Allelic variations in gene expression

Purpose of review: Genetic variants determine phenotypic variability. Many genetic studies suggest that protein structural variations predispose the population to more than 1000 different hereditary diseases. Unfortunately, despite the study of genetic polymorphisms for many decades, the milder phenotypic variations believed to account for most human physical and behavioral differences and underlying the most common human genetic diseases (including cancers) cannot be accounted for easily by these variations in the protein coding sequences. Thus, it has been hypothesized that the study of natural differential expression presenting within and among populations may enhance understanding of human phenotypic variation. Recent findings: During the last year, reports identifying variations in gene expression in different organisms and finding subtle changes of gene expression associated with common genetic disease have pointed to variations in gene expression as playing a central role in molecular evolution and human disease. Advances in the functional analysis of gene regulatory networks-in particular, new methods for distinguishing cis-acting components from trans-acting factors-have provided the impetus for these discoveries. Summary: This review represents current knowledge about allelic variation in gene expression and its increasingly important role in understanding the genotype-phenotype relation. Characterization of these allelic variations may open largely uncharted territory in genomics for biomedical researchers and may eventually lead to the discovery of the causative genes of common hereditary diseases and their mechanism of action.