For the first time, scientists have decoded and published a nearly complete readout of both sets of chromosomes in an individual. The diploid genome, of biologist J. Craig Venter, reveals much more human genetic variation than scientists had expected.
In 2001, two competing projects, one run by the federal government and the other by a private company, announced the sequencing of the human genome. However, those sequences, or readouts of DNA’s letter order, were in essence only half finished.
Individuals inherit two copies of each of the 23 human chromosomes—one copy from each parent. To speed the task of sequencing the human genome, both teams decided to decode only one of each pair. The resulting genomes were haploid, meaning that they represented only half the chromosomes.
“It turns out with the haploid genomes, we missed most of human [genetic] variation,” says Venter, who led the project to decode his own genome at the J. Craig Venter Institute in Rockville, Md.
Earlier, while at Celera Genomics, also in Rockville, Venter had led the private human-genome project that competed with the government effort. Celera compiled DNA from five individuals, including Venter, into a composite haploid genome.
Then, starting in 2003, the private-institute team isolated Venter’s DNA sequence from the earlier project and, using an older but highly accurate DNA-sequencing technology, filled in the missing pieces.
New computer algorithms distinguished the genetic inheritances that Venter got from each of his parents and found that those two contributions to his DNA differed in many more ways than had been expected. Venter’s team reported that 44 percent of known genes displayed variations between the versions inherited from each parent. In a few cases, Venter inherited one copy or more of a gene from one parent and no copies from the other parent.
Previously, scientists had estimated that all human genomes are about 99.9 percent identical. But when Venter’s team compared his genome with the results of the government’s Human Genome Project, it found that the degree of similarity may be only 98 to 99 percent. The comparison showed that Venter’s genome and the government’s reference genome differed at 4.1 million locations. Of these differences, 1.3 million were newly identified.
Except for the sex chromosomes, the project did not identify which parent contributed which piece of DNA. It simply marked the segments as coming from different parents. But Venter says the technology exists for precisely mapping each parent’s individual contributions.
Edward Rubin, director of the Department of Energy’s Joint Genome Institute, says Venter’s project used a relatively old and expensive technology that produced a “Rolls Royce” version of Venter’s genome. “I don’t think there are any giant surprises,” Rubin says. “But we now have a unique genome we can refer back to.”
The effort to decode Venter’s genome, reported online in the October PLoS Biology, took 5 years and cost about $10 million.