Mouse genome revealing which DNA sequences activate human genes

BERKELEY, CA -- The already high value of the mouse as a model for studying the human genome has been raised even higher with the results of a new study by researchers with the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California at San Francisco (UCSF).

In a paper published in the April 7 issue of the journal Science, the researchers report that comparative analysis techniques used to identify DNA sequences coding for genes in mice and humans can also be used to identify sequences that regulate the "expression" or activation of genes.

"You could call this finding jewels in junk DNA," says Edward Rubin, a geneticist with Berkeley Lab's Life Sciences Division, and co-leader, along with Kelly Frazer, of the study. "By comparing human and mouse sequences we can identify those segments of the genome that contain information which instructs surrounding genes on when and where they are to be active. Identifying these sorts of regulatory sequences using classical biological approaches is labor intensive and difficult."

Evolutionary conservation of non-coding DNA sequences that play an important role in regulating gene expression is the key to the success of this study, just as it has been a key to identifying DNA sequences that code for genes across different species.

"If evolution conserved a sequence over the 70-90 million years since mice and humans diverged, it likely has a function," says Frazer. "Whether its function is to determine the structure of a protein coded for by a gene or to regulate gene expression, we should be able to identify these sequences through mouse to human sequence comparisons."

In addition to Rubin and Frazer, other authors of the Science paper were Gabriela Loots and Cathy Blankespoor of Berkeley Lab, Richard Locksley and Zhi-En Wang of UCSF and the Howard Hughes Medical Institute, and Webb Miller at Penn State University.

As the various genome projects

Contact: Lynn Yarris
DOE/Lawrence Berkeley National Laboratory

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