{"id":"hum0368","version":1,"url":"https://humandbs.dbcls.jp/research/hum0368/v1","datePublished":"2022-11-29","versions":[{"version":1,"datePublished":"2022-11-29"}],"title":{"ja":"全ゲノム配列決定によるICF症候群の新規原因遺伝子の探索および機能解析","en":"Identification and functional analysis of novel causative genes of ICF syndrome by whole genome sequencing"},"summary":{"aims":{"ja":"ICF（immunodeficiency, centromeric instability, facial anomaly）症候群は免疫不全、DNAの低メチル化を伴う染色体の不安定性、顔貌異常を特徴とする稀な先天性の常染色体潜性遺伝病である。これまでの研究により、ICF患者は原因遺伝子（DNMT3B、ZBTB24、CDCA7、もしくはHELLS）によって4つのsubtypeに分けられることが明らかにされている。しかしながら、依然、原因遺伝子が不明の患者が少数存在する。本研究ではそのような患者のうち1名の原因遺伝子がUHRF1であることを突き止め、この患者の末梢血細胞から抽出したDNAの全ゲノムメチル化解析を行い、当該患者に特徴的なDNAの低メチル化パターンを明らかにした。","en":"ICF (immunodeficiency, centromeric instability, facial anomaly) syndrome is a rare congenital autosomal recessive genetic disorder characterized by immunodeficiency, chromosomal instability with DNA hypomethylation, and facial anomalies. Previous studies have revealed that ICF patients can be divided into four subtypes according to their causative genes (DNMT3B, ZBTB24, CDCA7, or HELLS). However, there are still a few patients whose causative genes are unknown. In this study, we identified UHRF1 as a novel causative gene in one such patient and performed whole-genome bisulfite sequencing analysis of DNA extracted from peripheral blood cells of this patient to identify a DNA hypomethylation pattern characteristic of this patient."},"methods":{"ja":"末梢血細胞からDNAを抽出し、Post-bisulfite adaptor-tagging（PBAT）法にてライブラリーを調整後、全ゲノム配列決定を行なうことで全シトシンのメチル化状態を決定した。","en":"DNA was extracted from peripheral blood cells, and prepared libraries by the post-bisulfite adaptor-tagging (PBAT) method. Then whole genome sequencing was performed and determined the methylation status of all cytosines."},"targets":{"ja":"ICF症候群1症例","en":"ICF syndrome"},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"メチル化","en":"Methylation profiling"},"targets":{"ja":"ICF症候群：1症例\n（日本人）","en":"ICF syndrome: 1 case\n(Japanese)"},"typeOfData":{"ja":"NGS\n（PBAT-seq）","en":"NGS\n(PBAT-seq)"}},"releaseNote":{"ja":"ICF症候群1症例の末梢血から抽出したDNAを用いた全ゲノムバイサルファイトシークエンス解析の結果をfastqファイルにて提供する。","en":"DNAs extracted from peripheral blood cells of a patient with ICF syndrome were used for the whole genome bisulfite sequencing analysis. Fastq files are provided."},"dataProviders":[{"name":{"ja":"鵜木 元香","en":"Motoko Unoki"},"organization":{"name":{"ja":"九州大学生体防御医学研究所 エピゲノム制御学分野","en":"Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University"}}}],"researchProjects":[],"grants":[{"title":{"ja":"DNAメチル化によるゲノム情報安定化機構の解明","en":"Mechanisms underlying maintenance of genome integrity by DNA methylation"},"agency":{"ja":"科学研究費助成事業 新学術領域研究（研究領域提案型）","en":"KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)"},"grantIds":["19H05740"]},{"title":{"ja":"ICF症候群の分子病態基盤：新しいエピゲノム安定維持機構の解明を目指して","en":"Molecular pathogenesis of ICF syndrome"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["18K06961"]},{"title":{"ja":"ICF症候群とエピゲノム制御の分子基盤","en":"ICF syndrome and the molecular network regulating the human epigenome"},"agency":{"ja":"科学研究費助成事業 基盤研究（A）","en":"KAKENHI Grant-in-Aid for Scientific Research (A)"},"grantIds":["26253020"]},{"title":{"ja":"セントロメア・ペリセントロメア反復配列の新たなDNAメチル化維持機構","en":"Novel DNA methylation maintenance mechanism for centromeric and pericentromeric repeats"},"agency":{"ja":"山田科学振興財団 研究援助","en":"Yamada Science Foundation"},"grantIds":null}],"relatedPublications":[{"title":"Novel compound heterozygous mutations in UHRF1 are associated with atypical immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome with distinctive genome-wide DNA hypomethylation.","doi":"https://doi.org/10.1093/hmg/ddac291","datasets":["JGAD000681"]}],"datasets":["JGAD000681"],"controlledAccessUsers":[]}