Some inherited pathological disorders are caused by a single mutation and others have susceptibility components which are heritable, but polygenic (arising from the contribution of several genes) in origin. Often, these genes have biological functions that are not obviously related to the symptoms, and pathology of the disorder, and their contribution is not thus recognized. The same is true when the susceptibility (or resistance) of individuals is assessed in relation to chemically induced toxicity, or in relation to the activity of molecules with pharmacological properties. Working on the premise that any genes which contribute to a susceptibility, or resistance, phenotype may be differentially expressed in relation to those in a normally responsive individual or tissue, we are using microarray technology to screen for differential gene expressions that may be contributing to the phenotype. We have built an arrayer based on the Stanford design, with some modifications, and are using this to produce arrays of up to 2-56K clones (depending on requirement). We are arraying both known genes and cDNA library clones from the rat, mouse and human. Initial analytical work has been carried out on human drug resistance cell lines, and increased expression of some well-characterized genes have been observed (MDR1, GST), as well as some changes of expression which are consistent with other phenotypic traits of these cells. This work is currently being extended, and all relevant findings will be presented.
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