First Human Chromosome Finished

22 down, 22 to go: Scientists announced today that they have finished sequencing nearly an entire human chromosome. Although chromosome 22 is the second smallest, the accomplishment helps set a standard for how completely sequenced all 23 chromosomes should be when the Human Genome Project wraps up in 2003.

This milestone is a key one for the Human Genome Project. Many project members are racing to finish a rough draft of the 3 billion bases in our DNA by March, although this error-ridden version is expected to have lots of holes. In contrast, scientists working on chromosome 22 had the task of accurately determining each and every base in the chromosome's coding region (Science, 24 September, p. 2038). Although they didn't quite succeed, "it's the first time that we're seeing [the level of detail] we actually want" from the genome project, says Peter Little, a molecular geneticist at Imperial College, London. If this success is replicated with the other chromosomes, he adds, "we're going to know what human beings are made of."

Over the last 5 years, the consortium--including the Sanger Centre in Cambridge, United Kingdom, the University of Oklahoma, Norman, and Keio University School of Medicine in Tokyo, Japan--determined the order of the 33.5 million nucleotide bases in chromosome 22's lower arm, the so-called q region. This contains almost all of the chromosome's genes, whereas the upper arm, called the p region, doesn't seem to code for proteins and thus was not sequenced at all. The team failed to fill 11 small gaps in the q region, says Ian Dunham, whose team at Sanger did a large part of the sequencing, because the DNA was too difficult for current sequencing technology to obtain and decipher.

Of the 545 genes tentatively identified, 247 have already been identified as human genes, while another 150 have equivalents in other organisms. The genes range in size from a 1000-base-long pipsqueak to a blockbuster of 583,000 bases, aptly dubbed LARGE. Some 27 disorders, from cancers to birth defects, have been linked to chromosome 22. Little says that the completed sequence, published in tomorrow's issue of Nature, should speed the search for culprit genes for eight of the disorders whose exact genetic flaw is unknown.