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Mouse genome sequenced (yet again)

News Analysis

The international Mouse Genome Sequencing Consortium announced the completion this week of a draft sequence of the mouse genome, produced using the whole-genome shotgun method. What the announcement doesn't say is that almost exactly a year ago scientists at Celera Genomics in Rockville, Maryland, issued a similar announcement.

The Consortium's mouse data, which have not yet been published as a scientific paper, are available to researchers on the Web sites of the European Bioinformatics Institute, the National Center for Biotechnology Information, and the University of California, Santa Cruz. A comparison between the mouse sequence and the human sequence can be found at all three sites.

The Celera mouse data, generally said to be of high quality, have been available to subscribers of the company's database for at least a year. Clearly, they are being used to generate information in laboratories around the world. Researchers at academic institutions have published findings based on the Celera mouse sequence in peer-review journals.

For example, in January researchers from the University of Melbourne reported a novel human relaxin gene and its counterpart in the mouse, which they identified in the Celera databases. The findings appeared in the Journal of Biological Chemistry. In the February issue of Nature Neuroscience, two researchers from Columbia University in New York published important data about a new gene superfamily—nearly 1,300 previously unknown mouse odorant receptor genes mined from the Celera sequence.

A paper by Celera scientists on the mouse genome has been submitted to Science. The paper is expected to report complete data on mouse chromosome 16; those data will be available on the Celera website. Researchers who wish access to the full data set will be asked to subscribe.

The International Consortium reports that the assembly of its draft was achieved "in such a short time and with such great accuracy" using the whole-genome shotgun method—the same method that Celera scientists used in pioneering fashion to sequence both the human and Drosophila genomes. The method has been roundly criticized by some of Celera's competitors, who are funded by the so-called 'public' Human Genome Project, and are themselves part of the mouse consortium.

Challenges from scientists in the 'public' group and a rebuttal from Celera have appeared both in the press and in the scientific literature, most recently in papers in Proceedings of the National Academy of Sciences.

The International Consortium, which, in a press statement, calls its mouse draft a "landmark advance in genomics," hopes to complete the genome sequence of the mouse within the next three years. "The milestone concludes the second phase of the consortium's mouse-sequencing effort: the production of a draft sequence by the whole-genome shotgun method." The statement adds that the "quality of the working draft far exceeds the consortium's initial expectations…"

In its statement to the press on April 27th 2001, Celera announced that it had achieved "approximately 6-x fold coverage…ensuring greater than 99 percent representation of the mouse genome," using three medically important strains. At the time, former Celera president and chief scientific officer J. Craig Venter said, "The mouse is a key biological model used by researchers around the world to decode the pathways and mechanisms of human disease."

In its press release dated May 6, 2002, the International Consortium echoed this truism, saying their "advanced draft of the mouse sequence will greatly accelerate identification of genetic contributors to [human] illnesses."

One cannot argue with that.

—Edward R. Winstead and Barbara J. Culliton

. . .

International team of researchers assembles draft sequence of mouse genome. Press release, The National Human Genome Research Institute (NHGRI), Bethesda, Maryland (May 6, 2002).
Myers, E.W. et al. On the sequencing and assembly of the human genome. Proc Natl Acad Sci USA 99, 4145-4146 (April 2, 2002).
Waterston, R.H., Lander, E.S. & Sulston, J.E. On the sequencing of the human genome. Proc Natl Acad Sci USA 99, 3712-3716 (March 19, 2002).
Zhang, X. & Firestein, S. The olfactory receptor gene superfamily of the mouse. Nat Neurosci 5, 124-133 (February 2002).
Bathgate, R.A. et al. Human relaxin gene 3 (H3) and the equivalent mouse relaxin (M3) gene. Novel members of the relaxin peptide family. J Biol Chem 277, 1148-1157 (January 11, 2002).
Celera completes assembly of the mouse genome. Press release, Celera Genomics, Rockville, Maryland (April 27, 2001).

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