Question

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 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?

Short answer

Answer: The gene therapy technique might be effective in treating loss-of-function dominant mutations but is less likely to be effective for gain-of-function dominant mutations. This is because, in the case of gain-of-function mutations, the mutated gene will still be present and continue to produce its altered gene product, which might not be overcome by the presence of an additional normal copy.

Step-by-step solution

Understanding the gene therapy technique

The gene therapy technique mentioned involves adding a normal copy of the gene to the mutant somatic cells. In other words, this technique doesn't remove or replace the mutated copy of the gene, but simply introduces an additional normal copy.

Analyzing loss-of-function dominant mutations

In a loss-of-function dominant mutation, one copy of the normal gene product is insufficient to produce a normal phenotype. So, in this case, introducing a normal copy of the gene (through gene therapy) without removing the mutated copy might work, because the cell will now have two normal copies of the gene, which could be sufficient to produce a normal phenotype.

Analyzing gain-of-function dominant mutations

In a gain-of-function dominant mutation, the mutated copy of the gene leads to either a new activity or an increase in activity/expression of the gene or gene product. Since the gene therapy technique adds a normal copy of the gene without removing or replacing the mutated copy, this mutated gene will continue to produce its altered gene product. Thus, the presence of an additional normal copy might not be enough to override the adverse effects of the mutated gene product.

Conclusion

The gene therapy strategy that involves the addition of a normal copy of the gene without removing or replacing the mutated copy could potentially work for loss-of-function dominant mutations. However, this strategy might not be effective for gain-of-function dominant mutations, as the mutated copy of the gene will still be present and continue to produce its altered gene product.