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J-GLOBAL ID：201802274833036402   整理番号：18A0976291

未解決臨床エクソーム症例の追加研究分析から学んだ教訓【JST・京大機械翻訳】

Lessons learned from additional research analyses of unsolved clinical exome cases

著者 (71件)： Eldomery Mohammad K. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Eldomery Mohammad K. (Present Address: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, USA) ,  Coban-Akdemir Zeynep (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Harel Tamar (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Rosenfeld Jill A. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Gambin Tomasz (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Gambin Tomasz (Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland) ,  Stray-Pedersen Asbjorg (Norwegian National Unit for Newborn Screening, Women and Children’s Division, Oslo University Hospital, Oslo, Norway) ,  Kuery Sebastien (CHU Nantes, Service de Genetique Medicale, Nantes, France) ,  Mercier Sandra (CHU Nantes, Service de Genetique Medicale, Nantes, France) ,  Mercier Sandra (Atlantic Gene Therapies, UMR1089, Nantes, France) ,  Lessel Davor (Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany) ,  Denecke Jonas (Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany) ,  Wiszniewski Wojciech (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Wiszniewski Wojciech (Texas Children’s Hospital, Houston, USA) ,  Penney Samantha (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Liu Pengfei (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Liu Pengfei (Baylor Genetics, Baylor College of Medicine, Houston, USA) ,  Bi Weimin (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Bi Weimin (Baylor Genetics, Baylor College of Medicine, Houston, USA) ,  Lalani Seema R. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Lalani Seema R. (Texas Children’s Hospital, Houston, USA) ,  Schaaf Christian P. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Schaaf Christian P. (Texas Children’s Hospital, Houston, USA) ,  Schaaf Christian P. (Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, USA) ,  Wangler Michael F. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Wangler Michael F. (Texas Children’s Hospital, Houston, USA) ,  Bacino Carlos A. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Bacino Carlos A. (Texas Children’s Hospital, Houston, USA) ,  Lewis Richard Alan (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Lewis Richard Alan (Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, USA) ,  Potocki Lorraine (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Potocki Lorraine (Texas Children’s Hospital, Houston, USA) ,  Graham Brett H. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Graham Brett H. (Texas Children’s Hospital, Houston, USA) ,  Belmont John W. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Belmont John W. (Texas Children’s Hospital, Houston, USA) ,  Scaglia Fernando (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Scaglia Fernando (Texas Children’s Hospital, Houston, USA) ,  Orange Jordan S. (Department of Pediatrics, Baylor College of Medicine, Houston, USA) ,  Orange Jordan S. (Texas Children’s Hospital Center for Human Immuno-Biology, Houston, USA) ,  Jhangiani Shalini N. (Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA) ,  Chiang Theodore (Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA) ,  Doddapaneni Harsha (Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA) ,  Hu Jianhong (Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA) ,  Muzny Donna M. (Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA) ,  Xia Fan (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Xia Fan (Baylor Genetics, Baylor College of Medicine, Houston, USA) ,  Beaudet Arthur L. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Beaudet Arthur L. (Baylor Genetics, Baylor College of Medicine, Houston, USA) ,  Boerwinkle Eric (Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA) ,  Boerwinkle Eric (Human Genetics Center, University of Texas Health Science Center at Houston, Houston, USA) ,  Eng Christine M. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Eng Christine M. (Baylor Genetics, Baylor College of Medicine, Houston, USA) ,  Plon Sharon E. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Plon Sharon E. (Texas Children’s Hospital, Houston, USA) ,  Plon Sharon E. (Department of Pediatrics, Baylor College of Medicine, Houston, USA) ,  Plon Sharon E. (Texas Children’s Cancer Center, Texas Children’s Hospital, Houston, USA) ,  Sutton V. Reid (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Sutton V. Reid (Texas Children’s Hospital, Houston, USA) ,  Gibbs Richard A. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Gibbs Richard A. (Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA) ,  Gibbs Richard A. (Baylor-Hopkins Center for Mendelian Genomics, Baltimore, USA) ,  Posey Jennifer E. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Yang Yaping (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Yang Yaping (Baylor Genetics, Baylor College of Medicine, Houston, USA) ,  Lupski James R. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA) ,  Lupski James R. (Texas Children’s Hospital, Houston, USA) ,  Lupski James R. (Department of Pediatrics, Baylor College of Medicine, Houston, USA) ,  Lupski James R. (Human Genome Sequencing Center, Baylor College of Medicine, Houston, USA) ,  Lupski James R. (Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA)
資料名： Genome Medicine (Web)  (Genome Medicine (Web))
巻： 9  号： 1  ページ： 26  発行年： 2017年 
JST資料番号： U7320A  ISSN： 1756-994X  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： イギリス (GBR)  言語： 英語 (EN)

抄録/ポイント： 【背景】ほとんどの単一遺伝子メンデル疾患の希少性において,臨床的および科学的コミュニティの間のデータ交換の協調的努力は,分子診断および新規疾患遺伝子発見を最適化するために重要である。【方法】著者らは,妥当な分子診断が臨床ゲノミクス診断研究室(すなわち,未解明の臨床的exomes)で達成されなかった症例の研究のためのプロトコルを設計して実行した。このような事例を,潜在的に分析するための研究室に採用した。(1)新しい疾患遺伝子発見を加速する;(2)全エキソソーム配列決定(WES)の分子診断収率の増加;(3)疾患の遺伝的機構への洞察。パイロットプロジェクトデータは,主に親-子孫トリオから成る74の家族を含んだ。研究に基づいて行った分析は,追加のファミリーメンバーからのWESと相補的生物情報学アプローチとプロトコルの両方を用いた。【結果】単一ヌクレオチド変異体(SNV)とコピー数変異体(CNV)対立遺伝子の両方に焦点を合わせて,メンデル遺伝のすべての可能なモードの分析は,症例の36%(27/74)における可能性のある寄与変異体をもたらした。もし1つが単一ファミリー内で同定された変異体を持つ候補遺伝子を含むならば,このパイロット研究に登録されたケースの全部で~51%(38/74)に潜在的寄与変異体が同定された。分子診断は,30/63トリオ(47.6%)で達成された。これに加えて,分析ワークフローは,4/6シングルトン症例(66.6%)における疾患関連遺伝子における病原性変異体に対する証拠,3つの影響同胞を含む1/1多重家族,および3/4(75%)四重項家族をもたらした。診断研究所と研究所の間の分析的パイプラインと共同努力の両方が,最近の疾患遺伝子発見(PURA,TANGO2,EMC1,GNB5,ATAD3A,およびMIPEP)を可能にし,新しい遺伝子の数を増加させ,1つ以上のファミリー(DHX30とEBF3)で同定された遺伝子として定義された。【結論】診断研究室における臨床的配列決定に続く効率的なゲノミクス・パイプラインは,追加の家族からのWESデータを補足し,情報科学パイプラインにおける緩和変異体フィルタリングパラメータを含む補助生物情報学分析に従い,分子診断収率を強化し,メンデル障害に対する機構的洞察を提供する。これらのアプローチの実施には,共同臨床分子診断と研究努力が必要である。Copyright 2018 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： 対立遺伝子 ,  *遺伝 ,  ワークフロー ,  病原性 ,  コピー数 ,  コミュニティ ,  遺伝子 ,  プロトコル ,  情報科学
準シソーラス用語： ゲノミクス ,  候補遺伝子 ,  バイオインフォマティクス ,  疾患遺伝子 ,  分子診断 ,  *エクソーム , 【Automatic Indexing@JST】

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

引用文献 (108件)：

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タイトルに関連する用語 (6件)： 臨床 ,  エクソーム ,  症例 ,  研究 ,  分析 ,  教訓