Broad Institute scientists awarded $18M CARE grant

May 04, 2006

The Broad Institute of MIT and Harvard announced today an award from the National Heart, Lung, and Blood Institute (NHLBI) for more than $18M to support genomic studies aimed at unveiling the genetic variations that underlie common human diseases. These funds will help to build a common data resource for the entire biomedical community that systematically combines genetic analyses of heart, lung, blood, and sleep disorders with detailed information about disease characteristics in a range of patient groups.

"The research funded by this award should result in new insights into how genetic variation contributes to health and disease," said Stacey Gabriel, principal investigator of the grant and the director of the Genetic Analysis platform and the National Center for Genotyping and Analysis at the Broad Institute. "We will work together with other members of the CARE network to combine new methods for measuring genetic variation with an unprecedented collection of large, well-characterized clinical cohorts."

Known as the candidate gene association resource, or CARE, this project will survey the DNA of 50,000 individuals, using large-scale genotyping technologies and advanced informatics, to highlight the differences contained in specific genes of interest. These "candidate" genes represent a prioritized list of the likely sources of inherited variation that are most relevant for human disease.

"The sheer scale of this project with genetic data collected from as many as 50,000 participants allows for more in-depth analyses of diseases across multiple races and ethnicities," said NHLBI Director Elizabeth G. Nabel, M.D. "The database will be a tremendous resource for scientists -- speeding identification of risk factors and genetic variants associated with disease and disorders."

While inherited differences within our genes likely play roles in common diseases that affect major organ systems, such as the heart, lung and blood, their contributions appear to be complex and multifaceted, and therefore, difficult for scientists to identify. The sequencing of the human genome and recent completion of the Haplotype Map ("HapMap"), a comprehensive catalogue of common genetic differences in humans, has laid the groundwork needed to begin this task. Combining this knowledge with the NHLBI's information about the incidence and progression of disease in diverse populations allows scientists to now draw meaningful inferences about the genes that contribute to human disease.

"By applying new, cutting-edge genetic, genomic and statistical methods to cohorts collected by NHLBI-funded investigators, we will definitively test the most promising genes for association with many important diseases and pre-disease states," said Joel Hirschhorn, a principal investigator, an associate member of the Broad Institute and coordinator of its Metabolic Disease Initiative, and an assistant professor at Children's Hospital Boston and Harvard Medical School. "The discoveries that stem from this work will enlighten us as to why some people become ill and others remain healthy, and can help focus future efforts to develop improved disease therapies and preventive measures."

Over a 4-year period, the scientists will complete a comprehensive analysis of more than 1,700 candidate genes in individuals enrolled in NHLBI disease studies. This includes cataloguing tiny differences in DNA sequence known as single nucleotide polymorphisms (SNPs, pronounced "snips"). By using advanced bioinformatic methods to correlate this data with the observed features of disease, the researchers will be able to estimate the frequency of a particular SNP in the overall population, to predict the level of disease risk that it confers, and to approximate the degree to which it contributes to the severity of a particular disease. Marcia Nizzari, a co-investigator and the director of informatics development for the Medical and Population Genetics program at the Broad Institute, will help lead this computational effort.

"This project is truly groundbreaking in the scope of genes that will be examined, the number of patients examined, and the quality of clinical information that is available," said co-investigator David Altshuler, director of the Program in Medical and Population Genetics at the Broad Institute and an associate professor at Massachusetts General Hospital and Harvard Medical School. "By working together with the other members of the CARE network and making the results of this large-scale, collaborative effort accessible to other researchers, we hope to dramatically accelerate the pace at which gene variants provide insight into the root causes of human health and disease."
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About the Broad Institute of MIT and Harvard

The Broad Institute of MIT and Harvard was founded in 2003 to bring the power of genomics to biomedicine. It pursues this mission by empowering creative scientists to construct new and robust tools for genomic medicine, to make them accessible to the global scientific community, and to apply them to the understanding and treatment of disease.

The Institute is a research collaboration that involves faculty, professional staff and students from throughout the MIT and Harvard academic and medical communities. It is jointly governed by the two universities.

Organized around Scientific Programs and Scientific Platforms, the unique structure of the Broad Institute enables scientists to collaborate on transformative projects across many scientific and medical disciplines.

For further information about the Broad Institute, go to http://www.broad.mit.edu.

To contact the NHLBI, please call the press office, 301 496-4236 or nhlbi_news@nhlbi.nih.gov.

Broad Institute of MIT and Harvard

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