Geisinger Genomics Researchers Take Leading Role in Clinical Genome Project

$25 million in NIH grants to continue study of DNA variation and its clinical impact

Article ID: 608178

Released: 25-Sep-2013 6:00 PM EDT

Source Newsroom: Geisinger Health System

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Newswise — DANVILLE, Pa. –- Four Geisinger Health System researchers have taken center stage in the national arena of genomics thanks to new funding from the National Human Genome Research Institute (NHGRI), an arm of the U.S. National Institutes of Health (NIH). It recently awarded three grants totaling $25 million to initiate the Clinical Genome (ClinGen) Project.

Completed in April 2003, the Human Genome Project represents a landmark international research effort that mapped the genes making up human DNA. Today, the ClinGen Project is now harnessing data from hundreds of thousands of clinical genetics tests being performed each year and determining which variants are most relevant to improving patient care.

David Ledbetter, Ph.D., FACMG, executive vice president and chief scientific officer of Geisinger Health System; is principal investigator on two of the grants, one of which also includes Christa Lese Martin, Ph.D., FACMG, director of the Geisinger Autism & Developmental Medicine Institute, as a co-principal investigator. Andy Faucett, MS, CGC, director of policy and education, Geisinger Health System, is a key contributor to the ClinGen efforts, as is Marc S. Williams, M.D., FACMG, director, Geisinger Genomic Medicine Institute (, who will lead efforts to make Geisinger the first institution in the nation to pilot the incorporation of this information into electronic health records.

Drs. Ledbetter and Martin founded the International Standards for Cytogenomic Arrays (ISCA) Consortium in 2007. Their initial effort has evolved into the ClinGen Project.

Because of the grant award and the major role Geisinger researchers played in securing it, Geisinger patients may now be among the first in the nation to bear witness to the benefits of advances in personalized medicine.

“Technological advances are quickly allowing genome-wide analysis to become commonplace in the care of patients. However, the ability to detect DNA variants has greatly surpassed the ability to interpret their clinical impact, which has thus far limited the benefit of these technologies,” said Dr. Ledbetter. “Improving genomic interpretation will require a coordinated effort from both the clinical and research communities.”

“The ClinGen Project builds upon several years of work supporting data sharing of structural genomic variants among a large group of clinical cytogenetic laboratories through the ISCA Consortium,” said Martin. “By expanding our scope to include both structural and sequence variants, we will provide broader benefit to the community.”

In 2012, Ledbetter and Martin, along with Joyce Mitchell, Ph.D. , University of Utah, Salt Lake City; Robert Nussbaum, M.D., University of California, San Francisco; and Heidi Rehm, Ph.D., Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.; founded the International Collaboration for Clinical Genomics (ICCG), an organization of laboratories, clinicians and researchers dedicated to improving the quality of genomic testing through data sharing and collaboration.

As part of the ClinGen Project, the ICCG ( has been awarded an $8.25 million U41 grant from the NHGRI and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, divisions of NIH, to continue its work to develop a unified clinical genomics database from clinical laboratories. The ICCG will work closely with a team at the National Center for Biotechnology Information (NCBI), part of the National Library of Medicine, a division of the NIH, to develop a database to house the data, known as ClinVar

A unique aspect of this project is that it represents a strong public-private partnership that relies on the collaboration between academic and commercial genetic testing laboratories, many of which have not participated extensively in such an effort in the past. The project will result in improved patient care through data sharing that supports evidence-based curation of genes and variants.

In addition to providing key leadership in the project, Geisinger Health System will take the lead in developing a unique, patient-centered registry. This registry will serve not only as a community resource for individuals undergoing genetic testing, but as an innovative resource essential in the interpretation of genomic variants.

“The privacy of patient data is of the utmost importance, but making medical progress requires that we share knowledge wisely and appropriately to provide the best care for our patients,” said Faucett. “Clinical practitioners not only have a longstanding tradition of sharing our knowledge with each other, but also a duty to share information in ways that improve the diagnosis and treatment of patients. Of course, this must be done in a way that both respects patient privacy and allows active use by the scientific community to expand our knowledge.”

Geisinger is also a key participant in the second aspect of the ClinGen Project – identifying clinically relevant variants and incorporating this information into patient care. In a second grant awarded to Ledbetter, Jonathan Berg, M.D., Ph.D. , University of North Carolina, Chapel Hill; and Michael Watson, Ph.D. , American College of Medical Genetics and Genomics, Bethesda, Md., data deposited in ClinVar will be assessed using evidence-based methods to identify those that may potentially have a clinical impact on patient care. Another grant, awarded to Carlos Bustamante, Ph.D., Stanford University, Palo Alto, Calif.; and Sharon Plon, M.D., Baylor College of Medicine, Houston, Texas; will primarily focus on computational and machine-learning approaches to this same issue.

“Integration of these clinically relevant variants into routine patient care will give Geisinger patients access to truly personalized genomic medicine,” Dr. Williams said.

Geisinger and Stanford will jointly develop a process to evaluate the ethical and social issues associated with variants deemed medically actionable to ensure the information is shared safely with patients and families.

About Geisinger Health SystemGeisinger Health System is an integrated health services organization widely recognized for its innovative use of the electronic health record, and the development of innovative care models such as ProvenHealth Navigator® and ProvenCare®. As the nation’s largest rural health services organization, Geisinger serves more than 2.6 million residents throughout 44 counties in central and northeastern Pennsylvania. The physician-led system is comprised of more than 19,500 employees, including a 1,000-member multi-specialty group practice, six hospital campuses, two research centers and a 448,000-member health plan, all of which leverage an estimated $6.1 billion positive impact on the Pennsylvania economy. The health system and the health plan have repeatedly garnered national accolades for integration, quality and service. In addition to fulfilling its patient care mission, Geisinger has a long-standing commitment to medical education, research and community service. For more information, visit, or follow the latest Geisinger news and more at and



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