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Mouse in the House
Scientists compare mouse and human genomes
By Kate Dalke

Featured Article.

Scientists have sequenced the genome of the mouse, the furry creature that fuels genetic research around the world. They have also compared the mouse and human genomes, which together are expected to help researchers find genes for diseases and lead to new treatments for human illness.

With most of the same genes as humans, but far easier to manipulate and study, mice are essential tools for studying disease. Deciphering how each human gene works is no easy undertaking. But in mice, researchers can manipulate genes, insert new genes, or remove genes altogether to learn about their functions.

The mouse genome is essentially a reference manual for understanding the human genome. Virtually every gene in the mouse is also present in people, and the neighborhoods in which these genes reside are strikingly similar in humans and mice. These similarities have been hypothesized for decades, and now there is new proof.

The researchers, an international group known as the Mouse Genome Sequencing Consortium, report that approximately 99 percent of mouse genes have counterparts in humans. The mouse genome contains about 30,000 genes, and so probably does the human genome.

Diagram of conserved regions in humans and mice. View larger

How quickly will the mouse genome help cure diseases like cancer, obesity and diabetes? No one knows for sure. But the new information could help researchers create improved versions of genetically modified mice that develop human-like diseases.

For instance, the mouse sequence revealed that mice have two genes related to the gene involved in Lowe's syndrome, an inherited metabolic disorder in humans. Now, when engineering mice to study the disease, researchers can obtain a better model by deleting both genes in the mouse.

"The genome gives finite boundaries to what we have to learn [in terms of complex diseases] and the comparison between two genomes makes the search more refined," says Robert H. Waterston of the Washington University Genome Sequencing Center in St. Louis and a leader of the consortium.

Diagram of mouse chromosomes. View full

Comparing humans and mice has the potential to reveal key features of mammalian biology, and more insights will emerge as more genomes are completed. Soon it will be possible to line up the genomes of the rat, the dog and the chimpanzee, among others.

The genes in humans and mice are essentially the same genes—they were inherited from a common mammalian ancestor millions of years ago. If we have essentially the same genes, then why are mice and people such different creatures?

One reason is that evolution changes genomes through the duplication and specialization of genes. In fact, though many human and mouse genes appear to be similar, they may have taken on slightly different roles, or be active at different times during the life of a person or a mouse.

There are probably no "distinctly human genes that make us human,'" says Eric S. Lander of the Whitehead Institute Center for Genome Research in Cambridge, Massachusetts, and a consortium scientist. Rather, how genes are controlled may help determine whether we have hair or fur or other distinct characteristics.

By looking at the two genomes, scientists confirmed a genetic basis for the mouse's mighty sense of smell. These genes are not only for sniffing out cheese but also for propagating the species. Mice, the researchers found, have expanded families of genes involved in producing hormones related to sex and pheromones compared to humans.

Although both man and mouse share genes, they also share 'non-gene' regions that may regulate genes. And these could be critical to understanding why we develop certain diseases.

More than 2,000 of the shared regions identified in this study (out of 3,500) do not contain genes. What precisely these non-gene regions, sometimes called 'junk DNA', are doing in the genome is not yet known.

The consortium researchers discovered about 9,000 previously unknown mouse genes and about 1,200 previously unknown human genes. The mouse genome is 14 percent smaller than the human genome and contains about 2.5 billion letters of DNA.

The consortium includes institutions such as the Wellcome Trust Sanger Institute in the U.K., the Whitehead Center for Genome Research, and the Washington University Genome Sequencing Center. A comparative analysis of the mouse sequence and five related studies appear in tomorrow's issue of Nature.

The new findings confirm and expand a study published in Science in May 2002 by scientists at Celera Genomics in Rockville, Maryland. Using their own draft of the mouse genome, which is available to subscribers of their database, they compared mouse chromosome 16 to the human genome.

The researchers found just fourteen mouse genes on mouse chromosome 16 that have no obvious counterparts in humans. They also found that the human genes reside together and in virtually the same order as in the mouse genome.

See related GNN articles
» Revelations about the mouse genome
» Humans and Mice Together at Last:
Scientists compare mouse chromosome 16 to the human genome

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Waterston, R. H. et al. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520-562 (December 5, 2002).
Dermitzakis, E. T. et al. Numerous potentially functional but non-genic conserved sequences on human chromosome 21. Nature 420, 578-582 (December 5, 2002).
Mural, R.J. et al. A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome. Science 296, 1661-1671(May 31, 2002).

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