wholeexome

Whole exome sequencing (WES) is a genomic technique for sequencing the protein-coding regions of the genome, collectively known as the exome. The exome comprises about 1-2% of the genome but contains a large proportion of known disease-causing variants, making it a practical focus for diagnostic testing and research.

The typical workflow involves extracting DNA, enriching exonic regions with capture probes, and performing high-throughput sequencing. The resulting reads are aligned to a reference genome, variants are called and annotated, and clinicians or researchers interpret the findings to assess potential pathogenicity. The approach relies on established pipelines for variant prioritization and uses guidelines to classify variants and decide on reporting.

Common applications include diagnostic testing for individuals with suspected genetic disorders, especially rare Mendelian diseases, where a single gene or a small set of genes may explain the phenotype. WES is also used in research to identify novel disease genes and, in some contexts, to study tumor somatic mutations in cancer.

Arguments for WES include its cost effectiveness relative to whole-genome sequencing (WGS) and its higher depth of coverage in coding regions, which increases the likelihood of detecting coding variants. Limitations include incomplete coverage of all exons due to capture biases, missed noncoding or regulatory variants, undetected structural variants, and incidental findings that raise ethical considerations. Diagnostic yield varies by indication and is generally lower for complex or non-M Mendelian disorders.

Compared with WGS, WES excludes most noncoding regions and many complex structural variants but remains a widely used, clinically accessible option for identifying coding genetic variants.