An exome sequencing study starts with exome capture and sequencing of DNA samples followed by the identification of sequence variants. Exome capture may be realized on many platforms (e.g., Illumina HiSeq, Roche 454, ABI SOLiD) and through a variety of probe definitions (e.g., Agilent SureSelect, Nimblegen SeqCap EZ). Recent advances have enabled sequencing an entire exome or even several exomes at deep coverage in a single run of the sequencing instrument. However, exome capture technologies differ in what they target, how much they capture, and how consistently they do so8. Moreover, only 80-90% of the targeted regions are covered above 10×, which may leave 4–8Mb (or 1000–2000 genes) without sufficient coverage for variant detection.
