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Of mice and men: Researchers compare mammals’ genomes to aid human clinical research

Mouse ENCODE analyzed more than 100 mouse cell types and tissues to annotate the regulatory elements of the mouse genome and compare them to the regulatory elements in the human genome. Both ENCODE and Mouse ENCODE are funded and coordinated by the National Human Genome Research Institute. Because mice are used as model organisms for many human clinical studies and drug discovery, understanding the similarities and differences can help researchers understand how the results found in mouse studies can translate to humans.

“The mindset is when you compare things, it helps understand genome annotation,” said Mark Gerstein, PhD, the Albert L. Williams Professor of Biomedical Informatics at Yale University. “It’s making the mouse a more meaningful model organism.” Gerstein collaborated on previous ENCODE research but is not part of the Mouse ENCODE consortium, which is composed of researchers from more than 30 institutions.

Snyder is a co-senior author of the main paper — published in Nature on Nov. 19 — that describes the overall findings of the project, and of two companion papers (one to be published in the same issue of Nature, the other published online Nov. 17 in the Proceedings of the National Academy of Sciences) that explain individual components of the project.

Stanford postdoctoral scholars Yong Cheng, PhD, and Zhihai Ma, PhD, are co-lead authors of the Nature companion paper. They compared where 34 transcription factors attach to the DNA strand to control gene expression on regions called binding sites.

“Transcription factors are kind of like people: They work together in many different combinations to execute certain tasks,” said Snyder, who holds the Stanford W. Ascherman, MD, FACS Professorship in Genetics. “What we discovered is that the general principles are the same in mice and people, but the details are quite different. In general, the mouse factors are binding at different locations than the human ones in terms of the exact gene targets.”

The researchers’ abundant data is a valuable resource for others studying disease-related genes in mice. They can use the Mouse ENCODE data to see whether the transcription factors regulating their studies’ gene expression are the same or different for humans.

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