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DECIPHERING THE HUMAN CODE International consortium of laboratories obtains DNA sequence of chromosome 22
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milestone event in the Human Genome Project—the DNA sequence of a chromosome—has been achieved [Nature, 4 0 2 , 489 (1999)]. The accomplishment sprang from a collaboration among researchers at the Sanger Centre, Cambridge, England; Keio University School of Medicine, Tokyo; Washington University School of Medicine, St. Louis; and the University of Oklahoma, Norman. Ian Dunham, a senior research fellow at the Sanger Centre, coordinated the Dunham credits strength of collaboration. international effort. Press conferences held on Dec. 1 in quence obtained identifies 97% of them. London; Washington, D.C.; and Tokyo For want of appropriate DNA clones, announced the sequencing feat. Speak- the remaining 3%—distributed among ing in Washington, D.C., Francis S. Col- 11 small sections—could not be selins, director of the National Human Ge- quenced. Nonetheless, the chromonome Research Institute at the National some's sequence is considered comInstitutes of Health, Bethesda, Md., of- plete, Collins said, because standards fered three reasons to celebrate. "For adopted by the international genome the hundreds of genes that are on this community allow for a 5% gap in sechromosome, we now know their anato- quencing. 'We've now set the standard my," he said. "Secondly, the sequence to 97%," he noted, with an accuracy of gives us for the first time a glimpse at less than one error in 50,000 bases. the landscape of an entire human chroAll told, chromosome 22 contains mosome, the basic element of inherit- 545 genes that encode previously identiance And thirdly, it gives us confidence that this can be — done for the rest of the [huChromosome 22 sequence is man] genome and for other finished, 7 is not far behind mammals as well." The international consortium sequenced the proteinencoding arm of chromosome 22, avoiding the short arm, which is deemed to proH duce the RNA part of the ribosomal machinery that manufactures proteins rather than 3 4 11 12 genes that encode them. The group constructed a map of the chromosome from a combination of known cloning sequences, divvying up the clone map into adjacent sec13 20 2Î 22 Χ Υ tions for sequencing in their Note: Red and orange regions contain DNA sequenced to a high degree of accuracy; blue regions contain highly repetitive DNA labs. sequences that are thought not to encode proteins; green and white regions are at various stages of sequencing. Chromosome 22 contains Source: National Institutes of Health 34,491,000 bases, and the se-
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fied proteins, and computer modeling suggests another 325 genes may exist. It's a small chromosome—only chromo some 21 is smaller—but it's believed to contain genes associated with as many as 35 disorders, including schizophre nia and several birth defects. Having the sequence will enable "disease-gene hunters" to design strategies to zero in on their target more efficiently and rap idly, Collins said. For example, he sug gested, with this kind of informa tion, the gene for schizophrenia could be found in a few months in stead of a decade. Dunham credits the sequenc ing milestone to "the strength of the collaboration and the sense of purpose of the groups involved." But the consortium also received constant input from research groups around the world, he not ed, and "immense help from the community of geneticists whose life's work has been the study of chromosome 22" and the diseases associated with it. Indeed, 217 authors are listed on the Nature paper, a trib ute to the international network of contributors. While congratulating the consor tium on its accomplishment, NIH Di rector Harold E. Varmus offered some advice at the news conference held in Washington, D.C. The scientific com munity must not forget that the "se quence is not enough," he said. "If we simply had all the sequence informa tion and didn't have computer technol ogy and bioinformatics specialists who understand how to analyze individual genes . . . and protein structures and signaling pathways, the information would be meaningless" and progress would not be made. In fact, new techniques for DNA test ing and new statistical tools will be needed for analyzing the interactions of genes, genetic variation, and the effect of environment, notes Peter Little, a pro fessor of biochemistry at Imperial Col lege, London. "Biology is entering a new world," he states in an accompany ing commentary in Nature. "Not only do we face a revolutionary leap in what we know, we also face radical changes in the tools we must use to understand that information. I am not sure that we are prepared for the full impact of ei ther, but we have already made our first tentative steps into the new world of the genome." Mairin Brennan DECEMBER 6,1999 C&EN
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