Polymorphisms in the microRNA pathway as a source of phenotypic variation in animals

MicroRNA (miRNA) are expected to regulate 30% of coding genes. Moreover, dbSNP database reports more than 23 million SNP in the human genome (April 2010), many of which might alter miRNA-related genes. Thus, polymorphisms affecting miRNA gene regulation may have a widespread effect on phenotypes. Polymorphisms directly altering miRNA gene regulation were first reported in 2005. To date, many of these types of genetic variants have been described in the miRNA processing machinery, the miRNA genes, and the miRNA target sites, and have been related to a wide range of phenotypes such as cancer, heart disease, neurological disorders or muscle development. These polymorphisms can exert their effect at three different hierarchical levels. Firstly, they can be located in and modify a miRNA binding site, affecting the target gene and any other gene interacting with it. Secondly, mutations may affect the expression, the processing, or the mature sequence of a miRNA, in which case their effect on phenotypes is likely to be broader and influence more phenotypes. Finally, a polymorphism can perturb any of the genes involved in the miRNA biogenesis and have a downstream impact on the expression of thousands of genes. Consequently, this latter type of variant is likely to be lethal at early stages of development or have a dramatic impact on fitness, therefore, if present, would be expected to be very rare. Knowledge and technical development are required to accelerate the discovery and understanding of this type of genetic variation and how it shapes phenotypic traits. © 2011 by Nova Science Publishers, Inc. All rights reserved.