The paradigm that originally dominated human gene finding efforts was that of linkage analyses. Linkage studies ascertained families with multiple members affected with the disorder of interest. Highly polymorphic genetic markers (those having many alleles) were genotyped across the genome. Usually around 400 of these highly variable markers were genotyped across the genome. The basic technique compared whether affected individuals in a family were more likely than expected by chance to carry the same version of that genetic marker. If so, this suggested that there was a gene (or genes) in that chromosomal region that was related to susceptibility for the disorder. Ming Tsuang, a senior leader in the field of psychiatric genetics, once gave the analogy that gene finding is like hunting for a criminal. You start out with the entire world (genome) to search in order to find your criminal (gene). Finding linkage to a particular chromosomal region is like someone giving you a zip code in which your criminal resides – you still do not know exactly where he is; you still have a lot of houses
