NEW YORK (GenomeWeb News) – Almost a year after announcing their completion of Jim Watson’s genome sequence, researchers at Roche’s 454 Life Sciences and at Baylor College of Medicine have published an analysis of the DNA and details about the project — the first published human genome sequenced by a post-Sanger DNA sequencing platform.
Based on the results of the study, which used 454’s sequencing technology, Baylor is now planning to sequence additional human genomes. “The 454 technology has improved even more since the project, and we are looking forward to carrying out more whole human genome sequencing projects with even better performance,” said Richard Gibbs, director of the Baylor’s Human Genome Sequencing Center, in a statement published by 454.
According to the report, which will appear in tomorrow's issue of Nature, the scientists sequenced both chromosome sets of Watson’s genome, mapping unpaired sequence reads from 454’s Genome Sequencer FLX to the human reference genome. The data, which covers the reference genome with 7.4-fold redundancy, was generated at 454 within two months for less than $1 million.
The teams identified 3.3 million single nucleotide polymorphisms in the genome, of which more than 600,000 were previously unknown. About 10,500 of the SNPs cause amino-acid substitutions, potentially altering the function of proteins.
In addition, they detected more than 200,000 small insertion and deletion polymorphisms, as well as a small number of copy number variations, which result in local gains or losses in chromosomal regions.
Notably, they were able to sequence parts of the human genome that are not contained in the human reference genome, which was sequenced by the Sanger method. The researchers assembled reads that did not map to the reference and found they contain about 50 potential new genes.
“The number of genetic variants that were detected and the completeness of how much of the genome was characterized both show the high quality of the data,” said Gibbs in a statement. “It replaces the Sanger sequencing method.”
Watson, who received his genome sequence at Baylor College of Medicine last May, allowed the researchers to make the data publicly available but omitted the Apoliprotein E gene and neighboring sequences associated with Alzheimer’s disease. A map of Watson’s genome can be viewed here.
In a “News & Views” article published along with the paper, Maynard Olson, a professor of medical genetics at the University of Washington School of Medicine, said that the cost of genome sequencing is “now low enough to make the era of personal genomics a reality rather than a distant dream.”
However, he cautioned that “it will be extremely difficult to extract medically, or even biologically, reliable inference from individual sequences” like Watson’s. More genomes need to be sequenced, he said, to learn how genotype correlates with phenotype.
“The symbolic significance [of the paper] is greater than its immediate contributions to human biology,” he said. “But it is irresistible to speculate on how biologically revealing the data will ultimately prove to be.”