An intrepid group of volunteers will be granted a glimpse at their genomes today as part of the first release of data from the Personal Genome Project (PGP).
Headed by Harvard University genomics pioneer George Church, the project aims to capitalize on rapid improvements in gene-sequencing technologies to better understand human health and disease. The PGP will serve as both a technological and an ethical test bed, assessing new methods of reading, sorting, and analyzing DNA, and highlighting societal issues that could spring up in the era of personal genomics–most notably, the privacy of genetic information.
Over the past year, the first 10 volunteers, including the linguist Steven Pinker, the entrepreneur Esther Dyson, and Church himself, have surrendered blood and skin samples, subjected themselves to medical examinations, and filled out extensive personal and medical questionnaires. Scientists have since gone to work sequencing their DNA, and an initial analysis of a portion of their genomes will be released today.
The data will be deposited into a database that Church and his collaborators hope will serve as a public resource for personal-genomics research, allowing other scientists to search for specific genetic variations linked to diseases and other traits. The researchers aim to grow the database rapidly and are now enrolling the next wave of volunteers, possibly as many as 100,000 participants. They are also creating cell lines from participants’ tissue samples, which they will make available for research.
Church envisioned the PGP as a way to explore the ongoing revolution in gene-sequencing technology. Over the past 10 years, the cost of sequencing has plummeted: current estimates for a human-genome sequence are approximately $100,000, compared with the $3 billion price tag for the Human Genome Project. By some reckoning, the price could fall to between $5,000 and $10,000 per genome within the next six months. Church and others predict that the capacity to sequence thousands and then millions of human genomes could transform not only medicine but also society. “We went from complete ignorance of computers in the 1970s to complete dependence today,” says Church. “You can imagine something analogous for DNA.”
To date, most large-scale studies of the genomics of disease have focused on specific portions of the genome, uncovering hundreds of variations that raise the risk of common ailments, including diabetes, heart disease, and schizophrenia. But these variations account for only a small increased risk. Scientists hope that sequencing entire genomes will allow them to identify much rarer, disease-linked variations that have not been detected previously.
The PGP is focusing first on the coding regions of the genome (the portions that direct the production of proteins), which accounts for about 1.5 percent of the entire sequence and covers 20,000 genes. Joseph Thakuria, the PGP’s medical director and a clinical geneticist at Massachusetts General Hospital, in Boston, says that the sequencing of 20,000 genes in a patient is remarkable. With current clinical diagnostics, it’s possible to test only about 1,370 genes, and patients get at most two or three, he says.
Perhaps the biggest challenge for the project will be interpreting differences in individual genomes. Human genomes are about 99.5 percent identical, and variations in the rest can have a range of effects, from lethal to benign. In preparation, Thakuria and his colleagues pored over the only two full human-genome sequences that are publicly available: those of Craig Venter, who led the private sector’s race to sequence the human genome, and James Watson, codiscoverer of the structure of DNA. Thakuria’s analysis and that of others have found that each man has about three million base-pair changes out of the three billion chemical letters that make up their genomes.