Our laboratory has developed Optical Mapping, a system for the construction of ordered restriction maps from individual DNA molecules. Our work centers on the development of new systems for genome analysis, including Optical Mapping, which exploit novel macromolecular phenomena to answer important biological problems. These are built upon a complex mix of principles derived from multiple disciplines including chemistry, genetics, computer science, biochemistry, optics, surface science and micro/nanofabrication. Recently, "Shotgun" Optical Mapping was used to construct whole genome restriction maps of Escherichia coli O157:H7, Deinococcus radiodurans, and Plasmodium falciparum (the major causative agent of malarial disease) without the use of PCR, electrophoresis, or clones. Presently we are applying Shotgun Optical Mapping to the analysis of more complex genomes, including human and rice, as well as of numerous microorganisms, where our mapping efforts are offering new routes to understanding genome plasticity across closely related species. These efforts are also helping to facilitate the ongoing microbial sequencing projects at JGI, in terms of providing means for validation and aids for assembly.

With the advent of a high-throughput Optical Mapping System, we are developing novel approaches for human association studies using a new class of genome markers that are designed to encompass SNPs (Single Nucleotide Polymorphisms), yet reveal genome variation on a scale not previously discerned for large populations. Current thinking in the field is centered on the use of a limited number of SNPs to leverage the apparent state of linkage disequilibrium, which is indicative of a young species; however, current approaches based on chips or mass spectrometry are pendant on huge numbers of oligonucleotides. This requirement limits analysis to a series of discrete loci and renders such approaches inadequate for the assessment of a broad spectrum of genome variation motifs. This limitation of current systems used for large-scale association studies may neglect discovery of important factors contributing to complex traits. In this regard, haplotyping is emerging as the means to perform detailed analysis of mutations and is expected to play a major role in the emerging field of pharmacogenomics. The Optical Mapping platform is uniquely suited for haplotyping since analysis of single molecules allows for the unambiguous phasing of genetic markers within populations of unrelated individuals.