Identification of disease genes by expression profiling.

The human genome has been completely sequenced. The development of innovative methodologies and tools to understand the functions of human genes in health and disease will allow the data of the human genome project to be utilized. This paper reviews methods that can be used to detect and isolate genes that are specifically expressed in certain diseases or that are specific to cell types. First, classical methods, such as differential screening of complementary deoxyribonucleic acid libraries and subtractive techniques, are described. Methods based on polymerase chain reaction (PCR), such as differential display PCR or serial analysis of gene expression, will then be discussed. Finally, recent developments in gene chip technology and basic principles of functional genomics will be illustrated. Future developments will link the results of genomic approaches to data obtained by other systematic methods, such as proteomics (i.e. the systematic, large scale analysis of proteins), and will allow the production of a detailed molecular characterization of diseases, disease stages, tissues, or cell types. Methods to detect disease or cell type-specific gene expression patterns will play an important role in the future of basic research, as well as the development of novel diagnostic procedures and identification of therapeutic targets.