What is Exome Sequencing?
Exome sequencing, also known as Whole Exome Sequencing (WES), is a genomic technique for sequencing all the protein-coding regions (exons) of genes in a genome. The exome makes up only 1–2% of the human genome, yet it contains approximately 85% of known disease-related mutations.
🧪 What Does It Sequence?
The exome includes:
- Exons: DNA sequences transcribed into mRNA and translated into proteins.
- UTRs (sometimes included): Untranslated regions flanking the exons that regulate expression.
🔬 How Exome Sequencing Works
1. DNA Extraction
High-quality DNA is isolated from blood, saliva, or tissue samples.
2. Library Preparation & Target Capture
DNA is fragmented, and probes are used to selectively capture the exonic regions.
3. Next-Generation Sequencing (NGS)
Captured fragments are sequenced using platforms like Illumina, producing millions of short reads.
4. Bioinformatic Analysis
- Align sequences to a reference genome
- Detect SNPs, insertions/deletions (indels), and point mutations
- Annotate variants using databases (ClinVar, dbSNP, etc.)
✅ Advantages:
- Cost-effective compared to WGS
- High coverage of coding regions
- Ideal for clinical diagnostics
- Efficient for identifying rare or inherited genetic variants
🧬 Applications of Exome Sequencing
1. Rare Disease Diagnosis
- Ideal for identifying mutations responsible for Mendelian disorders
- Helps in diagnosing undiagnosed syndromes in children and adults
2. Cancer Genomics
- Detects somatic mutations in coding regions of tumor DNA
- Guides precision oncology and targeted therapies
3. Prenatal & Pediatric Testing
- Can identify de novo mutations in developmental disorders or congenital anomalies
5. Population Genetics & Evolutionary Biology
- Used in gene discovery, disease gene mapping, and comparative genomics
“Exome sequencing has rapidly become the gold standard for identifying the genetic basis of Mendelian diseases.”