Researchers Compare WGS, Exome Sequencing-Based Mendelian Disease Diagnosis

For a paper appearing in the European Journal of Human Genetics, investigators at the University of New South Wales, the Garvan Institute of Medical Research, and other centers compare Mendelian disease diagnostic rates and cost considerations of whole-genome sequencing and exome sequencing. The team turned to whole-genome sequencing (WGS) to assess more than three dozen Mendelian disease-affected individuals ranging in age from infancy to 73 years old who had not been diagnosed with prior exome sequencing tests, revisiting WGS-diagnosed cases with contemporary exome sequencing to see if the culprit could have been found with exome testing approaches used today. While WGS led to diagnoses in 13 of the 38 cases, for example, the researchers note that contemporary exome sequencing could have diagnosed seven of the previously exome-negative cases, bringing the WGS-specific diagnoses down to around 19 percent. Together with findings from their health economic analyses, which looked at the incremental addition of WGS after exome sequencing or WGS alone, the authors suggest that WGS "is the optimal genomic test choice for maximal diagnosis in Mendelian disorders. However, accepting a small reduction in diagnostic yield, [whole-exome sequencing] with subsequent reanalysis confers the lowest costs."