For the first time, researchers have published the DNA sequence from both sets of chromosomes in a single person. That person is none other than pioneering genome researcher J. Craig Venter. The new sequence suggests that there is substantially more variation between humans than previously recognized and pushes personalized medicine a step closer.
In 2001, Celera Genomics, a company then headed by Venter, and, separately, the International Human Genome Project consortium each published a genetic blueprint for a human. To save time and money, both teams combined samples from several individuals and created composite genomes that contained only half of a human's DNA. Humans have a diploid genome with 23 pairs of chromosomes--with one of each pair contributed by the father and the other by the mother—and the researchers hoped that these partial "haploid" genomes wouldn't sacrifice much detail. Wrong, says a massive 31-page paper published in the October 2007 PLoS Biology by Venter, his colleagues at the J. Craig Venter Institute in Rockville, Maryland, and collaborators from three universities.
According to the study, haploid genomes underestimate the amount of genetic variation between individuals by a factor of 5. "We all had very naïve assumptions because we didn't have that much data to go on," says Venter.
Venter and co-workers compared his two haploid genomes to assess the differences between the DNA he inherited from his mother and that from his father. They looked for everything from easy-to-find differences in single bases to much more obscure variations in chunks of DNA sequence that had been inserted or deleted from chromosomes. All told, the analysis found more than 4 million variants between Venter's maternal and paternal chromosomes. This suggests that humans differ by 0.5%, not 0.1% as suggested by earlier estimates. (Some researchers, however, note that recent studies of insertions and deletions have emphasized the same point.)
"This is a great study," says Harvard University geneticist George Church, an early proponent of the Human Genome Project. "We need to have diploid genomes to sort out our full inheritance. If I walk in to a doctor, it isn't going to do either of us any good if he just gets my dad's genome."
Venter won't be the only celebrity to have a published diploid genome for long: James Watson, co-discoverer of the structure of DNA, had his completed in May. And the advent of cheaper, faster technologies like the one used to sequence Watson's genome means that ever more individuals will join the diploid genome club.