A single mutation causes a spectrum of cardiovascular defects: the potential role of genetic modifiers, epigenetic influences, and stochastic events in phenotypic variability.

摘要

How can an identical mutation result in distinct pheno-types in different individuals? This simple question underscores the importance of genetic background in disease severity and progression and highlights one of the challenges in understanding complex diseases. The role of genetic modifier genes in phenotypic variability and disease progression has long been appreciated, but the identification of modifiers has been difficult particularly in the highly variable human population . There are numerous examples of variability in disease progression in humans, even in cases where identical causative mutations are present, indicating a strong influence of familial history and genetic background.