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Friday, 19 May, 2000, 16:27 GMT 17:27 UK
Human gene numbers questioned
DNA BBC
The number of genes encoded in human DNA may be far fewer than thought.

Until now, the main estimates have ranged from 65,000 to 120,000. But two research teams, using independent methods, estimate there may be as few as 30,000 or 34,000 genes.

However, a third group, which also reports its work in the journal Nature Genetics, has come up with a figure of 120,000 genes.

The number of genes, and their location and function, is of intense interest to medical researchers who are searching for new ways to treat disease.

Gene mimics

The large discrepancies in the figures could be caused by the behaviour of stretches of DNA called expressed tagged sequences (ESTs). ESTs represent parts of genes and can be easily synthesised in the laboratory. The number of different ESTs is taken to be the number of different genes.

But it is becoming increasingly clear that ESTs may not directly mimic the gene content of a genome. Furthermore, it may be that one gene can generate two or more different kinds of ESTs, thereby overestimating the number of genes.

Two of the groups used ESTs - John Quackenbush and colleagues at The Institute of Genome Research (120,000 genes) and Brent Ewing and Philip Green of Washington University (34,000 genes).

Both groups took precautions to minimise the complications of duplication but both used different methods to do so, as well as using different analytical approaches.

Published chromosomes

However, the third estimate of 30,000 genes, by Jean Weissenbach and colleagues at Genoscope, France, is strikingly similar to that of Ewing and Green.

This estimate was arrived at by comparing the human genome to that of another vertebrate, the pufferfish Tetraodon.

The lower results are also consistent with predictions based on the combined number of genes in chromosomes 21 and 22. These have recently been as fully sequenced as possible and contained fewer genes than expected.

Researchers who favour the lower estimates of human genes suggest that biological complexity does not depend on the number of genes, but on how the genes are regulated, spliced and modified through evolution.

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