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Of mice and men: Stanford researchers compare mammals' genomes to aid human clinical research

Scientists have long considered the laboratory mouse one of the best stand-ins for researching human disease because of the animals' genetic similarity to humans. Now Stanford researchers, as part of a consortium of more than 30 institutions, have confirmed the mouse’s utility in clinical research by showing that the basic principles controlling genes are similar between the two species. However, they also found some important differences.

From our press release on the work:

“At the end of the day, a lot of the genes are identical between a mouse and a human, but we would argue how they’re regulated is quite different,” said Michael Snyder, PhD, professor and chair of genetics at Stanford. “We are interested in what makes a mouse a mouse and a human a human.”

The research effort, Mouse ENCODE, complements a project called the Encyclopedia of DNA Elements, or ENCODE, both funded by the National Human Genome Research Institute. ENCODE studied specific components in the human genome that guide genes to code for proteins that carry out a cell’s function, a process known as gene expression. Surrounding the protein-coding genes are noncoding regulatory elements, molecules that regulate gene expression by attaching proteins, called transcription factors, to specific regions of DNA.

The Mouse ENCODE consortium annotated the regulatory elements of the mouse genome to make comparisons between the two species. Because many clinical studies and drug discovery use mice as model organisms, understanding the similarities and differences in gene regulation can help researchers understand whether their mouse study applies to humans.

Snyder is co-senior author of Mouse ENCODE’s main paper, published in Nature today, as well as two companion papers. One that published in the same issue of Nature with Stanford postdoctoral scholars Yong Cheng, PhD, and Zhihai Ma, PhD as co-lead authors, compared the binding sites for 34 transcription factors. They found that in general, mouse factors bind at different locations of the DNA strand than human factors.

The other companion paper appeared online in the Proceedings of the National Academy of Sciences earlier this week, with postdoctoral scholar Shin Lin, MD, PhD, MHS and Yiing Lin, MD, PhD as co-lead authors. The researchers compared gene expression profiles across 15 tissue types in humans and mice and found that the expression patterns in mouse tissues are more similar to one another than to their human counter parts.

The Mouse ENCODE consortium’s abundant data are available to researchers studying disease-related genes in mice. Like an encyclopedia, scientists can simply look up how their particular mouse gene is regulated. If the regulatory elements controlling the gene are similar to a human’s, then the study’s results could translate more easily to human patients. Said Snyder in the release:

The mouse is the premier organism for modeling human disease and many other things — a lot of what we know about human biology does come from the mouse… We’re interested in trying to understand the basic processes about how they’re similar or different across some of the most important species people are studying. It’s just fundamentally important.

Previously: Flies, worms and humans — and the modENCODE projectWhen mice mislead, medical research lands in the trap and Scientists announce the completion of the ENCODE project, a massive genome encyclopedia

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