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Abstract Much of the focus of human disease genetics is directed towards identifying nucleotide variants that contribute to disease phenotypes. This is a complex problem, often involving contributions from multiple loci and their interactions, as well as effects due to environmental factors. Although some diseases with a genetic basis are caused by nucleotide changes that alter an amino acid sequence, in other cases, disease risk is associated with altered gene regulation. This paper focuses on how studies of gene expression variation might complement disease studies and provide crucial links between genotype and phenotype.

Abstract The regulation of gene expression plays an important role in complex phenotypes, including disease in humans. For some genes, the genetic mechanisms influencing gene expression are well elucidated; however, it is unclear how applicable these results are to gene expression on a genome-wide level. Studies in model organisms and humans have clearly documented gene expression variation among individuals and shown that a significant proportion of this variation has a genetic basis. Recent studies combine microarray surveys of gene expression for thousands of genes with dense marker maps, and are beginning to identify regions in the human genome that have functional effects on gene expression. This paper reviews recent developments and methodologies in this field, and discusses implications and future directions of this research in the context of understanding the influence of human genomic variation on the regulation of gene expression.