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Implementation of Exome Sequencing Assay

  • Samya Chakravorty
  • Arunkanth Ankala
  • Madhuri R. HegdeEmail author
Chapter

Abstract

Next-generation sequencing (NGS) is driving our current approaches to molecular diagnosis and characterization of inherited genetic disorders and is also enabling the discovery of genetic variants that induce susceptibility to non-inherited disorders. Advancements in NGS platforms and bioinformatics pipelines have allowed high-throughput, cost-effective, and efficient coverage of all coding regions of the genome, making whole-exome sequencing (WES) highly feasible in a clinical setting. Consequentially, the specificity and sensitivity for detecting all coding changes have tremendously improved, and the efforts and duration required to narrow down to the precise disease-associated variant(s) have significantly reduced. Rightly so, WES and whole-genome sequencing (WGS) are fast becoming the one-for-all clinical genetic tests, leading our way to precision medicine. In this chapter, we summarize the evolving roles of WES, which range from its use as a disease diagnostic tool for rare single-gene Mendelian disorders to a routine screening tool for monitoring disease progression and treatment response in cancer patients, as well as a tool for novel gene discovery in a research setting. This chapter highlights the achievements and limitations of the technology and emphasizes the challenges involved in the implementation of WES assays for clinical care.

Keywords

Whole-exome sequencing NGS Variant annotation Molecular diagnostics Whole-genome sequencing WES WGS Functional annotation of variants Medical genetics and genomics Mendelian disorders Complex disorders Neoplastic diseases Clinical care Challenges of exome sequencing Gene panel sequencing Personalized medicine 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Samya Chakravorty
    • 1
  • Arunkanth Ankala
    • 1
  • Madhuri R. Hegde
    • 1
    Email author
  1. 1.Department of Human GeneticsEmory University School of MedicineAtlantaUSA

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