Variation in Gene Expression and Its Relevance to Medicine

The regulated expression of genes in the human genome involves a set of complex interrelationships among different levels of control, including proper gene dosage (controlled by mechanisms of chromosome replication and segregation), gene structure, chromatin packaging and epigenetic regulation, transcription, RNA splicing, and, for protein-coding loci, mRNA stability, translation, protein processing, and protein degradation. For some genes, fluctuations in the level of functional gene product, due either to inherited variation in the structure of a particular gene or to changes induced by nongenetic factors such as diet or the environment, are of relatively little importance. For other genes, even relatively minor changes in the level of expression can have dire clinical consequences, reflecting the importance of those gene products in particular biological pathways. The nature of inherited variation in the structure and function of chromosomes, genes, and the genome, combined with the influence of this variation on the expression of specific traits, is the very essence of medical and molecular genetics and is dealt with in subsequent chapters.