NIH Research Festival
Large genomic structural variations (SV, > 1 kb) known to be associated with complex traits diseases. Also, the genome-wide mutational signatures, ‘kataegis’, hyper-mutation localized to small genomic regions are found in many cancer types. But to understanding of the biological processes generating these mutations is limited, as the current genome build, however, contains numerous gaps and areas of potential misassembly. To address those challenges, we are utilizing a high-throughput, NanoChannel-based genome mapping technology (Irys® System) to characterize complex regions of the human genome and comprehensively discover genome-wide Structural Variants (SVs) using long single molecules (>150 kb) in a global fashion. Irys® System is a rapid genome-wide analysis method that confines and linearizes individual molecules of DNA to nearly 85% of their respective contour length. Once confined, extremely long DNA molecules (100 to 1,000 kilobases) are imaged with a custom three-color epifluorescence microscope. Genomic DNA is stained with YOYO and can be labeled specifically at the ‘GCTCTTC’ or ‘CCTCAGC’ sequence with different colored fluorescent probes allowing for each molecule to have a unique pattern and mapped to its corresponding location in a reference. By imaging hundreds of gigabases per run, a high-resolution genome map was assembled de novo from the extremely long single molecules, which retain the original context and architecture of the genome. This allows for the cataloging of complex repetitive regions and large-scale rearrangements. The advantages of genome mapping for rearrangement analysis can identify hallmark fusions as well as rearrangements from cancer cells.
Scientific Focus Area: Cancer Biology
This page was last updated on Friday, March 26, 2021