Targeted capture of the sequences of interest is often desirable. We have used the Agilent SureSelectXT target enrichment system. We have designed and used several custom-designed targeted capture sets against both nuclear and mtDNA from a number of organisms, including humans, mice and flies, with good success. Hybridization-based enrichment methods offered by other manufacturers would probably work as well. However, we have not evaluated these technologies, and they are likely to require some optimization. Of note, PCR-based enrichment methods are not compatible with DS because the targeted duplex DNA is melted into its single-stranded components during PCR, and the complementarity of the original DNA is lost.