Whole Exome Sequencing (WES)

Whole Exome Sequencing (WES) is a revolutionary genetic test designed to sequence the exonic regions of DNA, which account for 1-2% of the entire genome but hold approximately 85% of known disease-causing mutations. The exome contains about 23,000 protein-coding genes, which are directly linked to various Mendelian disorders and disease-predisposing Single Nucleotide Polymorphisms (SNPs). WES offers deep insights into genetic variations that are crucial for diagnosing complex conditions and personalizing medical care. This technology is transforming how clinicians and patients approach rare genetic disorders, enabling faster diagnosis, tailored treatments, and better health outcomes.

WES is a comprehensive sequencing technique focused on analyzing the exonic regions of the genome. While the human genome is vast, containing billions of base pairs, only a small portion (about 1-2%) codes for proteins. These protein-coding regions, known as exons, play a pivotal role in many genetic disorders.

WES is especially beneficial in cases where patients have undergone a "diagnostic odyssey" — multiple medical tests with no definitive results. The ability of WES to provide a molecular diagnosis can end this long search, offering clarity and a path forward for both patients and healthcare providers. The data obtained from WES allows for a more targeted clinical management approach, leading to personalized treatments, preventive strategies, and better prognostic understanding.

Clinical Utility

Whole Exome Sequencing offers vast clinical utility, including:

1. Diagnosing Genetic Disorders: WES is instrumental in identifying disease-causing variants. For patients suspected of having genetic disorders with no clear diagnosis, WES provides the molecular insights necessary to understand the condition.

2. Understanding Disease Progression: The differentiation between inherited and de novo mutations helps clinicians predict disease progression and inform family members about the risks of recurrence.

3. Precision Medicine: WES influences the clinical management of disorders by identifying specific genetic mutations, allowing for personalized medical interventions, including lifestyle modifications, targeted therapies, and preventive care.

4. Resolving Diagnostic Uncertainty: WES often serves as the final test in cases where traditional diagnostic methods fail, helping to identify the root cause of a patient‘s condition.

5. Family Planning: In addition to providing insights into a patient’s health, WES also helps in family planning by identifying risks for hereditary conditions that may be passed to future generations.
   
   

When to Consider Whole Exome Sequencing

WES is highly recommended for the following clinical scenarios:

1. Undiagnosed Conditions: For patients with unexplained symptoms, developmental delays, intellectual disabilities, or neurodevelopmental disorders, WES can uncover the genetic cause of the condition. It is especially useful when other tests have yielded inconclusive results.

2. Molecular Diagnosis: WES identifies mutations in exon regions, offering a molecular diagnosis for conditions caused by heterozygous variants (in autosomal dominant conditions) or homozygous/compound heterozygous variants (in autosomal recessive conditions).

3. Genetic Disorders in Complex Syndromes: WES is ideal for diagnosing multigene conditions such as global developmental delay, autism spectrum disorder, and neurodevelopmental disorders. These conditions often result from complex genetic mutations, which WES can effectively detect.

4. Ending the Diagnostic Odyssey: For patients who have undergone extensive testing with no clear results, WES can provide the final answer, helping clinicians identify the disease-causing mutation and put an end to the diagnostic uncertainty.

5. Risk Assessment for Family Members: WES provides critical information about recurrence risks, helping families make informed decisions about their health and future pregnancies.
   
   

MapmyGenome Offerings

At MapmyGenome, we provide advanced WES services with the following key features:

1. Comprehensive Gene Coverage: Our WES test covers all ~23,000 protein-coding genes in the human genome, along with mitochondrial genes. This extensive coverage ensures a detailed analysis of genetic variations.

2. Bioinformatics Analysis: The raw data from WES is processed using a robust bioinformatics pipeline. Pathogenic, likely pathogenic, and variants of uncertain significance (VuS) are reported based on the guidelines from the American College of Medical Genetics (ACMG) and ClinVar.

3. High Sensitivity and Specificity: Our WES test covers more than 98% of targeted exons, offering a sensitivity of 95.9% and specificity of 98.7%, ensuring accurate and reliable results.

4. Primary and Incidental Findings: We report primary findings according to the patient’s clinical phenotype and ACMG guidelines. Incidental and carrier findings are also reported based on ACMG and ACOG recommendations, providing valuable insights into potential genetic risks.

5. Genetic Counseling: Our services include genetic counseling to guide patients and their families through the findings. Our counselors explain the test results, discuss available management and treatment options, and offer support in making informed decisions about health and family planning.

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