Whole Exome Sequencing Process Overview

Whole Exome Sequencing

• Combines NGS methods and/or array platforms to sequence all genes simultaneously
• Identifies the unique order of DNA bases and compares it to a reference sequence and often to close family members' sequences
• Detects single nucleotide changes, small deletions or insertions, and some methodologies can detect deletions, duplications, and chromosomal rearrangements
• Used when other genetic testing options have been exhausted and suspicion for a hereditary condition remains high
• Ideal when results of testing could significantly alter management or family risk assessment
• Best when family trios are available to participate in testing

Limitations of Whole Exome Sequencing

• Slow and costly
• Inevitably detects multiple variants of uncertain significance and incidental findings
• Requires multiple family members for best interpretation of results
• Does not capture 100% of genetic material or all types of genetic variation

Benefits of Whole Exome Sequencing

• Comprehensive coverage
• May identify rare diagnoses with atypical presentation

Single Gene Sequencing

• Detects single nucleotide changes, such as single base substitutions or small insertions or deletions
• Used when the family mutation is unknown and one gene is significantly more likely than other genes associated with the same condition
• Can be performed in a targeted region or across the entire gene

Whole Genome Sequencing vs. Whole Exome Sequencing

• Whole Exome Sequencing analyzes only the protein-coding portions of the genome
• Whole Genome Sequencing analyzes protein-coding regions, regulatory regions, and sections with unknown function

General Considerations for Genetic Testing

• Testing can often be targeted when a familial variant is known
• Testing can be targeted to one or a few variants when they are more common in a specific population
• More than one testing method may be required
• Multiple tests may be bundled together by a laboratory for certain indications
• The wider the scope of testing, the greater the sensitivity and the risk for uncertain/uninformative and incidental findings

Learn about the methodology and process of whole exome sequencing, which involves a combination of Next-Generation Sequencing (NGS) methods and/or array platforms to simultaneously sequence all genes. It helps in identifying single nucleotide changes, small deletions or insertions, and can also detect deletions and duplications.