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Mutating the entire genome


A new, fast and inexpensive way to mutate genes and large, non-gene pieces of DNA has been developed by University of Utah geneticists. They tested the method by mutating a gene involved in bone formation, resulting in short, malformed tail and limbs in the mutant mouse on the left, compared with the skeleton of a normal mouse on the right. The new method promises to speed efforts to learn more about how non-gene portions of DNA control genes to cause human defects and diseases. Credit: Sen Wu, University of Utah
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. University of Utah researchers report in the journal Nature Genetics that they have developed a faster, less expensive technique for mutating those large, non-gene stretches of DNA.

“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.”

The new method for mutating large,
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Source:University of Utah Health Sciences Center


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