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How do nonsense mutations become fatal factors? A genetic story you can't miss!
In human genetics, nonsense mutation is a mutation that leads to the formation of an early stop code (stop codon). This mutation can cause the transcribed mRNA to terminate translation prematurely, thereby producing an incomplete protein. According to the latest research, nonsense mutations do not necessarily cause harm in some cases. The extent of their impact depends on where the mutation occurs and the impact on the function of the corresponding protein.
About 10% of patients with gene-related diseases are directly related to nonsense mutations. Common diseases include Duchenne muscular dystrophy, cystic fibrosis and certain cancers.
What characterizes these nonsense mutations is that they are located at specific positions in the mRNA that are critical to the function and structure of the protein. For example, if a nonsense mutation occurs close to the initial stop code, the mutation may have less impact on the function of the protein. On the contrary, if the mutation occurs in a more computationally critical region, it will cause the protein to fail to structure normally. , thereby affecting the biological processes of cells.
Different results of nonsense mutations
Harmful consequences
Nonsense mutations mostly exhibit deleterious consequences and are the most common observation in the natural environment. Such mutations tend to reduce an organism's fitness and chances of reproductive success.
For example, if nonsense mutations occur in genes that control important protein synthesis, they may cause structural or functional defects, thereby affecting the survival of organisms.
Neutral vs. beneficial results
In addition, not all nonsense mutations are deleterious. In some cases, their effects may be neutral, meaning the change does not significantly affect the organism's overall health or function. More rarely, nonsense mutations can trigger beneficial outcomes, such as improving an organism's adaptations if the mutation stops the production of certain toxic proteins.
How to suppress the impact of nonsense mutations
Many biological mechanisms help cope with the damage caused by these mutations. An example is the nonsense-mediated mRNA degradation system, which effectively degrades mRNAs containing nonsense mutations to avoid the production of non-functional proteins during translation.
Disease-related nonsense mutations
According to research, nonsense mutations account for approximately 20% of single nucleotide substitutions that cause human diseases. Currently known diseases include cystic fibrosis, beta-thalassemia, and others.
For example, the G542X mutation in cystic fibrosis is a nonsense mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene.
Treatment for nonsense mutation diseases
Current therapeutic strategies for diseases related to nonsense mutations include reducing the effects of NMD and promoting the process of bypassing early stop codes during translation. Certain small molecule drugs, such as amikacin and Ataluren, have been shown to promote the "reading" of false termination codes.
Ataluren has been approved in some areas for the treatment of Duchenne muscular dystrophy, but it has not met the main indicators in clinical trials for cystic fibrosis, which has caused continued concern in the field of disease treatment.
The significance of nonsense mutations in genetics cannot be ignored. They not only affect the function of proteins themselves, but also trigger many thoughts about genetic diseases and their potential treatments. Have you ever thought that nonsense mutations might be an opportunity for future gene therapy?
