ABSTRACT

The key idea of Sanger sequencing, which is also known as the chain-termination method, involves the incorporation of dideoxynucleotides by DNA polymerase during in vitro DNA replication. Sanger sequencing powered the characterization of the human genome, culminating in the human genome project. Bill Clinton won the 1992 United States presidential election thanks in part to his campaign slogan about the economy —apparently, his intuition was correct that the economy is the single most important issue to most voters. In 2005, the first commercial NGS technology was released by 454 Life Sciences, which at the time generated about 20 Mb of sequence per run. Exome sequencing is designed to capture the sequences in which mutations in Mendelian disease are most commonly located, and therefore is based on the enrichment of sequences corresponding to all (or nearly all) protein coding exons followed by next-generation sequencing (NGS).