Figure 2. Three Strategies for Exome Sequencing in Gene Discovery.

Panel A shows the sequencing of DNA samples from multiple, unrelated, similarly affected subjects to identify genes in which some or all of the subjects carry a mutation. Panel B shows trio analysis, in which samples from the affected child and both unaffected parents are analyzed to identify de novo changes in the child. Panel C shows recessive analysis, in which samples from one or more affected children are sequenced to identify the genes that harbor two mutations (one on each allele). Open circles and squares represent unaffected female and male subjects, respectively; solid symbols indicate affected status. In all the panels, horizontal lines represent exonic sequences, and X represents a sequence change as compared with the reference human genome.