Identification of unique DNA methylation sites in Kabuki syndrome using whole genome bisulfite sequencing and targeted hybridization capture followed by enzymatic methylation sequencing

• Material Type: 博士論文
• Title: Identification of unique DNA methylation sites in Kabuki syndrome using whole genome bisulfite sequencing and targeted hybridization capture followed by enzymatic methylation sequencing
• Author/Editor: 濵口, 陽
• Author Heading: 濵口, 陽
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2023-03-20
• Publication Date (W3CDTF): 2023-03-20
• Alternative Title: 全ゲノムバイサルファイトシーケンス、ターゲットハイブリダイゼーションキャプチャー法と酵素メチル化シーケンス法を使った歌舞伎症候群の特異的DNAメチル化部位の同定
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2023-03-20
• Date Granted (W3CDTF): 2023-03-20
• Dissertation Number: 甲共医歯薬第31号
• Degree Type: 博士(医学)
• Text Language Code: eng
• Subject Heading: DNA methylation; Kabuki syndrome; enzymatic conversion technology; hybridization capture
• Target Audience: 一般
• Note (General): Background: Kabuki syndrome (KS) is a congenital malformation syndrome caused by mutations in the KMT2D and KDM6A genes that encode histone modification enzymes. Although KS is considered a single gene disorder, its symptoms vary widely. Recently, disease-specific DNA methylation patterns, or episignatures, have been recognized and used as a diagnostic tool for KS. Because of various crosstalk mechanisms between histone modifications and DNA methylation, DNA methylation analysis may have high potential for investigations into the pathogenesis of KS.Results: In this study, we investigated altered CpG-methylation sites that were specific to KS to find important genes associated with the various phenotypes or pathogenesis of KS. Whole genome bisulfite sequencing (WGBS) was performed to select target CpG islands, and enzymatic conversion technology was applied after hybridization capture to confirm KS-specific episignatures of 130 selected differently methylated target regions (DMTRs) in DNA samples from the 65 participants, 31 patients with KS and 34 unaffected individuals, in this study. We identified 26 candidate genes in 22 DMTRs that may be associated with KS. Our results indicate that disease-specific methylation sites can be identified from a small number of WGBS samples, and hybridization capture followed by enzymatic methylation sequencing can simultaneously test the sites.Conclusions: Although DNA methylation can be tissue-specific, our results suggest that methylation profiling of DNA extracted from peripheral blood may be a powerful approach to study the pathogenesis of diseases.; 長崎大学学位論文 学位記番号:共博(医歯薬)甲第31号 学位授与年月日:令和5年3月20日; Author: Yo Hamaguchi, Hiroyuki Mishima, Tomoko Kawai, Shinji Saitoh, Kenichiro Hata, Akira Kinoshita & Koh-ichiro Yoshiura; Citation: Journal of Human Genetics, 67, pp. 711-720; 2022; identifier:Nagasaki University (長崎大学), 博士(医学) (2023-03-20); http://hdl.handle.net/10069/00042277
• Persistent ID (NDL): info:ndljp/pid/12864069; https://dl.ndl.go.jp/pid/12864069
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• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2023-05-05T22:12:35+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
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• Periodical Title (URI): http://hdl.handle.net/10069/00042341
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp