Capture is readily performed on large targets, or on high-copy-number targets such as mtDNA. However, capture is inefficient when targeting small, low-copy-number regions. The reason is that capture typically results in a 10,000-fold enrichment of the target DNA. For example, the mitochondrial genome, owing to its high copy number, composes ~0.2% of the total mass of DNA in a human cell. Therefore, a 10,000-fold enrichment will result in nearly 100% purity of the targeted DNA. However, a 20-kb locus in genomic DNA, which is present in a single copy per haploid genome, composes only 0.0007% of the total DNA. Thus, a 10,000-fold enrichment will result in only 7% of the final DNA being on-target. However, we have found that repeating the targeted capture steps typically results in >85% of reads mapping to the target sequence.
