The accurate mapping of clones derived from genomic regions containing complex arrangements of repeated elements presents special problems for DNA sequencers. Recent advances in the automation of optical mapping have enabled us to map a set of 16 BAC clones derived from the DAZ locus of the human Y chromosome long arm, a locus in which the entire DAZ gene as well as subsections within the gene copies have been duplicated. High-resolution optical mapping employing seven enzymes places these clones into two contigs representing four distinct copies of the DAZ gene and highlights a number of differences between individual copies of DAZ.

Current moIecuIar bioIogy techniques were deveIoped primarily for characterization of single genes, not entire genomes, and, as such, are not ideally suited to high resolution analysis of complex traits and the moiecular genetics of very large populations. Despite rapid progress in the human

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.