WARF: P06119US

Assessing the Mutability of a DNA Sequence


Yuyuan Guo

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing a method for determining how susceptible a DNA sequence is to mutation.
OVERVIEWDNA mutation is associated with many diseases, including cancer. Mutation also is the primary strategy used by disease-causing bacteria and viruses to develop resistance to treatments. As a result, there are many applications for methods that evaluate how easily a DNA sequence can be mutated. For example, these methods could be used to determine if an environmental factor increases the mutation rate of an oncogene and therefore increases the risk of cancer.

However, existing techniques for characterizing mutability involve sequencing DNA from many individuals to identify areas that are susceptible to high levels of mutation. Faster, more efficient methods are needed to enable genome-wide screening for these mutation hotspots.
THE INVENTIONA UW-Madison researcher has developed a quicker method for determining how susceptible a DNA sequence is to mutation. The method involves comparing the DNA sequence of interest to a mutation hotspot sequence to evaluate whether it is more or less mutable than the hotspot sequence.

For this method, the DNA sequence of interest and the hotspot sequence are each linked in-frame to a reporter gene and expressed in bacterial cells. A nonsense or frameshift mutation in either sequence results in an easily detectable loss of function in the reporter gene product. For example, if the reporter gene is a “killer gene,” the bacterial cell will survive only if there is a mutation in the DNA sequence that destroys the function of the reporter gene.

To determine if the sequence of interest is easier to mutate than the hotspot sequence, the number of surviving bacterial colonies can be compared. If more bacteria that contain the sequence of interest survive than bacteria that contain the hotspot sequence, the sequence of interest is more mutable. 
  • Enables genome-wide screening to identify mutation hotspots
  • May provide additional information about the cause of cancer in a patient
  • Capable of identifying mutation hotspots
  • Faster and more efficient than sequencing DNA from many individuals
  • Screening can be done under different conditions to determine, for example, if a particular sequence is only susceptible to mutation in the presence of an environmental factor.
Contact Information
For current licensing status, please contact Jennifer Gottwald at or 608-960-9854.
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