文献

J-GLOBAL ID：202002252418235064   整理番号：20A0188963

22q11.2欠失症候群を有する1,053被験者における22q11.2対立遺伝子の完全配列は,円錐動脈心欠損の修飾因子を明らかにする【JST・京大機械翻訳】

Complete Sequence of the 22q11.2 Allele in 1,053 Subjects with 22q11.2 Deletion Syndrome Reveals Modifiers of Conotruncal Heart Defects

著者 (70件)： Zhao Yingjie (Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA) ,  Diacou Alexander (Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA) ,  Johnston H. Richard (Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA) ,  Musfee Fadi I. (Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, Texas 77225, USA) ,  McDonald-McGinn Donna M. (Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia 19104, USA) ,  McDonald-McGinn Donna M. (Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia 19104, USA) ,  McGinn Daniel (Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia 19104, USA) ,  McGinn Daniel (Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia 19104, USA) ,  Crowley T. Blaine (Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia 19104, USA) ,  Crowley T. Blaine (Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia 19104, USA) ,  Repetto Gabriela M. (Center for Genetics and Genomics, Facultad de Medicina Clinica Alemana-Universidad del Desarrollo, Santiago 7710162, Chile) ,  Swillen Ann (Center for Human Genetics, University of Leuven (KU Leuven), Leuven 3000, Belgium) ,  Breckpot Jeroen (Center for Human Genetics, University of Leuven (KU Leuven), Leuven 3000, Belgium) ,  Vermeesch Joris R. (Center for Human Genetics, University of Leuven (KU Leuven), Leuven 3000, Belgium) ,  Kates Wendy R. (Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY 13202, USA) ,  Kates Wendy R. (Program in Neuroscience, SUNY Upstate Medical University, Syracuse, NY 13202, USA) ,  Digilio M. Cristina (Department of Medical Genetics, Bambino Gesu Hospital, Rome 00165, Italy) ,  Unolt Marta (Department of Medical Genetics, Bambino Gesu Hospital, Rome 00165, Italy) ,  Unolt Marta (Department of Pediatrics, Gynecology, and Obstetrics, La Sapienza University of Rome, Rome 00185, Italy) ,  Marino Bruno (Department of Pediatrics, Gynecology, and Obstetrics, La Sapienza University of Rome, Rome 00185, Italy) ,  Pontillo Maria (Department of Neuroscience, Bambino Gesu Hospital, Rome 00165, Italy) ,  Armando Marco (Department of Neuroscience, Bambino Gesu Hospital, Rome 00165, Italy) ,  Armando Marco (Developmental Imaging and Psychopathology Lab, University of Geneva, Geneva 1211, Switzerland) ,  Di Fabio Fabio (Department of Pediatrics, Gynecology, and Obstetrics, La Sapienza University of Rome, Rome 00185, Italy) ,  Vicari Stefano (Department of Neuroscience, Bambino Gesu Hospital, Rome 00165, Italy) ,  Vicari Stefano (Department of Psychiatry, Catholic University, Rome 00153, Italy) ,  van den Bree Marianne (Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Wales CF24 4HQ, UK) ,  Moss Hayley (Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Wales CF24 4HQ, UK) ,  Owen Michael J. (Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Wales CF24 4HQ, UK) ,  Murphy Kieran C. (Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 505095, Ireland) ,  Murphy Clodagh M. (Department of Forensic and Neurodevelopmental Sciences, King’s College London, Institute of Psychiatry, Psychology, and Neuroscience, London SE5 8AF, UK) ,  Murphy Clodagh M. (Behavioural and Developmental Psychiatry Clinical Academic Group, Behavioural Genetics Clinic, National Adult Autism and ADHD Service, South London and Maudsley Foundation National Health Service Trust, London SE5 8AZ, UK) ,  Murphy Declan (Department of Forensic and Neurodevelopmental Sciences, King’s College London, Institute of Psychiatry, Psychology, and Neuroscience, London SE5 8AF, UK) ,  Murphy Declan (Behavioural and Developmental Psychiatry Clinical Academic Group, Behavioural Genetics Clinic, National Adult Autism and ADHD Service, South London and Maudsley Foundation National Health Service Trust, London SE5 8AZ, UK) ,  Schoch Kelly (Department of Pediatrics, Duke University, Durham, NC 27710, USA) ,  Shashi Vandana (Department of Pediatrics, Duke University, Durham, NC 27710, USA) ,  Tassone Flora (Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California, Davis, CA 95817, USA) ,  Simon Tony J. (Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California, Davis, CA 95817, USA) ,  Shprintzen Robert J. (The Virtual Center for Velo-Cardio-Facial Syndrome, Syracuse, NY 13206, USA) ,  Campbell Linda (School of Psychology, University of Newcastle, Newcastle 2258, Australia) ,  Philip Nicole (Department of Medical Genetics, Aix-Marseille University, Marseille 13284, France) ,  Heine-Suner Damian (Genomics of Health and Unit of Molecular Diagnosis and Clinical Genetics, Son Espases University Hospital, Balearic Islands Health Research Institute, Palma de Mallorca 07120, Spain) ,  Garcia-Minaur Sixto (Institute of Medical and Molecular Genetics, University Hospital La Paz, Madrid 28046, Spain) ,  Fernandez Luis (Institute of Medical and Molecular Genetics, University Hospital La Paz, Madrid 28046, Spain) ,  Bearden Carrie E. (Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA 90095, USA) ,  Vingerhoets Claudia (Department of Psychiatry and Psychology, Maastricht University, Maastricht, 6200 MD, the Netherlands) ,  van Amelsvoort Therese (Department of Psychiatry and Psychology, Maastricht University, Maastricht, 6200 MD, the Netherlands) ,  Eliez Stephan (Developmental Imaging and Psychopathology Lab, University of Geneva, Geneva 1211, Switzerland) ,  Schneider Maude (Developmental Imaging and Psychopathology Lab, University of Geneva, Geneva 1211, Switzerland) ,  Vorstman Jacob A.S. (Program in Genetics and Genome Biology, Research Institute, Toronto, Ontario, Canada) ,  Vorstman Jacob A.S. (Department of Psychiatry, The Hospital for Sick Children, Toronto, Ontario, Canada) ,  Vorstman Jacob A.S. (Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A1, Canada) ,  Vorstman Jacob A.S. (Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht, 3584 CG, the Netherlands) ,  Gothelf Doron (The Child Psychiatry Unit, Edmond and Lily Sapfra Children’s Hospital, Sackler Faculty of Medicine, Tel Aviv University and Sheba Medical Center, Tel Aviv, 52621, Israel) ,  Zackai Elaine (Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia 19104, USA) ,  Zackai Elaine (Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia 19104, USA) ,  Agopian A.J. (Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, Texas 77225, USA) ,  Gur Raquel E. (Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania Philadelphia, PA 19104, USA) ,  Gur Raquel E. (Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA) ,  Bassett Anne S. (Dalglish Family 22q Clinic, Clinical Genetics Research Program, Toronto M5T 1L8, Ontario Canada) ,  Bassett Anne S. (Toronto General Hospital, Centre for Addiction and Mental Health, Toronto M5T 1L8, Ontario, Canada) ,  Bassett Anne S. (Department of Psychiatry, University of Toronto, Toronto M5T 1L8, Ontario, Canada) ,  Emanuel Beverly S. (Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia 19104, USA) ,  Emanuel Beverly S. (Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia 19104, USA) ,  Goldmuntz Elizabeth (Division of Cardiology, Children’s Hospital of Philadelphia Philadelphia, PA 19104, USA) ,  Goldmuntz Elizabeth (Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA) ,  Mitchell Laura E. (Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, Texas 77225, USA) ,  Wang Tao (Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA) ,  Morrow Bernice E. (Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA) ,  See Table S1
資料名： American Journal of Human Genetics  (American Journal of Human Genetics)
巻： 106  号： 1  ページ： 26-40  発行年： 2020年 
JST資料番号： B0360B  ISSN： 0002-9297  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： 22q11.2欠失症候群(22q11.2DS)は,LCR22と称する低コピー反復間の非対立遺伝子相同組換えから生じる。LCR22A-Dからの典型的な3メガガーゼ(Mb)欠失を有する個人の約60%~70%は先天性心疾患を有しており,大部分はコノトランジェント型(CTD)であり,他は正常な心臓解剖を有している。本研究において,著者らは,半接合性LCR22A-D領域における変異体が105322q11.2DS個体からの22q11.2領域の配列に基づいてCTDsのリスクと関連するかどうかを試験した。CRKLを有する350kb間隔における単一連鎖不均衡(LD)ブロックにおける62の共通変異体を有するCTDサブセットの有意な関連(FDRp<0.05)を見出した。62の変異体の合計45は,CTDsのリスク増加と関連していた(オッズ比[OR]範囲:1.64~4.75)。4つの変異体の関連性は,22q11.2DSのない影響を受けた個体におけるCTDsの3つのゲノムワイド関連研究のメタ分析において複製された。複製された変異体の1つ,rs178252はオープンクロマチン領域に位置し,二重エリートエンハンサー,GH22J020947に存在し,CRKL(CRK様プロトオンコジーン,細胞質アダプター)発現を調節すると予測される。nested LCR22C-D欠失を有する患者の約23%はCTDsを有し,マウスにおけるCrklの不活性化はCTDsを引き起こし,この遺伝子を修飾剤として意味する。Rs178252とrs604160はCRKLの発現量的形質遺伝子座(eQTL)である。さらに,座位に基づく試験により,CRKLを標的とすると予測されるエンハンサーを同定し,22q11.2DSコホートにおけるCTDリスク(GH22J020946,シーケンス角膜関連試験(SKAT)p=7.21×10~5)と有意に関連した。これらの知見は,22q11.2DS集団におけるCTD浸透率の分散がCRKL発現に影響する変異体によって部分的に説明できることを示唆する。Copyright 2020 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： 母集団 ,  *動脈 ,  心臓 ,  角膜 ,  プロトオンコジーン ,  *遺伝子 ,  部分集合 ,  浸透率 ,  細胞質 ,  *対立遺伝子 ,  座位 ,  解剖 ,  *先天性心疾患 ,  染色体
準シソーラス用語： オッズ比 , 【Automatic Indexing@JST】

著者キーワード (11件)： 染色体22q11.2欠失症候群 ,  DiGeorge症候群 ,  先天性心疾患 ,  遺伝的修飾因子 ,  円錐角膜心欠損 ,  コピー数変動 ,  遺伝的関連 ,  CRKL ,  ハプロ不全 ,  Tbx1 ,  複雑な形質

分類 (2件)： 先天性疾患・奇形一般  (GD03010V) ,  遺伝的変異  (EC01030Y)

タイトルに関連する用語 (7件)： 欠失 ,  症候群 ,  被験者 ,  対立遺伝子 ,  円錐 ,  動脈 ,  心欠損