To speed the identification of genes related to human diseases and to aid in the understanding of basic biological processes, the Howard Hughes Medical Institute (HHMI) and the Washington University School of Medicine in St. Louis are collaborating to identify and partially sequence the majority of mouse genes.

Researchers plan to generate up to 400,000 partial sequences of genes that are expressed during the embryonic and fetal stages, in an effort to survey the entire set of mouse genes. The availability of these gene fragments, or expressed sequence tags (ESTs), should accelerate the rate at which HHMI researchers and other biomedical scientists find disease-related genes as well as genes that control normal cell function.

The $2.3 million, two-year project, will be conducted at Washington University and directed by Robert Waterston, James S. McDonnell professor and head of the department of genetics at Washington University School of Medicine.

Waterston's research group will begin the mouse EST project with gene libraries that contain samples of nearly all embryonic and fetal mouse tissues. The libraries, developed by Bento Soares, professor of genetics at Columbia University with support from the National Center for Human Genome Research, will provide a source of genetic material in which individual messenger RNAs are copied to form complementary DNAs (cDNAs). Waterston's research team will sequence segments of the individual cDNAs to create the ESTs.

"Once the sequences are completed and verified, they will be made available immediately via the Internet. This resource will be of great value to geneticists and developmental biologists who are using mouse models to seek clues to basic biological processes and the genetic origins of human diseases," said Purnell W. Choppin, M.D., president of HHMI. "This collaboration is an excellent opportunity to make these important data available to scientists around the world."

"HHMI should be commended for making this research collaboration possible," said Waterston. "These results will provide immediate access to many mouse genes for investigators worldwide. They also will be invaluable in interpreting sequences generated by the international Human Genome Project."

The ESTs will come from throughout the entire mouse genome, and can subsequently be used to create genetic "milepost markers" that notify scientists where genes are located. This information should speed the pace at which geneticists identify genes of known and unknown function. "We will get a lot of genes out of this project that we still will not know anything about," said Richard K. Wilson, research assistant professor of genetics at Washington University. "But we can take those bits of DNA and use them as probes to compare worm, mouse and human DNA sequences."

This effort, which underscores the importance of mouse models of human diseases, will complement the ongoing work of several research groups who are developing ESTs of the human genome. Waterston's team at Washington University, with support from Merck, has already made more than 250,000 human ESTs freely available to scientists. A team led by Craig Venter of The Institute for Genomic Research in Rockville, Md., has also sequenced a large number of human ESTs, which are being made available on an individual basis to scientists under the terms of a database access agreement.

A committee chaired by Shirley Tilghman, an HHMI investigator at Princeton University and an authority on the mouse genome, will provide advice and oversight to Waterston's research team.

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Jim Keeley 301.215.8858