ABSTRACT
Psoriatic and atherosclerotic plaques were examined using the real-time polymerase chain reaction. Expression of the FOSL1 gene proved to substantially increase in both psoriatic lesions of the skin and atherosclerotic lesions of vessels as compared with nonlesion samples.
Subject(s)
Atherosclerosis/genetics , Gene Expression , Proto-Oncogene Proteins c-fos/genetics , Psoriasis/genetics , Adult , Atherosclerosis/pathology , Blood Vessels/metabolism , Blood Vessels/pathology , Humans , Male , Middle Aged , Polymerase Chain Reaction , Psoriasis/pathology , Skin/metabolism , Skin/pathology , Young AdultABSTRACT
The comparative bioinformatic analysis of psoriasis and Crohn disease pathological processes was carried out using the results of microarray experiments deposited in GEO DataSets database. Several common for both pathologies genes and molecular-genetical processes were found. It is suggested that some transcriptional factors including AP-1 system of transcriptional factors are involved in pathological processes both under psoriasis and Crohn disease.
Subject(s)
Chromosomes, Human/genetics , Crohn Disease/genetics , Databases, Genetic , Transcription Factor AP-1/genetics , Crohn Disease/physiopathology , Humans , PsoriasisABSTRACT
Psoriasis was used as a model to analyze the pathogenetic pathways of immune-mediated inflammatory diseases, and the results of bioinformatic, molecular-genetic and proteomic studies are provided. Cell mechanisms, common for the pathogenesis of psoriasis, as well as Crohn's disease, are identified. New approaches for immune-mediated diseases are discussed.
ABSTRACT
The product of gene NAT2 (N-acetyltransferase 2) is involved in the biotransformation system and participates in detoxication of some arylamine derivatives (in particular 2-aminofluorene, 4-aminobiphenyl and 4-naphthylamine) which are strongly mutagenic and carcinogenic. It also renders toxicological and pharmacological influence on a metabolism of medical products metabolized by the enzyme. We developed a microchip for detection of 16 functionally significant mutations coding 36 alleles of gene NAT2. Combinations of these alleles allow us to reveal more than 660 genotypes, which can be divided into four groups according acetylation phenotype: "fast" (R/R), "intermediate" (R/S), "slow" (S/S) and group with average or slow acetylating (R/S or S/S) alleles. The groups "R/S or S/S" include alleles, formed by a combination of 7 mutations (191G/A, 282C/T, 341T/C, 481C/T, 590G/A, 803A/G, 857G/A), theirs cis-trans position can be revealed by restriction analysis. In 37 of 71 DNA samples we unequivocally defined NAT2-genotypes, and other 34 samples have been characterized by more than two genotypes. 16 samples out of 34 had acetylation phenotype of group "R/S or S/S", which is characterized by the following combination of mutations: 282C/T, 341T/C, 481C/T, 590G/A and 803A/G. Thus, the developed biochip is a convenient screening method for primary detection of the majority of polymorphic replacements in gene NAT2.
Subject(s)
Arylamine N-Acetyltransferase/genetics , DNA Mutational Analysis/methods , Oligonucleotide Array Sequence Analysis , Point Mutation , Gene Frequency , Humans , Polymorphism, GeneticABSTRACT
Psoriasis is an autoimmune multifactorial dermatological disease frequently occured in European population. As for other multifactorial genetic diseases success in psoriasis treatment may be achieved due to determination of molecular genetic mechanisms of pathogenesis triggering and psoriasis candidate genes and proteins searching as targets for drugs. Using bioinformatic analysis of transcriptome data AP-1 transcriptional factor components were revealed as psoriasis candidate genes.
Subject(s)
Genetic Predisposition to Disease , Psoriasis/genetics , Transcription Factor AP-1/metabolism , Gene Expression Profiling , Humans , Psoriasis/metabolism , Transcription Factor AP-1/geneticsABSTRACT
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.
Subject(s)
Ethnicity/genetics , Genetics, Population/methods , Multifactorial Inheritance/genetics , Psoriasis/ethnology , Psoriasis/genetics , Dagestan , Genetic Predisposition to Disease , Humans , Models, GeneticABSTRACT
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.
Subject(s)
Arylamine N-Acetyltransferase/genetics , Polymorphism, Genetic , Acetylation , Gene Frequency , Genotype , Humans , PhenotypeABSTRACT
The review is dedicated to molecular-and-genetic aspects of psoriasis. The paper contains a general characterization of this skin disease and a range of hypotheses concerning its appearance, clinical manifestations, and maintenance. Its autoimmune nature with the central role played by T-cells is considered to be the basic theory of the appearance of psoriasis. According to the results of analysis of experimental data on psoriasis genetics, including family background, psoriasis is defined as a complex multigene multifactor disease, whose manifestations are determined by a combination of certain genes as well as by various environmental trigger factors. The authors consider ethnic features of psoriasis, and genes that determine predisposition to the disease. Prospects of the search of predisposition genes, including analysis of the polymorphism of unit nucleotides, are outlined in the article.
Subject(s)
Molecular Biology/methods , Psoriasis/genetics , Animals , Genetic Predisposition to Disease , Humans , Risk FactorsABSTRACT
The bacterial gene of the thermostable endo-beta-1,4-glucanase (cellulase) was shown to retain its activity and substrate specificity when expressed in transgenic tobacco plants. The leader peptide of the carrot extensin was efficient in transferring the bacterial enzyme into the apoplast. The expression of the bacterial cellulase gene leads to changes in the plant tissue morphology. In the transgenic plant lines, regeneration of primary shoots from callus occurred at the three to five times higher cytokinin (6-BAP) concentration than in control plants. The transgenic plants that expressed the bacterial gene exhibited increased business and altered leaf shape. The transgenic plants developed can be used as models for studying the cellulases role and function in plants.
Subject(s)
Cellulase/genetics , Nicotiana/genetics , Plants, Genetically Modified , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Cellulase/metabolism , Daucus carota/genetics , Enzyme Stability , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Plant , Genetic Vectors , Glycoproteins/genetics , Phenotype , Plant Leaves/anatomy & histology , Plant Proteins/genetics , Plant Shoots/drug effects , Plant Shoots/physiology , Transformation, GeneticABSTRACT
The main properties (pH and temperature range, stability, substrate specificity) of the modified cellulase CelE (endo-beta-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 beta-1,4-glucanase CelEM1, when expressed in plants, will be a good model to study the role of cellulases in plants.
Subject(s)
Carboxymethylcellulose Sodium/metabolism , Cellulase/genetics , Cellulase/metabolism , Clostridium/enzymology , Glucans/metabolism , Sequence Deletion/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Cellulase/chemistry , Clostridium/genetics , Computer Simulation , Enzyme Activation , Gene Expression/genetics , Gene Expression Regulation, Bacterial/genetics , Gene Expression Regulation, Plant/genetics , Models, Genetic , Mutation/genetics , Plants/enzymology , Plants/geneticsABSTRACT
Major properties (pH and temperature optimum, stability) of lichenase (beta-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.
