PARIS - Researchers at France's National Sequencing Center, known familiarly as the Genoscope, have produced a new and lower estimate of the number of genes in the human genome by comparing part of the human genome with that of a fish.

Genoscope Managing Director Jean Weissenbach said Monday that the human genome probably contained no more than 28,000 to 34,000 genes, rather than the 100,000 to 120,000 estimated by a lot of other scientists, and that he was personally betting on the lower end of that scale.

While acknowledging that this was ''good news,'' since it meant a smaller workload as regards the functional analysis and annotation of the genome, Weissenbach observed that ''this result inconveniences people. It inconveniences nearly everyone, especially those researchers and scientists who predict that there are far more genes.'' And he added: ''Scientists are absolutely not agreed on the number at present: their estimates range from 27,000 to 150,000 genes.''

Nevertheless, Weissenbach went on, "everything points to a smaller number of genes than originally expected.'' Those who were still claiming that there were 100,000, 120,000 or even 150,000 genes in the human genome were using very flawed analytical tools, he said. But "by the end of this year or in early 2001, we will have a much clearer picture. Within two to three years, we will have identified all human genes, give or take a few hundred.''

The Genoscope, which is located within the Genopole biotechnology research and business park at Evry, south of Paris, produced its estimate by analyzing 30 percent of the genomic sequence of Tetraodon nigroviridis, a species of pufferfish, and comparing it with 42 percent of the working draft sequence of the human genome. The fish genome is very compact, since it is only one-eighth the size of the human genome, but substantial data-processing capacity was required for this research, since it involved making some 2 billion comparisons of DNA sequences.

Weissenbach and his team carried out these calculations and the analysis of the resulting data using the LASSAP (Large Scale Sequence Comparison Package) software developed by the French company Gene-IT. In that regard, Weissenbach pointed out that, because of the explosion in the volume of genomics data, both worldwide and in his own center, the Genoscope had to reconfigure its IT systems to handle six times more data than initially anticipated.

Weissenbach described the results as ''still very controversial,'' despite the fact that the research methodology had been validated by a team of international experts. Moreover, the Genoscope's estimate is backed up by a new one produced by Brent Ewing and Philip Green of Washington State University in Seattle, who used a completely different approach to reach the conclusion that the human genome is composed of 33,630 to 34,700 genes. Further corroboration is provided by predictions based on the combined number of genes in chromosomes 21 and 22, the only human chromosomes whose DNA has been sequenced to date.

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