Whole Exome Sequencing: A Strategic, Cost-Effective, and High-Throughput Genomic Tool for Rapidly Identifying Causal Coding Variants in Inherited Rare Diseases, Undiagnosed Disorders, and Cancer Research
Whole Exome Sequencing (WES) is a widely adopted Next-Generation Sequencing (NGS) technique that focuses on sequencing the protein-coding regions of the genome, known as the exome, which constitutes less than 2% of the total genetic material but harbors approximately 85% of known disease-causing mutations. By focusing only on these functional regions, WES offers a more cost-effective and streamlined approach than whole-genome sequencing (WGS), making it particularly valuable in clinical diagnostics and for the rapid identification of de novo or rare variants linked to Mendelian and complex diseases.
This methodology enables researchers to achieve higher coverage depth in the critical coding regions, which significantly improves the reliability of variant calling, a crucial step for accurately pinpointing pathogenic changes. Despite covering a smaller fraction of the genome than WGS, the functional implications of variants within the exome are much better understood, allowing for more immediate and actionable clinical interpretation, especially in rare disease genomics.