransposon insertions in introns are the cause of the disease.

Free Research Field

臨床遺伝学

Academic Significance and Societal Importance of the Research Achievements

知的障害/発達遅滞発症の患者において、エクソーム解析により多くの原因遺伝子が同定されている。しかし、半数以上の症例は原因不明であり、新たな解析手法の確立が必要である。我々の研究はAIを利用したゲノム解析とRNA解析によるマルチオミクス解析により、新しい疾患発症原因を同定することができた。今後の遺伝学的解析の発展に十分に貢献することができた。