High throughput analysis of gene expression in the human brain

The human brain is thought to have the greatest complexity of gene expressi on of any region of the body, reflecting the diverse functions of neurons a nd glia. Studies of gene expression in the human brain may yield fundamenta l information about the phenotype of brain cells in different stages of dev elopment, in different brain regions, and in different physiological and pa thological states. As the human genome project nears completion, several te chnological advances allow the analysis of thousands of expressed genes in a small brain sample. This review describes available sources of human brai n material, and several high throughput techniques used to measure the expr ession of thousands of genes. These techniques include expressed sequence t ag (EST) sequencing of cDNA libraries; differential display; subtractive hy bridization; serial analysis of gene expression (SAGE); and the emerging te chnology of high density DNA microarrays. Measurement of gene expression wi th microarrays and other technologies has potential applications in the stu dy of human brain diseases, including cognitive disorders for which animal models are typically not available. Gene expression measurements may be use d to identify genes that are abnormally regulated as a secondary consequenc e of a disease state, or to identify the response of brain cells to pharmac ological treatments. (C) 2000 Wiley-Liss, Inc.