February 01, 1999
A New Encyclopedia of Mouse Genes
The laboratory mouse, small and
easy to breed, has long been biologists' favorite model organism for
studying mammalian development. Now, a multi-laboratory project with
collaboration from the Howard Hughes Medical Institute has produced
a free, publicly accessible catalog of mouse gene fragments that will
help ensure that the mouse remains an important model in the genomic
era.
The catalog, a collection of more than 360,000 gene fragments, is
helping scientists get a handle on particular genes that they want
to study. The database should also be a valuable tool for interpreting and comparing the
genome sequences of mouse and human as vast stretches of chromosome
sequence are cranked out in the months and years ahead.
Marco Marra of the Washington University Genome Sequencing Center
in St. Louis led a team of 42 scientists who surveyed the genes of
the mouse, hoping to snare many genes that are important during development.
In the February 1999 issue of the journal
Nature Genetics
,
the researchers describe how they generated their large database of
expressed sequence tags (ESTs).
ESTs provide quick access to genes. They are fragments of sequences
from messenger RNA molecules, the molecules that act as intermediaries
between genes and proteins.
Since the array of messenger RNA molecules in a cell varies according
to the type of cell and its developmental stage, the biologists generated
ESTs from a broad range of cell types to get the largest possible
sample of genes. The ESTs arose from various adult mouse organs as
well as from mice in the earliest stages of development.
"The mouse provides a very powerful mammalian model system," Marra
points out. "If we want to understand the function of a human gene,
we can cross reference to the mouse sequence and identify the mouse
gene, which can be the starting point for elucidating the biological
function of that sequence. The ESTs are an entry point."
Another thing that scientists can do in mice is "knock-out," or inactivate,
a gene to try to determine its function. Today, researchers routinely
create knock-outs in yeast and in nematode worms, model organisms
whose genomes are now thoroughly sequenced. With the new mouse EST
encyclopedia, such studies are likely to become more common in mice.
The scientists have released their data over the Internet as it has
been generated during the last three years. The mouse ESTs Marra and
his colleagues have produced represent 93 percent of all mouse ESTs
available in the public domain.
Researchers at Washington University, working with Marra, have sequenced
the gene fragments, analyzed them, and submitted the ESTs into public
databases. Their colleagues at the University of Iowa and the Oklahoma
Medical Research Foundation created the libraries of messenger RNA
clones that were used for sequencing, and a team of scientists from
the Lawrence Livermore National Laboratory in California distributed
them.
Many scientists have not waited for a formal announcement to begin
using the data, some of which has been available since early 1996.
Marra says, "This is a useful resource not only for mouse biologists
but for all biologists. It emphasizes the universal nature of DNA."
Tools such as the mouse EST database permit scientists to look for
related genes among a range of organisms. A gene can then be studied
in parallel in different organisms, each of which may be suited for
revealing different aspects of the gene's role.
Now that the EST database is well stocked, scientists at Washington
University are trying to determine just how many genes the 360,000
ESTs represent. Since the mouse is thought to have fewer than 100,000
genes, many ESTs represent portions of the same gene.
Though ESTs are versatile tools in helping to map genes onto chromosomes
and in revealing disease gene candidates, for example, they do not
provide the whole picture. "What you need in the end is genome sequence,"
Marra says. "But when you have genome sequence, ESTs aid massively
in analyzing the structure and organization of the genome. Having
the two together is more powerful than having either alone."
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