BioEd Online

A much-anticipated international project to sequence the entire genomes of 1,000 people was launched on Tuesday, but some question whether the three-year project is ambitious enough in its scope.

The '1,000 Genomes Project' will create a highly detailed reference map of human genetic variation and is the largest such project announced to date. "This is a historic turning point in genomics," says Yang Huanming, director of the Beijing Genomics Institute, whose Shenzen branch is one of the three institutes launching the project. The other two are the Wellcome Trust Sanger Institute in Cambridge, UK; and the National Human Genome Research Institute in Bethesda, Maryland.

The project is expected to cost just US$30 million to $50 million — a fraction of what it would cost if they used the 'older' technologies used in the Human Genome Project. Instead, the initiative will use 'next-generation' sequencing technologies, although these are still being tested. "Projects such as this drive technology development," says David Altshuler, a geneticist at Massachusetts General Hospital in Boston. The project leaders have not yet decided what the depth of coverage of the genome will be — that is, how many repeats they will carry out for each chromosome.

All the participants in the first phase of the project will be drawn from the International HapMap Project, a large study on genetic diversity, although more people may be recruited later. HapMap has guided scientists to hundreds of 'single nucleotide polymorphisms', or SNPs — places where people's genetic codes differ by a single DNA base — in genetic regions associated with disease. But these associations explain only a small part of an individual's risk for any particular disease. And scientists must undertake large, expensive follow-up studies to hunt down the specific causes of disease risk lurking in these genetic regions.

The new project aims both to guide scientists towards more disease-associated regions, and to hasten much of the costly follow-up research. Sequencing 1,000 individuals will allow scientists to look at more types of variation — most notably, structural variation, in which large stretches of DNA are duplicated, deleted or rearranged in different individuals. And it will capture more rare variants than the HapMap, which aimed to catalogue SNPs present in 10% of the human population.

"This will give us a much more complete catalogue of genetic variation, and that is going to have a profound impact on our ability to understand the risk factors underlying disease," says Francis Collins, director of the National Human Genome Research Institute.

Yet some scientists question how accurate the finished genomes will be, given the project's short timeline and low budget. Others say that the project should have included some phenotypic information about the participants — such as medical records or basic data such as height and weight. "It's curious that the disease-association studies don't exploit much sequencing — and the sequencing studies don't use the disease data. It would be helpful to hear a clear explanation of why, after 17 years and billions of dollars, these studies still aren't coordinated," says George Church, who is leading a venture called the Personal Genome Project out of his lab at Harvard University in Cambridge, Massachusetts. Church's project is collecting and releasing genetic and phenotypic data on ten individuals, including himself.

But leaders of the 1,000 Genomes Project say that their venture isn't large enough to give definitive answers about the genetic roots of traits. They also say that collecting phenotypic information might bias their study and raise difficult issues, such as how to protect participants' identities while still releasing all the relevant data. The project will not collect or release any information about its participants, beyond their ethnicity and genome sequence.

"No single study with 1,000 people is going to contain enough individuals with any condition to give you any power at all to say whether genotypes or phenotypes are correlated," Collins says. Such work is best left to follow-up studies, he says.