June 2, 2000

Celera Gains in Decoding the Genome of the Mouse

By NICHOLAS WADE

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ith the outcome of the race to decode the human genome expected to be declared sometime this month, one of the two competitors said yesterday that it had made progress in an important follow-up race, decoding the genome of the mouse, which is expected to be critical to interpreting the human genome.

The company, Celera Genomics, said that in the last two months it had sequenced, or determined the order of, more than a billion units of DNA from the mouse genome.

Celera's rival, a public consortium of academic centers in the United States, Europe and Japan, has sequenced only 85 million DNA units of the mouse genome.

Biologists believe the mouse genome will be essential to interpreting the human genome. Although the two species diverged about 100 million years ago, their genomes are about the same size, three billion units of DNA, and most human genes have counterparts in the mouse genome, recognizable because of the similarity of their DNA sequences.

The fastest general method for identifying all the human genes may be simply to lay the mouse and human genomes side by side and to look for regions where the strings of DNA units are similar. The DNA units in genes will have mostly stayed the same in mouse and human whereas the 97 percent of the genome that does not code for genes will have diverged over the course of evolution, biologists expect.

Also, the mouse genome should help identify the role of human genes, most of which are largely unknown. A researcher with a mystery human gene can locate the counterpart mouse gene on the mouse genome, create a strain of mouse that lacks the gene and figure out what the mouse can no longer do.

Celera Genomics, a subsidiary of PE Corporation, will need to sequence a further two billion units of DNA, an additional four months' work, to cover the mouse genome once over.

Celera's president, Dr. J. Craig Venter, said that he would draw the DNA from three strains of mouse, to study the natural variation of the mouse genome, and that he would assemble a "humanized mouse genome," one with the genes arranged in the same order as their counterparts on the human genome instead of in the natural mouse order.

"The sequence will be enormously useful," said Dr. Peter Mombaerts, a mouse geneticist at Rockefeller University, because genes can be targeted by reading off their DNA sequence from a database.

Celera said its mouse genome would be available only to subscribers to its database. The company's main business plan is to sell genomic data, but its problem is that the public consortium makes all its genomic data available free. With the mouse genome, however, Celera will be able to offer human-mouse searches exclusively, at least until the consortium catches up on the mouse front.

Dr. Venter said that after the mouse he was considering decoding the genomes of the dog, the rat or the chimpanzee, depending on his clients' interests.

Mouse tissue was provided to Celera by the Jackson Laboratory of Bar Harbor, Me., a leading mouse colony. The laboratory's director, Dr. Kenneth Paigen, said mice were a better vehicle for gene analysis than people because mouse tissues can be analyzed in a fresher state and the cells' perishable gene transcripts captured more efficiently.

"Being able to combine the mouse with the human genome will be a big plus," Dr. Paigen said.