New Single Molecule Approaches to Genomic Analysis: Optical Mapping

Abstract

Abstract Current molecular biological approaches were developed primarily for characterization of single genes, not entire genomes, and, as such, are not ideally suited to analysis of complex traits and population-based molecular genetics. Despite rapid progress in the human genome project effort, there is little doubt that radically new conceptual approaches are needed before routine whole genome-based analyses can be undertaken by both basic research and clinical laboratories. Physical mapping of genomes, using restriction endonucleases, has played a major role in the identification and characterizing various loci, for example, by aiding clone contig formation and by characterizing genetic lesions. Restriction maps provide precise genomic distances, unlike ordered sequence-based landmarks such as Sequence Tagged Sites (STSs), that are essential for optimizing the efficiency of sequencing efforts, and for determining the spatial relationships of specific loci. When compared to tedious hybridization-based fingerprinting approaches, ordered restriction maps offer relatively unambiguous clone characterization that is useful in contig formation, establishment of minimal tiling paths for sequencing, and preliminary characterization of sequence lesions.