By Julia Karow
This article, originally published Oct. 1, has been updated with additional information and with comments from a Broad Institute researcher.
The National Heart, Lung, and Blood Institute said last week that it is granting more than $64 million to five institutions over two years for a large-scale DNA sequencing project that will analyze the exomes of 12 well-phenotyped cohorts involving more than 8,000 people.
$50 million of the funding goes to two sequencing centers, split equally between the University of Washington in Seattle, with principal investigator Deborah Nickerson, and the Broad Institute, with PI Stacey Gabriel.
Of the remainder, $4.5 million will go to Ohio State University Medical Center in Columbus, with PI Rebecca Jackson, to manage the contributions of the Women's Health Initiative cohort; $5.2 million will go to the University of Washington, with PI Michael Bamshad, to manage the NHLBI lung cohorts; $2.5 million will go to Washington University in St. Louis, with PI Timothy Graubert, to manage data from patients with myelodysplastic syndrome; and $2.3 million will go to the University of Virginia Health System in Charlottesville, with PI Stephen Rich, to coordinate data from six NHLBI cohorts.
The project will sequence the exomes of more than 8,000 participants in 12 long-term studies: the Women's Health Initiative, Atherosclerosis Risk in Communities, Coronary Artery Risk Development in Young Adults, the Cardiovascular Health Study, the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, the Framingham Heart Study, Genomic Research on Asthma in the African Diaspora, the Lung Health Study, a Pulmonary Arterial Hypertension population, the Acute Lung Injury cohort, and a cystic fibrosis cohort.
Gabriel, co-director of genome sequencing and analysis at the Broad Institute, told In Sequence last week that she and her colleagues plan to enrich the exomes of the cohort samples using a hybridization-based in-solution method that Broad researchers developed and published earlier this year and that Agilent has since commercialized (see In Sequence 2/24/2009), and to sequence them on the Illumina GA platform.
The awards, made under the American Recovery and Reinvestment Act of 2009's Research and Research Infrastructure "Grand Opportunities" program, are the NHLBI's largest single capital investment of stimulus funding, the institute said.
With the project, NHLBI hopes to identify specific gene variants that are associated with heart, lung, and blood diseases. Genome-wide association studies "have provided tantalizing hints about the genetic causes and contributors" of such diseases, according to the institute's website, "but these 'fly-over' genome-scanning approaches have not provided enough detail to assign a particular gene or genes to various phenotypes."
Last year, NHLBI, in collaboration with the National Human Genome Research Institute, granted $12 million to three institutions — Harvard Medical School, the Broad Institute, and the University of Washington — to develop exon-capture methods and to integrate them with next-generation sequencing for future large-scale studies of well-phenotyped clinical samples (see In Sequence 11/7/2008).
Earlier this year, the UWash researchers published two articles detailing exome sequencing methods they have developed, one using padlock probes combined with sequencing on Illumina's Genome Analyzer (see In Sequence 4/21/2009), the other one using Agilent microarrays and Illumina sequencing (see In Sequence 9/1/2009).