Next-generation sequencing technologies: breaking the sound barrier of human genetics

Mutagenesis. 2014 Sep;29(5):303-10. doi: 10.1093/mutage/geu031.


Demand for new technologies that deliver fast, inexpensive and accurate genome information has never been greater. This challenge has catalysed the rapid development of advances in next-generation sequencing (NGS). The generation of large volumes of sequence data and the speed of data acquisition are the primary advantages over previous, more standard methods. In 2013, the Food and Drug Administration granted marketing authorisation for the first high-throughput NG sequencer, Illumina's MiSeqDx, which allowed the development and use of a large number of new genome-based tests. Here, we present a review of template preparation, nucleic acid sequencing and imaging, genome assembly and alignment approaches as well as recent advances in current and near-term commercially available NGS instruments. We also outline the broad range of applications for NGS technologies and provide guidelines for platform selection to best address biological questions of interest. DNA sequencing has revolutionised biological and medical research, and is poised to have a similar impact on the practice of medicine. This tool is but one of an increasing arsenal of developing tools that enhance our capabilities to identify, quantify and functionally characterise the components of biological networks that keep us healthy or make us sick. Despite advances in other 'omic' technologies, DNA sequencing and analysis, in many respects, have played the leading role to date. The new technologies provide a bridge between genotype and phenotype, both in man and model organisms, and have revolutionised how risk of developing a complex human disease may be assessed. The generation of large DNA sequence data sets is producing a wealth of medically relevant information on a large number of individuals and populations that will potentially form the basis of truly individualised medical care in the future.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Computational Biology
  • Genetics, Medical / methods*
  • Genetics, Medical / trends
  • Genome, Human*
  • Genotype
  • High-Throughput Nucleotide Sequencing / methods*
  • High-Throughput Nucleotide Sequencing / trends
  • Humans
  • Phenotype
  • Sequence Analysis, DNA / methods
  • Sequence Analysis, DNA / trends