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Beyond sequencing: optical mapping of DNA in the age of nanotechnology and nanoscopy
Institution:1. Department of Biomedical Engineering and Lokey Interdisciplinary Center for Life Sciences & Engineering, Technion-IIT, Haifa, 3200003, Israel;2. Russell Berrie Nanotechnology Institute, Technion-IIT, Haifa 3200003, Israel;3. Department of Electrical Engineering, Technion-IIT, Haifa 3200003, Israel;4. Department of Engineering Physics, Polytechnique Montréal, Montreal H3T 1J4, Quebec, Canada;1. Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA;2. Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA;3. Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, Minnesota, USA;4. Department of Translational Oncology, National Center for Tumor Diseases, Heidelberg, Germany;5. German Cancer Research Center (DKFZ), Heidelberg, Germany;6. Molecular Pathology Unit, Center for Computational & Integrative Biology, and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA;7. Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA;8. Department of Pathology, Harvard Medical School, Boston, MA, USA;1. Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA;2. Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA;3. Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA;4. German Cancer Research Center (DKFZ), Heidelberg, Germany;5. Department of Translational Oncology, National Center for Tumor Diseases, Heidelberg, Germany;6. Ben Towne Center for Childhood Cancer Research, Seattle Children''s Research Institute, Seattle, Washington, USA;7. Department of Pediatrics, University of Washington, Seattle, Washington, USA;8. Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA;9. Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA;10. Seattle Children''s Research Institute, and University of Washington School of Medicine, Seattle, Washington, USA;1. Department of Oncologic Sciences, University of South Alabama Mitchell Cancer Institute, Mobile, AL, 36604, USA;2. School of Chemistry, Center for Nanoscience and Nanotechnology, Center for Light-Matter Interaction, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel;1. Raymond and Beverly Sackler Faculty of Exact Sciences, School of Chemistry, Tel Aviv University, Tel Aviv, 6997801, Israel;2. Sagol Center for the Epigenetics of Metabolism and Aging, Tel Aviv Sourasky Medical Center, Tel Aviv, 6423906, Israel;1. Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden;2. Laboratory of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden;3. Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Abstract:
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  • Highlights► Individual DNA molecules hundreds of kbp long may be stretched and visualized by optical microscopy. ► An optical barcode is generated by fluorescent labeling of short sequence motifs along the stretched DNA. ► Optical maps complement DNA sequencing for gap closing, finishing, validation and de novo assembly of genomes. ► Genome structural variations not accessible to sequencing or DNA arrays may be directly visualized. ► Epigenetic marks such as DNA methylation and DNA binding proteins may also be mapped on single genomic fragments.
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