Next-generation sequencing technologies and applications for human genetic history and forensics

Determining the DNA sequence is the most comprehensive way of obtaining information about the genome of any living organism. For decades, Sanger sequencing [1] using fluorescently labeled terminating nucleotides and electrophoresis has been the gold standard sequencing technology. Sanger sequencing made an early impact in the field of microbial genomics, with the first complete bacterial genome, Haemophilus influenzae, sequenced in 1995 [2]. Multicenter collaborations using numerous sequencing instruments and automated sample preparation also made it possible to use Sanger sequencing in the human genome project, which took more than 10 years and US$2.7 billion to complete [3,4].In recent years, we have witnessed a rapid development of a new generation of DNA sequencing systems followed by a multitude of novel applications in biology and medicine. The major advantage of the new 'second-generation' or 'massively parallel' sequencing technologies, compared to Sanger sequencing, is their considerably higher throughput and thereby lower cost per sequenced base. On a second-generation sequencing (SGS) machine several human genomes can be sequenced in a single run in a matter of days. Here, we review recent technological advances of SGS technologies and discuss the bioinformatic and computational implications of the sequencing revolution. Finally we highlight some applications of SGS technology with a focus on human population genetics and genetic history, and genetic forensics.There are three major SGS systems that are routinely used in many laboratories today. The first system to become commercially available was the Genome Sequencer from 454 Life Sciences (Branford, CT, USA) (later acquired by Roche [5]) in 2005, which was also the first SGS technology to sequence a complete human genome, that of Dr. James D. Watson [6]. The Genome Analyzer, first conceived by Solexa and later further developed by Illumina (San Diego, CA, USA) [7] was launched in 2006, and the SOLiD sys