Dominant mutations can be categorized according to whether they increase or decrease the overall activity of a gene or gene product. Although a loss-of-function mutation (a mutation that inactivates the gene product) is usually recessive, for some genes, one dose of the normal gene product, encoded by the normal allele, is not sufficient to produce a normal phenotype. In this case, a loss-of-function mutation in the gene will be dominant, and the gene is said to be haploinsufficient. A second category of dominant mutation is the gain-of-function mutation, which results in a new activity or increased activity or expression of a gene or gene product. The gene therapy technique currently being used in clinical trials involves the 'addition' to somatic cells of a normal copy of a gene. In other words, a normal copy of the gene is inserted into the genome of the mutant somatic cell, but the mutated copy of the gene is not removed or replaced. Will this strategy work for either of the two aforementioned types of dominant mutations?

Key Concepts

Haploinsufficiency

Haploinsufficiency occurs when a single functional copy of a gene is insufficient to maintain normal function, leading to a dominant phenotype. In this scenario, a loss-of-function mutation in one allele results in a phenotype that is expressed even in the presence of a normal allele. This concept is crucial for understanding how certain genetic disorders can manifest despite having one normal gene copy.

Gain-of-Function Mutations

Gain-of-function mutations lead to an increase in the activity or expression of a gene product, often resulting in a dominant phenotype. These mutations can create new functions or enhance existing ones, which can contribute to various diseases, including cancers. Understanding this concept is essential for analyzing how certain mutations can lead to abnormal cellular behavior.

Gene Therapy

Gene therapy involves introducing a normal copy of a gene into somatic cells to compensate for a mutated gene, aiming to restore normal function. This technique is particularly relevant for conditions caused by loss-of-function mutations. However, its effectiveness can vary depending on whether the mutation is haploinsufficient or a gain-of-function mutation, as the underlying mechanisms differ significantly.