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Genome Annotation by Mutation

University of Utah researchers have developed a faster, less expensive technique for mutating those large, non-gene stretches of DNA. Genes account for only 2.5 percent of DNA in the human genetic blueprint , yet diseases can result not only from mutant genes, but from mutations of other DNA that controls genes.

Diseases are known to occur as a consequence of deleting non-gene DNA sequences, and this new method allows us to evaluate what these sequences do, says Mario Capecchi, distinguished professor and co-chair of human genetics at the University of Utah and an investigator for the Howard Hughes Medical Institute (HHMI).

The new method is significant because it makes it practical to do this for a vast amount of the total genome, he adds.

Because mice are used to study human disease, we want to know the function of every piece of DNA in the mouse genome, says Sen Wu, a postdoctoral fellow in human genetics at the University of Utah and HHMI. The best way to know the function of the genetic blueprint is by removing part of the DNA and seeing what goes wrong. We have found a way to do this job on a large scale that is simple and practical.

Capecchi says: We developed a method for deleting any piece of DNA from the mouse genetic blueprint very efficiently.

In the journal paper, the University of Utah scientists report: They found a way to delete or duplicate moderately long to very long pieces of DNA and make those mutations happen much more frequently than other methods can. That makes it easier to find out what defects or diseases arise due to such mutations, and thus what the DNA does normally.

They devised a much more efficient method for mixing and recombining pieces of two chromosomes, making it easier to breed mice with human cancers. Such mice are needed to develop new treatments.

Vast, Non-Gene Stretches of the Genetic Blueprint The genome is the genetic blueprint of
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