How do you identify the disease-causing mutation in a patient with an inherited disease? This video illustrates the steps involved—testing for genes that are the “usual suspects,” searching for mutations in novel genes, and assessing links between genotype and phenotype.
Just before his sophomore year in college, Sam Walker was diagnosed with retinitis pigmentosa (RP), a progressive disease that leads to blindness. It can be caused by mutations in one of over a hundred known genes. We all carry mutations in our genes, but most of those mutations do not cause disease. So how would a researcher go about identifying the rare mutation that is responsible for a disease? In this video, we watch physician-scientist Dr. Ed Stone go through the step-by-step process of looking for the RP-causing mutation in Sam’s DNA. The process involved 1) testing the most likely candidate genes, such as the ones with mutations already associated with RP in other patients, 2) analyzing the sequences of genes not previously associated with RP to search for the causative mutation, 3) finding additional individuals with the same mutation, who also have RP, and 4) determining the effect of the mutation identified in this study in a model organism. Having identified the likely root of Sam’s RP, Dr. Stone can now devise a gene therapy to stop disease progression.