Strande Natasha T, Berg Jonathan S
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; email:
Annu Rev Genomics Hum Genet. 2016 Aug 31;17:303-32. doi: 10.1146/annurev-genom-083115-022348. Epub 2016 May 26.
As with all fields of medicine, the first step toward medical management of genetic disorders is obtaining an accurate diagnosis, which often requires testing at the molecular level. Unfortunately, given the large number of genetic conditions without a specific intervention, only rarely does a genetic diagnosis alter patient management-which raises the question, what is the added value of obtaining a molecular diagnosis? Given the fast-paced advancement of genomic technologies, this is an important question to address in the context of genome-scale testing. Here, we address the value of establishing a diagnosis using genome-scale testing and highlight the benefits and drawbacks of such testing. We also review and compare recent major studies implementing genome-scale sequencing methods to identify a molecular diagnosis in cohorts manifesting a broad range of Mendelian monogenic disorders. Finally, we discuss potential future applications of genomic sequencing, such as screening for rare conditions.
与所有医学领域一样，对遗传性疾病进行医学管理的第一步是获得准确的诊断，这通常需要进行分子水平的检测。不幸的是，鉴于大量遗传性疾病尚无特定干预措施，基因诊断很少能改变患者的治疗方案——这就引出了一个问题，获得分子诊断的附加价值是什么？鉴于基因组技术的快速发展，这是在基因组规模检测背景下需要解决的一个重要问题。在此，我们探讨使用基因组规模检测进行诊断的价值，并强调此类检测的利弊。我们还回顾并比较了近期实施基因组规模测序方法以在表现出广泛孟德尔单基因疾病的队列中确定分子诊断的主要研究。最后，我们讨论基因组测序未来的潜在应用，例如罕见病筛查。
