Public, Private Sectors Join in Mouse Consortium

Sequencing Results will Spur Discovery of Human Genes and Their Functions

In October, a collaboration was announced to speed up sequencing of the mouse genome and produce a draft map by spring 2001. The Mouse Sequencing Consortium (MSC) consists of six NIH institutes, the Wellcome Trust philanthropy, and three private companies. It provides another example of public and private sectors joining forces to support large-scale genomics research and generate freely available data crucial for basic biomedical research (see related article).

MSC members and their contributions are SmithKline Beecham ($6.5 million), the Merck Genome Research Institute ($6.5 million), Affymetrix, Inc. ($3.5 million), Wellcome Trust ($7.75 million), and NIH ($34 million). Total funding of $58 million will support sequencing for 6 months at three centers: Whitehead Institute (Cambridge), Washington University (St. Louis), and the Sanger Centre in the United Kingdom.

Why the Mouse?
With the working draft sequence of the human genome in hand, scientists in industry and academia now seek to interpret its meaning. The mouse genomic sequence is a powerful comparative tool because genes in the two organisms are very similar. Understanding gene function in the mouse will accelerate knowledge about comparable human genes and will aid in understanding human disease and in developing new treatments.

On average, protein-coding regions in the mouse and human genomes are 85% identical. These regions are evolutionarily conserved because they are required for biological functions shared by both organisms. In contrast, noncoding genomic regions are less than 50% identical. When comparing the same DNA regions from human and mouse, therefore, functional elements stand out clearly because of greater similarity.

Data from this project will be invaluable to us in annotating the final draft of the human genome, observed researcher John McPherson (Washington University). It is exciting that we are moving rapidly toward completion of both projects, he said.

Rapid Data Release
The consortium project focuses on the black six (C57Black/6) mouse strain, which is different from the three strains being sequenced by Celera Genomics. Celera's data are available by paid subscription.

The MSC data-release policy calls for raw data (individual DNA sequence traces, about 500 bases long) taken directly from automated instruments to be deposited in two public databases. These are operated by the National Center for Biotechnology Information and the European Bioinformatics Institute. Individual sequences will be assembled into larger units as soon as a working draft is obtained.

Sequencing Strategy
MSC sequencing melds the best features of two strategies used to produce a working draft of the human genome: the map-based shotgun method used by the public Human Genome Project consortium and the whole-genome shotgun system used by Celera. The overall depth of coverage for the mouse genome will be 2.5x to 3x, a level of detail useful to researchers; a finished, highly accurate sequence is expected at a later date.

Trans-NIH Mouse Initiative

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