The next-generation sequencing revolution and its impact on genomics

Abstract

Genomics is a relatively new scientific discipline, having DNA sequencing as its core technology. As technology has improved the cost and scale of genome characterization over sequencing's 40-year history, the scope of inquiry has commensurately broadened. Massively parallel sequencing has proven revolutionary, shifting the paradigm of genomics to address biological questions at a genome-wide scale. Sequencing now empowers clinical diagnostics and other aspects of medical care, including disease risk, therapeutic identification, and prenatal testing. This Review explores the current state of genomics in the massively parallel sequencing era.

Figure 1. Growth in the Numbers of dbSNP Variants in the Human Genome

Increases in the numbers of SNPs submitted (dotted line) and cataloged as unique reference variants (solid line) in dbSNP are charted over the periodic database releases from August 2002 until the most recent release in June 2012. As indicated by the two lines, while overall submissions have increased exponentially since 2008 (when large projects such as the 1,000 Genomes Project began), the number of unique variants has not increased at a comparable rate.

Figure 2. dbSNP Growth due to Rare Variant Discovery

This graphic illustrates the amount of rare and extremely rare variant discovery in two recent releases of the NCBI dbSNP database, where a global minor allele frequency of >0.05 is considered a common variant. As indicated, rare variant discovery has increased dramatically in the most recent build of dbSNP (137).

Figure 3. Growth in COSMIC Database Reports of Identified and Unique Mutations

Increases in the numbers of mutations and unique variants identified from DNA sequencing of cancer samples as cataloged in the COSMIC database, from November 2004 until the most recent release in July 2013. Note that the numbers of unique variants identified are increasing at a rate equal to the numbers of mutations discovered.