Mapping psychiatric disease genes: impact of new molecular strategies.

Genetic mapping of genes which predispose to psychiatric illness is discussed in relation to recent developments in molecular genetic technology. Among the psychiatric disorders, the mechanism by which genetic factors contribute to illness is poorly understood, and the classification of phenotype (ill-status) is extremely complicated. These uncertainties, together with other complicating factors, tend to undermine the effectiveness of genetic linkage analysis. Two very powerful new molecular strategies have the potential to improve the overall gene mapping effort. First, new applications of polymerase chain reaction (PCR) technology will allow laboratories to generate much more genetic data than has been previously possible. Some of the factors which confound psychiatric linkage analysis should be mitigated by the larger data sets that will be generated with this technology. Second, the cloning of large segments of human chromosomes into yeast artificial chromosomes (YACs) has given rise to strategies to clone and catalog the entire human genome. The goal of constructing overlapping YAC clones (contigs) end-to-end across each human chromosome now appears imminent. This development will have immense effect upon our ability to identify disease genes.