June 27, 2000

READING THE BOOK OF LIFE

Whose DNA Is It? In a Way, Nobody's

By NICHOLAS WADE

	Related Articles • The Human Genome Project Video • The Composition of Life narrated by Nicholas Wade, science reporter, The New York Times. (Requires Macromedia Flash Plugin) 3D Interactive Images • DNA Replication Process (Requires Hypercosm Player) • The Scale of DNA (Requires Hypercosm Player) Biographies • Francis Collins: Dedicated Researcher, Family Man Heads Public Project • Craig Venter: A Maverick Making Waves Chronology • Timeline: Journey to the Genome Glossary • Genetic Terms
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hose DNA was sequenced in the human project? Surely some fitting representative of the human species, some Homo sapientissimus, someone chosen for special qualities of health or intellect, some screen or sports star, maybe technoplutocrat-in-chief Bill Gates. Or why not Dr. James D. Watson or Dr. Francis Crick, the co-discoverers of the structure of DNA?

Scientists and federal officials do not think in such terms. Both the public consortium and Celera have chosen to do their decoding at celebrity's opposite pole, with the DNA of anonymous individuals.

Celera has sequenced the DNA of five individuals from different ethnic groups -- two Caucasian men and three women, one black, one Hispanic and one of Chinese descent -- though the principal sequence has been done on a single anonymous male. Call him Celer.

Celera will make public a reference DNA sequence based on the genomes of all these individuals. Where their DNA sequence differs, one nucleotide will be shown, selected by being the commonest or some other criteria, said Dr. Sam Broder, Celera's vice president for medical affairs.

Subscribers to Celera's database, however, will be able to see the separate genomes for all these individuals.

The consortium's object of analysis is not an individual, but a patchwork composite of DNA sections drawn from a number of men and women it will not identify. Call him Mosaic Man.

One reason for the anonymity is the revealing nature of DNA. In terms of public exposure, being stripped naked in Times Square would be only mildly revealing compared with having one's genome accessible on an open database.

That is because probably all people carry some gene variants that could predispose them or their children to disease. By the time all such genetic flaws are cataloged, it will be apparent that quite a few are present in the decoded human genome. To preserve the privacy of the donors -- and their family and descendants -- anonymity is the best course.

But anonymity is an anomalous kind of mask, because DNA is the ultimate identifier. It is always possible that Celer and maybe even the components of Mosaic Man could be recognized if their DNA were to show up in any forensic database.

Most of the consortium's DNA comes from a single man, but 12 men and women of different ethnic backgrounds have also contributed DNA. Mosaic Man is truly a nobody.

Biologists are just as happy with an anonymous genome as with a celebrity's, because with one genome in hand to serve as a reference sequence, it should be quite easy to catalog all the common variants found in most human populations.

Most of these variants are sites on the DNA where one unit is changed to another. These single unit changes are called single nucleotide polymorphisms, or SNP's, and account for a large proportion of human genetic variation.

A variant SNP may change a gene's coding for its protein product, leading to a protein with different properties.

Everyone, as far as is known, has the same set of genes, but because of SNP's (pronounced "snips") many of these genes come in several different flavors. And because everyone has a different combination of flavors, no individuals are completely alike, save for identical twins.

A catalog of the most common human SNP's should be valuable in tracking down genetic dispositions to disease, particularly those caused by multiple variant genes, each of which makes a small and elusive contribution.

By tracking the patterns of SNP's inherited in families where a disease is prevalent, biologists hope to identify the gene variants that contribute to the disease.

A second public consortium, known as the SNP Consortium, aims to identify 300,000 human SNP's and publish them for general use. The SNP Consortium is supported by 11 pharmaceutical companies and the Wellcome Trust of London.