Mechanisms of Mendelian Dominance

Genetic dominance has long been considered as a qualitative reflection of interallelic interactions. Dominance arises from many multiple sources whose unifying theme is the existence of non-linear relationships between the genotypic and phenotypic values. One of the clearest examples are dominant negative mutations (DNMs) in which a defective subunit poisons a macromolecular complex. Dominance can also be due to the presence of a heterozygous null allele, as is the case of haploinsufficiency. Dominance can also be influenced by epistatic (interloci) interactions. For instance, a pre-existing genetic variant can make possible the expression of a pathogenic variant in a seemingly "dominant" fashion. Such interactions, which can make an individual more or less sensitive to a particular pathogenic variant, will also be discussed here.