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Massive man versus mouse genome project publishes results

24 November 2014
Appeared in BioNews 781

A comprehensive international study has revealed striking similarities as well as some significant differences in the regulation of mouse and human genomes.

A series of papers published by the mouse ENCODE (ENCyclopedia Of DNA Elements) consortium shows that many regulatory sequences in humans do have counterparts in the mouse genome. However, the regulation of some key genes varies between mice and humans.

It was already known that most human genes coding for protein have closely related genes in mice, and this makes the mouse a useful model organism for studying human disease. However, these coding genes only make up a small percentage of the genome. The genome contains a much larger proportion of regulatory regions and differences between these regions in mice and humans account for many of the differences between the two species.

'There are a substantial number of mouse genes that are regulated in ways different from similar genes in humans,' said Professor Bing Ren of the University of California at San Diego, a principal author on the study. 'The differences are not random. They are clustered along certain pathways such as in genes regulating the immune system.'

In one companion study published in PNAS, researchers compared gene regulation patterns from 15 different types of cells and tissues from mice and humans. They found that any two tissues in mice were more similar to each other than to the relevant human tissues. For example, mouse liver and mouse kidney show greater similarity in gene expression than do mouse liver and human liver.

Commenting on the results, study co-author Dr Michael Beer of Johns Hopkins University said that evolution had 'carefully preserved the regulatory sequences for the most fundamental core cell processes but has left the rest to change as each organism required'.

Taken together, the published data could help determine when the mouse is an appropriate model to study human disease.

'Now we know which genes have expression patterns conserved between mouse and humans. For biological processes using these genes, mouse is an excellent model for aspects of human biology', said Professor Ross Hardison of Pennsylvania State University, a senior author.

However, Hardison also noted that the opposite would also sometimes be true; the study may explain why for some diseases, the mouse is unsuitable as a model organism.

The ENCODE project is funded by the US National Institutes of Health. Its findings were reported in four key papers in Nature, as well as in companion papers in PNAS and Science.

A comparative encyclopedia of DNA elements in the mouse genome
Nature |  19 November 2014
Comparison of the transcriptional landscapes between human and mouse tissues
PNAS |  20 November 2014
Conservation of trans-acting circuitry during mammalian regulatory evolution
Nature |  19 November 2014
Humans and mice: So similar but yet so different
EurekAlert! (press release) |  19 November 2014
Major new study reveals new similarities and differences between mice and humans
EurekAlert! (press release) |  19 November 2014
Mouse, Human Genomes Compared, Contrasted
Genetic Engineering and Biotechnology News |  20 November 2014
New view of mouse genome finds many similarities, striking differences with human genome
EurekAlert! (press release) |  19 November 2014
Of mice, not men
EurekAlert! (press release) |  19 November 2014
Principles of regulatory information conservation between mouse and human
Nature |  19 November 2014
Scientists map mouse genome's 'mission control centers'
EurekAlert! (press release) |  19 November 2014
Scientists substitute mice for humans, but new research shows just how similar we are
Washington Post |  19 November 2014
Stanford researchers compare mammals' genomes to aid human clinical research
EurekAlert! (press release) |  19 November 2014
Topologically associating domains are stable units of replication-timing regulation
Nature |  19 November 2014
Why tests on mice may be of little use
The Telegraph |  19 November 2014
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