UW to explore genetic origins of common heart, lung, and blood diseases in federal project


The National Heart, Lung, and Blood Institute (NHLBI) announced Oct. 1 that the University of Washington (UW) will receive two of the six "Grand Opportunity"NHLBI Large-Scale DNA Sequencing Project awards. The multi-institutional genomics project will examine the genetic connections to heart, lung, and blood diseases that account for three of the leading causes of death in the United States.

The research is co-funded by the National Institutes of Health (NIH) Director's Office. The two-year national project, at a total funding of $64 million, was made possible by the American Recovery and Reinvestment Act of 2009.

The UW will receive $25 million to launch the Northwest Genomics Center, one of two sequencing centers for the project. The second sequencing center will be located at the Broad Institute of MIT and Harvard in Cambridge, Mass.

The UW will also receive a $5.2 million grant, under the direction of Dr. Michael Bamshad, UW professor of pediatrics in the Division of Genetic Medicine, to manage the lung disease population research portion of the national project. Ohio State University, Washington University in St. Louis, and the University of Virginia are the other participating institutions managing cardiovascular and blood disease projects

"This extraordinary collaboration promises to deepen our understanding of the complex interactions of genetics, the environment, and lifestyle choices, helping us bring the best science to the patients who need it most," said NHLBI Director Dr. Elizabeth G. Nabel.

The Northwest Genomics Center in Seattle will be among the first new, large-scale genomics centers focused entirely on medical sequencing to be created in the United States in more than a decade. The UW also received $2 million in funding from the state's Life Sciences Discovery fund to support the Center's infrastructure.

"The Northwest Genomics Center will apply cutting edge, next generation sequencing technology to uncover the differences in our genetic code and explore how these may influence traits, such as cholesterol and blood pressure, that impact our risk for developing cardiovascular disease,"said Dr. Debbie Nickerson, UW professor of genome sciences and one of the principal investigators for the new Center. Other principal investigators are Drs. Jay Shendure, Philip Green, and Mark Rieder, who are also faculty members in the UW Department of Genome Sciences.

"This is an extraordinary team effort to which we all bring individual expertise,"Nickerson said. She and Rieder are leaders in medical sequencing of cardiovascular, blood and lung diseases. Shendure is one of the pioneers in the development and application of next generation sequencing technology, and Green is a world leader in developing new software tools for sequence analysis, including the tools that helped to generate the human genome sequence.

Bamshad, who will head the lung disease component of the national project, is noted for his work on common genetic variations in the United States population and how these affect individual and ethnic group differences in susceptibility to disease. he NHLBI Large-Scale DNA Sequencing Project will explore many common forms of heart, lung, and blood diseases. The ethnically diverse individuals to be studied from the large, long-term population studies have given their permission for the information from their DNA to be shared with other investigators.

"The national project will tackle not only susceptibility to these common, complex diseases, but also resistance,"Nickerson said. She noted that it is possible that understanding disease resistance could provide new avenues for the prevention and treatment of these disorders. For example, some of the research groups will compare samples from people who have very high cholesterol against those who have very low cholesterol to see what genes and differences contribute to these extremes.

"Cardiovascular disease is a complex, common disorder that affects millions of people and leads to early death in adults from heart attacks and strokes,"said Nickerson. Chronic lung diseases affect more than 35 million Americans. One out of every 7 deaths is from lung disease, making it the third leading cause of death.

"Unlike rare diseases, which usually follow a simple pattern of inheritance of variation in one gene,"she explained, "it has been very difficult to sort out the complicated genetics of the multiple factors that contribute to heart disease and to lung disease, and how they interact with environmental influences, such as smoking or nutrition. For example, heart disease runs in some families, but the inheritance doesn't follow simple rules.

In the lung disease section of the NHLBI Large-Scale DNA Sequencing Project, Bamshad will lead an effort to identify rare and common gene variations that influence the severity of lung diseases such as asthma, chronic obstructive pulmonary disease, acute lung injury, pulmonary hypertension, and cystic fibrosis.

"Our goal is to better understand the biology of lung diseases, improve their diagnosis and treatment, and gather information that may lead to novel therapeutics,"Bamshad noted. "We want to make strides in the management of a group of diseases that impact the youngest and the oldest in our country."

Grand Opportunities, or GO, is a Recovery Act program which supports high-impact ideas that may lead to new fields of investigation and that may accelerate critical breakthroughs.

"This is one of those times in science when it is just the right moment to scale newly emerging technologies to obtain important medical insights,"Nickerson said. "Over the past two years genome technology has improved vastly in terms of lower costs and faster methods that have increased research productivity. It's the right time for genome sciences to begin to have an impact on medicine.

The UW has been among the world's leaders in developing and testing new technologies and analytical approaches for genomics. These advances have prepared UW scientists to take on the challenge of large population studies to uncover the genetics of cardiovascular and lung diseases. This new genome science effort also builds on a 60-year history of UW research on the heritability of lipid disorders leading to premature heart attacks and on the medical genetics of other common, chronic diseases.

A few of the many UW advances in genome research that will be applied at the Northwest Genomics Center include:


Methods to isolate the protein-coding regions of the human genome known as the exome, a development that contributes to the ability to analyze thousands of human genomes (Jay Shendure)
Studies of how differences in single nucleotides in human DNA can underlie certain forms of genetic diseases and responses to medications (Debbie Nickerson and Mark Rieder)
The creation of computer programs that reduce the noise in and improve the reliability of sequence data (Philip Green)

Several other recently funded economic stimulus research projects, such as studies of the genetics of neuropsychiatric disorders, including autism and schizophrenia, will also benefit from the expertise and powerful next generation technology of the Northwest Genomics Center.

Nickerson said that the scale-up of next generation sequencing is poised to "change medicine in ways we cannot predict. The American Recovery and Reinvestment Act of 2009 is medicine's moon shot, and we are looking forward to participating in this exciting new effort.

For more information on the NHLBI Large-Scale DNA Sequencing Project, see
http://www.nhlbi.nih.gov/recovery/media/stimulus.htm

Watch the NHLBI video on the UW project


Published on: 2009-10-03



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