By Monica Heger
This story has been updated from a version posted Feb. 3 to include information from Sigma Life Science.
In an effort to create better animal models of human disease, Sigma Life Science and Cofactor Genomics said this week that they will collaborate to sequence the genomes of the six rat strains most commonly used in research.
Cofactor Genomics will provide the sequencing and analysis using Life Technologies' SOLiD system, while Sigma's Sage Labs will fund the study, provide the samples and also create a free, public database to host the sequence data.
The plan is to sequence the rats to a low coverage — around 4- or 5-fold — and compare the variation found in those genomes to the reference Brown Norway rat genome, Cofactor Genomics' chief operating officer Jon Armstrong told In Sequence.
While Cofactor Genomics owns sequencing systems from the three major providers, including the SOLiD, the Illumina Genome Analyzer, and Roche's 454 GS FLX, Armstrong said the company decided to do this project on the SOLiD because "we can leverage the low error rate of the SOLiD system for the best possible SNP detection at this amount of coverage."
He said the coverage would allow them to cover around 90 percent of the non-repetitive areas of the genome with two or more reads, and about 65 percent with four or more reads. There is also the possibility of doing more sequencing or sequencing more rat strains in the future.
They will be creating two types of sequencing libraries, a short-insert paired end library and also a long-insert mate pair library. For the short-insert library, the mean insert size will be 200 base pairs, with 50 by 35 base paired reads. For the mate paired library, the mate pairs will have read lengths of 50 base pairs, and the mean insert size will be 3,000 base pairs.
The combination of the two libraries helps protect against any biases that are inherent with just one library, Armstrong said. While the shorter inserts allow for greater resolution, the long-insert library provides better physical coverage, which "allows us to look for larger insertions and deletions, as well as inversions and translocations," he said.
The goal of the project is to catalog the variation that's seen against the reference genome, which will help researchers create better animal models of human disease.
The project will also help Sigma's Sage Labs create better rat knockouts, said Edward Weinstein, director of Sage Labs.
The company creates customized mice and rat knockouts for its customers with a technology called zinc finger nuclease, a method that relies on knowing the sequence of the gene the researcher wants to knock out. Currently, though, researchers working on strains other than the Brown Norway rat are at a disadvantage since there is only limited sequence information on other species. Anytime a researcher wants to make a knockout rat for another species, "you have to use the sequence from the Brown Norway rat and hope you're hitting the right spot," Weinstein said.
Sequencing species that are frequently used for research will "make the whole process of creating a knockout rat more straightforward," he added, since it will provide more accurate species-specific sequence data.
While researchers have long used animal models to study disease and create drugs, recently there's been an increased interest in sequencing these disease models. Last May, for instance, an international team sequenced the genome of a spontaneously hypertensive rat, identifying 60 genes that had been completely knocked out and 47 genes with deletions of one or more coding exon (IS 5/4/2010).
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