What is the difference between whole exome sequencing (WES) and whole genome sequencing (WGS), and when is each used?

• A. WES targets exons; WGS covers coding and noncoding regions; WES is cost-effective for suspected Mendelian disorders.
• B. WES covers coding and noncoding regions; WGS targets exons; WES is cost-effective for Mendelian disorders.
• C. WES sequences the entire genome.
• D. WGS is never used for Mendelian disorders.

Answer: (A)

The main distinction is the scope of what is sequenced. Whole exome sequencing focuses on the exons—the protein-coding parts of the genome—by capturing and sequencing those regions. Whole genome sequencing, in contrast, sequences the entire genome, including coding and noncoding regions, plus structural variants across the genome.

This difference drives how they’re used. Many Mendelian disorders arise from variants in coding regions, so sequencing only the exome captures the majority of actionable mutations at a lower cost, with simpler data analysis. That’s why exome sequencing is a cost-effective first-line option when a monogenic cause is suspected.

If a patient’s phenotype suggests involvement of noncoding regions, regulatory elements, or structural changes, or if exome sequencing hasn’t found a likely cause, whole genome sequencing is preferred because it offers a more comprehensive view, though it comes with higher cost and more complex data interpretation.

Keep in mind that exome sequencing can miss variants in exons that aren’t well captured and can miss noncoding or large structural changes, while genome sequencing covers those gaps but requires more resources to analyze.