UNC scientists funded to study genome sequencing in clinical settings

UNC scientists have received a four-year $6.4 million grant to establish an effort they have named the North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing (NCGENES).

UNC scientists funded to study genome sequencing in clinical settings click to enlarge James P. Evans, MD, PhD

Media contact: Dianne G. Shaw 919-966-7834, dgs@med.unc.edu

Tuesday, Dec. 6, 2011

CHAPEL HILL, N.C. - The complete sequence of an individual’s genome – all 3 billion DNA building blocks - will soon be affordably available to doctors, patients and even consumers. While knowledge of one’s genome may have important medical benefits, tremendous questions remain regarding an avalanche of such data means and how they should be used. Many clinical, ethical and social issues arise from the evaluation, use and sharing of the data.

To address these issues, UNC scientists have received a four-year $6.4 million grant to establish an effort they have named the North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing (NCGENES). UNC is one of five Clinical Sequencing Exploratory Research projects that will study ways for healthcare professionals to use genome sequencing information in a clinical setting. The grant is funded by the National Human Genome Research Institute, part of the National Institutes of Health.

The exome is the complete set of exons, or protein-coding sequences within the human genome, and whole exome sequencing captures it all. The exome comprises only about 1 percent of human DNA, but for cancer studies, that 1 percent is valuable because cancer is a genetic disease.

James P. Evans, MD, PhD, Bryson Distinguished Professor of Genetics in the UNC School of Medicine, is the principal investigator. He says, ”We’re thrilled to have the opportunity to investigate how best to use the new technologies of rapid DNA sequencing in patient care. In this effort we will sequence all of the genes in each of about 750 patients to determine how well this technology performs as a diagnostic tool to figure out why these patients are ill.

“We will also carefully investigate how patients and their doctors use this information in both a medical and a non-medical context. For example, sometimes whole exome sequencing will discover things about a person that they might not have wanted to know: being at high risk of an untreatable disease such as dementia. We will investigate how such information is best handled in a way that is sensitive to patient preferences.

“We now have powerful technology that can provide us with much genetic data about an individual.  How do we move this technology into the clinical practice arena and successfully address the technical, logistical, psychosocial and ethical issues that arise from its use?”

Evans leads the Clinical Genetics Program of UNC Lineberger Comprehensive Cancer Center, and is a member of the Carolina Center for Genome Sciences.

“Our UNC team is a very broad, interdisciplinary team, drawing upon expertise in a variety of fields, ranging from bioinformatics to social medicine. We will also be making a strong effort to include patients from traditionally underrepresented groups such as the African-America, Hispanic and Native American communities, an especially exciting aspect of the work given the existing strong relationships that UNC has with such groups. We also hope that this grant will enable us to further strengthen these important relationships.”  

The UNC team has several projects within their grant. Whole exome sequencing (WES) will be performed on 750 UNC patients, in whom there is a reasonable suspicion that a discrete genetic error lies at the root of their disorder.  For example, we will focus on individuals with cancer at young ages, those with a strong family history of cancer, and children with developmental disorders.

UNC scientists will evaluate the use and performance of WES as a diagnostic tool, while addressing the impact of the diagnostic WES information on patients and families. WES will also identify what is called “incidental information,” information that may or may not be clinically relevant or medically actionable.

Thus, the team will assess how frequently such incidental information is found and whether or how patients want information about these findings, with the goal of developing best practices. The team will implement WES in medically underserved groups and work to identify barriers to recruitment and retention of patients in the study as well as how WES can be expanded to practices beyond UNC.

Brad Ozenberger, PhD, NHGRI’s program director for Genomic Medicine,, says, “At NHGRI, we foresee genome sequencing becoming a routine part of medical care. These projects are exploring the best ways to widen the use of genomic medicine in a responsible, respectful way.”  Ozenberger is overseeing the new initiative with Jean McEwen, JD, PhD, program director for the Ethical, Legal, and Social Implications Program.

Early funding for this research and support of next-generation sequencing technology has been provided by the University Cancer Research Fund. The grant will be administered through the Carolina Center for Genome Sciences (CCGS).

Other UNC scientists, all CCGS members, leading specific components of the grant are: Jonathan Berg, MD, PhD, assistant professor of genetics; Gail Henderson, PhD, professor and chair of the department of social medicine; Karen Weck-Taylor, MD, PhD, professor of pathology and laboratory medicine and director of the UNC Molecular Genetics Laboratory; and Kirk Wilhelmsen, MD, PhD, professor of genetics and neurology.

Other institutions receiving grants are Baylor College of Medicine, Houston, Texas; Brigham and Women’s Hospital, Boston; Children’s Hospital of Philadelphia, and the University of Washington in Seattle.

For more information, see the NHGRI news release at: http://www.nih.gov/news/health/dec2011/nhgri-06.htm

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