January 30, 1996
HHMI and Washington University to Develop Mouse Gene Library
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.
“Robert Waterston and colleagues at Washington University School of Medicine in St Louis plan to make up to 400,000 partial sequences of mouse genes available to scientists worldwide.”
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
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.