Filter-based hybridization capture of subgenomes enables resequencing and copy-number detection

To exploit contemporary sequencing technologies for targeted genetic analyses, we developed a hybridization enrichment strategy for DNA capture that uses PCR products as subgenomic traps. We applied this strategy to 115 kb of the human genome encompassing 47 genes implicated in cardiovascular disease. Parallel sequencing of captured subgenomic libraries interrogated 99.8% of targeted nucleotides ≥20 times (~40,000-fold enrichment), enabling sensitive and specific detection of sequence and copy number variation.