Which mechanism of autosomal dominant disorders involves mutations that inhibit the function of normal proteins?

• A. Haploinsufficiency
• B. Dominant negative mutations
• C. Gain-of-function mutations
• D. Epistatic interactions

Answer: (B)

Dominant negative mutations are characterized by alterations in a gene that result in a protein product capable of interfering with the function of the normal protein encoded by the wild-type allele. In the context of autosomal dominant disorders, such mutations lead to a situation where the mutated protein can still form complexes with the normal protein but disrupts the function of those complexes. This interference can reduce overall functionality, leading to disease.

In contrast, haploinsufficiency occurs when a single functional copy of a gene is not sufficient to maintain normal function, resulting in a loss-of-function phenotype. While gain-of-function mutations enhance or create new functions of the protein, they do not inhibit the normal protein's function. Epistatic interactions refer to the influence of one gene over another, which does not specifically address the functional inhibition caused by a mutation within a single gene. Therefore, dominant negative mutations specifically align with the mechanism described in the question, highlighting how mutations can inhibit normal protein function in the context of autosomal dominant disorders.