ABSTRACT
Many early WES studies examined cohorts of patients with the same diagnosis in order to search for the causative gene. Exome sequencing and the computational analysis of WES data has been a moving target since WES was first used for the analysis of Mendelian disease in 2010. The kits used to capture exons and other sequences have been updated and improved multiple times, and the databases used to investigate the variants have grown in volume and sophistication. A key assumption in WES analysis is that a common variant cannot be the cause of a rare disease. In the initial years of exome sequencing, a number of studies were performed using the intersection strategy. More recently, it seems that there are fewer large cohorts of patients available for this approach. More sophisticated strategies have been developed to apply more robust statistical approaches.
