Johns Hopkins Gazette: October 30, 1995

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

     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

     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

     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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