Just a year after the first individual human genomes were sequenced, an international team announced today that it will probe the entire genomes of about 1000 people. The aim is to create the most detailed catalog yet of human genetic diversity to help biomedical researchers home in on disease genes.
The 1000 Genomes Project will delve much deeper than the three celebrity genomes completed last year, including those of genome researcher J. Craig Venter and DNA co-discoverer James Watson (ScienceNOW, 4 September 2007). It will build on the recently completed HapMap, which describes how blocks of DNA tagged by common variants, called single-nucleotide polymorphisms (SNPs), vary in different populations (ScienceNOW, 26 October 2005). These SNPs have turned up more than 100 new DNA markers associated with common illnesses such as diabetes and heart disease (Science, 21 December 2007, p. 1842). But the HapMap includes only the most common markers, those present in at least 5% of the population.
To find rarer SNPs that occur at 1% frequency, genome leaders say, they need to sequence about 1000 genomes. The 3-year project, which will cost $30 million to $50 million, will take advantage of new technologies that have slashed the cost of sequencing. The work will be funded by the U.S. National Human Genome Research Institute (NHGRI) in Bethesda, Maryland, the Sanger Institute in Hinxton, U.K., and the Beijing Genomics Institute in Shenzhen, China.
The consortium will start with three pilot projects. One will exhaustively sequence the entire genome of six individuals: two adults and both sets of their parents. A second project will sequence 180 individual genomes at light coverage, leaving gaps. The third project will fully sequence the protein-coding regions of 1000 genes (5% of the total) in about 1000 genomes. The samples, all anonymous and with no clinical information, will mainly be drawn from those collected for the HapMap, which includes people of European, Asian, and African descent. The first data from the pilot projects should become public later this year.
The new catalog could help disease gene hunters in several ways. It will potentially eliminate the need to sequence around a newly discovered disease SNP to find the variant that actually alters the gene product, says NHGRI Director Francis Collins. The project will also catalog genes that are sometimes lost or duplicated--such copy-number variants can cause disease. By compiling rarer variants, the project should also help resolve a debate about the relative contribution of these mutations to disease risks. Most disease SNPs found so far raise risk only 50% or less, for example, and some researchers suspect that there are rarer SNPs that raise risk twofold, threefold, or more. "There's no question it's going to be a tremendous resource," says Yale University's Judy Cho, who has used the HapMap to find a new gene for Crohn's disease.