title: Mutational Spectrum Analysis of Neurodegenerative Diseases and Its Pathogenic Implication.
abstract: 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.
authors.affiliation: Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Shandong University of Technology, Zibo 255049, China. shen@sdut.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Shen
authors.affiliation: Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Shandong University of Technology, Zibo 255049, China. jhf@sdut.edu.cn.
authors.forename: Hong-Fang
authors.initials: HF
authors.lastname: Ji
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011487:Protein Conformation
keywords: conformation change; distribution pattern; mutation; neurodegenerative diseases; pathogenesis