The consortium, which is led in the United States by the National Human Genome Research Institute (NHGRI) and the Department of Energy (DOE), has published its scientific description of the finished human genome sequence in the October 21 issue of the journal Nature.

In the paper, researchers describe the final product of the Human Genome Project, which was the 13-year effort to read the information encoded in the human chromosomes that reached its culmination in 2003.

The Nature publication provides rigorous scientific evidence that the genome sequence produced by the Human Genome Project has both the high coverage and accuracy needed to perform sensitive analyses, such as focusing on the number of genes, the segmental duplications involved in disease and the "birth" and "death" of genes over the course of evolution.

Clearest Genome Picture Yet

"Only a decade ago, most scientists thought humans had about 100,000 genes," said NHGRI Director Francis S. Collins, M.D., Ph.D. "When we analyzed the working draft of the human genome sequence three years ago, we estimated there were about 30,000 to 35,000 genes, which surprised many. This new analysis reduces that number even further and provides us with the clearest picture yet of our genome," he said.

"The availability of the highly accurate human genome sequence in free public databases enables researchers around the world to conduct even more precise studies of our genetic instruction book and how it influences health and disease," added Collins.

One of the central goals of the effort to analyze the human genome is the identification of all genes, which are generally defined as stretches of DNA that code for particular proteins. According to the new findings, researchers have confirmed the existence of 19,599 protein-coding genes in the human genome and identified another 2,188 DNA segments that are predicted to be protein-coding genes.

"The analysis found that some of the earlier gene models were erroneous due to defects in the unfinished, draft sequence of the human genome," said Jane Rogers, Ph.D., head of sequencing at the Wellcome Trust Sanger Institute in Hinxton, England. "The task of identifying genes remains challenging, but has been greatly assisted by the finished human genome sequence, as well as by the availability of genome sequences from other organisms, better computational models and other improved resources."

'Finished' Work in Progress

The Nature paper also provides the scientific community with a peer-reviewed description of the finishing process, and an assessment of the quality of the finished human genome sequence, which was deposited into public databases in April 2003. The assessment confirms that the finished sequence now covers more than 99 percent of the euchromatic (or gene-containing) portion of the human genome and was sequenced to an accuracy of 99.999 percent, which translates to an error rate of only 1 base per 100,000 base pairs -- 10 times more accurate than the original goal.

"Finished" doesn't mean that the human genome sequence is perfect. There still remain 341 gaps in the finished human genome sequence, in contrast to the 150,000 gaps in the working draft announced in June 2000. The technology now available cannot readily close these recalcitrant gaps in the human genome sequence. Closing those gaps will require more research and new technologies, rather than industrial-scale efforts like those employed by the Human Genome Project.

"The human genome sequence far exceeds our expectations in terms of accuracy, completeness and continuity," said Eric Lander, Ph.D., director of the Broad Institute of MIT and Harvard in Cambridge, Mass. "It reflects the dedication of hundreds of scientists working together toward a common goal -- creating a solid foundation for biomedicine in the 21st century,"