Whole exome sequencing (WES) is a genetic testing method which has been widely-adopted within both clinical and research settings.[1]

Alongside costs which have decreased over time, accessibility has increased significantly.[2]

Let’s take a brief look at the history of genome science, and then touch on how WES measures up to two more common traditional diagnosis methods.

Genome Science Timeline 📜

The timeline of genome science as we know it is as important as it is interesting. Much of the foundational knowledge we know and utilize today is in part thanks to the research done by many dozens of scientists over the course of the last two centuries.

By having a surface-level overview of how DNA was discovered, how sequencing of it evolved, and when it became more applicable to disease diagnosis, we can posit that it will only improve in both the near and distant future. Eventually, as a go-to way for helping patients with rare mendelian diseases and beyond.

  • 1871: Friedrich Miescher discovers DNA, originally deemed nuclein
  • 1953: James Watson and Francis Crick discover the double helix structure of DNA
  • 1977: Frederick Sanger introduces dideoxy chain-termination for DNA sequencing, later known as the Sanger method
  • 2003: DNA of the entire euchromatic human genome is sequenced successfully
  • 2009: First instance of exome sequencing shown to diagnose rare mendelian disease[3]

WES vs. Genetic Panel Testing 📊

  • Provides more extensive coverage and evaluation of genomic variants in various conditions[1] [4]
  • Superior when attempting to measure scope of driver and passenger mutations [1][5]
  • Costs[6] as low as $400 and as high as $3,500[7]
  • Diagnostic rates often cited between 25-58% but reliant on reanalysis upon no variance discovery[8]
Genetic Panel Testing
  • Common type of panel testing, which has increased susceptibility and prevalence to variants of uncertain significance (VUS)
  • May cause further conflicts between patient and healthcare providers, pertaining to what is classified as a deleterious mutation[9]
  • Methodology and processes have variation between each laboratory; this poses potential analytical dissimilarity within comparisons[9]
  • Often is not as specific as other techniques, which brings the testing aspect’s salience into question[4]
  • Costs as low as $700 and as high as $2,900[7]
  • Diagnostic rates of >70% for cardiovascular diseases, but becomes fractional and inconsistent for complex genetic architectures[5]

High variance reliant on numerous factors, especially patient location and ailment

WES vs. CMA 🔎

  • Used often with Chromosomal Microarray Analysis (CMA) in prenatal settings[10]
  • Primarily utilized to detect exonic variant etiology pertaining to common and rare mendelian disorders
  • Classified as Next-Generation Sequencing (NGS) technique[11]
  • Qualitatively better diagnostic rates and utility compared to CMA[12]
Chromosomal microarray analysis (CMA)
  • Technique used for measuring gain or loss of DNA within a patient’s genome[10]
  • Can detect abnormalities which are large and structural or submicroscopic in nature[10]
  • Not classified as NGS technique[11]
  • Prices hover around $2,500, but with cost-saving algorithms applied, can be as low as $800 [13]
Automated DNA chip loading at the Cancer Genomics Research Laboratory courtesy of Unsplash

What’s the future of WES? 🧬

  • Since 2011, WES has been used widely for etiologic diagnosis within laboratories[12] as technology advances and accessibility increases, a wider audience of patients will be able to afford and undergo WES
  • Improved and more widespread usage for diagnosis of rare childhood genetic diseases through precision medicine[12]
  • As cost dwindles, the chances of WES becoming, ideally, a standardized first-line protocol increases
  • Currently, CMA is the recommended first-line genomic test for genetic diseases within children[12]
  • Accounts for discovering ~85% of known disease-causing variants; this may increase as technology advances[14]

  1. WEScover: selection of whole exome sequencing vs. gene panel testing
  2. Innovation and Illumina: The road to the $600 human genome
  3. Exome sequencing identifies the cause of a Mendelian disorder
  4. Hereditary cancer gene panel test reports: wide heterogeneity suggests need for standardization
  5. Beyond Gene Panels
  6. Personal Genome Test Will Sell at New Low Price of $250
  7. Estimating the costs of genomic sequencing in cancer control
  8. A three-year follow-up study evaluating clinical utility of exome sequencing and diagnostic potential of reanalysis
  9. Clinical Advantages and Disadvantages of Panel Testing for Cancer Susceptibility
  10. Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology
  11. Genetic Testing, Including CMA and NGS Panels …
  12. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing …
  13. Cost-effectiveness analysis of chromosomal microarray …
  14. Whole Exome Sequencing Market Latest Innovations and Future Opportunities
  15. The Promise and Challenges of Next-Generation Genome Sequencing for Clinical Care
  16. Chromosomal microarray and whole‐exome sequence analysis in Taiwanese patients with autism spectrum disorder
  17. Help With Autism Spectrum Disorder
  18. Re-analysis of whole-exome sequencing …

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