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. Hypermorph – increased expression Ex. A mutated protein that signals continuously and can’t be shut off. Neomorph – the protein is expressed somewhere ‘new’ 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 Hypomorph – reduced, or “leaky” expression; usually the result of a missense mutation, since that is a less drastic change Amorph – no expression, or null; usually the result of a more drastic mutation (deletion, nonsense, frameshift) 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 Property: common, leaky Typical mutation: missense Gene product activity: reduced Recessive/Semi-dominant/Dominant: usually recessive; semi-dominant if gene is unusual. Amorph Property: common, null Typical mutation: deletion, nonsense, frameshift Gene product activity: absent Recessive/Semi-dominant/Dominant: usually recessive; semi-dominant if gene is unusual. Antimorph Property: relatively rare, dominant negative Typical mutation: missense, nonsense Gene product activity: antagonist Recessive/Semi-dominant/Dominant: semi-dominant Hypermorph Property: relatively rare Typical mutation: missense, translocation Gene product activity: massively increased Recessive/Semi-dominant/Dominant: semi-dominant or dominant Neomorph Property: relatively rare Typical mutation: translocation Gene product activity: different, or same but in different location Recessive/Semi-dominant/Dominant: semi-dominant or dominant