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?

Verified step by step guidance

1. Understand the two types of dominant mutations described in the problem: haploinsufficiency (loss-of-function mutation where one normal allele is insufficient for a normal phenotype) and gain-of-function mutation (mutation that increases or alters the activity of the gene product).
2. Consider the gene therapy strategy mentioned: adding a normal copy of the gene to somatic cells without removing or replacing the mutated copy. This means the mutant allele remains present in the genome.
3. For haploinsufficient mutations, analyze whether adding a normal copy of the gene would restore the phenotype. Since haploinsufficiency arises from insufficient gene product, adding a normal copy could potentially increase the gene product to a sufficient level, thereby restoring the normal phenotype.
4. For gain-of-function mutations, evaluate whether adding a normal copy of the gene would counteract the effects of the mutant allele. Gain-of-function mutations typically result in a dominant phenotype due to the abnormal activity of the mutant allele, and simply adding a normal copy would not negate the effects of the mutant allele.
5. Conclude that the gene therapy strategy might work for haploinsufficient mutations but is unlikely to be effective for gain-of-function mutations, as the latter requires a different approach, such as silencing or removing the mutant allele.

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 behaviors.

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 of these mutations influence treatment outcomes.