Familial fatal insomnia (described in Table 24.6) is a prion disease inherited as an autosomal dominant trait. Researchers have identified the PrP gene, located on the short arm of chromosome 20, and tried to understand the relationship between the PrP gene sequence and the molecular basis of familial fatal insomnia.
A. It has been found that a rare mutation at codon 178, changing an aspartic acid to an asparagine, can cause this disease.
In addition, codon 129 seems to play a role. The human population is polymorphic at codon 129, which may encode valine or methionine. If codon 178 is the normal aspartic acid (Asp) codon, it does not seem to matter if valine or methionine is found at position 129. In other words, if codon 178 is aspartic acid, Met-129 and Val-129 codons are not associated with disease symptoms. However, if codon 178 specifies asparagine (Asn), then it does matter. Familial fatal insomnia seems to require an asparagine at codon 178 and a methionine at codon 129 in the PrP gene sequence. Suggest a possible reason why this is the case.
B. Also, researchers have compared the sequences of the PrP gene in many people with familial fatal insomnia. Keep in mind that this is a dominant autosomal trait, so people with this disorder have one mutant copy of the PrP gene and one normal copy. People with familial fatal insomnia must have one abnormal copy of the gene that contains Asn-178 and Met-129. The second copy of the gene has Asp-178, and it may have Met-129 or Val-129. Some results suggest that people having a Met-129 codon in this second copy of the PrP gene causes the disease to develop more rapidly than in people who have Val-129 in the second copy. Propose an explanation why disease symptoms may occur more rapidly when Met-129 is found in the second copy of the PrP gene.