Polymorphic miRNA-mediated gene regulation: contribution to phenotypic variation and disease

The expression of at least a third of mammalian genes is post-transcriptionally fine-tuned by ∼1000 microRNAs (miRNAs), assisted by the RNA silencing machinery, comprising tens of components. Polymorphisms and mutations in the corresponding sequence space (machinery, miRNA precursors and target sites) are likely to make a significant contribution to phenotypic variation, including disease susceptibility. Here we review basic miRNA biology in animals, survey the available evidence for DNA sequence polymorphisms affecting miRNA-mediated gene regulation and thus phenotype, and discuss their possible importance in the determination of complex traits.