Diagnostic gene sequencing panels: from design to report-a technical standard of the American College of Medical Genetics and Genomics (ACMG)
Diagnostic gene sequencing panels: from design to report-a technical standard of the American College of Medical Genetics and Genomics (ACMG)
复制标题
DOI：
10.1038/s41436-019-0666-z
复制
发表时间：
2020-03-01
影响因子：
8.8
通讯作者：
Bayrak-Toydemir, Pinar
中科院分区：
文献类型：
--
作者：
Bean, Lora J. H.;Funke, Birgit;Bayrak-Toydemir, Pinar
基因测序面板是一个强大的诊断工具，许多临床表现与遗传性疾病。DNA测序技术的进步使基因组更加经济、灵活和高效。因为基因板上包含的基因在基因含量方面在实验室之间差异很大（例如，数量、入选原因、基因-疾病关联的证据水平）和技术完整性（例如，覆盖深度），需要解决基因组的技术和临床方面的标准。本文件作为实验室设计、提供和报告基因组检测的技术标准。虽然这些原则可以适用于基因检测的多种适应症，但主要重点是诊断基因组（而不是载体筛选或预测性检测），重点是检测特定基因的技术考虑。本技术标准专门讨论了基因组内容对临床灵敏度、特异性和有效性的影响-在基因证据对基因-疾病相关性的贡献和证据强度的背景下-以及技术考虑因素，如测序限制、假基因/基因家族的存在、嵌合现象、转录本选择、拷贝数变异的检测、报告和检测限制的披露。
Gene sequencing panels are a powerful diagnostic tool for many clinical presentations associated with genetic disorders. Advances in DNA sequencing technology have made gene panels more economical, flexible, and efficient. Because the genes included on gene panels vary widely between laboratories in gene content (e.g., number, reason for inclusion, evidence level for gene-disease association) and technical completeness (e.g., depth of coverage), standards that address technical and clinical aspects of gene panels are needed. This document serves as a technical standard for laboratories designing, offering, and reporting gene panel testing. Although these principles can apply to multiple indications for genetic testing, the primary focus is on diagnostic gene panels (as opposed to carrier screening or predictive testing) with emphasis on technical considerations for the specific genes being tested. This technical standard specifically addresses the impact of gene panel content on clinical sensitivity, specificity, and validity-in the context of gene evidence for contribution to and strength of evidence for gene-disease association-as well as technical considerations such as sequencing limitations, presence of pseudogenes/gene families, mosaicism, transcript choice, detection of copy-number variants, reporting, and disclosure of assay limitations.