title: Next-generation sequencing for research and diagnostics in kidney disease.
abstract: 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.
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, KC04.048.02, PO Box 85090, Utrecht, 3508 AB, Netherlands.
authors.forename: Kirsten Y
authors.initials: KY
authors.lastname: Renkema
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, KC04.048.02, PO Box 85090, Utrecht, 3508 AB, Netherlands.
authors.forename: Marijn F
authors.initials: MF
authors.lastname: Stokman
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, KC04.048.02, PO Box 85090, Utrecht, 3508 AB, Netherlands.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Giles
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, KC04.048.02, PO Box 85090, Utrecht, 3508 AB, Netherlands.
authors.forename: Nine V A M
authors.initials: NV
authors.lastname: Knoers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D003598:Cytoskeletal Proteins; D030881:Disclosure / Q000941:ethics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D033162:Incidental Findings; D007668:Kidney / Q000002:abnormalities / Q000502:physiology; D052177:Kidney Diseases, Cystic / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000235:genetics*; D050396:TRPP Cation Channels / Q000235:genetics; D014551:Urinary Tract / Q000002:abnormalities; D014564:Urogenital Abnormalities; D014718:Vesico-Ureteral Reflux / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D050396:TRPP Cation Channels; C108725:NPHP1 protein, human