Whole Exome Sequencing: Current and Future Perspectives


Genes are like the story, and DNA is the language that the story is written in ~ Sam Kean.

A Quick Look Through: 

Sam Kean, an author who penned The Violinist’s Thumb was spot on in the lines above. Yes, genes give us a real picture, a picture of our true selves. Our genes represent something unique in each and every one of us. A message more intriguing than ever is, they are the proud carriers of genetic information in the form of DNA. Henceforth, in one way, a DNA sample is like possessing tiny films that were photographing you since kilo years. Knowing our DNA, the biological entity that is a part of us, life ever since new life has been conceived will give a clear picture of the foods to be preferred, the time and duration of the exercises and the type of lifestyle to be adopted. Genes, in short, play a pivotal role in our overall health. Even though it is understood that adopting an active lifestyle and indulging in physical fitness on a regular basis have an important say in one’s health, it’s the genes that encode a larger picture.

Testing genetic material includes testing your genomic and exome data. Genome, in short, is the genetic makeup of an organism, whereas exome constitutes to about only 01% of the total genome. In cases where a potential diagnosis of patient’s symptoms is otherwise challenging, the physician would advise a strategy away from the monotonous step-wise diagnostic strategy. It is to be understood; any delay in diagnosis would only delay the onset of treatment and have an impact in the quality of life.

Understanding The Concept of Whole Exome Sequencing (WES):

For manifestations like these, a comprehensive technique whole exome sequencing (WES) is preferred and has got its own advantages. WES is a transcriptomics technique for sequencing all of the expressed genes in a genome. The goal of this test is to identify genetic variants that alter protein sequences. Also interestingly, clinicians are using WES as a diagnostic tool in their regular practice, especially in the case of heterogeneous, complex phenotypes.

If targeted testing of genes lay emphasis on single gene or a finite group of predetermined genes, WES tests investigates every region that codes for protein in the genome. Research reports reveal more than 85% of the mutations are found in exons, paving more acceptable ways to identify disease causing mutations in unexpected genes that would be missed by targeted approaches. Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES) have tested remarkably prosperous in characteristic the causes of genetic diseases. These analyses have generally depended on the availability of more than one unrelated affected individual and/or linkage evidence in at least one family. However, next-generation sequencing (NGS) has conjointly succeeded in characteristic causes of genetic conditions even once they are seen in precisely one patient. Alternatively, there’s growing interest within the introduction of NGS into the clinic to help within the designation of conditions that no genetic cause may be found with targeted testing or chromosomal arrays. That said, in an exceedingly clinical setting, patients with unknown genetic conditions tend to gift with a good vary of clinical options, and it is often necessary to consider each patient’s genome on an individual basis, rather than looking for common disrupted genes in multiple cases with a similar phenotype. (Need, Anna C., et al, 2012).

Exome Sequencing Graphic

(Source: https://dnalabsindia.com/blog/what-is-clinical-exome-sequencing)

Clinical Exome Sequencing:

This is a composite report of your genetic makeup from Mapmygenome. We help you understand what your genetic variations mean and how it may affect you. In order to help you understand this report better, our genetic counselor will be available to answer questions and can help you in taking further actions.

Why Whole Exome Sequencing (WES)?:

The following are the advantages for proceeding with WES.

  • Molecular Diagnosis: For confirming a clinically diagnosed genetic condition. This provides a genetic diagnosis that can inform appropriate treatment, management, inheritance, accurate recurrence risks, and reproductive decision making.
  • Discovery: In cases where no diagnosis has been made, but clinical presentation is suggestive of a genetic condition. 
  • Efficiency: Cost-effective and time-effective solution (as compared to sequential single-gene testing) for cases where a change in one of many genes may result in a specific clinical picture.
  • Extensive Scope: All clinically important genes covered. Tests for single-gene and multi-gene conditions. Ideal for targeted management of complex syndromes, epilepsy, ASDs, neuropathy and heterogeneous phenotypes. WES allows comprehensive analysis of ~ 23,000 genes in the human genome with a single NGS run.
  • Better management and screening: Through WES, we identify the genetic cause of disease followed by subsequent testing in blood relatives (cousins, siblings and children etc).

Why Mapmygenome:

  • Uses the Next – Generation Sequencing (NGS) technology on the basis of Illumina Novaseq platform
  • Covers more than 95% of the target region
  • High precision analysis and reporting as per American College of Medical Genetics (ACMG) guidelines
  • Variant of Uncertain Significance (VOUS) included
  • Incidental findings included (unless otherwise requested)
  • Detailed pre and post-test counseling with certified experts
  • Valuable inputs for the physician with respect to management or treatment options in case of clinical findings.

 Variant Classification:

American College of Medical Genetics (ACMG) classifies variants in exome sequencing as follows.

  • Pathogenic: Variant previously known to be disease causing
  • Likely pathogenic: High certainty that the variant is disease causing based on literature
  • Variant of Uncertain Significance (VOUS): Uncertain, or conflicting literature about the pathogenicity of the variant.
  • Likely Benign: High certainty that the variant is not disease causing based on literature
  • Benign: Variant previously known to be not associated with the disease

However, exome sequencing does have a few limitations, CNVs and large deletions/duplications/insertions cannot be detected. Structural changes and chromosomal anomalies cannot be detected. Moreover, in few cases, its highly possible that NGS will prove faster and least expensive than any prolonged diagnostic commutation, endured by many a family. In a word, knowing genetic variants helps us provide attractive details into human malady for interference methods, diagnostic applications and therapeutic ways. WES is a short-term alternative for getting an image of genome that is being coded. WES is pleasing itself deep in the fields of research, diagnostics and clinical setting; used for detecting variants in both all the disease types and in SNPs associations and pharmacogenetics. Going forward, WES can prove a valuable tool for capturing specific targets across diagnostic settings.                                      


  1. Marian, Ali Jk. “Medical DNA sequencing.” Current opinion in cardiology vol. 26,3 (2011): 175-80. doi:10.1097/HCO.0b013e3283459857
  2. Need, Anna C., et al. “Clinical application of exome sequencing in undiagnosed genetic conditions.” Journal of medical genetics 49.6 (2012): 353-361.
  3. Rabbani, Bahareh, Mustafa Tekin, and Nejat Mahdieh. “The promise of whole-exome sequencing in medical genetics.”Journal of human genetics 59.1 (2014): 5.



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