Whole exome sequencing (WES) is a genomic technique used to sequence all the protein-coding regions of genes in a genome, collectively known as the exome.
While the exome makes up only about 1% to 2% of the total human genome, it contains approximately 85% of all known disease-causing mutations.
Employs high throughput sequencing to identify disease causing mutations in a person’s exome.
The exome comprises 180,000 exons, encoding 22,000 genes, that contain the protein coding information and accounts for approximately 1% of the whole genome.
Whole-exome sequencing can evaluate 90-95% of the exome.
It is sequencing of proteins-coding DNA allowing assessment of a wide range of genetic variants for diagnostic purposes in epilepsy, autism, and intellectual disabilities.
Genome sequencing, sequences nearly all DNA.
A tyypical exome sequencing identifies a proximally 40,000 sequence variants, and a genome sequence identifies approximally 3 million variants that differ from the human genome reference.
DNA Extraction: Genetic material is typically taken from blood or saliva samples.
DNA is fragmented into smaller pieces, and adapters are added to these fragments.
Specific probes selectively find and enrich only the exonic DNA while discarding the non-coding intronic regions.
The enriched DNA is sequenced using high-throughput technologies like Next-Generation Sequencing (NGS).
Algorithms compare the sequence to a reference genome to identify variants such as single nucleotide variants and small insertions or deletions.
WES is primarily used to identify the molecular basis of suspected genetic diseases, providing a definitive diagnosis for roughly 20–50% of patients with rare disorders.
WES is often used for patients with unexplained symptoms that have not been identified through standard testing.
WES helps identify somatic mutations in tumor tissue to guide personalized treatment plans.
Pediatrics: Recommended as a first-tier test for developmental delays, intellectual disabilities, and congenital anomalies.
Testing is most effective when the patient (proband) is sequenced alongside both biological parents to better interpret inherited versus new (de novo) mutations.
Comparison: WES vs. Whole Genome Sequencing (WGS)
Protein-coding regions (~2% of genome) vs Entire genome (100% of DNA)
More cost-effective vs Significantly more expensive
Data Size Smaller, manageable (~10 Gb) vs| Very large (~90 Gb)
| Depth Higher depth (often 100x+) for better variant calls s Typically lower depth (~30x)
Limitations-Misses non-coding/regulatory variants vs Captures all variants but harder to interpret
WES does not capture the 98–99% of the genome that does not code for proteins, including regulatory regions.
WES has limited sensitivity for detecting large structural changes like translocations or repeat expansions such as Huntington’s disease.
Testing may reveal genetic risks for conditions unrelated to the original symptoms, such as an increased risk for cancer or heart disease.