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
   1. Ex. A mutated protein that signals continuously and can’t be shut off.
2. Neomorph – the protein is expressed somewhere ‘new’
   1. 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