We are in a phase of unprecedented progress in identifying genetic loci that cause variation in traits ranging from growth and fitness in simple organisms to disease in humans. However, a mechanistic understanding of how these loci influence traits is lacking for the majority of loci. Studies of the genetics of gene expression have emerged as a key tool for linking DNA sequence variation to phenotypes. Here, we review recent insights into the molecular nature of regulatory variants and describe their influence on the transcriptome and the proteome. We discuss conceptual advances from studies in model organisms and present examples of complete chains of causality that link individual polymorphisms to changes in gene expression, which in turn result in physiological changes and, ultimately, disease risk.
Bibliographical noteFunding Information:
The authors thank members of L.K.’s laboratory and many colleagues for discussions. L.K. is supported by funds from the Howard Hughes Medical Institute, the US National Institutes of Health and the James S. McDonnell Foundation. F.W.A. was supported by the German Science Foundation (DFG).
© 2015 Macmillan Publishers Limited.