Scientists from the University of Chicago and Johns Hopkins University have developed a new technique that promises to significantly enhance the rate of novel-gene discovery, a process that becomes increasingly difficult as the Human Genome Project moves closer to completion.

"We have identified and corrected a fundamental flaw in the current genomewide gene studies," note the authors in the April 11 issue of the Proceedings of the National Academy of Sciences. The technique they developed "provides a much higher degree of novel gene identification than the current approaches," adds lead author San Ming Wang, Ph.D., assistant professor of medicine at the University of Chicago.

Although two thirds, more than 90,000, of the estimated 140,000 human genes have already been identified, finding the final third could be far more challenging. These elusive, as yet undiscovered genes tend to be expressed at low levels or only in certain cell types, or turned on only during specific developmental stages or growth conditions. Yet these genes may play important roles in normal processes or in the development or prevention of various diseases.

To speed the search for these unknown genes, scientists use a "subtraction" method to remove the bulk of ubiquitous, already-identified genes from a sample pool of genetic material, leaving behind a higher percentage of the undiscovered genes expressed less frequently or at low levels in an attempt to increase the probability of discovering these genes.

However, this subtraction method often results in a nightmare; many of these unknown genes disappear after this treatment. The authors have figured out how and why this occurs.

Genes are located in DNA. They are expressed as messenger RNA from which protein is made. This messenger RNA is the target for gene discovery.

In order to identify genes, the messenger RNA needs to be converted back into DNA molecules called complementary DNA. The subtraction met
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Contact: John Easton
jeaston@uchospitals.edu
773-702-6241
University of Chicago Medical Center
10-Apr-2000