Mutational Spectrum Analysis of Neurodegenerative Diseases and Its Pathogenic Implication

One of the most conspicuous features of neurodegenerative diseases (NDs) is the occurrence of dramatic conformation change of individual proteins. We performed a mutational spectrum analysis of disease-causing missense mutations in seven types of NDs at nucleotide and amino acid levels, and compared the results with those of non-NDs. The main findings included: (i) The higher mutation ratio of G:C→T:A transversion to G:C→A:T transition was observed in NDs than in non-NDs, interpreting the excessive guanine-specific oxidative DNA damage in NDs; (ii) glycine and proline had highest mutability in NDs than in non-NDs, which favor the protein conformation change in NDs; (iii) surprisingly low mutation frequency of arginine was observed in NDs. These findings help to understand how mutations may cause NDs.