exome

An exome is the portion of a genome that is transcribed and translated into proteins, consisting primarily of exons of protein-coding genes and, in practical terms, a subset that includes many untranslated regions and splice-site sequences. In human genomics, the exome accounts for about 1-2% of the genome but harbors a large proportion of known disease-causing variants.

Exome sequencing (or whole-exome sequencing, WES) is a targeted sequencing approach that enriches for exonic regions before sequencing. It uses capture probes or multiplex PCR to isolate coding regions, followed by next-generation sequencing. The resulting data are analyzed by mapping reads to a reference genome, calling variants, and prioritizing those in coding sequences and splice sites.

Advantages include higher sequencing depth at coding regions and lower cost and data burden compared with whole-genome sequencing, enabling efficient discovery of coding variants in large cohorts or clinical settings. Limitations include incomplete capture of all exons due to design gaps, variability in capture efficiency, and exclusion of most noncoding regulatory regions. Exome sequencing also has limited sensitivity for detecting structural variants, CNVs, and variants in poorly annotated exons, and relies on up-to-date annotation of gene models.

Applications span clinical diagnostics for suspected monogenic disorders and research into gene function and disease. In cancer, paired tumor-normal exome sequencing identifies somatic coding mutations. Interpretation depends on annotation resources (RefSeq, Ensembl, GENCODE) and databases of allele frequencies and predicted impact.

Typical workflow: DNA extraction, library preparation, exome capture, sequencing, alignment to a reference genome, variant calling, annotation, and interpretation. Exome sequencing continues to complement genome sequencing, especially when focus is on coding variation and when cost or data management is a concern.