Department of Medical Genetics, University Medical Center Utrecht, KC04.048.02, PO Box 85090, Utrecht, 3508 AB, Netherlands.
Department of Nephrology and Hypertension, University Medical Center Utrecht, KC04.048.02, PO Box 85090, Utrecht, 3508 AB, Netherlands.
Nat Rev Nephrol. 2014 Aug;10(8):433-44. doi: 10.1038/nrneph.2014.95. Epub 2014 Jun 10.
The advent of next-generation sequencing technologies has enabled genetic nephrology research to move beyond single gene analysis to the simultaneous investigation of hundreds of genes and entire pathways. These new sequencing approaches have been used to identify and characterize causal factors that underlie inherited heterogeneous kidney diseases such as nephronophthisis and congenital anomalies of the kidney and urinary tract. In this Review, we describe the development of next-generation sequencing in basic and clinical research and discuss the implementation of this novel technology in routine patient management. Widespread use of targeted and nontargeted approaches for gene identification in clinical practice will require consistent phenotyping, appropriate disease modelling and collaborative efforts to combine and integrate data analyses. Next-generation sequencing is an exceptionally promising technique that has the potential to improve the management of patients with inherited kidney diseases. However, identifying the molecular mechanisms that lead to renal developmental disorders and ciliopathies is difficult. A major challenge in the near future will be how best to integrate data obtained using next-generation sequencing with personalized medicine, including use of high-throughput disease modelling as a tool to support the clinical diagnosis of kidney diseases.
下一代测序技术的出现使遗传肾病学研究能够超越对单个基因的分析，转而同时研究数百个基因和整个途径。这些新的测序方法已被用于鉴定和描述导致遗传性肾脏疾病（如肾单位纤 维化和先天性肾和尿路畸形）的因果因素。在这篇综述中，我们描述了下一代测序在基础和临床研究中的发展，并讨论了该新技术在常规患者管理中的应用。在临床实践中广泛使用针对特定基因和非特定基因的方法进行基因鉴定需要一致的表型分析、适当的疾病建模以及合作努力来组合和整合数据分析。下一代测序是一项非常有前途的技术，有潜力改善遗传性肾脏疾病患者的治疗效果。然而，确定导致肾脏发育障碍和纤毛病的分子机制是困难的。未来的主要挑战将是如何最好地将下一代测序获得的数据与个体化医学相结合，包括利用高通量疾病建模作为支持肾脏疾病临床诊断的工具。
