Gene Map Larger Than Thought

One of the groups racing to map every human gene says there are thousands more than previously thought - a daunting prospect for scientists trying to unravel genetic disorders.

There are about 140,000 genes making the proteins that program cells in the human body, say researchers at Incyte Pharmaceuticals Inc. Previous estimates put that number between 80,000 and 100,000.

"It simply means the human genome is probably more complex than previously predicted," Randy Scott, president of the Palo Alto-based company, said Thursday.

While some inherited disorders are caused by single genes, other diseases seem to result from groups of genes. Research into these diseases will be more difficult if there are more genes, since there could be more possible interactions between them.

"It's more of a job. Finding the genes in simply inherited disorders like Huntington's disease, cystic fibrosis, sickle cell anemia, has been relatively simple," said Victor McKusick, a genetics professor at Johns Hopkins University in Baltimore.

"The focus now is on common disorders high blood pressure, asthma in which it isn't just one gene but a whole cadre that cause the disorder," he said. "That's already a very complex problem to tackle. If there are more genes it will complicate that issue appreciably."

Scientists are fairly certain that the entire human genome includes about 3 billion base pairs of DNA molecules. However, the number of genes each a particular sequence of DNA has always been an estimate. Biologists cannot yet tell exactly where one sequence ends and another begins in the strands of molecules.

Incyte scientists came up with the new estimate by combining data from two decoding methods.

In one, they decoded the heads and tails of transcribed copies of DNA, known as RNA, and determined there were 130,000 genes in the genome. In the second method, based on a feature that occurs in about half of known genes, they calculated 143,000 genes in every human cell. The two figures produced the 140,000 estimate.

Adam Felsenfeld, a scientist with the National Human Genome Research Institute, said the new gene estimate does not change the 3 billion estimate for the number of base pairs of DNA molecules.

Gerald Rubin, who leads a federally funded consortium at the University of California, Berkeley working to map the fruit fly's much smaller genome, said he believes scientists do not yet have definitive information on the number of human genes.

"I think the jury is still out on what the real number is," he said, adding that if 140,000 is accurate, "it is surprisingly high."