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HGP to Support New Sequencing Technologies, Quality Control Center

WASHINGTON, Feb 16 - Now that the hoopla surrounding the human genome has died down, the Human Genome Project's future plans include finishing the most difficult parts of the genome, supporting the development for new sequencing technologies, selecting new organisms to sequence, and awarding a contract for an independent quality assessment center to help meet its goal of verified 99.99 percent accuracy.  

"What we want to produce is archival quality product, that will be right for all the ages," Mark Guyer, assistant director for scientific coordination at the National Human Genome Research Institute, told GenomeWeb.

After two years of looking for a professional outside evaluator, the NHGRI expects to assign an award to a quality assessment center within the next few weeks. Previously, checks were done in a more informal way.

"We've actually tried [to find an assessment center] for the last two years," Guyer said. "We've tried to award a contract, and tried to award grants, but we haven't been successful in finding an offeror that has passed peer review. But now we have, so we will have an independent quality assessment center on an ongoing basis."

NHGRI also recently announced that it would offer grants for the development of technologies that could help close the gaps and improve methods for sequencing difficult regions of the genome. Certain gaps in the genome are not "closable" at present because, for example, particular sequences can't be cloned with existing vectors, are unstable in all existing vectors, or are impervious to the enzymes currently used, Guyer said.

While the budget for genomics at NHGRI, approximately $182.5 million for 2001, is expected to plateau over the next few years, the institute will look to allocate some of its funds for the development of technologies that would reduce the unit cost of sequencing, Guyer said.

"If we could make sequencing a tenth of a cent per base instead of ten cents a base, a lot of the hard decisions we're going to have to make about which organisms to sequence would all go away," he said.

The Human Genome Project expects to complete the human genome by 2003.

While no specific deals are in the works to involve industry in these technology efforts, the institute is always open to their participation, Guyer said.

"We've been interacting with industry for the whole life of the genome project, and we'll continue to do that," he said. "A lot of the early development of the chip technology was based on grants that we made to Affymetrix, and a significant amount of the development of the MegaBACE instrument was based on grants we made to Molecular Dynamics [now part of Amersham Pharmacia Biotech]. We've made grants to ABI as well, and a number of other companies."

New and better technologies might also help researchers to better understand when Celera's whole genome shotgun approach works best and when BAC maps, the method championed by the Human Genome Project, should be employed.

"In the end, I think the difference between the two was in the ratios. The question is whether there is a best ratio of whole genome shotgun and more localized information," Guyer said.

"I suspect it will be an evolving answer. Right now, given the kind of data, the quality of data, the length of reads, the particular dyes used, all of that kind of stuff, a one-to-one mix is best. If two years from now we can get thousand-base reads instead of 500-base reads, and more even representation of sequence across the genome, it may be a different mix."

To hash out how to make future genome sequencing efforts more effective, the public sequencing team and their Celera counterparts will hold a hands-on workshop in April.

"The idea for it evolved during the discussions late last spring and early summer, about what kind of productive interactions there could be between the public consortium and the private effort," Guyer said.

Guyer also noted that future sequencing projects would likely concentrate on select organisms that could be used to address specific biological problems, as opposed to the human or mouse genome which are applicable to almost any question in biomedical research.

"The zebrafish, for example, is primarily of interest because it's going to be very revealing about development," he said.

The Sanger Center began on Monday a three-year project to sequence the tiny zebrafish, Danio rerio , which is thought to be an optimal model organism for discovering gene function, according to Tim Hubbard, the center s director of genomic analysis.

Work on the rat has also begun and two species of pufferfish are also on the priority list for the public program. The Chinese genome project has expressed interest in the pig, while the Department of Energy's Joint Genome Institute is concentrating on microbial and fungal genomes.

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