NHGRI has spent hundreds of millions of dollars ramping up its sequencing capacity, and now it’s aiming that arsenal at a new target: medical sequencing designed to better understand both rare and common diseases.
The new function of the institute’s Large-Scale Sequencing Network, or the big five production centers, was officially announced last fall, but actually the centers had been involved in pilot projects for a good six or eight months by that point. The centers, which have an amassed capacity of about 12 gigabases per month, were asked in early 2005 to submit proposals for medical sequencing pilot projects using no more than 10 percent of their capacity. “We wanted to begin to figure out how this works,” says NHGRI Director Francis Collins, adding that all of the proposals went through review by institute advisors. The shift from shotgun sequencing to PCR clone sequencing will be significant, so it came as little surprise that “a lot of the interest is to test out the new sequencing technology,” he says.
The Broad Institute, for instance, used all of its allotted medical sequencing capacity “to test out the new polony-based sequencing effort — the 454 technology,” Collins says. “They thought this would be the best use of the pilot funds.” Baylor, meanwhile, leapt right into disease-focused research, choosing to study epilepsy.
The funds for the pilot projects were approved by the NHGRI coordinating committee, which evaluates the five centers’ budgets and capacity every four months, taking the opportunity to add organisms or tweak projects where necessary. This time, Collins says, the committee decided it was important for the centers to begin to budget space for medical sequencing.
While the centers are already getting their feet wet in this new area, community researchers are voicing opinions, concerns, and encouragement about the program. NHGRI officials issued a request for information and have been meeting with scientists in the past several months to get community views on issues such as how diseases should be prioritized (would a white paper system, like the one used to select organisms to sequence, be appropriate?), how samples should be collected, and how external scientists can team up with the sequencing centers. At one such meeting held last fall in Salt Lake City, a packed room indicated overall enthusiasm for the initiative. Collins assured attendees that, because funding would be allocated by NHGRI as part of the centers’ annual budgets, scientists would not be responsible for tracking down funding for the programs they suggested.
In general, Collins says, response to the program has been, “Oh, wow, I didn’t know we had gotten to that point yet.” There’s been particular interest in studying X-linked diseases, a target that will be given high priority by proposal reviewers. Other goals high up on the list for the program involve identifying genes responsible for rare, single-gene diseases and surveying variants in genes linked to common diseases.
The big five centers — Agencourt, Baylor, Broad, Venter, and WashU — are entering the final year of their large-scale sequencing grants from NHGRI, and will be competing for new awards in the coming months. While Collins says there will continue to be a steady stream of organisms assigned to each for genome sequencing, the centers will be charged “to make proposals of what they would like to be doing,” and he expects to see increased interest in medical sequencing “over the course of the next few years.”