The completion of the draft human genome opened a new era in neuroscience research, providing tools to investigate brain diseases of unknown etiology and to isolate new drug targets for these disorders. The Human Genome Project led to the creation of databases containing vast amounts of genetic sequence data and the isolation of thousands of partial cDNA sequences representing previously unknown genes. This information, together with the development of new technologies for analyzing gene expression, now allows scientists to analyze the expression of thousands of genes simultaneously, providing a powerful means for investigating brain diseases and discovering new drug targets. (Shilling & Kelsoe, 2002)
The next era of genomics involves elucidating the function of thousands of newly discovered genes. Functional genomics describes studies that focus on this process of determining gene function and how the genome works together to generate complete patterns of biological function. These methodologies serve to complement traditional techniques that are limited to studying several genes at a time (Northern blotting, RNase protection, reverse transcription-polymerase chain reaction (RT-PCR), and in situ hybridization) and include DNA microarrays, differential display PCR, serial analysis of gene expression (SAGE), total gene expression analysis (TOGA), and chemical mutagenesis of mice. DNA microarrays are the most powerful of the techniques that address global questions in functional genomics, allowing the analysis of the expression of thousands of genes in a single experiment, thus facilitating the study of global patterns of genes that are affected together by specific diseases and drug treatments. (Shilling & Kelsoe, 2002)
The Brain and Its Challenges:
The brain is the most complex organ in the human body and one of the most diverse in gene expression, with the expression of thousands of genes that are unique or highly enriched in the brain. The brain regulates complex tasks involved in cognition, emotion, memory, integration of sensory information, and motor coordination. Disruptions in these functions underlie many brain diseases. Such complex tasks mediated by the CNS utilize multiple brain regions and biochemical systems. To understand the changes in genetic programs that result in altered gene expression and protein function, it is necessary to use technologies that can address multiple changes in gene expression in multiple brain regions simultaneously. (Shilling & Kelsoe, 2002)
DNA Microarrays and the Revolution in Research:
DNA microarrays have been used to investigate regional differential expression of neural genes in mouse and human genomes. Furthermore, the use of functional genomics approaches may lead to new methods of disease diagnosis. Gene expression patterns that are associated with a specific disease can be used as diagnostic markers for the disease. This type of analysis would be especially useful for the diagnosis of psychiatric disorders such as schizophrenia and bipolar disorder, which lack biological markers and are diagnosed based on behavioral phenotype. There are two main types of DNA microarrays: oligonucleotide microarrays and cDNA-based microarrays. (Shilling & Kelsoe, 2002)
Conclusion:
The completion of the draft sequence of the human genome and the recent development of technologies that allow analysis of the expression of thousands of genes simultaneously in the brain have revolutionized our ability to address the mechanisms underlying human brain disorders. Previously, gene expression studies were limited to the analysis of one or two changes in gene expression. Now, global changes in gene expression can be investigated, and common functional attributes of gene alterations can be identified in human brain diseases. (Shilling & Kelsoe, 2002)
Reference:
Shilling, P. D., & Kelsoe, J. R. (2002). Functional genomics approaches to understanding brain disorders. Pharmacogenomics, 3(1), 31-45.
