2011 Cardiovascular Lecture
The Fifth Annual NHLI/RBHT Paul Wood Cardiovascular Lecture was held on Thursday 16 June 2011. The lecture entitled ‘Next generation sequencing: a revolution for cardiovascular genetics’ was presented by Professor Christine Seidman, Departments of Medicine and Genetics, Harvard Medical School and Brigham and Women’s Hospital, USA.
- In the Chair: Professor Dudley Pennell, Professor of Cardiology, National Heart and Lung Institute, Imperial College London
- Vote of Thanks: Professor Michael Schneider, British Heart Foundation Simon Marks Chair of Regenerative Cardiology, National Heart and Lung Institute, Imperial College London
The lecture was sponsored by the Royal Brompton and Harefield NHS Foundation Trust and the National Heart and Lung Institute.
Biography
Christine Seidman is the Thomas W. Smith Professor of Medicine and Genetics at the Brigham and Women’s Hospital and Harvard Medical School and an Investigator of the Howard Hughes Medical Institute. She was an undergraduate at Harvard College and received an M.D. 
from George Washington University School of Medicine. Dr. Seidman served as an intern and resident in Internal Medicine at John Hopkins Hospital and received subspecialty training in cardiology at the Massachusetts General Hospital. In 1987 she joined the staff at Brigham and Women’s Hospital where she serves as the Director of the Cardiovascular Genetics Service. Dr. Seidman’s research program focuses on the discovery of genetic mechanisms for human heart disease, work that continues to be informed by her continued care of patients.
Dr. Seidman is a member of Institute of Medicine and the National Academy of Science. She is the recipient of the American Heart Association Basic Science Prize, the American Society for Clinical Investigation Award, the Glorney-Raisbeck Prize and the Jay and Jeannie Schottenstein Prize. With Dr. Jonathan Seidman she has received the Pasarow Foundation Award in Cardiovascular Research, the Bristol-Myers Squibb Award for Distinguished Achievement in Cardiovascular Research and the Institut de France Fondation Lefoulon-Delalande Grand Prix for Science Award.
Abstract
The ultimate opportunity presented by discovering the genetic basis of human heart disease is accurate prediction and prevention of disease. For these genetic discoveries to change medicine requires the ability to identify at-risk individuals prior to overt disease manifestations and developing novel therapies which delay or prevent clinical expression. The cardiomyopathies provide a paradigm for fulfilling these opportunities.
The Seidman laboratory has discovered genetic etiologies for hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Using traditional human genetic methodologies, the laboratory initially showed that HCM is caused by mutations in genes encoding cardiac myosin heavy chain, α tropomyosin, cardiac troponin T and cardiac myosin binding protein-C, therein establishing an “idiopathic” condition as a disease of the sarcomere. Parallel analyses of DCM revealed a diverse range of genetic etiologies, including mutations in sarcomere protein genes, calcium regulating genes, and molecules with unknown functions in myocyte biology, thus indicating a multiplicity of mechanisms that predispose the heart to fail.
Based on the discovery of HCM and DCM disease genes and the advent of next generation sequencing technologies this research has been translated into clinical gene-based diagnosis, providing the opportunity for early and accurate identification of individuals at risk for developing cardiomyopathies. Application of advanced sequencing strategies for characterization of the consequences of human cardiomyopathy mutations on myocyte biology has also provided unexpected insights into the molecular pathways that are activated by gene mutations. Selective targeting of key molecules in these pathways has enabled novel pre-emptive strategies that show promise for attenuating the development and progression of cardiomyopathies in human patients.
