Aug. 31, 2004 Flagstaff, Ariz., and Rockville, MD, August 30, 2004 -- Scientists have capitalized on genomic data to define novel diagnostic tests and to gain insight into the evolutionary and genetic history of the deadly pathogen Bacillus anthracis (anthrax).
Researchers at Northern Arizona University (NAU), the Translational Genomics Research Institute (TGen) and The Institute for Genomic Research (TIGR) used nearly 1000 single nucleotide polymorphisms (SNPs) to define the genetic and evolutionary types of several anthrax isolates with extremely high resolution.
The results are scheduled for publication online this week by the journal Proceedings of the National Academy of Sciences.
"This level of detail is not possible without whole genome sequences from multiple strains," said the paper's senior author Dr. Paul Keim, Director of Pathogen Genomics at TGen and the Cowden Endowed Chair of Microbiology at NAU. "This work now provides the raw material for highly specific and sensitive tests for anthrax in human cases, animal cases and within the environment. Specific and sensitive tests for this pathogen are needed for effective bio-defense and forensic investigation into previous events."
TIGR's scientists sequenced the genomes of five isolates, or strains, of anthrax and then compared the results of each sequence to detect minute variations (SNPs). TGen and NAU researchers used that data to develop a typing, or identification, system for various anthrax strains.
"This is the first time that a new bacterial typing system has been developed from an analysis of multiple sequenced genomes of the same species," said Dr. Jacques Ravel, who led the sequencing effort at TIGR. "Comparing the sequence of entire microbial genomes is helping scientists unravel the complex evolutionary history of this lethal agent."
The SNPs described in this work were highly stable. Only one SNP was not entirely stable across the entire study, which means that diagnostic and forensic tests developed using this information will have extremely low false positive, or misidentification rates, a crucial criterion for advanced tests. False positives from anthrax environmental tests would have an inordinate impact on public health should an outbreak occur.
The work also shows for the first time that how researchers "discover" DNA fingerprints is crucial to what they can be used for. The selection of anthrax strains for whole genome sequencing was guided by prior work on the large global anthrax collection, which maximized the information that was ultimately obtained from the whole genome sequencing effort. Similar efforts without such forethought would be ineffective at defining major bacterial populations.
This study shows that diverse strains of pathogens will not be recognized unless they are contained within the scope for the discovery process.
"That the genetic relationships of anthrax have been defined to a new level of precision provides a critical step toward future detection of this potential public threat," added Keim. "In addition, this study established a model for other biothreat pathogens, and common public health related diseases such as E. coli, Strep, Staph, and Salmonella."
The National Institutes of Health and the Department of Homeland Security provided funding for this study. The anthrax genome sequencing effort was funded by a contract from the National Institute of Allergy and Infectious Diseases.
NAU has earned a solid reputation as a comprehensive university with a personal touch and an outstanding research component. The personal attention comes in many forms, including small classes with full-time professors who know their students' names and a caring and committed staff whose goal is to help every student succeed. While our emphasis is undergraduate education, we offer graduate programs and research that build from our base on the Colorado Plateau and extend to such national concerns as forest health and genetics. www.nau.edu. Internationally recognized environmental research, including disease ecology, programs give student unique training opportunities.
The Translational Genomics Research Institute (TGen) is a not-for-profit organization whose primary mission is to make and translate genomic discoveries into advances in human health. Translational genomics research is a relatively new field employing innovative advances arising from the Human Genome Project to apply to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases. For more information, visit http://www.tgen.org.
The Institute for Genomic Research (TIGR) is a not-for-profit research institute based in Rockville, Maryland. TIGR, which sequenced the first complete genome of a free-living organism in 1995, has been at the forefront of the genomic revolution since the institute was founded in 1992. TIGR conducts research involving the structural, functional, and comparative analysis of genomes and gene products in viruses, bacteria, archaea, and eukaryotes. http://www.tigr.org.
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