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Jonathan S. Berg, MD, PhDJonathan Berg, MD, PhD, Distinguished Professor of Genetics and Medicine at the UNC School of Medicine, is a principal investigator of The Clinical Genome Resource, a multi-institution consortium initially launched in 2013 by the National Human Genome Research Institute to provide evidence-based evaluations of clinically relevant genes and variants.

CHAPEL HILL, NC – Doctors have accurate diagnostic tests for some single-gene conditions, such as sickle cell disease or cystic fibrosis. But when it comes to understanding the genetic variants underlying most rare genetic conditions, there is still much to learn. This is where the Clinical Genome Resource Consortium (ClinGen) comes in.

This week, the NIH renewed three awards totaling $73.2 million over five years to continue building the Clinical Genome Resource, an effort to collect and archive information about clinically relevant genes and genomic variants – alterations in the DNA sequence of a particular gene – for use in precision medicine.

The ClinGen team at UNC-Chapel Hill, led by Jonathan Berg, MD, PhD, Bryson Distinguished Professor of Genetics and Medicine, was awarded a $24-million, five-year grant to scale biocuration and expert evaluation of genes and variants.  The grant includes key contributors at the American College of Medical Genetics and Genomics (ACMG), ARUP Laboratories, Baylor College of Medicine, Georgetown University, Kaiser Foundation Research Institute (KFRI), Massachusetts Eye and Ear Infirmary, Mayo Clinic, the University of Miami, and RTI International.

This UNC-led project is part of a consortium including two other major programs: one spearheaded by the Broad Institute at MIT and Harvard and Geisinger, and a second led by Baylor College of Medicine and Stanford University. Read more from the NIH here.

“Optimal clinical care depends on accurate information about the causes, natural history, and management of diseases,” said Berg, director of the Program in Precision Medicine in Healthcare at the UNC School of Medicine (PPMH). “With genomic analysis becoming more routine for patients suspected to have rare genetic conditions, the public availability of well-curated and expert knowledge about genes and variants is critical. Our goal is for ClinGen to provide a readily accessible and trusted resource that can be used by diagnostic laboratories, providers, and patients.”

Over the next five years, ClinGen investigators, with the help of physician and patient stakeholders, will fill this important gap in care through the collection and evaluation of structured evidence on genetic conditions and the variants that cause them. The researchers will utilize frameworks developed during the initial phases of ClinGen to evaluate gene-disease relationships, classify genetic variants, and assess clinical actionability of genetic conditions; all results are made freely available online. Notably, ClinGen obtained FDA recognition for the methods used by its expert panels that classify genetic variants.

The core of the expert curation work is being conducted by diverse, international teams of clinical experts, basic scientists, clinical molecular geneticists, genetic counselors, biocurators and project coordinators. “As part of our project, we intend to utilize the truly remarkable network of ClinGen contributors to conduct stakeholder engagement in multiple clinical domains, to improve the quality and impact of the resource and respond to the specific needs of each specialty,” Berg said. UNC’s project emphasizes the critical importance of data sharing, stakeholder engagement, assessment of physician and patient needs, and sustainability of the resource. The project also will focus on diversity of data sources, people, and organizations involved in generating the resource.

Investigators at RTI and KFRI are leading ClinGen’s efforts to assess clinical actionability – utilizing a structured literature review and evaluation process developed in the early phases of ClinGen for both adult and pediatric conditions. The results of this work are already informing practice guidelines such as the ACMG recommendations for reporting of secondary findings in clinical exome and genome sequencing. In the current funding period, the team will develop a methodological framework for examining actionability of polygenic risk scores that are now being developed for common multifactorial conditions.

The ClinGen resource has had a broad impact in the genomics community and patient care, as demonstrated by use in professional guidelines and achievement of FDA recognition. The exceptional participation of more than 1,500 clinicians and scientists worldwide, many of whom are volunteers, reflects how the genomics community has embraced the ClinGen expert curation processes. ClinGen’s well-structured evidence-based assertions about clinically relevant genes and variants represents a body of genomic knowledge that is essential to reduce inconsistency in clinical practice and to facilitate the widespread application of genomic technologies to improve health.

The mission of Program in Precision Medicine in Healthcare at the UNC School of Medicine, funded by UNC Health system, is to use genomics and other technologies to advance precision medicine approaches to screening, prevention, diagnosis, and health management for North Carolinians in the UNC Health system and beyond. This Clinical Genome Resource grant will accelerate these endeavors and will significantly improve patient care. 


This article appeared in UNC Health Newsroom.