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Breakthrough Technique Developed for Massive Parallel Genomic Analysis of Long DNA Molecules
Researchers from McGill University and the Génome Québec Innovation Centre have achieved a technical breakthrough that should result in speedier diagnosis of cancer and various pre-natal conditions. The key discovery, which was described online on August 4, 2014 in PNAS, lies in a new tool developed by Professors Sabrina Leslie and Walter Reisner of McGill’s Physics Department and their collaborator Dr. Rob Sladek of the Génome Québec Innovation Centre. The new tool allows researchers to load long strands of DNA into a tunable nanoscale imaging chamber in ways that maintain the strands’ structural identity and under conditions that are similar to those found in the human body. This newly developed “Convex Lens-Induced Confinement” (CLIC) will permit researchers to rapidly map large genomes, while at the same time clearly identifying specific gene sequences from single cells with single-molecule resolution, a process that is critical to diagnosing diseases like cancer. CLIC, the new tool, can sit on top of a standard inverted fluorescence microscope used in a university lab. The innovative aspect of CLIC lies in the fact that it allows strands of DNA to be loaded into the imaging chamber from above, a process which allows the strands of DNA to maintain their integrity. Existing tools used for genomic analysis rely on side-loading DNA under pressure into nanochannels in the imaging chamber, a practice that breaks the DNA molecules into small pieces, making it a challenge to reconstruct the genome. “It’s like squeezing many soft spaghetti noodles into long narrow tubes without breaking them,” explains Professor Leslie as she describes what it is like to use CLIC.