The Advanced Biomedical Computing Center (ABCC) is a part of the Information Systems Program at Leidos Biomedical Research, Inc. The ABCC provides technology development, scientific consultation, collaboration and training, and high-performance computing support to the National Cancer Institute (NCI) and National Institutes of Health (NIH) scientists and staff. We propose to investigate underlying causes for instability in these regions due to genomic factors related to the physicals characteristics of the specific sequences making up these fragile regions. Here, we define features as miRNA, simple tandem repeats (STRs), large purine or pyrimidine tracts (Pu/Py), inverted and mirror repeats, G-plexes, segmental duplications and CNVs, and other DNA sequences known to give rise to physical structures that affect replication and translation and can lead to genomic instability. In addition, these "polymorphisms maps" can be used to set guidelines for determining thresholds in GWAS studies by taking into account natural variation within the genome. Once we have performed these analyses and made the results public and accessible, we propose to analyze human genomes from different ethnic groups using the latest genomes and HapMap data to determine whether regions associated with genomic instability identified in the first phase of the study correlate with differences between ethnic groups and their associated risks to different cancers.