Discriminant analysis of prion sequences for prediction of susceptibility

Prion diseases, including ovine scrapie, bovine spongiform encephalopathy (BSE), human kuru and Creutzfeldt-Jakob disease (CJD), originate from a conformational change of the normal cellular prion protein (PrPC) into abnormal protease-resistant prion protein (PrPSc). There is concern regarding these prion diseases because of the possibility of their zoonotic infections across species. Mutations and polymorphisms of prion sequences may influence prion-disease susceptibility through the modified expression and conformation of proteins. Rapid determination of susceptibility based on prion-sequence polymorphism information without complex structural and molecular biological analyses may be possible. Information regarding the effects of mutations and polymorphisms on prion-disease susceptibility was collected based on previous studies to classify the susceptibilities of sequences, whereas the BLOSUM62 scoring matrix and the position-specific scoring matrix were utilised to determine the distance of target sequences. The k-nearest neighbour analysis was validated with cross-validation methods. The results indicated that the number of polymorphisms did not influence prion-disease susceptibility, and three and four k-objects showed the best accuracy in identifying the susceptible group. Although sequences with negative polymorphisms showed relatively high accuracy for determination, polymorphisms may still not be an appropriate factor for estimating variation in susceptibility. Discriminant analysis of prion sequences with scoring matrices was attempted as a possible means of determining susceptibility to prion diseases. Further research is required to improve the utility of this method.

Protein Backbone Torsion Angle-Based Structure Comparison and Secondary Structure Database Web Server

Structural information has been a major concern for biological and pharmaceutical studies for its intimate relationship to the function of a protein. Three-dimensional representation of the positions of protein atoms is utilized among many structural information repositories that have been published. The reliability of the torsional system, which represents the native processes of structural change in the structural analysis, was partially proven with previous structural alignment studies. Here, a web server providing structural information and analysis based on the backbone torsional representation of a protein structure is newly introduced. The web server offers functions of secondary structure database search, secondary structure calculation, and pair-wise protein structure comparison, based on a backbone torsion angle representation system. Application of the implementation in pair-wise structural alignment showed highly accurate results. The information derived from this web server might be further utilized in the field of ab initio protein structure modeling or protein homology-related analyses.

Comparative study of codon substitution patterns in foot-and-mouth disease virus (serotype O)

We compared genetic variations in the VP1 gene of foot-and-mouth disease viruses (FMDVs) isolated since 2000 from various region of the world. We analyzed relative synonymous codon usage (RSCU) and phylogenetic relationship between geographical regions, and calculated the genetic substitution patterns between Korean isolate and those from other countries. We calculated the ratios of synonymously substituted codons (SSC) to all observed substitutions and developed a new analytical parameter, EMC (the ratio of exact matching codons within each synonymous substitution group) to investigate more detailed substitution patterns within each synonymous codon group. We observed that FMDVs showed distinct RSCU patterns according to phylogenetic relationships in the same serotype (serotype O). Moreover, while the SSC and EMC values of FMDVs decreased according to phylogenetic distance, G + C composition at the third codon position was strictly conserved. Although there was little variation among the SSC values of 18 amino acids, more dynamic differences were observed in EMC values. The EMC values of 4- and 6-fold degenerate amino acids showed significantly lower values while most 2-fold degenerate amino acids showed no significant difference. Our findings suggest that different EMC patterns among the 18 amino acids might be an important factor in determining the direction of evolution in FMDV.

Comparative study of codon substitution patterns in foot-and-mouth disease virus (serotype O)

We compared genetic variations in the VP1 gene of foot-and-mouth disease viruses (FMDVs) isolated since 2000 from various region of the world. We analyzed relative synonymous codon usage (RSCU) and phylogenetic relationship between geographical regions, and calculated the genetic substitution patterns between Korean isolate and those from other countries. We calculated the ratios of synonymously substituted codons (SSC) to all observed substitutions and developed a new analytical parameter, EMC (the ratio of exact matching codons within each synonymous substitution group) to investigate more detailed substitution patterns within each synonymous codon group. We observed that FMDVs showed distinct RSCU patterns according to phylogenetic relationships in the same serotype (serotype O). Moreover, while the SSC and EMC values of FMDVs decreased according to phylogenetic distance, G + C composition at the third codon position was strictly conserved. Although there was little variation among the SSC values of 18 amino acids, more dynamic differences were observed in EMC values. The EMC values of 4- and 6-fold degenerate amino acids showed significantly lower values while most 2-fold degenerate amino acids showed no significant difference. Our findings suggest that different EMC patterns among the 18 amino acids might be an important factor in determining the direction of evolution in FMDV.

Genetic Association between Eotaxin Genes and Asthma and Its Relationship to Birth Season in Korean Children

Asthma is a chronic disease associated with airway constriction due to inflammation caused by eosinophils, mast cells, and T lymphocytes, leading to serious chronic illness in children. The eotaxin gene family has been shown to play an important role in the pathogenesis of asthma. We hypothesized that the distinctive variations among the four seasons in Korea may affect the expression of eotaxin polymorphisms, especially in children. We examined the possible effects of birth season (spring, March-May; summer, June-August; fall, September-November; and winter, December-February) on the phenotype of asthma in children. All SNP data sets of the eotaxin-2 and eotaxin-3 genes were collected from 78 asthma patients and 101 controls. Here, we investigated the effects of birth season on the expression of eotaxin-2 and eotaxin-3 in Korean children. Using the HAPLOTYPE procedure with the HTR method in SAS/Genetics, we showed that children born in spring and summer show significant haplotypes in both the eotaxin-2 and eotaxin-3 genes. Thus, the expression of polymorphisms in eotaxin-2 and eotaxin-3 may vary by season.