U. team's research may offer hope in developing disease treatments

Researchers at the University of Utah have created a less-expensive, less-time-consuming way to mutate large, non-gene stretches of DNA. And that could speed understanding of different disease processes and help to develop treatments.

Their technique is reported this week online in the journal Nature Genetics.

Diseases may develop from gene mutations. But they can also result from mutations in the non-gene DNA. And it is those portions of DNA that the research targets, according to Mario Capecchi, distinguished professor and co-chairman of human genetics at the U. and an investigator for the Howard Hughes Medical Institute.

Capecchi likens the human genome to a large book — about 5 billion letters or 1,000 volumes of 1,000 pages each. The new technique is a "way to cut out as much text as we want" from the DNA sequence, which forms the genome.

DNA, or deoxyribonucleic acid, is a molecule made from numerous "base pairs" of four nucleic acids designated A, C, G and T. Genes are about 2.5 percent of that DNA "text." The rest is noncoding sequence. To remove it using existing methods has been "enormously expensive."

The new method "is significant because it makes it practical to do this for a vast amount of the total genome," he said. "We can look at a lot of DNA that's been neglected completely."

Mice are used to model human disease. In a release regarding the study, one of the researchers, Sen Wu, a postdoctoral fellow in human genetics at the U., said a key to understanding the function of the genetic blueprint is to take out part of the DNA sequence and see what happens. This discovery makes it simple and practical.

Other researchers on the project were human geneticists Guoxin Ying, a postdoctoral fellow, and Qiang Wu, an assistant professor (no relation to Sen Wu).

Besides figuring out how to delete long pieces of DNA in a simpler, cheaper fashion, they also devised an "efficient" method for mixing and recombining pieces of two chromosomes, making it easier to breed mice with human cancers.

The non-gene DNA sequences are important because they turn genes on or off, up or down. Still other sequences fold and pack DNA into the nucleus of each cell. Much of it is considered "useless junk," but Capecchi and the other researchers believe much of it will turn out to be important. They believe that mutations in the non-gene sequences can cause genes to malfunction. And making their removal faster and cheaper has the benefit of targeting the genes they regulate, as well.