Structural Biochemistry/Properties of Mutant Alleles

Overview
If the DNA mutation changes the amino acid sequence of the protein, then it can have one of these functional consequences (morph = form).

Gain-of-function are typically a missense or translocation that changes the promoter.
 * 1) Hypermorph – increased expression
 * 2) Ex. A mutated protein that signals continuously and can’t be shut off.
 * 3) Neomorph – the protein is expressed somewhere ‘new’
 * 4) Ex. In a new location on the organism - perhaps the neomorph is now expressed in the eyes, where it was normally expressed in the feet. At a different time during development – perhaps the neomorph is now expressed during adulthood, when normally it is expressed only during childhood, such as lactose tolerance.

Loss-of-function
 * 1) Hypomorph – reduced, or “leaky” expression; usually the result of a missense mutation, since that is a less drastic change
 * 2) Amorph – no expression, or null; usually the result of a more drastic mutation (deletion, nonsense, frameshift)
 * 3) Antimorph – against the form/protein, dominant negative; a poisonous protein, the antimorph will actually harm the normal protein when both are present in heterozygotes; usually this is a situation where the protein forms a multi-subunit complex.

Hypomorph

 * 1) Property: common, leaky
 * 2) Typical mutation: missense
 * 3) Gene product activity: reduced
 * 4) Recessive/Semi-dominant/Dominant: usually recessive; semi-dominant if gene is unusual.

Amorph

 * 1) Property: common, null
 * 2) Typical mutation: deletion, nonsense, frameshift
 * 3) Gene product activity: absent
 * 4) Recessive/Semi-dominant/Dominant: usually recessive; semi-dominant if gene is unusual.

Antimorph

 * 1) Property: relatively rare, dominant negative
 * 2) Typical mutation: missense, nonsense
 * 3) Gene product activity: antagonist
 * 4) Recessive/Semi-dominant/Dominant: semi-dominant

Hypermorph

 * 1) Property: relatively rare
 * 2) Typical mutation: missense, translocation
 * 3) Gene product activity: massively increased
 * 4) Recessive/Semi-dominant/Dominant: semi-dominant or dominant

Neomorph

 * 1) Property: relatively rare
 * 2) Typical mutation: translocation
 * 3) Gene product activity: different, or same but in different location
 * 4) Recessive/Semi-dominant/Dominant: semi-dominant or dominant