Comparing The Genomes Of Mice And Humans To Aid Clinical Research

Chuck Bednar for redOrbit.com Your Universe Online

An international research consortium investigating the functional genome of the mouse have managed to map the creatures so-called mission control centers, and found new clues as to why certain processes and systems in the rodents prevent the results of mouse studies from being successfully replicated in humans.

Members of the Mouse ENCODE project, a project designed to complement the National Human Genome Research Institutes (NHGRI) Encyclopedia of DNA Elements (ENCODE) program, were able to produce an exhaustive description of the functional genome elements of mice, and compared that information to the human genome. Their findings produced similarities between the two mammals, as well as some significant differences.

ENCODE, which began in 2003, analyzed specific components in the human genome responsible for gene expression, or the process of coding for proteins that carry out a cells function. The Mouse ENCODE study looked at 100 mouse cell types and tissues to annotate the regulatory elements of the mouse genome and compared them to the human genome useful research, since mice are so often used as model organisms in clinical studies.

According to the National Institutes of Health (NIH), which oversees the NHGRI, the researchers reported their findings in four separate studies published in the journal Nature and other prominent scientific journals. In those papers, the authors examined the genetic and biochemical programs involved in regulating both mouse and human genomes, finding that the systems responsible for controlling gene activity in each have many similarities that have been conserved through the evolutionary process.

Their findings could provide new insight into genetic regulation and other systems essential to mammalian biology, the NIH said. Furthermore, their work could provide new information to determine in which cases the mouse will continue to be an appropriate model for studies involving the effect of drugs and disease on humans, as well as help explain some of the limitations of this model and why the results of such studies sometimes fail to translate to people.

The mouse has long been a mainstay of biological research models, said NHGRI Director Dr. Eric Green. These results provide a wealth of information about how the mouse genome works, and a foundation on which scientists can build to further understand both mouse and human biology. The collection of mouse ENCODE data is a tremendously useful resource for the research community.

This is the first systematic comparison of the mouse and human at the genomic level, added Dr. Bing Ren, a professor of cellular and molecular medicine at University of California, San Diego (UCSD) and co-senior author of the Consortiums primary Nature study. We have known that the mouse was mostly a good model for humans [and] this allows us to study human disease by studying those aspects of mouse biology that reflect human biology.

Among the discoveries made during the course of the research was the discovery as to why the immune system, metabolism and stress response of mice are so different from humans, the Centre for Genome Regulation (CGR), one of the institutions involved in the project, explained. They compared various processes involved in gene expression, including gene transcription and chromatin modification, and repeated those investigations in various different tissues and cell types from both mice and humans.

Our lab took part in analyzing the group of RNA or transcriptome, that results from transcription, the process by which the instructions in the genes are read, said Alessandra Breschi, a CGR researcher and one of the first co-authors of the main study. We have discovered that human and mice transcriptome contains both preserved and divergent elements. Surprisingly we have found that the differences seem bigger between species rather than between fabrics when initially we thought that the gene activity in the same kinds of tissues would be similar.

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Comparing The Genomes Of Mice And Humans To Aid Clinical Research