June 15, 2007

Flies, worms may help crack human genome code

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Decoding the functional "parts" in the genomes of model organisms like flies and worms will assist investigators in understanding the human genome. (courtesy of Lawrence Berkeley National Laboratory)

Flies, worms may help crack human genome code

David Miller, Ph.D.

David Miller, Ph.D.

A newly launched consortium is looking to the genomes of flies and worms for assistance in untangling the complexity of the human genome.

The effort, announced last month by the National Human Genome Research Institute (NHGRI), builds on the foundation laid by the ENCyclopedia of DNA Elements (ENCODE) consortium, which aims to create a comprehensive “parts list” of functional elements in the human genome.

These elements include genes that code for proteins and functional RNAs, regulatory regions of the DNA that control gene expression, and DNA sequences that control the structure of chromosomes.

The new effort, dubbed model organism ENCODE (modENCODE), will apply the methods and technologies that have been generated by the ENCODE consortium since its inception in 2003, to the smaller, more manageable genomes of the fruit fly (Drosophila melanogaster) and the round worm (Caenorhabditis elegans).

“We are making great strides in identifying functional elements in the human genome, but we still don't know much about their biological relevance,” NHGRI Director Francis Collins, M.D., Ph.D., said in a release. “This parallel effort in the fruit fly and worm genomes will provide us with information about the functional landscape of two key model organisms, which should aid our efforts to tackle such questions in humans.”

The first grants in the four-year, $57 million program were awarded to 10 teams of investigators.

David Miller, Ph.D., professor of Cell and Developmental Biology at Vanderbilt, is a member of the team headed by Robert Waterston, M.D., Ph.D., chair of the Department of Genome Sciences at the University of Washington in Seattle. This group, which also includes investigators at Yale University and Washington University in St. Louis, was awarded $5.4 million.

Waterston, Miller and colleagues aim to identify all transcribed elements — the DNA sequences that are actively “copied” as RNA for making proteins and other purposes — in the C. elegans genome.

“Computational analysis of the C. elegans genome sequence predicts about 20,000 genes,” Miller said. “But actual transcripts have been detected for only about half of these likely genes.”

Miller's laboratory will use microarray technology to profile specific C. elegans tissues and isolated cell types in the effort to identify all transcripts.

“Our approach is designed to detect rare transcripts that may be expressed in only a few cells, and thus should significantly expand the catalog of confirmed C. elegans genes,” he said.

“We also expect to uncover new classes of genes that encode RNAs but not proteins. These “RNA” genes have been largely overlooked in the past and have been dubbed by some as the “dark matter” of the emerging genomic universe.”

By comparing data from studies of the worm, fly and human genomes, investigators expect to learn much more about functional elements than from analyzing the genome of a single species alone.