WGS versus Exome Sequencing
Dr. Jongbloed’s clinic is one of eight in the Netherlands that provides comprehensive sequencing services including WGS, exome analysis, and gene-panel testing. About 75 patients are evaluated there each month; however, WGS is still relatively rare.
“We do about one entire genome per month,” Dr. Jongbloed says. “While we can sequence a lot of genes at the same time, some regions are more difficult to sequence than others, such as those with high GC content, and repetitive elements in certain sequences make them difficult to map.” Another issue he and other laboratory specialists face is determining whether certain mutations are indeed pathogenic. “For this, the only solution is to find other affected family members with the same mutation, which can be difficult for a rare disease.”
Dr. Jongbloed believes that WGS, exome sequencing, gene-panel-based resequencing, and Sanger all currently have their place in the clinic. “WGS is actually faster because we don’t need to enrich for the genes as we do for exome analysis. Also, WGS should be the method of choice for neonatal screening “where we don’t know what’s going on.”
Regarding exome sequencing, he states, “It isn’t necessarily faster, but it is cheaper. For now, we should focus on exomes because it is easier to understand the consequences.” Sanger sequencing will always have its place in the clinic, he thinks: “It is well established and [Sanger] panels already exist for many diseases…we will always need to use it to validate NGS results and to look in other family members.”
Dr. Jongbloed would like to see lower costs for NGS technologies and more collaboration in the field through a centralized facility. He believes that other applications, such as Ion Torrent (Thermo Fisher Scientific) sequencing, will help reduce the cost of NGS itself and ultimately replace Sanger.