BETHESDA, Md. - The National Human Genome Research Institute (NHGRI) has announced a pair of new processes that it will use to choose the genomes of additional animals for cloning and sequencing. The new processes are needed because the Human Genome Project (HGP) has completed a draft sequence of the human genome and expects to complete a high quality finished human sequence by 2003. In addition, the HGP has completed the genome sequences of all the model organisms that it initially set out to do, and has already begun to sequence the genomes of three more important model organisms: the mouse, the rat and the zebrafish. The genomic sequence information has kindled a revolution in biomedical and biological research, leading scientists to propose large-scale genomic projects for even more animal models as they explore the mysteries of human health and disease.
"The NHGRI and its partners have built a tremendous capacity for sequencing genomic DNA and this is already leading us in new directions," said NHGRI Director Francis S. Collins, M.D., Ph.D. "As we approach the completion of the human sequence, we need to think about the best ways to continue to use this capacity to advance human health. Decades of biomedical research have demonstrated the tremendous benefits of studying animal biology and animal models of human disorders. Adding the power of genomic information about these systems should speed the day we will be able to treat many maladies much more effectively, delay their onset or even prevent them."
From the outset of the HGP, the institute and its partner agencies included as project goals the mapping and sequencing of the genomes of several other organisms in addition to the human. The additional organisms originally included the bacterium E. coli, the yeast S. cerevisiae, the roundworm C. elegans, the fruit fly D. melanogaster, and the laboratory mouse.
These new processes will expand the number of organisms for which scientists will have extensive genomic information. With these procedures, any investigator may propose a new organism for certain types of genomic analysis, including complete genome sequencing. Researchers already have informally suggested sequencing a wide range of animal genomes, including the chimpanzee, macaque, dog, frog, cat, cow, chicken, kangaroo, opossum, rabbit, earthworm, and even the house fly and the platypus, as well as the genomes of many fungi, protozoa, plants and bacteria.
Already, the amount of scientific demand exceeds even the very considerable sequencing and analysis capacity that the NHGRI and its partners have developed. The large-scale sequencing centers can currently completely sequence a mammalian genome in one to two years. How to best deploy these capacities among the many suggestions being made was the driving force for the development of the new processes.
To help NHGRI decide on the most fair and informative way to choose new targets for genomic analysis, the institute consulted with many of its advisors and convened a workshop last summer to obtain input from a representative sample of the interested scientific community. Based on these discussions, the new methods were designed as a competitive system involving investigator-initiated proposals and peer review, in the tradition of other National Institutes of Health (NIH) decision-making processes. The selection criteria will include the contribution to the improvement of human health, the scientific utility of the new data, and technical considerations.
Scientists who want to champion an organism for genomic sequencing must write a white paper that clearly presents the arguments for putting their favorite at the head of the line. White papers can come from a single scientist, collaborative research groups - including scientists at the sequencing centers - or an entire research community.
The white papers will be evaluated by a review committee that will function as a subcommittee of the institute's National Advisory Council for Human Genome Research (NACHGR). The committee, although similar to those that are part of the regular NIH peer review system, will be distinct. In part, this is to allow the new evaluation process to proceed very rapidly, requiring on the order of just two to three months to establish an organism's priority for sequencing. The new process will not involve the actual funding decisions about the sequencing centers themselves; those will continue to be based on the standard NIH peer review process. After a priority for sequencing an organism has been determined, sequencing will begin when enough capacity becomes available at one of the sequencing centers.
In addition to the new sequencing work, NHGRI has recently decided to expand the national capacity to construct bacterial artificial chromosome, or BAC, libraries up to as many as 20 organisms per year for at least the next few years. A BAC library provides a convenient resource for cloning all regions of the genome of an organism. To sequence the enormous human genome, for example, scientists fragmented human DNA into a size range that was convenient to work with and inserted those fragments into BACs where they were maintained and duplicated. These cloned fragments provided a ready supply of human DNA to be sequenced. A similar approach has been taken for the sequencing of several model organisms.
As a resource for the construction of new BAC libraries, NHGRI, along with the National Center for Research Resources, the National Institute of Mental Health, and the National Institute for Child Health and Human Development, recently established the NIH BAC Resource Network. A new process, very similar to that being implemented for choosing new sequencing targets, will be used to accept requests to use the network's resources to create new BAC libraries of various organisms, additional strains of an organism or even individuals.
These two new approaches for selecting organisms for BAC library-making and genome sequencing will only apply to projects funded by NHGRI and, therefore, to requests for constructing libraries from, or sequencing the genome of, any organism except those of bacteria, archeae or plants. The latter organisms tend to be the province of other NIH institutes or federal research agencies.
There will be three submission deadlines each year for the requests to make BAC libraries and for the white papers to propose sequencing: Oct. 1, Feb. 1 and June 1.
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Last Reviewed: September 20, 2007