Next-generation Sequencing in Clinical Molecular Diagnostics

Next-generation sequencing is based upon the concept of massively parallel chemical reactions in which millions of independent DNA sequencing events occur simultaneously, and this is achieved using a relatively similar concept across all of the currently available platforms. Current clinical molecular genetics labs offer testing mainly for single-gene defects and a few multigene panels. However, for whole-exome and whole-genome sequencing, as the cost per sample continues to fall, there is little question that the clinical application of this technology will soon become abundant in diagnostic labs. Before that happens, we will need to prepare ourselves to handle certain types of unexpected and potentially unwanted information, since this technology should prove to be of tremendous value for the practice of medicine in the future. Key Concepts: Next-generation sequencing is based upon the concept of massively parallel chemical reactions in which millions of independent DNA sequencing events occur simultaneously. There are several commercial vendors of next-generation sequencing instruments, though the market is currently dominated by Roche, Illumina and Life Technologies. Most clinical labs prefer to sequence multiple samples or many regions of the genome in one run, and there are several methods that can be used to accomplish this. Next-generation sequencing can also be used to effectively detect both large and small chromosome aberrations. Next-generation sequencing has the potential to increase the scope of tests for sequence variants in the areas of infectious disease testing and oncology. Clinical laboratories are currently observing caution in the adoption of this new technology. Keywords: sequencing; parallel; Sanger; bioinformatics; library; capture

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