Bruce Roe, director of University of Oklahoma’s Advanced Center for Genome Technology, has an almost religious devotion to Chromosome 22. As part of the Human Genome Project, his center led sequencing of that chromosome, which achieved fame as the first to be completed back in December 1999. As this year’s grant submission deadline came up in March, Roe and his colleagues busily prepared requests to do comparative and functional genomics with Chromosome 22.
“The whole idea is that we’re taking the regions that are orthologous to Chromosome 22. We’re beginning with chimp and baboon and trying to move on from there,” says Roe, 60, adding that work with zebrafish and fruitflies may be in the stars if the grants go through. “I don’t think that in the future we’ll get a lot of complete sequences from other genomes. We need to have some large 10-, 20-megabase regions just so we have a feel for these organisms,” he says.
The ACGT is also hard at work on various bacterial genomes, as well as an alfalfa relative — the center received a $5 million grant from the Noble Foundation to sequence Medicago truncatula last fall.
One of the challenges for Roe’s center is maintaining a role in the genomics community given its size. “We’re bigger than small but we’re smaller than big,” he jokes. The roughly 80-person-strong center, which has the resources “if everything’s working all the time [to] collect 8 million bases a day of raw data” still has just 14 sequencers compared to the 75 and up at Baylor, Washington University, or Whitehead. Also, “we’re the only genome center that’s really at a core university,” Roe says. “The others are at medical schools or research institutions.” It can’t compete for the huge projects, but ACGT has carved itself a niche with its knack for finishing work and comparative genomics.
It kicked off in 1990, when Roe won one of the first three NIH grants to start a genome center. He had begun his own career studying transfer RNA and as a postdoc worked with the sixth tRNA ever sequenced. He took a sabbatical at Fred Sanger’s Cambridge, UK, lab and came back eager for more DNA sequencing. Someone asked Roe to work on leukemia genes on Chromosomes 9 and 22. He recalls, “I presented that [research] at a Chromosome 22 meeting and everyone said, ‘Ooh, sequence my gene too.’”
Now, Roe spends his time trying to figure out the function of mystery genes on his favorite stretch of DNA. Of the 1,000 genes predicted for the chromosome, 600 are genes whose functions are unknown, pseudo-genes, or genes whose expression and function are unknown. Maybe they’ll be expressed one day, he deadpans, “if a meteorite hits.”
— Meredith Salisbury