by Susan Reslewic, Jill Herschleb, and David C. Schwartz
Recent advances in genomics have created an arena of enormous opportunity for biological
discoveries. Capitalizing on this opportunity requires novel experimental designs, high-throughput data collection and analysis systems, and creative approaches to formerly elusive
problems. As genomic analysis systems become more flexible and comprehensive, one key trend is the emergence of platforms with singlecell and single-molecule detection, applicability to entire genomes, and the throughput to produce massive data sets. Among these innovative platforms is the Optical Mapping system (University of Wisconsin-Madison, WI), which enables a view of whole genomes, one molecule at a time.
The Optical Mapping system creates physical maps of whole genomes from collections of individual molecule maps. Physical maps mark the locations of particular DNA sequences in the genome and the physical distances between them. These maps are invaluable for characterizing
and comparing genomes in terms of insertions, deletions, inversions, duplications, translocations, and gross rearrangements.1 Through a creative interplay of DNA preparation and manipulation, surface chemistry, high-speed data collection via imaging, and an array of processing options, Optical Mapping produces physical maps with unique features that open up persistent problems in genomics to new solutions. For example, Optical Mapping’s single-molecule detection allows genomic analysis of heterogeneous populations, like those contained in solid tumors, and microbial communities. Molecules are mapped directly after their extraction from cells; no amplification or subcloning steps are required. Thus, every area of the genome is accessible via Optical Mapping, making the system a true whole-genome method. In this light, Optical Mapping shares some of the advantages of lower-resolution cytogenetic methods that operate on entire chromosomes for genomic comparisons. Yet, with a resolution in the tens of kilobases, Optical Mapping fills a largely unexplored gap between lower-resolution methods and base-pair resolution genotyping approaches. Whole genome resolution in the kilobase range opens up a host of previously inaccessible genomic variations, such as medium- to large-sized insertions and deletions, to detection and interpretation. More importantly…
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