A researcher in Arizona is in discussions with a number of biotech companies for the rights to commercialize SNP-genotyping assays designed to genetically fingerprint individual Bacillis anthracis genomes.
The novel technology, which may become a useful forensics tool in criminal cases that involve anthrax, might also produce the kind of sure-fire, standardized results prosecutors would require in court.
“Today, there are cases [of microbe-related bioterror] that are more likely to come up in court,” according to Abigail Salyers, a professor of microbiology at the University of Illinois at Urbana-Champaign. “We must put into place ... standards that provide proper validation and interpretation, so microbial evidence involving genetic information will be [considered] acceptable in a courtroom,” said Salyers.
At Northern Arizona University, Paul Keim has been devising what might become the standard forensic anthrax test.
At his lab in Flagstaff, Keim has been developing assays derived from the roughly 5,000 B. anthracis SNPs his group has identified in a partnership with the Institute for Genomic Research. The work led him to identify “canonical SNPs,” which he said “set the rule for all other SNPs” within the organism. “By using this technology we can predict these other SNPs based on the canonical SNPs,” Keim told SNPtech Reporter.
Right now his lab is sorting through the 5,000 TIGR SNPs to identify “those that give us the unique information. We take the ones that don’t and we don’t put them in the assays,” he said.
To be sure, SNPs “will be important for forensics in bacteria, especially clonal bacteria. But it’s different than in human genomics,” Keim stressed. Because humans have sexual recombination in their genomes, their SNPs will at least be driven toward equilibrium. In clonally propagated bacteria, “SNPs between genomes are going to be mostly clustered in the phylogenetic sense on the long branch of the tree,” he said. “So what that means is the information you get from [microbial] SNPs is probably going to be redundant with other SNPs.”
Since B. anthracis genomes are very homogenous, “sequencing a single gene across a battery of strains gets you nowhere,” he said. In fact, in a 1999 paper, Keim described how he managed only to find six SNPs on one gene. “It’s a very hard way to find SNPs.”
Instead, TIGR’s lead anthrax researcher, Tim Read, has been identifying SNPs by comparing whole-genome sequences, according to Keim. “It may be the only efficient way of finding SNPs in this case,” he said. “Since B. anthracis genomes are so small compared to the human genome, the twist … is that of those 5,000 SNPs, most of them are going to be located on those long [phylogenetic] branches. And if you have information from one SNP against a sample, you actually know what all the other SNPs will be on that branch,” he said.
Keim, who discussed his technology at the AAAS meeting last week, said canonical genotyping can be used for other clonal organisms, but the individual SNPs “will have to be identified for each new organism. We are working on other biothreat pathogens like plague, and also food-borne pathogens like E.coli O157:H7,” he said.
Today Keim is negotiating with “a number” of undisclosed biotech companies to commercialize the technology. “I think these [assays] will be extremely useful primarily due to easy of SNP typing versus other methodologies,” he said.