Whole genome sequencing as a diagnostic test: challenges and opportunities

Clin Chem. 2014 May;60(5):724-33. doi: 10.1373/clinchem.2013.209213. Epub 2013 Nov 13.


Background: Extraordinary technological advances and decreases in the cost of DNA sequencing have made the possibility of whole genome sequencing (WGS) as a highly accessible clinical test for numerous indications feasible. There have been many recent, successful applications of WGS in establishing the etiology of complex diseases and guiding therapeutic decision-making in neoplastic and nonneoplastic diseases and in various aspects of reproductive health. However, there are major, but not insurmountable, obstacles to the increased clinical implementation of WGS, such as hidden costs, issues surrounding sequencing and analysis, quality assurance and standardization protocols, ethical dilemmas, and difficulties with interpretation of the results.

Content: The widespread use of WGS in routine clinical practice remains a distant proposition. Prospective trials will be needed to establish if, and for whom, the benefits of WGS will outweigh the likely substantial costs associated with follow-up tests, the risks of overdiagnosis and overtreatment, and the associated emotional distress.

Summary: WGS should be carefully implemented in the clinic to allow the realization of its potential to improve patient health in specific indications. To minimize harm the use of WGS for all other reasons must be carefully evaluated before clinical implementation.

Publication types

  • Review

MeSH terms

  • Costs and Cost Analysis
  • Disease / genetics*
  • Genetic Predisposition to Disease
  • Genetic Testing / economics
  • Genetic Testing / ethics
  • Genetic Testing / methods*
  • Genetic Testing / standards
  • Genome, Human / genetics*
  • Genome-Wide Association Study / economics
  • Genome-Wide Association Study / ethics
  • Genome-Wide Association Study / methods*
  • Genome-Wide Association Study / standards
  • Humans
  • Quality Control