Introduction: The study of genetic imbalance in uterine leiomyoma cells is important for understanding of the disease pathogenesis. Purpose: To study the spectrum of chromosome 1 aberrations and their frequency in non-cultured uterine leiomyoma cells depending on the presence or absence of MED12 mutations. Materials and Methods: The study was performed on 4 samples from large uterine leiomyomas (d = 7-20 cm). The spectrum of chromosome 1 aberrations was revealed by aCGH. The frequency of cells containing chromosome 1 aberrations was determined by FISH using DNA probes for 1pTEL, 1p36, 1q25. The detection of MED12 mutations in exon 2 and adjacent introns was performed by PCR-direct sequencing. Results: The chromosome 1 genetic imbalance was detected in all studied samples. No MED12 mutations were revealed in either sample. The spectrum of chromosome 1 aberrations included both deletions and duplications and was similar in all tumors. However, the cell subpopulations with different aberrations were present to different degrees among samples. In all uterine leiomyomas, cells with chromosome 1 aberrations were present by minor subpopulations, whereas cells with two copies of chromosome 1 represented major subpopulations. Conclusions: Chromosome 1 genetic imbalance is typical for uterine leiomyoma. The detected aberrations, most likely, are not leiomyoma triggers, but may have significance for tumor growth.

Background: BLM gene belongs to the RecQ helicase family and has been implicated in the maintenance of genomic stability. Homozygous and compound heterozygous BLM gene mutations cause Bloom syndrome, an inherited recessive clinical syndrome, which is characterized by chromosomal instability and a predisposition to cancer. The aim: To reveal BLM gene mutations in prostate cancer patients. Methods: We analyzed 124 DNA samples of prostate cancer patients from the Republic of Bashkortostan and used the following methods: the DNA isolation from peripheral blood by phenol-chloroform extraction; polymerase chain reaction (PCR); high resolution melting (HRM) analysis; direct sequencing. The functional significance of the mutations was analyzed using the following programs: SIFT, PolyPhen-2, Mutation Assessor, Mutation Taster, CADD. Results: We revealed 4 missence mutations (c.C1237A (p.L413I), c.A1490C (p.Q497R), c.C2603T (p.P868L), c.G3961A (p.V1321I) and several synonymous variants (с.G3102A (p.T1034T), c.C3531A (p.A1177A)) in the BLM gene.

Introduction: Copy number variations of single gene (CNVs), that have been described in patients with intellectual disability, frequently affect not only the central nervous system, but also some other systems. We and other authors have shown that isolated microdeletions and microduplcations of CNTN6 gene in patients with intellectual disability were accompanied by cranial malformations, facial dysmorphism, scoliosis, cardiological abnormalities, and seizures. However, it is unclear what underlies this effect. Aim. This work aims to search for molecular pathways and partners of CNTN6 that may regulate craniogenesis. Materials and methods. The molecular karyotyping for 117 children of 3-17 years old with developmental delay, intellectual disability and dysmorphic features was performed using 44K and 60K arrays (Agilent Technologies). The analysis of possible molecular interactions of CNTN6 and proteins encoded by genes of likely pathogenic CNVs was done by STRING gene networks. Results. Pathogenic and potentially pathogenic CNVs were found in 30 patients, among which 24 patients had skull anomalies. For three children with isolated CNTN6 mutation the Notch and CAM signaling pathways with NOTCH1 and ALCAM participating in osteogenesis appeared to be significant. When building gene networks for the 17 patients with the CNVs, affecting other chromosomal regions, with skull abnormalities (N = 11) and without them (N = 6), the involvement of CAM pathway genes was shown for one more child with skull anomaly. Notch signaling pathway was found in both groups. Conclusions. Skull anomalies in patients with CNTN6 microdeletions and microduplications are more likely mediated by CAM signaling pathway through the interaction of CNTN6 with the product of ALCAM gene

One of the key components in the development of atherosclerosis is the metabolic imbalance of lipids. However, the role of epigenetic mechanisms in this process is studied insufficiently. The aim of our study was to characterize variability of the PNPLA2 lipase gene methylation in the cells of differently localized arteries and peripheral blood leukocytes in atherosclerosis. Materials and methods. Using bisulfite pyrosequencing, we performed the assessment of DNA methylation level in atherosclerotic plaques of coronary and carotid arteries, and in the wall of unaffected internal thoracic arteries, and in peripheral blood leukocytes of patients with atherosclerosis. Statistical data analysis was performed in R software environment. Results and conclusions. Cells of coronary atherosclerotic plaques were found to have higher levels of methylation in the promoter of PNPLA2 gene compared to unaffected wall of internal thoracic arteries. Methylation level of analyzed gene region in leukocytes of patients with atherosclerosis was associated with smoking and statins.

Background. Aberrant alterations of DNA methylation patterns in tumour cells are recognised as cancer-specific markers with high potential for clinical applications. Breast cancers represent one of the most common malignancies, what necessitates the development of molecular biomarkers to improve their diagnostics. Aim. Current work aimed at DNA methylation profiling of Wnt signalling pathway components SFRP2, PYGO1 and WIF1 and testing the biomarker potential for the detection of breast cancer specimens. Materials and Methods. Bisulfite pyrosequencing was employed for DNA methylation profiling in the vicinity of transcription start sites of the candidate genes. Analytical sensitivity and specificity of cancer detection were calculated using ROC curve analysis and SPSS software package. Results. In the breast cancer specimens, DNA hypermethylation was detected within the explored regions of SFRP2 , PYGO1 and WIF1 that included 14, 5 and 7 CpG-sites, respectively. Generally, a significantly higher methylation degree was found in the cancer specimens than in the histologically normal control tissue. High sensitivity and specificity of cancer detection was achieved when considering the methylation percentages of most informative single CpG-sites as potential biomarkers, namely 88% and 94% ( SFRP2 , hereafter: sensitivity and specificity), 100% and 81% ( PYGO1 ), 81% and 88% ( WIF1 ). No significant difference in the DNA methylation degree was detected at different stages of breast cancer suggesting an early onset of aberrant DNA hypermethylation. Conclusions. Breast cancer specimens can be accurately detected by analysing the methylation degrees of single CpG-sites of the explored genes, which are of interest as potential diagnostic markers. Identification of aberrant DNA hypermethylation pattern already at the early stages of tumour progression holds promise in the context of developing epigenetics-based early diagnostics.

Relevance: TOMM40 and APOE genes are located in the same locus on chromosome 19 (19p13). The analysis of a contribution of polymorphism in these genes to variability of clinically relevant quantitative traits in healthy individuals can evaluate their contribution to cardiovascular diseases. Purpose: to study 8 SNP polymorphisms and poly-T repeat in TOMM40/APOE locus in a sample of healthy individuals and to investigate associations of the polymorphisms with quantitative characteristics of cardiovascular system. Materials and methods: rs741780, rs2075650, rs1160985, rs157580, rs8106922, rs10524523 (poly-T repeat) in TOMM40 gene and APOE: rs7259620, rs429358, rs7412 were studied in the sample of individuals without cardiovascular diseases (Tomsk, N = 183 and Kemerovo, N = 183). Genotyping was carried out with real-time PCR and the fragment analysis. The analysis of associations with quantitative traits was performed by ANOVA or Mann-Whitney and Kraskel-Wallace’s nonparametric criteria. Results: In respect of allele frequencies Russian population of West Siberia is close to other Caucasian populations. Rare alleles of rs741780 and rs1160985 were associated with lower levels of triglycerides (p = 0,031 and p = 0,044, respectively); a long allele (L) of the poly-T repeat (rs10524523) was associated with higher glucose level (p = 0,027); rs7412 contributes to the variability of the total cholesterol level (p = 0.02) and low-density lipoprotein cholesterol (p = 0.06); rs2075650 was associated with systolic blood pressure and low-density lipoprotein cholesterol in males (p = 0,026 and p = 0,002); GG genotype of the rs8106922 was associated with triglycerides in females (p = 0,036); rs429358 was associated with the total cholesterol and low-density lipoprotein cholesterol (p = 0,002 and p = 0,006). Conclusions: Polymorphisms in TOMM40/APOE locus contribute to the variability of lipid parameters, glucose level, and arterial blood pressure in Russian inhabitants of Western Siberia.

The aim of the study is to identify the role of of polymorphic variants of genes IL1b (+3953)C/T and IL8 (-251)A/T at Н.pylori -associated chronic gastritis. The study included 104 patients with superficial chronic gastritis, associated with H.pylori infection and 64 healthy patients. Discovered the dominance of homozygous genotype of IL1b (+3953) C/C in patients with SCG. The haplotype IL1b (+3953)C/C + IL8 (-251)A/A dominated at patients with SCG. It is revealed the most frequent at patients with H.pylori -associated chronic gastritis in comparison with group of healthy donors were the genotype of IL1b (+3953)С/С and combination of genotypes of IL1b (+3953)С/С+ IL8 (-251)А/А.

Regulatory single nucleotide polymorphisms (rSNPs) play a significant role in the development of human pathology by altering the level of candidate genes expression. The purpose of this research was to study preeclampsia (PE) genetics components via the regulatory polymorphic variants of the new CORO2A candidate gene. In this work we analyzed five rSNPs. Three ethnic group have been studied (Yakut, Russian, Buryat). We have detected significant associations of PE with 2 rSNPs in CORO2A gene: rs10985257 and rs735111.The results of this study provide evidence of a significant role of the new CORO2A candidate gene in development of variability of placental tissue expression level in PE and in normal pregnancy.

Actuality: Phenomenon of chromosomal mosaicism often recorded the in human embryos at the preimplantation stage of development. This may be due to features of chromosome segregation at this stage of ontogenesis. The use of extracellular DNA from the intracavitary fluid may contribute to the study of the frequency and mechanisms of occurrence of chromosomal mosaicism in the blastocyst. This is achieved by molecular karyotyping of cells undergoing apoptosis and inaccessible for karyotyping using traditional technologies of cytogenetic studies. Objective: Evaluation the frequency of chromosomal mosaicism in human embryos at the blastocyst stage. Materials and Methods: CGH-analysis of 14 human embryos on day 5 of a division of the inner cell mass, trophectoderm and blastocoel fluid. Results: Comparative analysis of karyotypes of embryoblast and trophoblast of 14 blastocysts revealed that mosaicism in each embryo is observed on average in five chromosomes. Additional use of cell-free DNA leads to increase of spectrum of mosaic chromosomal abnormalities to 7 per sample. Analysis of molecular karyotypes using extracellular DNA proves the predominant elimination of embryoblast cells with autosomal monosomy. Conclusions: The use of extracellular DNA from the cavity of the blastocyst increases the frequency of chromosomal mosaicism registration in the cycles of in vitro fertilization and preimplantation genetic diagnosis. This is accomplished primarily due to the identification of aneuploidies presented in the inner cell mass of the blastocyst.

The original cause of development of any hereditary disease and steroid-resistant nephrotic syndrome (SRNS) in particular are the nucleotide substitutions leading to pathogenic changes in the encoded proteins. This research is directed to development of optimum algorithm of diagnostics of various hereditary diseases of kidneys united by symptom complex of nephrotic syndrome. On the basis of next generation sequencing and Sanger sequencing technology we examined 45 patients aged from 0 to 6 years old with suspicion on a nephrotic syndrome. Resistance to hormonal therapy was observed at all patients. As a result of research we have found mutations in 35 patients in genes NPHS1, NPHS2, PLCE1, TRPC6, ACTN4, WT1, COL4A3, COL4A4, COL4A5, CD2AP, COQ2, COQ6 and moreover we have revealed 10 new mutations. The obtained data can confirm considerable heterogeneity of SRNS in the Russian Federation.

Despite the advances in uncovering of the genetic component of coronary heart disease (CHD), only a small fraction of the heritability of the disease has been explained. Currently, there are relatively few studies of copy number variation (CNV) in cardiovascular diseases. Aim. Assessment of the CNVs 10q24.31 ( ERLIN1 ) in the cells of the coronary arteries and white blood cells (WBC) in patients with CHD. Materials and methods. Detection of the CNVs was performed by qPCR using TaqMan-probes in WBC samples (n = 110) and atherosclerotic plaques of the coronary arteries (n = 33) in patients with CHD, as well as in WBC samples of healthy individuals (n = 100). Statistical analysis was carried out using a standard curve of Pfaffl method. Results and conclusions. We found the amplification in 10q24.31 ( ERLIN1 ) region in 3% of patients with CHD, whereas deletion was observed in 1% of healthy individuals. In addition, two patients had amplification in analyzed region only in WBC, but not in the atherosclerotic plaques of the coronary arteries.

The research of the reasons of non-developing pregnancy is actual as it represents a serious problem in practice of obstetrics and gynecology.The aim of the research was the comparative study of frequency and spectrum of chromosomal pathologies in patients with non-developing natural pregnancy. We present the results of cytogenetic analysis of spontaneously aborted tissues from 120 patients. Abnormal karyotype in сhоrion was revealed in 74% of cases. The major types of chromosomal abnormalities are trisomies in 54% of cases and triploidies in 12%. We also analyzed the frequency and spectrum of chromosomal pathologies with due regard for patients’ age, fact of non-devloping natural pregnancy in patients’ overall history and fetal age. The rate of abnormal karyotypes in our research is higher in comparison with similar Russian and foreign studies.

Genetic structure of Shors populations and genera (seoks) using Y-chromosome markers was investigated. The results of the analyses of haplogroup frequencies and YSTR- haplotypes indicate that Shor seoks are related associations, in most cases having the same ancestor in the patrilineage. The gene pool of Shors, more precisely a part marked by Y-chromosome haplogroups, was shown to be primarily structured on a generic principle. A strong genetic affinity of the seok members was shown for the vast majority of the samples.

The use of neoadjuvant chemotherapy in the treatment of patients with non-small cell lung cancer can reduce the tumor size, increase ablastics operations, as well as to plan carrying out post-operative chemotherapy. But one of the important reasons for the ineffectiveness of chemotherapy is chemoresistance due to the expression of ABC-transporter genes ( ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2 and gene metabolism GSTP1 ). Thus, the aim was to study the expression of ABC genes during chemotherapy. As a result, it was found that the expression of genes correlated with chemoresistance weakly basic clinical and morphological parameters. But it was found that the direction of change in gene expression ABCB1 , increase or decrease, associated with survival rates.

Analysis of variability of 27 SNPs, associated with immune-dependent diseases and their endophenotypes, in human populations and relationship of the level of infectious diseases with genetic variability was conducted. Most numerous correlations were reaveled for dengue, malaria and tripanosomes - infectious diseases caused by viruses and protozoa. No significant correlations for bacterial infections (typhus, plague) and one of helminth infections (schistosomes) were found. A tendency to increase the total genetic diversity (average expected heterozygosity) with the decrease the total load of pathogens was revealed. Data are discussed in the framework of the concept of decanalization of immune response during the dispersal of modern human.

The aim of this study was to investigate associations between single nucleotide polymorphisms (SNPs) in rs1333040 gene CDKN2B and rs7865618 gene CDKN2А and risk of BAVM in the residents of the West Siberian region. Method: The study included 191 patients (124 men and 67 women) with brain BAVM`s, confirmed with Magnetic resonance imaging (MRI) and cerebral angiography (CAG) in the clinical centers in Novosibirsk. The control group consisted of 480 residents of Novosibirsk without BAVM. Determination of polymorphic variants of genes was performed by Real Time qPCR using TaqMan-competing probes. Results: We found that the rs7865618 gene CDKN2A is associated with brain arteriovenous malformation (OR = 1,915, CI = [1,158-3,167], р = 0,01). Conclusion: The study showed that the genotype of GG rs7865618 polymorphic locus in CDKN2A is associated with the risk of BAVM in the West Siberians.