Genomics Approaches to Pathogen Characterization
Wednesday, December 7, 2005
Presented by the Genomic Medicine Discussion Group and Emerging Infectious Diseases and Microbiology Discussion Group
Organizers: Matt Lorence and Thane Kreiner, Affymetrix; David Perlin, Public Health Research Institute
The Genomic Medicine Discussion Group provides a forum for New York–area researchers to investigate topics related to genomics and genomic medicine in an interdisciplinary fashion across therapeutic areas. Meetings of this group are organized around the general theme of making connections between basic and clinical aspects of the genomics revolution. Meetings are focused on a particular theme as it relates to the field of genomic medicine, with special attention to the application of genomic approaches to disease diagnosis, staging, prognosis, treatment, and monitoring.
Paul Keim, Northern Arizona University & The Translational Genomics Research Institute (TGen), "Genomic and Population Analysis of Dangerous Pathogens (anthrax, plague, tularemia) to Establish a Scientific Basis for Forensic Investigations."
Barry Kreisworth, Public Health Research Institute, "A Molecular Epidemiologist's View of Bacterial Pathogenesis."
Dave Stenger, U.S. Naval Research Laboratory, "Sequence-Based Pathogen Diagnostics and Surveillance."
"Genomic and Population Analysis of Dangerous Pathogens (anthrax, plague, tularemia) to Establish a Scientific Basis for Forensic Investigations"
Forensic analysis of bioterrorism events must be based upon sound evolutionary and biological principles in order to be accepted by the courts. The identification of the Ames strain involved in the Anthrax Letter attacks in 2001 was based upon DNA fingerprints. The foundation of this identification comes from genomic analysis, population genetics and the estimation of mutation rates at hypervariable and phylogenetic stable loci. This combination of molecular signatures provides accurate clade identification along with resolution of subtypes within disease outbreaks or among closely related isolates.
"A Molecular Epidemiologist's View of Bacterial Pathogenesis"
The global molecular epidemiology of Mycobacterium tuberculosis and methicillin resistant Staphylococcus aureus (MRSA) has repeatedly identified successful clones that predominate in diverse populations. Precise and objective sequence-based genotyping methods and the identification of clone-specific genetic markers have led to the discrimination of specific pathogenic clones. The W-Beijing M. tuberculosis strains have caused large outbreaks in multiple prisons in Siberia and in New York City hospitals in the early 1990s. These clones have been genetically mapped to a distinct ancestral branch of the species, within principal genetic group 1. In vitro and in vivo studies with selected W-Beijing strains have identified a hypervirulent phenotype that is largely due top a unique phenolicglycolipid structure that is able to subvert the host immune system. The molecular epidemiology of MRSA has witnessed the dramatic change from a nosocomial pathogen to one that is able to rapidly spread in the community and cause an inordinate number of soft tissue infections in otherwise healthy populations. The mapping of genetic markers, including the staphylococcal chromosomal cassette that harbors methicillin resistance and the Panton-Valentine leucotoxin (PVL) and the identification of clonal background distinguish community and nosocomial MRSA and provide a rationale approach to study staphylococcal pathogenesis.
"Sequence-Based Pathogen Diagnostics and Surveillance"
The logarithmic accumulation of microbial genetic sequence information has invited its direct use for both the detection and detailed characterization of pathogens. Towards this, our group has developed multi-pathogen identification systems using re-sequencing microarrays and computer algorithms for pat