TEN DISEASES TO TACKLE: Wellcome, Perlegen, Affymetrix converge on genetic origin of diseases

LONDON—It's an ambitious effort that the Wellcome Trust Case Control Consortium (WTCCC) and the Wellcome Trust Sanger Institute are undertaking: More than ten institutes in Great Britain and Africa coming together to conduct one of the largest whole-genome association programs ever, all to search for genes associated with ten complex diseases. But the WTCCC needed help, thus its decision to partner with Perlegen Sciences of Mountain View, Calif., and Affymetrix of Santa Clara, Calif.

Perlegen Sciences will genotype 15,000 individuals and produce more than 10 billion individual genotypes using Affymetrix GeneChip technology, including the new Human Mapping 500K Array Set.

According to WTCCC, Perlegen and Affymetrix, the 500K Array Set will provide a more comprehensive and unbiased view of the entire genome than possible with previous Affymetrix arrays that Perlegen has used—and reportedly will enable scientists to analyze genetic variation across the genome in large populations for the first time.

The concept is that by identifying "genetic signposts," researchers will gain a better understanding of which people are most at risk and why, for the ten diseases in question—coronary heart disease, hypertension, types 1 diabetes, type 2 diabetes, bipolar disorder, Crohn's disease, rheumatoid arthritis, tuberculosis, obesity and malaria.

The genotyping of the more than 15,000 samples will span across 675,000 single nucleotide polymorphisms (SNPs) and, in addition to making use of the new 500K Array Set, the work will also make use of a custom 175K SNP panel, according to Peter Donnelly of the Department of Statistics at Oxford University, who chairs the WTCCC. "We liked the combination of the existing throughput and expertise of Perlegen with Affymetrix's 500K product that can be run in different labs," he says.

The results are expected to have a significant impact on drug discovery efforts, in addition to other areas of pharmaceutical science and biotechnology. "The discovery of genetic variations that increase susceptibility to these diseases will validate new drug targets and accelerate the development of new treatments, particularly treatments aimed at causes rather than symptoms," says Brad Margus, chief executive officer of Perlegen.

Margus is confident in his company's ability to rise to the task of processing so much genetic information, noting that while the Human Genome Project sequenced the equivalent of one genome at a cost of nearly $3 billion over a ten year period, his company's sequencing expertise and technology essentially replicated that work in a matter of months at a cost of less than $100 million.