Researchers Develop "Bar Code" To Speed Gene Discovery Researchers at the Hopkins Oncology Center and the Howard Hughes Medical Institute have developed a revolutionary new method to rapidly identify genes and measure gene expression. The researchers say that the technique, serial analysis of gene expression, can be widely used to speed the discovery of genes involved in a variety of diseases, including cancer, as well as to interpret the large amounts of gene sequence data coming from the Human Genome Project. They also believe the approach will provide new insights into the control of normal development. As reported in the Oct. 20 issue of Science, SAGE is analogous to the bar coding system used to catalog and monitor merchandise in grocery stores, said Kenneth W. Kinzler, an associate professor of oncology who, along with Bert Vogelstein, led the research effort. "Each time a [bar code on an item of merchandise] is scanned at the cash register, a computer receives the information," Kinzler said. "At the end of the day, it can generate a report that tells how many times that particular product was purchased. In genetic terms, we would call this gene expression. If a product was frequently purchased, we would call it high expression, and if rarely purchased, we would call it low expression. The accumulated bar code entries provide a picture of the store's sales. By analogy, SAGE gives us a picture of the cell's gene expression pattern," he said. Understanding the patterns of gene expression is the goal of much current biomedical research. Each human cell contains more than 100,000 genes, but only a subset of the total genes is expressed in each cell. The specific subset of genes expressed determines the biologic properties of the cell--for example, whether the cell acts as part of the pancreas or part of the liver. Genes are made up of many thousands of building blocks called base pairs. In the new approach, researchers assign a specific sequence of nine base pairs to each gene. These sequences are the "bar codes" that represent the individual genes. These bar codes are then identified and counted by sophisticated sequencing and computer methods. Once SAGE was perfected on liver and pancreatic tissue, it took researchers only days to obtain thousands of bar codes and identify genes that were specifically expressed in each of the two tissues. In the process, researchers discovered several new genes. The next project for the research team will be to use SAGE to compare the gene expression patterns in colon cancer cells to those of normal colon cells.
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