Yersinia pestis, the causative agent of the plague, poses a serious health threat to the United States, because of the potential for epidemics caused by either bioterrorists or naturally-occurring outbreaks. In the event of an epidemic, molecular diagnostic tools that enable rapid, cost-effective, and accurate differentiation of Y. pestis strains will be imperative for tracking the epidemic and identifying its source. Y. pestis strains show relatively little variation at the DNA level. Therefore the discovery of signature SNP patterns (patterns of nucleotide variation that allow differentiation between individual strains) will require analysis of nucleotide variation across the whole Y. pestis genome. In this study a SNP-discovery high density oligonucleotide array will be designed to interrogate the entire Yersinia genome base by base, with multiple redundancy, using sequence information derived from reference Yersinia pestis and the closely related Y. pseudotuberculosis strains. The genomes of 130 Y. pestis and 20 Y. pseudotuberculosis strains will be interrogated using the SNP-discovery high density array to identify a comprehensive genome-wide set of SNPs. The informative SNPs discovered (up to 8,000) will be tiled onto a SNP-genotyping high density array, which will then be used to verify the genotypes of the 150 Yersinia strains. These analyses will result in the identification of signature SNP patterns for each strain. These signature SNP patterns will be a valuable resource and will be made available to the public. This innovative use of high density oligonucleotide arrays will result in the development of a diagnostic tool that can be used to rapidly (within 24 hours), accurately, and cost-effectively identify specific Y. pestis strains. To our knowledge there is no other technology currently available that can effectively compare with the high density oligonucleotide array platform as a diagnostic tool for distinguishing Y. pestis strains. Thus, Perlegen Sciences could be used as a vital resource in the case of a national emergency caused by a terrorist-attack or naturally-occurring plague outbreak. ? ?
