文献

J-GLOBAL ID：202202234665885518   整理番号：22A1181076

GLI1の有害な稀な変異は,ヒト先天性心疾患におけるソニックヘッジホッグシグナル伝達を調節不全する【JST・京大機械翻訳】

Deleterious Rare Mutations of GLI1 Dysregulate Sonic Hedgehog Signaling in Human Congenital Heart Disease

著者 (18件)： Peng Rui (NHC Key Laboratory of Reproduction Regulation, State Key Laboratory of Genetic Engineering, Obstetrics and Gynecology Hospital, Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Children’s Hospital, Fudan University, Shanghai, China) ,  Peng Rui (Shanghai Key Laboratory of Metabolic Remodeling and Health, School of Life Sciences, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China) ,  Li Binbin (Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, United States) ,  Li Binbin (Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, United States) ,  Chen Shuxia (NHC Key Laboratory of Reproduction Regulation, State Key Laboratory of Genetic Engineering, Obstetrics and Gynecology Hospital, Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Children’s Hospital, Fudan University, Shanghai, China) ,  Chen Shuxia (Shanghai Key Laboratory of Metabolic Remodeling and Health, School of Life Sciences, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China) ,  Shi Zhiwen (NHC Key Laboratory of Reproduction Regulation, State Key Laboratory of Genetic Engineering, Obstetrics and Gynecology Hospital, Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Children’s Hospital, Fudan University, Shanghai, China) ,  Shi Zhiwen (Shanghai Key Laboratory of Metabolic Remodeling and Health, School of Life Sciences, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China) ,  Yu Liwei (NHC Key Laboratory of Reproduction Regulation, State Key Laboratory of Genetic Engineering, Obstetrics and Gynecology Hospital, Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Children’s Hospital, Fudan University, Shanghai, China) ,  Yu Liwei (SUNY Downstate Medical Center, Children’s Hospital at Downstate, Brooklyn, NY, United States) ,  Gao Yunqian (NHC Key Laboratory of Reproduction Regulation, State Key Laboratory of Genetic Engineering, Obstetrics and Gynecology Hospital, Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Children’s Hospital, Fudan University, Shanghai, China) ,  Gao Yunqian (Department of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Yang Xueyan (NHC Key Laboratory of Reproduction Regulation, State Key Laboratory of Genetic Engineering, Obstetrics and Gynecology Hospital, Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Children’s Hospital, Fudan University, Shanghai, China) ,  Yang Xueyan (Shanghai Key Laboratory of Metabolic Remodeling and Health, School of Life Sciences, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China) ,  Lu Lei (NHC Key Laboratory of Reproduction Regulation, State Key Laboratory of Genetic Engineering, Obstetrics and Gynecology Hospital, Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Children’s Hospital, Fudan University, Shanghai, China) ,  Lu Lei (Shanghai Key Laboratory of Metabolic Remodeling and Health, School of Life Sciences, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China) ,  Wang Hongyan (NHC Key Laboratory of Reproduction Regulation, State Key Laboratory of Genetic Engineering, Obstetrics and Gynecology Hospital, Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Children’s Hospital, Fudan University, Shanghai, China) ,  Wang Hongyan (Shanghai Key Laboratory of Metabolic Remodeling and Health, School of Life Sciences, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China)
資料名： Frontiers in Cardiovascular Medicine (Web)  (Frontiers in Cardiovascular Medicine (Web))
巻： 9  ページ： 798033  発行年： 2022年 
JST資料番号： U7061A  ISSN： 2297-055X  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： スイス (CHE)  言語： 英語 (EN)

抄録/ポイント： 亜鉛フィンガーDNA結合蛋白質のGlioma関連癌遺伝子(Gli)ファミリーメンバーは,Sonic hedgehog(SHH)シグナル伝達経路のコアエフェクターである。モデル生物における研究は,Gli遺伝子が,心臓,脳,腎臓などを含む器官発生の間に重要な役割を担っていることを同定し,GLI遺伝子における有害な変異が,いくつかのヒト発達障害で以前に明らかにされたが,先天性心疾患(CHD)ではほとんど明らかにされていない。本研究では,GLI1-3遺伝子の変異を,CHDの412人と民族的にマッチした正常対照の213人から成るヒトコホートにおける次世代配列決定により捕捉した。ヒトGLI1-3遺伝子のコード領域における合計20人の患者特異的非同義まれな変異を同定した。機能分析は,GLI1c.820G>T(p.G274C)が機能獲得変異であり,一方GLI1c.878G>A(p.R293H)とc.1442T>A(p.L481X)は機能喪失変異であることを示した。著者らの知見は,GLI1遺伝子の有害な希少変異がSHHシグナル伝達経路調節のバランスを破り,ヒトCHDへの大きな寄与を構成し,SHHシグナル伝達により調節される胚心臓発生の遺伝的メカニズムの理解に新たな光を投げることを示唆した。Copyright 2022 The Author(s) All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： 心臓 ,  遺伝 ,  遺伝子 ,  胚 ,  ヒト ,  機能分析 ,  *先天性心疾患 ,  母集団 ,  DNA結合タンパク質 ,  癌遺伝子 ,  *細胞情報伝達
準シソーラス用語： 亜鉛フィンガー ,  器官形成 ,  発達障害 ,  伝達経路 , 【Automatic Indexing@JST】

著者キーワード (5件)： 先天性心疾患(CHD) ,  GLI1 ,  遺伝的変異 ,  稀な変異 ,  Sonic hedgehog(SHH)シグナル伝達経路

分類 (2件)： 生物学的機能  (EB03040U) ,  遺伝子発現  (EC02040Q)

引用文献 (56件)：

• Triedman JK, Newburger JW. Trends in congenital heart disease: the next decade. Circulation. (2016) 133:2716-33. doi: 10.1161/CIRCULATIONAHA.116.023544
• Zhao LJ, Chen LZ, Yang TB, Wang TT, Zhang SM, Chen LT, et al. Birth prevalence of congenital heart disease in China, 1980-2019: a systematic review and meta-analysis of 617 studies. Eur J Epidemiol. (2020) 35:631-42. doi: 10.1007/s10654-020-00653-0
• Botto LD, Mulinare J, Erickson JD. Occurrence of congenital heart defects in relation to maternal multivitamin use. Am J Epidemiol. (2000) 151:878-84. doi: 10.1093/oxfordjournals.aje.a010291
• Botto LD, Mulinare J, Erickson JD. Do multivitamin or folic acid supplements reduce the risk for congenital heart defects? Evidence and gaps. Am J Med Genet A. (2003) 121A:95-101. doi: 10.1002/ajmg.a.20132
• Gelb BD, Chung WK. Complex genetics and the etiology of human congenital heart disease. Cold Spring Harb Perspect Med. (2014) 4:a013953. doi: 10.1101/cshperspect.a013953

タイトルに関連する用語 (7件)： Gli1 ,  変異 ,  ヒト ,  先天性心疾患 ,  ソニックヘッジホッグ ,  シグナル伝達 ,  調節