Satellite DNA forms large arrays within heterochromatic regions of chromosomes and constitutes an essential part of the «non-coding landscape» of eukaryotic genomes. Experimental data suggest that non-coding RNAs transcribed from satellite DNA, are strand- and tissue-specific, and its transcription depends on the cell type, cell cycle, cell differentiation and stage of development. It can be induced by various stress effect and cancerogenesis. Transcripts of satellite DNA which can be associated with the processes of implantation and regulation of the embryonic genome during early human development are of interest. The article covers general organization of the human satellite DNA, literature data on transcription of the satellite DNA and function of synthesized transcripts. Our own data on the transcriptional activity of satellite 3 of the chromosome 1 in the embryonic and extraembryonic human tissues are included.

Present study analyzes the methylation index of the imprinted genes GNAS ( NESP55 ) and GRB10 in the group of first trimester spontaneous abortions with normal karyotype. The DNA samples derived from extraembryonic mesoderm of 47 spontaneous abortions and 45 induced abortions were examined. A significant increase in the methylation index of the imprinted gene NESP55 and a decrease in GRB10 in the spontaneous abortions were observed. Based on the function of this imprinted genes, it can be assumed that an increase in the methylation index of the NESP55 gene and its decrease in GRB10 could enhance the suppression of embryo growth and lead to a possible disturbance of embryo development.

Rationale. Atherosclerosis is a complex age-dependent disease developed under contribution of epigenetic factors. Decreasing of global DNA methylation, estimated by methylation level of retrotransposon LINE-1 in blood leukocytes is associated with a risk of complications of atherosclerosis, but epigenetic status of LINE-1 in the lesion of artery wall is under-investigated. Aim. Analysis of the global DNA methylation variability (using methylation level of LINE-1) in human blood cells and carotid arteries in atherosclerosis. Materials and methods. Quantification of LINE-1 methylation level in match pairs of carotid arteries affected by atherosclerosis and blood leukocytes collected from patients (n = 92), as well as in white blood cells of the same-aged healthy individuals (n = 60) was performed using bisulfite pyrosequencing. Results. Global DNA methylation estimated as LINE-1 methylation level was lower in blood leukocytes of patients with advanced carotid atherosclerosis (66.2%) in comparison with healthy individuals (68.2%; p<0.05). Further decrease of LINE-1 methylation level was observed in cells of carotid atherosclerotic lesions compared to matched samples of blood leukocytes (64.8% vs. 66.2%, respectively, p<0.05). LINE-1 methylation level was negatively correlated with the chronological age of healthy individuals, as well as with the body mass index and the atherogenic index of both healthy individuals and patients with advanced carotid atherosclerosis. Conclusion. The decrease of global DNA methylation estimated as hypomethylation of LINE-1 in blood leukocytes and arterial cells was associated with advanced carotid atherosclerosis and its risk factors.

Introduction. Prostate cancers belong to the high-spread tumors among men. Objectives: The purpose of the study was to investigate Brn-3a, AR, ERa expression in prostate cancer tissues in association with AKT/mTOR signaling pathway activation, cancer invasion and grade. Materials and methods: 50 patients with locally advanced cancer of the prostate were included in the study. Expression of Brn-3a, AR, ERa, components of AKT/m-TOR signaling pathway was determined by RT-PCR. Results. Overexpression of Brn-3a was found in prostate cancer tissues, which was accompanied by high level of ERa mRNA. Activation of AKT/m-TOR signaling pathway was revealed in cancers. It was noted that the invasion of tumor was associated with high expression of ER, AR, PTEN as well as decreased mRNA level of m-TOR. The low activity of AKT/m-TOR signaling pathway was revealed in least-differentiated tumors. Decrease of AKT, GSK-3b expression and increase of 4E-BP1 happened in least-differentiated tumors compared to well-differentiated tumors (Gleason score 6-7). The altered protein kinase expression was associated with overexpression of PTEN. Conclusion. These data, reflecting the biological features of cancers, are the molecular pattern of prostate tumors progression.

Each hundredth newborn has a heart defect, and it is the cause of infant mortality in 10% of cases. Genetic changes can become the basis for the occurrence of cardiovascular anomalies. The part of patients with congenital heart defects (CHD) and extracardiac pathology have pathogenic copy number variations. In the present study 15 patients aged 1 month to 4 years, who underwent operative treatment for CHD, were examined using high-resolution DNA microarrays SurePrint G3 Human Genome CGH Microarray Kit, 8х60K. All patients had an extracardiac pathology. Seven out of 15 (46%) children had pathogenic and probably pathogenic copy number variations: 4 patients - microdeletion syndrome 22q11.2, one - microdeletion syndromes 7q11.23, microdeletion 1p36, microduplication at the 20p13. Thus, aCGH has a high diagnostic power in detecting genomic imbalance in children with CHD and extracardiac pathology.

It is expected that copy number variation (CNV) potentially contribute to the formation of a genetic structure of complex diseases thus they would explain a part of the missing heritability. However, a search for CNV in patients with coronary heart disease (CHD) using high-resolution technique of array comparative genome hybridization (aCGH) has not previously been conducted. The goal of our study was to evaluate CNV spectrum and characteristics in patients with CHD using aCGH. The CNV screening was performed using high-resolution microarrays SurePrint G3 Human CGH + SNP 2x400 K (Agilent Technologies). The DNA samples were obtained from peripheral blood leukocytes of men with CHD (n = 10). Agilent Euro male DNA was used as a reference. We identified 90 CNV, among them 72 (80%) contained genes encode proteins related to the immune and inflammatory response, activity of olfactory receptors and metabolic enzymes. Genes mapped in the CNV region in the 1p22.2 ( GBP3 ), 1p21.1 ( AMY2B ) and 22q11.23 ( GSTT1 , LOC391322 ), were previously reported as associated with atherosclerosis and its risk factors.

The roles of genetic polymorphisms in the pathogenesis of recurrent miscarriage (RM) have been intensively studied. The main problems of active search for genetic predictors RM has become the phenomenon of «missing heritability». Complex diseases, including miscarriage are believed to have a polygenic basis and gene-gene interactions can play a significant role in the etiology of the disease. Gene-gene interactions can be a source of RM «missing heritability». This study was conducted to investigate the association of gene-gene interaction of angiogenesis and endothelial dysfunction genes polymorphisms and RM. It is shown that alleles of the 677T gene of the MTHFR gene, 894T of the NOS3 gene, genotypes of the 936CT and 936TT of the VEGF gene are associated with a predisposition to this pathology in the Russian ethnic group. The significant role of additive and epistatic effects in the intergenic interactions of the polymorphic variants of the SERPINE-1, ACE, NOS3, MTHFR , and VEGF genes to recurrent miscarriage susceptibility has been demonstrated. It has been shown that the analysis of a combination of genotypes of several allelic variants is more informative in assessing the risk of developing miscarriage than an association analysis at the level of single polymorphic markers.

Fibrotic processes that occur in different organs and tissues and that lead to the formation of organ failure are characterized by many shared features. However, the pathogenic significance and the genetic component determining the fibrogenesis in various pathological states can have both shared and brightly expressed specific features. The aim of our study was to assess the similarity and specificity of the genetic components of susceptibility to diseases that characterized by fibrotic transformation of various organs: kidneys in diabetes mellitus type 1 (T1D) and liver in chronic hepatitis C (HCV). The group of patients with HCV included 184 persons (71% men and 29% women; mean age 40.2 ± 13.9 years old). The group of patients with T1D included 285 patients (47% men and 53% women; mean age 25.27 ± 12.6 years old). The population-based controls consisted of 285 persons (54% men and 46% women, mean age 56.7 ± 8.4 years old). Genotyping of 48 SNPs was performed using mass spectrometry on the Sequenom MassARRAY® tool (USA). Statistical data analysis was performed in the software environment R using the standard package «stats». We found that the T1D predisposing genotype was «AA» of rs3765124 of ADAMDEC1 gene (OR = 1.52(1.01-2.28), p = 0.004); «TT» of rs1007856 of ITGB5 gene (OR = 1.86(1.20-2.90), p = 0,040); «CC» of rs20579 of LIG1 gene (OR = 1.86(1.20-2.90), p = 0.008); «GG» of rs1143674 of ITGA4 gene (OR = 2.06 (1.29-3.29), p = 0.002); «AA» of rs679620 of MMP3 gene (OR = 2.03 (1.19-3.47), p = 0.008); the allele «C» of rs12980602 of IFNL2 gene (OR = 1.49 (1.04-2.14), p = 0.029) and allele «C» rs4986819 of the PARP4 gene (OR = 1.52 (1.01-2.28), p = 0.044). Comparison of the obtained results with the data on the frequency of studied SNPs in patients with HCV showed that SNPs of ADAMDEC1 (rs3765124), ITGB5 (rs1007856), MMP3 (rs679620) and LIG1 (rs20579) were the shared markers that contribute to predisposition to HCV and T1D. Associations were unidirectional, because the same alleles and genotypes contribute to the risk of as HCV and T1D. Diseases accompanied by fibrotic transformation of various organs characterized by the presence of shared components among the entire genetic landscape that determines the susceptibility to these pathologies. Among the number of shared genes contributing to the development of HCV and T1D, the protein products of genes ADAMDEC1 , ITGB5 and MMP3 are involved in the metabolism of the extracellular matrix and directly in the processes of fibrogenesis.

Despite the high frequency of early pregnancy losses in human embryo development, copy number variations (CNVs), as one of the possible causes of miscarriage, are insufficiently explored. The present study is aimed to search for copy number variations (CNVs) in euploid anembryonic pregnancies and missed abortions. The 29 samples of extraembryonic tissues from anembryonic pregnancies and 18 samples of extraembryonic mesoderm from missed abortions were analysed using array comparative genomic hybridization (CGH) on high-resolution microarrays. Copy number variations were detected in both experimental groups but their total number in anembryonic pregnancies (299 CNVs) were significantly higher than in the group of missed abortions (132 CNVs). Several CNVs were selectively verified using real-time PCR. The predominance of microdeletions in anembryonic pregnancies is noteworthy. Nineteen (54.3%) potentially pathogenic microdeletions and 16 (45.7%) microduplications were found in anembryonic pregnancies while there were only microduplications in the group of observed missed abortions.

The clinical description of a rare hereditary metabolic disease of an amino acid 3-hydroxy-3 methylglutaric aciduria is presented, which belonging to the group of organic aciduria and determined by a deficiency of the mytochondrial enzyme 3-hydroxy-3-methylglutaryl CoA lyase. The disease manifested on the third day of life with tonic convulsions with a violation of acid-base indicators. Against the backdrop of medical correction in the intensive care unit and within 36 hours, the patient’s condition was stabilized, the convulsions were stopped. Tandem mass spectrometry was performed, an elevated level of 3-hydroxy-isovaleryl-2-methyl-3-hydroxybutylarnitine was found in the blood. Determination of organic acids in the patient’s urine showed an increase in the concentrations of dicarboxylic acids, which is characteristic for the hereditary metabolic disease of 3-hydroxy-3 methylglutar aciduria. Partial analysis of the exon 5 HMGCL gene determined the mutation NM_00019 c.C392TS131L in the homozygous state, not previously described in the literature. Father and mother of the proband heterozygous state mutation is found. The family received recommendations for prenatal diagnosis based on molecular genetic diagnosis.