Whole Genome Sequencing or Exome Sequencing?
Many large scale exome sequencing projects are funded and underway to analyze rare Mendelian diseases. This technology is often the choice as it is more affordable than whole genome sequencing (WGS) and therefore allows analyzing more patients. In addition it has the advantage that resulting data volumes are much smaller and therefore easier to handle.
But – when looking only on those regions targeted by the exome technology – are the results of an exome sequencing experiment really comparable to a WGS experiment?
The study from Clark et al., 2011 focused on this question and found that neither of the technologies managed to cover all sequencing variants. When applying 50 million reads for exome sequencing and 35-fold coverage for WGS, the study came to the following results.
- WGS detected between 660 and 4600 SNPs that were not called from the exome sequencing data and
- Exome Sequencing detected between 2600 and 3200 SNPs that were not called from the WGS data.
What can we conclude from this? First, WGS can not and will not replace exome sequencing as due to genome characteristics there will always be regions that are not covered sufficiently for SNP calling. As oligonucleotide designs of available exomes are balanced regarding regions with low coverage, exome sequencing shows higher sensitivity towards these regions. Second, WGS has its value in detecting variants in regions that are not covered by exome enrichment technologies. These are regions where enrichment fails as well as regions that are not present on the current exome designs.
So for covering really all variants it might be worth thinking about doing both experiments in parallel. Both technologies complement each other.