Whole Genome Sequencing (WGS) allows for the analysis of the whole genome. We use this technique if neither our panel of genes for Sanger Sequencing nor Whole Exome Sequencing (WES) detects any Primary Adrenal Insufficiency causing mutations.
The main advantage of WGS over WES is that it sequences introns (non-protein encoding portions of genes). Mutations in these regions, that would have so far gone undetected, can cause the RNA to be spliced (intronic sections removed) in different locations and consequently the protein encoded could be misfolded and non-functional. These mutations could lead either to an exon being skipped or a pseudoexon (an exon starting at an alternative place and incorporating intronic sequence).
To further investigate how these intronic mutations can lead to non-functional proteins we can perform Splicing Analysis.