Progress in Detecting Genetic Alterations and Their Association with Human Disease Review Article

The completion of the Human Genome Project provided a reference sequence to which researchers could compare sequences from individual patients in the hope of identifying disease-causing mutations. However, this still necessitated candidate gene testing or a very limited screen of multiple genes using Sanger sequencing. With the advent of high-throughput Sanger sequencing, it became possible to screen hundreds of patients for alterations in hundreds of genes. This process was time consuming and limited to a few locations/institutions that had the space to house tens of sequencing equipment. The development of next generation sequencing revolutionized the process. It is now feasible to sequence the entire exome of multiple individuals in about 10 days. However, this meant that a massive amount of data needed to be filtered to identify the relevant alteration. This is presently the rate-limiting step in providing a convincing association between a genetic alteration and a human disorder.