Researchers at the University of Minnesota have used a gene identification system known as Sleeping Beauty to identify a gene mutation that triggers hyperactivity and, in the process, successfully reproduced the genetic mutation on a larger scale.

In a first-of-its-kind, large scale screening for disease traits, scientists randomly mutated genes in mice and pinpointed a possible genetic cause for hyperactivity. Mice that had a gene on Chromosome 11 mutated by the Sleeping Beauty system were more aggressive and hyperactive when placed in a new environment. The study was published in the September 2006 issue of the journal PLoS Genetics.

"The forward-genetic approach we have developed using Sleeping Beauty has allowed us to screen for traits relevant to human diseases and then pinpoint the mutated gene that caused the symptoms," said David Largaespada, Ph.D., lead author of the study and associate professor at the University of Minnesota Department of Genetics, Cell Biology, and Development. "It is our hope that similar research could lead to advances in understanding human behavior and the development of medications that target the genetic causes of many diseases."

In addition, the study has larger implications for gene identification methods that use jumping DNA such as Sleeping Beauty in mammals. Jumping genes, or transposons, insert themselves into or between genes and can activate or inactivate a gene's normal function. Related transposons are natural to the genetic makeup of humans, animals, and fish, but, through millions of years of evolution, most transposons became inactive. In a 1997 study, University of Minnesota researchers took defunct, non-functioning jumping genes from fish and made the genes jump again. This research had reactivated the jumping genes from millions of years of evolutionary sleep-hence, the name Sleeping Beauty.

In this study, researchers observed not only the mutation of individual genes with the use of the Sleeping Beauty system, but large-scale chromosomal rearrangements, similar to what can occur in nature as species evolve. Genome rearrangement on this scale could allow scientists to observe and study how gene transfer and mutation affect the evolutionary process.

"It is key that we learn more about how jumping DNA and gene mutation operate and how it can benefit modern medicine," said Largaespada. "The results from this study are only the beginning as far as understanding everything the Sleeping Beauty system can accomplish."