Division of Medical Genetics and Genomics and.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
J Clin Invest. 2022 Apr 1;132(7). doi: 10.1172/JCI154942.
Rare genetic disorders, when considered together, are relatively common. Despite advancements in genetics and genomics technologies as well as increased understanding of genomic function and dysfunction, many genetic diseases continue to be difficult to diagnose. The goal of this Review is to increase the familiarity of genetic testing strategies for non-genetics providers. As genetic testing is increasingly used in primary care, many subspecialty clinics, and various inpatient settings, it is important that non-genetics providers have a fundamental understanding of the strengths and weaknesses of various genetic testing strategies as well as develop an ability to interpret genetic testing results. We provide background on commonly used genetic testing approaches, give examples of phenotypes in which the various genetic testing approaches are used, describe types of genetic and genomic variations, cover challenges in variant identification, provide examples in which next-generation sequencing (NGS) failed to uncover the variant responsible for a disease, and discuss opportunities for continued improvement in the application of NGS clinically. As genetic testing becomes increasingly a part of all areas of medicine, familiarity with genetic testing approaches and result interpretation is vital to decrease the burden of undiagnosed disease.
罕见遗传病总体较为常见。尽管遗传学和基因组学技术取得了进步，对基因组功能和功能障碍的认识也有所提高，但许多遗传性疾病仍难以诊断。本综述的目的是提高非遗传学家对遗传检测策略的熟悉程度。随着遗传检测越来越多地应用于初级保健、许多亚专科诊所和各种住院环境，非遗传学家必须对各种遗传检测策略的优缺点有基本的了解，并具备解读遗传检测结果的能力。我们提供了常用遗传检测方法的背景知识，给出了各种遗传检测方法应用的表型示例，描述了遗传和基因组变异的类型，涵盖了变异识别的挑战，举例说明了下一代测序（NGS）未能发现导致疾病的变异，并讨论了在临床应用中继续改进 NGS 的机会。随着遗传检测越来越成为医学各个领域的一部分，熟悉遗传检测方法和结果解读对于减少未确诊疾病的负担至关重要。
