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Lander Questions Utility of Celera s Shotgun Sequencing Method, Discusses HGP Projects

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Eric Lander, director of the Whitehead/MIT Genome Sequencing Center, sharply criticized Celera’s whole genome sequencing method last week, saying there “is no evidence” the approach worked.

Addressing Harvard’s Genomics 2001 conference in the keynote speech, Lander said Celera used the Human Genome Project’s Sequence data, which contained about 90 percent of the sequence of the genome, for input into its whole genome shotgun assembler.

“If you use a source of data with 90 percent of the genome, put it in, and get 90 percent at the end, one does occasionally wonder where the beef is,” Lander said. “At the moment there is no evidence that the whole genome shotgun method worked at all for the human genome.”

Nevertheless, Lander said that researchers from the Human Genome Project and Celera were still planning to meet for a workshop to compare and analyze the data. The workshop was first proposed when the two groups published their papers in February.

He also said the public-private Mouse Sequencing Consortium will finish sequencing the mouse using the whole genome shotgun sequencing method, within “the next couple of weeks.” The consortium, which is funded by Affymetrix, GlaxoSmithKline, the Merck Genome Research Institute, the National Institutes of Health, and the Wellcome Trust, has been working to provide three-fold random shotgun coverage of the “black six” or C57BL6/J mouse for inclusion in the public databases. Celera has completed the sequence and assembly of a mouse genome, but the data is only available to its subscribers.

Meanwhile, as groups look for the next model organism genome to unravel, Lander said he has read “a few proposals” from groups wanting to sequence the chimpanzee genome. “There’s tremendous interest in sequencing the chimp,” he said. But Lander indicated that having another higher organism sequenced might not add that much given that scientists still have such a limited understanding of the functions of genes.

Lander and other scientists from the Human Genome Project are beginning to analyze different areas of the genome that are conserved between mouse and human to gain a clue to function. They also are seeking to discover functional significance by exploring small variations within the human genome — a single SNP in an exon, when linked to phenotypic variation, can provide clues to the function of this exon, he noted.

Luckily, said Lander, the human genome varies little from person to person. Rather than thinking of the human race as a population of 6 billion individuals, Lander said it is more accurate to think of humans as a population of about 10,000 people from the birthplace of humanity, in central Africa, that has changed little in the last 5,000 generations. “We’re walking around today with the genome we walked out of Africa with.”

Because of this striking similarity, Lander said he thought it would be possible to eventually construct a full map of genetic variations for different subsets of the human population.

— MMJ

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