NEW YORK (GenomeWeb News) — Solexa has been testing the genotyping ability of its 1G Genome Analyzer through a collaboration with Johns Hopkins University and the National Institutes of Health to re-sequence a specific genomic region, GenomeWeb News has learned.
To demonstrate the instrument’s ability to address different sequencing applications — among them micro RNA analysis, microbial sequencing, and whole human genome re-sequencing — the company presented study results at the recent Genomes, Medicine, and the Environment Conference in Hilton Head, SC.
In one such study, a pilot project, Solexa researchers re-sequenced a 140 kb genomic region on chromosome 1 in a HapMap sample. The project is a collaboration with Aravinda Chakravarti’s group at the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins and Eric Green, director of the NIH Intramural Sequencing Center.
“We are collaborating with Solexa to see how [its] technology measures up, and with Eric Green at the NIH to compare how conventional versus the new technologies do,” he wrote. “We are also working out the methods for sequencing targeted genomic regions,” Chakravarti told GenomeWeb News by e-mail.
Chakravarti’s group had earlier found that this region is associated with variations in the QT interval of an electrocardiogram, which measures cardiac repolarization. Both long and short QT intervals are associated with sudden cardiac death. Earlier this year, Chakravarti published an article in Nature Genetics identifying a gene called NOS1AP, or CAPON, in this region that is involved in cardiac repolarization.
“We are collaborating with Solexa to see how [its] technology measures up, and with Eric Green at the NIH to compare how conventional versus the new technologies do.”
For the pilot project, according to a presentation at GMEC by Tony Smith, Solexa's chief science officer, the Johns Hopkins researchers created 15 large PCR products covering the 140 kb stretch, which Solexa researchers sequenced.
Solexa confirmed 251 out of 252 known SNPs in this region. The researchers also discovered 154 new SNPs “with high confidence,” Smith said.
In parallel, the NIH researchers have begun analyzing the same material using clone-based standard capillary electrophoresis sequencing.
In order to find all of the variants in and around CAPON that are involved in the QT results, Chakravarti and his two collaborators now plan to sequence the entire genomic region in people with extreme QT values, he told GenomeWeb News, initially, probably in 50 individuals.
With this study Solexa wants to demonstrate that its platform can be used not only by genome centers but also by researchers “who are interested in disease genes, genetics, and who are doing genotyping but then wanted to go beyond the resolution that genotyping can achieve,” Smith told GenomeWeb News.
In a similar quest, ABI’s Beverly, Mass., group has been working with Victor Velculescu’s group at Johns Hopkins to see if the Agencourt next-gen sequencing platform can be used for re-sequencing genomic regions harboring mutations involved in cancer.
Solexa’s project with Chakravarti, who is also conducting other genetic association studies, arose from a “mutual interest,” according to Smith. “He wanted to find a technology that would enable him to go from an association to a high-resolution analysis at the sequence level,” he said. “We are hopeful that we will demonstrate to him just how powerful the system is.”
Asked whether his lab was planning to acquire a Solexa instrument, Chakravarti wrote it is “too early to tell but probably.”
In his conference talk, Smith also mentioned two recent collaborations between Solexa and the Wellcome Trust Sanger Institute. In the first one, the partners sequenced a human X chromosome (See GenomeWeb News 10/18/2006, [https://www.genomeweb.com/issues/news/136728-1.html]) as a pilot for sequencing the genome of a HapMap individual — an African man — to draft quality by the end of the year.
The second was an alliance with Sanger to sequence the 2 megabase genome of Streptococcus suis, which they completed recently with 99.99-percent coverage, according to Smith. He said that details of the project will be “described elsewhere.”
In terms of micro RNA analysis, he also mentioned that Solexa internally has been analyzing micro RNAs from human brain samples. According to Smith, 85 percent of the tags the researchers found in this project aligned to known sequences in miRNA databases, and 8 percent to other known small RNAs, leaving another 7 percent of potentially novel micro RNAs.
Julia Karow covers the next-generation genome-sequencing market for GenomeWeb News. E-mail her at [email protected]