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Of Mice and Men: Consortium Publishes Mouse Genome, Comparative Human Analysis

NEW YORK, Dec. 4 - An international sequencing consortium today published the full genome sequence of the common house mouse together with a set of comparative analyses of the genomes of mouse and man.


To sequence the mouse, at a cost of around $130 million, the consortium combined clone-based hierarchical shotgun and whole-genome shotgun techniques. More than 33 million sequencing runs were ultimately assembled into 88 ultracontigs of roughly 50 megabases.


At seven-fold coverage, the Mus musculus genome appears to be about 2.5 Gb long--significantly shorter than that of the human, thanks to a lower number of repeat sequences.


The mouse has roughly 27,000 to 30,500 genes, 99 percent of which have a sequence match in the human genome. Syntenic comparisons showed that a subset of 13,000 orthologous gene pairs had a mean sequence identity of about 78.5 percent.


Alongside the main mouse paper is a range of other new findings from the organism's DNA. For example, one study looked at gene expression during development and charts the activity of the mouse equivalents of many of the genes on human chromosome 21.


Another paper shows that even the non-coding regions of DNA on this chromosome are conserved between the two mammals, suggesting these regions play an important biological role. Meantime, another analysis shows that retrotransposons, those stretches of repeat DNA that replicate through an RNA intermediary, are apparently much more active in the mouse genome than in the human.


Other findings, all published in the current issue of Nature, will come as no surprise to anyone who has tried to keep the little beasts out of the pantry: Mice seem to have a wealth of genes that govern sexual behavior and the sense of smell.


All the data are publicly available, and the Ensembl browser of the European Bioinformatics Institutes reports that it has already handled 2.6 million mouse-sequence requests in the past six months. The consortium hopes to finish the mouse to 99.99-percent accuracy within two to three years.


Whitehead Institute researcher Kerstin Lindblad-Toh is the lead author on the paper; her institution lead the project and contributed about half of the sequence. Washington University School of Medicine delivered about 30 percent of the sequence, and created the mouse BAC-based physical map.


The Wellcome Trust Sanger Institute in the UK was the third major partner. Other institutes in the International Mouse Genome Sequencing Consortium included the University of California at Santa Cruz, the Institute for Systems Biology, and the University of Geneva.

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