Targeted capture and massively parallel sequencing of 12 human exomes

DNA sequencing costs have fallen dramatically in recent years, but they are still too high for whole-genome sequencing to be used routinely to identify rare and novel variants in large cohorts. Here Ng et al. demonstrate that targeted capture and massively parallel sequencing could be a cost-effective, reproducible, and robust strategy for the sensitive and specific identification of variants causing protein-coding changes in individual human genomes. Using this 'second generation' approach to sequencing they determine 307 megabases across the exomes (the protein-coding regions of the genome) of 12 individuals. Freeman–Sheldon syndrome is used as a proof-of-concept to show that candidate genes for monogenic disorders can be identified by exome sequencing of a small number of unrelated, affected individuals.