临床基因组测序解读与报告专家共识
卢宇蓝和李国壮并列第一作者。
收稿日期: 2024-10-17
修回日期: 2025-01-21
网络出版日期: 2025-01-22
基金资助
国家重点研发计划(2022YFC2703100);国家重点研发计划(2023YFC2507700);国家重点研发计划(2022YFC2703102);上海市科技创新行动计划(20Z11900600);上海市科技创新行动计划(22DZ2204800);中国医学科学院医学与健康科技创新工程(CIFMS)(2021-I2M-1-051);中国医学科学院医学与健康科技创新工程(CIFMS)(2021-I2M-1-052);中国医学科学院医学与健康科技创新工程(CIFMS)(2023-I2M-C&T-A-003);北京协和医院中央高水平医院临床科研专项(2022-PUMCH-D-004);北京协和医院中央高水平医院临床科研专项(2022-PUMCH-C-033);中央专项彩票公益金支持罕见病诊疗水平能力提升项目(UPWARDS);中国医学科学院中央级公益性科研院所基本科研业务费项目(2019PT320025)
Expert consensus on clinical genome sequencing interpretation and reporting
Received date: 2024-10-17
Revised date: 2025-01-21
Online published: 2025-01-22
Supported by
National Key Research and Development Program of China(2022YFC2703100);National Key Research and Development Program of China(2023YFC2507700);National Key Research and Development Program of China(2022YFC2703102);Shanghai Scientific and Technological Innovation Action Plan(20Z11900600);Shanghai Scientific and Technological Innovation Action Plan(22DZ2204800);CAMS Innovation Fund for Medical Sciences (CIFMS)(2021-I2M-1-051);CAMS Innovation Fund for Medical Sciences (CIFMS)(2021-I2M-1-052);CAMS Innovation Fund for Medical Sciences (CIFMS)(2023-I2M-C&T-A-003);National High Level Hospital Clinical Research Funding(2022-PUMCH-D-004);National High Level Hospital Clinical Research Funding(2022-PUMCH-C-033);Peking Union Medical College Hospital Public Welfare Project for Rare Disease Service Improvement(UPWARDS);Fundamental Research Funds for the Central Public Welfare Research Institutes of the Chinese Academy of Medical Sciences(2019PT320025)
基因组测序(genome sequencing，GS)是一种全面且系统地检测个体核基因组和线粒体基因组DNA序列的技术，旨在识别遗传变异并研究这些变异在人类健康和疾病发生发展中的作用。作为一种应用越来越广泛的检测技术，GS凭借高通量、高准确性和全面性的优势，为临床诊断提供了重要支持。然而，其复杂的数据分析与解读对专业知识和经验提出了较高要求，也带来了诸多挑战。运用GS技术进行遗传病分子诊断会涉及临床应用的伦理与技术问题，包括知情同意、诊断性数据解读、报告范围和内容等。本专家共识总结了临床基因组测序(clinical GS，cGS)的核心流程，明确了检测范围与技术局限性，提供了数据质控、分析、注释及变异解读的关键步骤，并对报告内容和知情同意的争议性问题展开讨论。本共识旨在帮助相关从业人员正确理解和规范使用临床基因组测序技术，提升遗传病诊断的准确性，优化技术的临床效用，推动医学科学研究的进步。
卢宇蓝, 李国壮, 王雅琼, 徐可欣, 董欣然, 蔡继昊, 吴冰冰, 王慧君, 方萍, 王剑, 王华, 孙路明, 叶勇裕, 李晴, 刘雅萍, 刘丽, 刘宁, 刘嘉琦, 宋昉, 杨琳, 邱正庆, 陈泽夫, 罗华夏, 郭丹, 郝婵娟, 赵森, 黄尚志, 彭镜, 蔡小强, 睢瑞芳, 李林康, 吴南, 周文浩, 张抒扬 . 临床基因组测序解读与报告专家共识[J]. 遗传, 2025 , 47(3) : 314 -328 . DOI: 10.16288/j.yczz.24-296
Genome sequencing (GS) refers to a technology that comprehensively and systematically detects the DNA sequences of an individual’s nuclear and mitochondrial genomes. It aims to identify genetic variants and investigate their roles in human health and disease progression. As an emerging diagnostic tool, GS offers significant support for clinical diagnosis due to its high throughput, accuracy, and comprehensiveness. However, the complexity of data analysis and interpretation requires substantial professional expertise and experience, posing considerable challenges. When applying GS technology for molecular diagnosis of genetic diseases, ethical and technical issues related to clinical application arise, including informed consent, diagnostic data interpretation, and defining the scope and content of clinical reports. This expert consensus outlines the core workflow of clinical genome sequencing (cGS), clarifies its testing scope and technical limitations, and provides key steps for data quality control, analysis, annotation, and variant interpretation. It also addresses controversial issues related to report content and informed consent. This consensus aims to assist professionals in accurately understanding and appropriately utilizing clinical genome sequencing, thereby improving diagnostic accuracy for genetic diseases, enhancing the clinical utility of the technology, and advancing medical scientific research.
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