Dominant negative mutation

Hermann J. Muller (1890–1967), who was a 1946 Nobel Prize winner, coined the terms amorph, hypomorph, hypermorph, antimorph and neomorph to classify mutations based on their behaviour in various genetic situations, as well as gene interaction between themselves. These classifications are still widely used in Drosophila genetics to describe mutations. For a more general description of mutations, see mutation, and for a discussion of allele interactions, see dominance relationship.

Key: In the following sections, alleles are referred to as +=wildtype, m=mutant, Df=gene deletion, Dp=gene duplication. Phenotypes are compared with '>', meaning 'phenotype is more severe than'

Amorphic describes a mutation that causes complete loss of gene function. Amorph is sometimes used interchangeably with "genetic null". An amorphic mutation might cause complete loss of protein function by disrupting translation ("protein null") and/or preventing transcription ("RNA null").

An amorphic allele elicits the same phenotype when homozygous and when heterozygous to a chromosomal deletion or deficiency that disrupts the same gene. This relationship can be represented as follows:

m/m = m/Df

An amorphic allele is commonly recessive to its wildtype counterpart. It is possible for an amorph to be dominant if the gene in question is required in two copies to elicit a normal phenotype (i.e. haploinsufficient).

Hypomorphic describes a mutation that causes a partial loss of gene function. A hypomorph is a reduction in gene function through reduced (protein, RNA) expression or reduced functional performance, but not a complete loss.

The phenotype of a hypomorph is more severe in trans to a deletion allele than when homozygous.

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