High-performance single-chip exon capture allows accurate whole exome sequencing using the Illumina Genome Analyzer

Here we present an adaptation of NimbleGen 2.1M-probe array sequence capture for whole exome sequencing using the Illumina Genome Analyzer (GA) platform.The protocol involves two-stage library construction.The specificity of exome enrichment was approximately 80% with 95.6% even coverage of the 34 Mb target region at an average sequencing depth of 33-fold.Comparison of our results with whole genome shot-gun resequencing results showed that the exome SNP calls gave only 0.97% false positive and 6.27% false negative variants.Our protocol is also well suited for use with whole genome amplified DNA.The results presented here indicate that there is a promising future for large-scale population genomics and medical studies using a whole exome sequencing approach.