Question

The importance of the translational molecular machinery to insert the correct amino acid into the primary structure of a polypeptide is of paramount importance to ensure the fidelity of the code. Part of the reason why this process is so accurate is due to the action of tRNA amino-acyl synthetase (ARSs) enzymes. Mutations within the genes for ARSs, are known to cause certain human maladies, such as the neurodegenerative disorder Charcot-Marie-Tooth (CMT) disease along with other central nervous system dysfunctions, and cancer. Interestingly, not all those who possess mutations within specific ARS genes do not display the disease phenotype. Provide at least one reason why a person might survive. Remember, do not just name a concept. Describe the concept and then explain WHY (on a molecular level) this explanation holds true.

Answer 1

The CMT disease is a special case between genetic diseases and this is because even though CMT is always related to mutations in ARS, it appears with not only one spcific mutation. Different muations in different ARS genes lead to the development of CMT. Some of this mutations lead to a type of CMT that are inherited in an autosomal dominant manner, and some others are autosomal recessive. That's why it is possible to be carrying a mutation for CMT and not really be showing the associated phenotype.

Some dominant types are: 2N, 2D, 2W

The type B is inherited in a recessive manner.

At molecular level, the recessive mutations work by being loss of function traits. The mutated gene stops producing functional proteins but the other copy of the gene located in the homologous chromosome is healthy and produces the correct protein, thus the function is covered by the other copy. Only the failure of the 2 copies will bring the disease expression.

For the dominant muations, the phenomenon occurs because the mutated genes produce mutated proteins that show an unexpectedly high activity for amino acylation but, since they are wrongly produced due to the mutation, they do a wrong job, thus affecting translation mechanism accuracy. We could say the mutated proteins compete with the wildtype proteins