During the middle 70s, the introduction of DNA sequencing concept by Fred Sanger gave rise to a new era in which it became possible to characterize genes and their structure in a systematic way as well as to predict their emerging protein products. Sanger sequencing is synonymous with first generation sequencing and was the basic method used for sequencing the whole human genome. The advent of massively parallel DNA sequencing technology has increased the throughput level of sequencing compared with the classical sequencing method and in combination with the yearly falling cost, this technology has been made quite affordable. Nowadays, different approaches have been established for the elucidation of the genetic basis of various disorders. Whole exome sequencing is one of the most commonly used approaches in order to identify the causative variants of many of these genetic diseases and different strategies for the disease gene identification, based either in unrelated individual or families, have been developed in parallel with this approach for the prioritization of the potentially pathogenic variants.