Comparative analysis of N-acetylation polymorphism in humans as determined by phenotyping and genotyping

The N-acetylation polymorphisms of volunteers from the Moscow population analyzed by phenotyping and genotyping have been compared. The ratios between the proportions of fast acetylators (FAs) and slow acetylators (SAs) estimated by phenotyping and genotyping do not differ significantly from each other (47 and 44%, respectively). The absolute acetylation rate widely varies in both FAs and SAs. The NAT2 genotype and allele frequencies in the population sample have been calculated. The most frequent alleles are NAT2*4 (a “fast” allele), NAT2*5, and NAT2*6 (“slow” alleles); the most frequent genotypes are NAT2*5/*5, NAT2*4/*6, and NAT2*4/*5. Comparative analysis of N-acetylation polymorphism estimated by phenotyping and genotyping in the same subjects has shown a complete concordance between the phenotype and genotype in only 62 out of 75 subjects (87%). Comparative characteristics and presumed applications of the two approaches (quantitative estimation of acetylation rate and qualitative determination of the acetylator genotype) to the identification of individual acetylation status are presented.     

Analysis of NAT2 point mutations with biological microchips

The NAT2 product, N-acetyltransferase 2, is involved in biotransformation and detoxification of several aromatic amines (in particular, 2-aminofluorene, 4-aminobiphenyl, and 4-naphthylamine), which are strongly mutagenic and carcinogenic, and acetylates some drugs, affecting their metabolism. A biological microchip was developed to detect 16 point mutations, which determine 36 alleles and 660 genotypes of NAT2. The genotypes can be divided into four groups according to the acetylator phenotype: groups with rapid (R/R), intermediate (R/S), or slow (S/S) acetylation and a group combining intermediate and slow alleles (“R/S or S/S”). The last group includes the alleles determined by combinations of seven mutations (191G/A, 282C/T, 341T/C, 481C/T, 590G/A, 803A/G, and 857G/A), whose cis or trans position is detectable by restriction enzyme analysis. The NAT2 genotype was unequivocally established for 37 out of 71 DNA specimens, while the other 34 specimens were characterized by more than two genotypes. By the acetylator phenotype, 16 out of the 34 genotypes were assigned to the group “R/S or S/S,” combining mutations 282C/T, 341T/C, 481C/T, 590G/A, and 803A/G. Thus, the biochip allows primary analysis of most NAT2 polymorphic substitutions, the acetylator genotype being important to know in predictive medicine and individualized therapy.     

Population analysis and determination of the ethnic background are necessary in the study of multifactorial diseases: A study using the Dagestan population as a model

Psoriasis, a multifactorial disease with genetic predisposition, has been used as an example to study the role of the ethnic background in multifactorial diseases in the Dagestan population. The individual information card (IIC) is proposed as the main tool for correct collection and processing of information. The results of the study demonstrate that the Dagestan population is a convenient and adequate model population for studying multifactorial diseases, such as psoriasis, and may serve as an object for studying the role of heredity in the etiologies and pathogeneses of this and other multifactorial diseases.     

Comparative analysis of N-acetylation polymorphism in humans as determined by phenotyping and genotyping

The N-acetylation polymorphisms of volunteers from the Moscow population analyzed by phenotyping and genotyping have been compared. The ratios between the proportions of fast acetylators (FAs) and slow acetylators (SAs) estimated by phenotyping and genotyping do not differ significantly from each other (47 and 44%, respectively). The absolute acetylation rate widely varies in both FAs and SAs. The NAT2 genotype and allele frequencies in the population sample have been calculated. The most frequent alleles are NAT2*4 (a "fast" allele), NAT2*5, and NAT2*6 ("slow" alleles); the most frequent genotypes are NAT2*5/*5, NAT2*4/*6, and NAT2*4/*5. Comparative analysis of N-acetylation polymorphism estimated by phenotyping and genotyping in the same subjects has shown a complete concordance between the phenotype and genotype in only 62 out of 75 subjects (87%). Comparative characteristics and presumed applications of the two approaches (quantitative estimation of acetylation rate and qualitative determination of the acetylator genotype) to the identification of individual acetylation status are presented.     

The Morphogenetic Potential of Transgenic Tobacco Plants Expressing Genes of Bacterial Glucanases with Distinct Substrate Specificity

The expression of the bacterial gene for thermostable -1,3-glucanase in transgenic tobacco plants was shown to induce substantial changes in plant morphogenetic potential, whereas the expression of -1,3; 1,4-glucanase did not affect essentially plant morphogenesis. Our results permit the suggestion that the expression of bacterial -1,3-glucanase in plants elevated the level of endogenous auxin.     

Morphology and Phytohormone Content in Transgenic Tobacco Plants Expressing Bacterial Thermostable Cellulase

Expression of the bacterial gene for thermostable -1,4-glucanase (cellulase) from Clostridium thermocellum in transgenic tobacco plants was shown to produce significant changes in tobacco plant structure and activities. The transgenic plants differed in their growth rate and morphology, and their hormonal status was affected. Thus, the transgenic plants expressing the gene for thermostable bacterial cellulase are a convenient model to study the role of -1,4-glucanases in plant physiological processes.     

Preparation and Properties of Clostridium thermocellum Lichenase Deletion Variants and Their Use for Construction of Bifunctional Hybrid Proteins

Major properties (pH and temperature optimum, stability) of lichenase (b-1,3-1,4-glucanase) deletion variants from Clostridium thermocellum were comparatively studied. The deletion variant LicBM2 was used to create hybrid bifunctional proteins by fusion with sequences of the green fluorescent protein (GFP) from Aequorea victoria. The data show that in hybrid proteins both GFP and lichenase retain their major properties, namely, GFP remains a fluorescent protein and the lichenase retains activity and high thermostability. Based on the results of this investigation and results that have been obtained earlier, the use of the deletion variants of lichenase and the bifunctional hybrid proteins as reporter proteins is suggested.     

Exploring the properties of thermostable Clostridium thermocellum cellulase CelE for the purpose of its expression in plants

The main properties (pH and temperature range, stability, substrate specificity) of the modified cellulase CelE (endo--1,4-glucanase) from Clostridium thermocellum have been analyzed with the goal of its expression in plants. The modified enzyme is similar to plant cellulases. Deletions in the N-terminus of the enzyme do not affect its biochemical properties. Based on the present investigation, we conclude that the modified -1,4-glucanase CelEM1, when expressed in plants, will be a good model to study the role of cellulases in plants.     

Integrated network analysis of transcriptomic and proteomic data in psoriasis

Background  

Psoriasis is complex inflammatory skin pathology of autoimmune origin. Several cell types are perturbed in this pathology, and underlying signaling events are complex and still poorly understood.     

A comparative analysis of the molecular genetic processes in the pathogenesis of psoriasis and Crohn’s disease

Molecular Biology - A comparative bioinformatics analysis of the molecular genetic processes in the pathogenesis of multifactorial diseases—psoriasis and Crohn’s disease—was...