FEATURE ARTICLE
Gene Chips and Functional Genomics
A new technology will allow environmental health scientists to track the expression of thousands of genes in a single, fast and easy test
Hisham Hamadeh, Cynthia Afshari
Gene Expression
The most basic living unit of an organism is the cell. Organs comprise a collection of multiple cell types that work in concert to provide structure and function to the organ system. Within the center of each cell lies the nucleus. And within the nucleus can be found the genetic material—DNA—that contains the code for producing almost all of the cellular machinery. DNA, or deoxyribonucleic acid, serves as a template for the enzymes and proteins that give each cell type its unique functional and morphological characteristics. Each DNA molecule is a string of smaller subunits called nucleotides, and encrypted in the sequence of DNA's nucleotides is the order in which different amino acids should be strung together to make proteins. Proteins are often referred to as "the workhorses of the cell," as they provide the cell with much of its structure and carry out almost all of its functions.
Within each cell of each individual the DNA code is identical. Yet the individual contains any number of specialized cells, such as those that make up muscle, skin, nerve and the immune system. This fact forces us to ask how specialized cell types become differentiated. How, for example, does an immune cell "know" to produce antibodies in response to bacteria? Why does a neuron manufacture the structures and chemicals to conduct nerve impulses but not to produce antibodies?
The answer is that only a subset of the DNA code is "expressed" in each cell type. The expressed genes of the immune cell, for example, include those encoding the manufacture of antibodies, whereas the antibody genes remain unexpressed in neurons. This differential expression of the DNA code is what makes each cell unique and provides the basis for cellular function and processes.
The first phase of the genomic era has focused on elucidating the exact sequence of the nucleotides in the DNA code. With that part of the work nearly completed, investigators now want to know how the DNA code translates into gene function. They want to learn which genes are responsible for important healthy functions and which, when they become damaged, contribute to disease. They also want to understand how and when signals external to the cell stimulate gene expression within it. Investigators would like to understand, for example, how the immune cell translates the presence of bacteria into gene expression of an antibody gene. Accordingly, the new field of "functional genomics" focuses on the expression of the DNA.
DNA expression proceeds in several steps. First, specific DNA segments corresponding to individual genes are copied from DNA into RNA molecules, which are chemically very similar to DNA. In this step, RNA molecules are said to be "transcribed" from DNA, an operation that takes place in the cell's nucleus. As the archive for a cell's genetic instructions, nuclear DNA is too precious to be shuffled around the cell. Instead, the shorter-lived RNA copy moves from the nucleus to the cytoplasm where its code—its nucleotide sequence—is "translated," such that amino acids are strung together to form proteins.
One way, then, to determine which genes are being expressed at any given time is to cull all of the RNA molecules transcribed in a cell at that moment. In this way, a scientist can determine which gene or genes are active during an important cellular activity—cell division, for example. Those RNAs are likely coding for proteins whose specific function is to contribute to cell division, particularly if they are not transcribed when the cell is at rest. To make that determination, scientists would want to compare the cluster of RNAs produced in a dividing cell with those produced by a resting cell. Microarrays allow for many such comparisons. In our lab, for example, we are primarily interested in comparing RNA molecules transcribed under normal conditions with those transcribed when the cell is exposed to a toxic environmental chemical. Microarrays allow us to assess very quickly all of the RNA molecules being transcribed in a cell at a given time under particular circumstances. We can do this, even if we do not know the exact function for each gene. Yet knowing when that gene is expressed may ultimately help us learn the gene's function as well.
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