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Joint Genome Institute, Lawrence Berkeley National Laboratory, National Center for Genome Resources, FDA, NHGRI

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‘Phylogenetic Shadowing’ Proven Effective for Comparative Genomics

Researchers at the DOE’s Joint Genome Institute and Lawrence Berkeley National Laboratory have successfully applied a new technique for comparative genomics to multiple primate species.

The approach, called “phylogenetic shadowing,” is described in an article in this week’s Science. While genome comparisons of distantly related organisms, such as mouse and human, have successfully identified conserved regions of basic biological function, phylogenetic shadowing offers a means by which to glean the more subtle similarities and differences between closely related species.

The technique, developed by Edward Rubin, Lior Pachter, and colleagues at JGI and Berkeley, samples data from select regions of many different related species, and then compares them within the context of their phylogenetic relationships. In the research described in the Science paper, Rubin and colleagues sampled 17 primate species closely related to human and spanning 40 million years of evolution —- insufficient time for significant genetic divergence to have taken place.

According to Rubin, phylogenetic shadowing compensates for the failure of traditional comparative genomics techniques, which “invariably miss recent changes in DNA sequence that account for primate-specific biological traits.” The approach overcomes the primary challenge of comparing genomes of closely related species: the difficulty in distinguishing functional from nonfunctional sequences. By pooling specific segments of the genomes of multiple species, the researchers found enough small differences in the nonhuman primates to combine them into a phylogenetic “shadow” that they could then compare to the human genome.

The phylogenetic shadow that Rubin and his colleagues created was distinct enough for them to see the boundaries between exons and introns for several genes. In addition, they report in their paper that they were able to identify regulatory elements for the apo(a) gene, which is found in humans, apes, and Old World Monkeys, but not in other mammals.

 

NCGR Awarded $500,000 in Federal Funding

The National Center for Genome Resources is slated to receive $582,000 in federal funds under a spending bill signed by President Bush in mid-February.

The funds will be used to continue the work of the Bioinformatics Institute for Model Plant Species, an initiative started in 2000 as a collaboration between NCGR, New Mexico State University, and Iowa State University to improve the productivity and nutrition of crops grown in the United States.

Initial appropriations for the institute, provided under the Agricultural Risk Protection Act of 2000, granted $3 million to establish the institute, with a provision for additional funding each fiscal year.

 

FDA Narrows Part 11 Guidelines

The FDA withdrew its draft guidance on electronic records on Feb. 20, as the first step in a plan to re-examine, and possibly revise, provisions of the CFR 21 Part 11 regulation that applies to authentication for electronic records submitted to the FDA.

The agency issued an interim draft guidance document (available at www.fda.gov/cber/gdlns/prt11elect.pdf) to explain how it intends to “more narrowly” interpret the scope of Part 11 during the re-examination process, which the agency called “an outgrowth of its current good manufacturing practice initiative for human and animal drugs and biologics.”

While the regulation is being assessed, the agency said that legacy computer systems would not be subject to regulatory action to enforce compliance.

The agency said it is seeking comments on the withdrawal until April 28, at which time it will issue a “final” guidance on its next steps.

 

Encode Project Issues Requests for Applications

The NHGRI’s nascent Encode (Encyclopedia of DNA Elements) project issued two requests for applications on Feb. 21: RFA HG-03-003 (Determination of All Functional Elements in Human DNA), and RFA HG-03-004 (Technologies to Find Functional Elements in Genomic DNA).

Both are available through the NHGRI website at: www.genome.gov/Pages/Research/ENCODE/#rfa.

The first request seeks participants for a “research network” to conduct a pilot project to test the ability of current methodologies to identify functional elements in a targeted region of the human genome.

The second RFA calls for “new and improved technologies for the efficient, comprehensive, high-throughput identification and verification of all types of sequence-based functional elements, particularly those other than coding sequences, for which adequate methods do not currently exist.”

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