PEARL OF A PROJECT: Perlegen nabs contract from The Women’s Health Initiative

MOUNTAIN VIEW, Calif.–The Women's Health Initiative (WHI) recently selected Perlegen Sciences, Inc. to conduct a comparative study of genetic variation among postmenopausal women with coronary heart disease, stroke, or breast cancer. The women are subjects in a 15-year observational study and clinical trial program that includes a component looking at estrogen plus progestin (E+P) therapy. The genetic analysis will investigate whether E+P contributed to incidences of the three diseases.

Perlegen's high-density whole-genome scan of single nucleotide polymorphisms (SNPs) will relate SNPs to disease and compare patients' data with matched, unaffected controls. Paul Cusenza, Perlegen's senior vice president of marketing and public sector collaborations, describes Perlegen's role as "helping with the reading of the genetic variance and interpreting the results, so we are helping to genotype the DNA samples." Perlegen, he says, will "work in concert with the scientists at the WHI" to make "a tremendous combination that will hopefully lead to a much better understanding" of how to treat disease in women.

Ross Prentice, WHI's principal investigator, says WHI chose Perlegen through a competitive process. "Perlegen was selected as the best offer," he says, adding "Perlegen was well set up to move ahead in the near term" because of its advances in a highly competitive field, track record, and a set of 250,000 tag SNPs with various subsets.

The first 6,000 DNA specimens for analysis were scheduled for delivery to Perlegen in July, says Prentice. A three-phase process will first employ pooled DNA, then undertake individual analysis of specimens. "The total time frame is a one-year period," says Prentice, and WHI is "impressed that [Perlegen] can do it in a short time frame."

Cusenza says Perlegen's wafers and chips are custom-designed at Affymetrix, which Perlegen spun off from in 2000. Perlegen benefits from Affymetrix technology that Cusenza says enabled the company to sequence 50 haploid genomes and use the data in association studies that began in fall 2002. Cuzenza says Perlegen also works in pharmacogenomics, investigating "differential drug response."

Perlegen recently won another new contract, to make a high density whole genome association study of bipolar disorder with the Pritzker Neuropsychiatric Disorders Research Consortium under National Institute of Mental Health funding.

Seattle-based WHI receives funding from the National Heart, Lung and Blood Institute of the NIH. This project, originally scheduled to run from 1993 to 2008 is being extended until 2010, says Prentice. The study involved 161,808 women aged 50-79 of all races and socioeconomic backgrounds with most still actively participating. WHI's three clinical trials looked at disease and hormone replacement therapy, dietary modification, and calcium and vitamin D supplements. Prentice says results from the

E+P trial are controversial and thought provoking.