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Building a better mousetrap
SANTA CLARA, Calif.—Affymetrix Inc. and Bar Harbor, Maine-based Jackson Laboratory recently kicked off the full commercial launch of the Affymetrix Mouse Diversity Genotyping Array, with Affymetrix actually selling the array and Jackson Lab making it available as part of the JAX Mouse Diversity Genotyping Array Service.
Both the California company and the New England nonprofit biomedical research institution tout the product as "the first high-density genotyping array that enables researchers to study the complexity of the mouse genome and the diversity among mouse strains." The significance of this, they note, lies in part because mice and humans share genomes of similar size, content and organization, and thus mouse-based studies are key elements in the quest to address human health issues.
Reporting results of research on the array in August 2009 in Nature Methods, Affymetrix and Jackson Lab have shown evidence that the array is the first that can simultaneously assay 623,124 single nucleotide polymorphisms (SNPs), a hundredfold increase over other currently available arrays, and more than 900,000 invariant genomic regions in the mouse genome. They note that researchers can use it to genotype virtually any mouse, identify genetic changes involved in disease phenotypes and genetically monitor important laboratory mouse strains.
Through JAX Services the array is now offered to provide hybridization and computational analysis services to researchers worldwide, and the array service is being provided by the same microarray and computational analysis group that participated in the design, validation and analysis of the Mouse Diversity Genotyping Array. Jackson Lab has run more than 1,000 samples on this array so far.
"The natural variation between inbred mouse strains provides us with an essential tool to study complex diseases involving the interaction of multiple genes," says Dr. Gary Churchill of the Center for Genome Dynamics at Jackson Lab, who developed the array along with Dr. Fernando Pardo-Manuel de Villena of the University of North Carolina. "This is a focal point of biomedical research and drug efficacy testing. Using Affymetrix technology, we have created a way for scientists around the world to analyze these variations with much greater specificity and data reproducibility."
The duo conceptualized the array and approached Affymetrix to help design, build and test it, according to an Affymetrix spokesperson, adding that the Mouse Diversity Genotyping Array complements a large- scale research project called the Collaborative Cross, which is generating thousands of new mice using recombinant inbred mouse strain crosses and intercrosses.
"These mice will more accurately model human genetic diversity and can be used as a tool to study systems genetics as well as human disease," the Affymetrix spokesperson says. "Future advancements are likely to include expanded data analysis capabilities."
"Two leading mouse geneticists have identified the most relevant and comprehensive collection of SNPs for studying mouse diversity," said Kevin King, president and CEO of Affymetrix, in the news release about the array's official launch. "Affymetrix was able to screen these to find the highest performing SNPs, and we believe that together we have produced the best tool for meeting researchers' needs in this field."
It won't be the last tool, of course, and Churchill notes that—as with any technology—this one will have a finite life span.
"With the development of new mouse strains, the Collaborative Cross and related populations, we see a need for another round of SNP selection to obtain a more focused high-density array that can be implemented on a low-cost platform," Churchill says. "This will be essential for projects that require genotyping of many hundreds of animals. Outbred crosses and wild mouse population studies are two cases where this will be the case."
He says that Affymetrix offered Jackson Lab the best overall value in terms of cost per genotype, "and as we worked through the design and development process, what they had to offer just got better," Churchill recalls. "There are some advantages to this platform that we are learning to leverage for specialized applications, but I am reluctant to show our hand before we get the papers into submission. It is certainly true that we can get a lot more out of this platform than just genotypes, but it is a real challenge from the analytical side. You have to think about what each assay is telling you and then scale that up to millions of probes."
Providing use of the array through JAX Services arose in part at Affymetrix's suggestion, recalls Dr. Doug Hinerfeld, senior manager of molecular phenotyping at Jackson Lab, as researchers who only wanted to do small runs might not find it economical to buy the arrays from Affymetrix.
"Affymetrix knew, and we realized, that there were a lot of people out there with interest in these arrays, and the only way to make it easily and widely available to many of them was for us to offer the JAX Mouse Diversity Genotyping Array Service," he says.