What is the first mechanism of autosomal dominant disorders?

• A. Haploinsufficiency
• B. Loss-of-function mutations
• C. Dominant negative mutations
• D. Polygenic inheritance

Answer: (A)

The first mechanism of autosomal dominant disorders is haploinsufficiency. In this context, haploinsufficiency occurs when a single functional copy of a gene is insufficient to maintain normal function. This typically happens when one allele of a gene is mutated or deleted, resulting in a situation where only 50% of the required gene product is produced. In many cells and tissues, this reduced level of gene product can lead to a phenotype that is characteristic of the disorder.

This mechanism is crucial to understanding conditions like certain types of muscular dystrophy or some familial hypercholesterolemia cases, where the loss of function from one allele leads to significant health consequences despite the presence of the normal allele. Haploinsufficiency highlights the importance of gene dosage for normal biological function and illustrates one way in which autosomal dominant disorders can arise simply due to the lack of sufficient gene product.

Other mechanisms, such as loss-of-function mutations and dominant negative mutations, can also contribute to autosomal dominant disorders, but they generally function when there’s a specific alteration in the protein's function or activity rather than a direct issue of gene dosage, which is the core concept of haploinsufficiency. Polygenic inheritance, on the other hand, refers to traits