Overview of Whole Genome Sequencing (WGS)

What does Whole Genome Sequencing (WGS) screen for?

WGS is used to looking for a broad range of genomic changes that may contribute to disease. This can include single nucleotide variants, small insertions and deletions, copy number variants, some structural rearrangements, and changes located in coding, intronic, regulatory, or other noncoding regions of the genome. Because it surveys the genome so broadly, WGS is particularly useful when the suspected cause is genetically heterogeneous or may lie outside the exome.

Why choose Whole Genome Sequencing (WGS)?

WGS may be chosen when clinicians need the broadest possible genomic assessment in a single test. It can increase the chance of finding clinically meaningful answers in complex, atypical, multisystem, or previously nondiagnostic cases, and it may detect important variants that narrower tests can miss. In some patient groups, professional guidance supports exome or genome sequencing as first-line testing, particularly for conditions such as congenital anomalies, developmental delay, intellectual disability, and unexplained epilepsy.

How is Whole Genome Sequencing (WGS) different?

• The key difference is scope. Whole exome sequencing focuses mainly on the protein-coding regions of genes, while WGS examines nearly the entire genome, including noncoding regions that may still be clinically relevant. WGS also offers a more uniform genome-wide view and may provide better detection of certain copy number and structural changes than exome-based methods. This makes WGS a stronger option when broader variant detection is required.

Who can consider Whole Genome Sequencing (WGS)?

• WGS can be considered for individuals with rare, complex, atypical, or unresolved clinical presentations, especially when prior testing has not established a diagnosis. It may be relevant for children or adults with developmental disorders, intellectual disability, epilepsy, congenital anomalies, or multisystem disease,. Rapid genome sequencing has also demonstrated clinical utility in critically ill infants and children. In addition, WGS may be appropriate when clinicians suspect a genetic etiology but require a broader diagnostic approach than that provided by single-gene, panel, or exome testing.

What to expect?

• The WGS process usually begins with clinical assessment and pre-test discussion, including the possible outcomes of testing, the chance of uncertain or unexpected findings, and the implications for family members. A DNA sample is then collected, and in some cases testing may include family members to improve interpretation. Results may show a causative finding, no causative finding, or a variant of uncertain significance (VUS), or secondary findings. Standard WGS results are typically reported within about 6-8 weeks, although turnaround time can vary by urgency.

Important Considerations