Open Access Senior Honors Thesis
In human DNA, there are loci that are prone to DNA breaks, stalled replication fork progression, and single-strand gaps when placed under replication stress. These loci are known as fragile sites and are common areas for copy number variations (CNVs). CNVs are duplications or deletions of large genomic regions and they have been linked to genetic diseases including tumor development and autism. Using a yeast chromosome modified to contain FRA3B human fragile site DNA, we investigated duplications and deletions of a reporter cassette at three locations that differ by their proximity to an AT-rich area of the fragile site, a sequence that can stall replication. Fluctuation analysis was used to compare the reporter cassette duplications and deletions. Our data show that CNV frequency is affected by which side of the AT-rich area the reporter cassette is integrated. The location located telomeric to the AT-rich area (Site C) exhibited the most duplications at an average rate of 5.533xl 0·2 duplications/cell division, while the location between the origin and AT-rich area (Site B) exhibited the most deletions at an average rate of l .265x I 0-2 deletions/cell division. Additionally, deletions were observed far more frequently than duplications. These results suggest that the mechanisms for duplications and deletions may be different rather than the same, as previously thought. Future studies are suggested in order to improve our knowledge about the nature of CNV events and the impact of CNV s on the development of linked diseases.
Bartolet, Samantha, "Investigating the Frequency of Copy Number Variations (CNVs) at Fragile Site FRA3B in Saccharomyces Cerevisiae" (2018). Senior Honors Theses & Projects. 608.