Building a Better Mouse Genome
Transcriptome information and a comparison of mouse and human sequences
indicate the extent of the unknown
By Maria W. Anderson

When hobbyist Chobei Zenya wrote The Breeding of Curious Varieties of the
Mouse in 1787, he probably never imagined the impact that mouse breeding
would eventually have on biomedical and genetic research. During the past
two centuries, the "fancy mice" once prized by breeders have evolved into
the multitude of inbred strains now used to study complex genetic traits and
to model human diseases. In the past 40 years, mouse biology has exploded,
as scientists added to the heap with transgenics, knockouts, and cloned
mice. This issue's Hot Papers chronicle the next milestone in the life of
Mus musculus, its genome.

In December 2002, the Mouse Genome Sequence Consortium (MGSC), led by Eric
Lander and Kerstin Lindblad-Toh at what is now the Broad Institute (then the
Whitehead Institute/MIT Center for Genome Research) and Robert Waterston,
then at the Genome Sequencing Center at Washington University in St. Louis,
published an analysis of the mouse genome.1 The MGSC generated a draft
sequence of a C57BL/6J (black 6) female by assembling more than 40 million
sequence reads containing 96% of the euchromatic genome and compared it to
the nearly complete human sequence. They found the 2.5-Gb mouse genome to be
14% smaller than the human genome but determined that both sequences have
approximately 30,000 protein-coding genes. Estimates have since crept
downward.

In the same issue of Nature, scientists at the RIKEN Genomic Sciences Center
in Yokohama, Japan, led by Yoshihide Hayashizaki, published an analysis of
the mouse transcriptome based on 60,770 full-length complementary DNA (cDNA)
clones.2 Their findings, not wholly inconsistent with other mammalian
annotations, indicate that 37,000 to 70,000 regions on the mouse genome
transcribe RNA. But many more actual transcripts are possible, suggesting
that earlier estimates approaching 120,000 human genes still have merit.

The mouse genome sequence and transcriptome open a new era in genetic and
biomedical research. "The publication of these articles really provided us
with the tools ... to start using the mouse in powerful new ways," said Rick
Woychik, director of the Jackson Laboratory in Bar Harbor, Maine.

Read the rest at The Scientist
http://www.the-scientist.com/yr2004/jul/hot_040719.html

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