Berg Lab

Genome-scale sequencing now allows us to generate massive amounts of genetic variant data that facilitates the discovery of new disease-associated genes.

Yet for many disorders we still only understand a fraction of the genes that (when mutated) cause disease. Our lab studies individuals and families with likely hereditary cancer susceptibility in order to discover new candidate genes for monogenic forms of hereditary breast cancer, polyposis, and other cancer types.
Advances in genetics are coming at a breathtaking pace, but our ability to utilize this information clinically remains a significant limitation of genomic medicine.

To this end, I am leading one of the groups involved in a consortium effort called the “Clinical Genomics Resource (ClinGen)” that includes two NHGRI-funded U01 projects, an NHGRI-funded U41 project, and the NCBI’s ClinVar database. The overall goal of this consortium is to develop a publicly available knowledge-base of clinically-relevant genes and genetic variants, in order to facilitate the deployment of clinical genomics.
We often hear that every newborn will have his or her genome sequenced at birth in order to guide their health care and prevent disease.

How can next-generation sequencing be most effectively employed to enhance current newborn screening? What types of genes and conditions should be sought in a healthy newborn? How should parents decide what information they would want to know or not to know? Are there certain types of information that should be withheld until the individual becomes an adult and chooses to know or not to know? We are exploring these issues and others in an NHGRI/NICHD-funded U21 project called “NC NEXUS” led by myself and Dr. Cindy Powell from the Department of Pediatrics, Division of Pediatric Genetics and Metabolism.
Molecular diagnosis is a key element in the care of patients with rare genetic disorders.

How can we best utilize genome-scale sequencing as a clinical diagnostic test? What are the most effective ways of sifting through many thousands of genetic variants to find the few variants that are clinically relevant for the patient? How should we manage the inevitable “incidental findings” that will be present in every genome-scale sequencing assay? These are some of the questions being asked in the NHGRI-funded U01 project called “NCGENES” led by Dr. Jim Evans in the Department of Genetics.
The integration of genomics with the medical care of has been widely touted as the natural extension of the Human Genome Project.

Should we start carrying out genomic “screening” in healthy adults? What types of genes and conditions would provide the most valuable information? What kinds of genomic information should we avoid? What is the right population in which to carry out screening? In what setting should the screening take place? These provocative questions will be tackled through a pilot study being carried out through the Center for Genomics and Society, an NHGRI-funded P50 Center for Excellence in ELSI Research led by Dr. Gail Henderson in the Department of Social Medicine.

Clinical Genomics – Bringing genome-scale sequencing into the clinic

My research group is broadly interested in the application of sequencing technologies in medical genetics and genomics, using a combination of wet lab and computational approaches. As a clinician, I am actively involved in the care of patients with hereditary disorders, and the questions that my group investigates have direct relevance to patient care. My research involves the application of next-generation sequencing for translational research projects including gene discovery, diagnostic testing, genomic medicine in healthy adults, and newborn screening. These projects are all intended to contribute to the knowledge base that will be required to make genomic medicine a reality.

– Jonathan Berg, MD, PhD

Berg Lab Photo