The purpose of the study. To estimate the concentration of IL-10 in blood serum of patients with psoriasis and psoriatic arthritis moderate severity, the carriers of different genotypes of the C-597А polymorphism of the IL10 gene. Materials and methods. The object of the study were psoriasis (PS, n = 39), and psoriatic arthritis (PsA, n = 41) patients and healthy blood donors (control, n = 94), Caucasians in three generations. The study included PS and PsA patients of medium disease severity. The serum concentration of IL-10 was determined by ELISA. IL10 gene polymorphism was studied by PCR-RFLP analysis. Results. The concentration of IL-10 in blood serum of PS patients, the carriers of C/A and A/A genotypes, significantly lower in comparison with the carriers of these genotypes in groups of PsA patients and control (р_1,2 = 0,02; р_1,3 = 0,003). The concentration of IL-10 in blood serum of PsA patients, carriers of the genotype C/C , significantly lower in comparison with carriers of this genotype in the control group (p_2,3 = 0,04) and carriers of genotype C/A and A/A group of patients with PsA (p = 0,04). Conclusions. Statistically significant low level of IL-10 in blood serum in PS and PsA of moderate severity depending on the presence of a particular genotype of polymorphism C-597А of IL10 gene revealed: in PS - patients with genotypes C/A and A/A , in PsA - patients with genotype C/C .

Introduction: It was shown that the pathogenic CNV are often associated with intellectual disability, neurological and neuromuscular diseases. However, the clinical significance of novel CNV is not always unambiguous. We report on 2-year-old male patient with drug-resistant epilepsy, in whom a 125 kb microduplication at 12q24.12 of maternal origin was detected by aCGH. Patient has marked physical and mental developmental delay, neuromotor retardation, and dysmorphic features. Materials and Methods: A 125 kb microduplication at 12q24.12 was detected by aCGH (8 x 60K, Agilent Technologies). Microduplication origin was analyzed by Real-Time PCR. Reaults: Affected region contains three genes: ACAD10 , which is expressed in fetal brain, MAPKAPK5 , which is involved in neurological processes, and ALDH2 , which is engaged in neurodegeneration. Clinical features and the genes content are important to further delineation of the 12q24.12 microduplication phenotype.

This paper presents results of analysis of the genetic relationships of populations on panel 66 X-SNP markers of the X chromosome included in the test system for DNA-identification XSNPid, and the results of evaluation of identification potential of this system for the populations of the world. The study included populations such as Russians, Tuvinians, Buryats, Kazakhs, Khakas, Siberian Tatars, Khanty, Utah residents of Central European origin, Italians, Mexicans, Japanese, Han, Indians, African Americans. The analysis showed that the genetic differences of the studied populations show geographic structuring. The test system XSNPid is the most informative for populations belonging to the Caucasoid racial type.

Numerical chromosome abnormalities are the most significant genetic failures. It is known that chromosomal aneuploidy may cause instability in tumor cells. However, it remains unknown whether the presence of numerical chromosome abnormalities in cell leads to the induction of chromosomal instability in embryogenesis. Goal. This work aims to identify the impact of numerical chromosome abnormalities on the frequencies of chromosome fragment and whole chromosome loss in fibroblasts of extraembryonic mesoderm of I trimester spontaneous abortions. Materials and methods. The frequencies of centromere-negative micronuclei containing the chromosome fragments, and centromere-positive micronuclei formed around the whole lagging chromosomes, were assessed in fibroblasts of extraembryonic mesoderm of 21 spontaneous abortions with different karyotypes (9 abortions with normal karyotype, 7 abortions with aneuploidy, and 5 triploid abortions). Nineteen induced abortions were used as a control group. Results. Despite the increased frequency of chromosome loss in the subgroup of spontaneous abortions with aneuploidy compared with spontaneous abortions with normal karyotype and induced abortions, significant differences were not found. Conclusions. Presence of aneuploidy is not enough for induction of chromosome instability in human cells indicating the existence of mechanisms of genome stability maintenance in the extraembryonic tissues, which are non-sensitive to aneuploidy and polyploidy.

Relevance. The information about the frequency and spectrum of TP53 gene mutations in Russian patients with diffuse large cell lymphoma (DLBCL) is not represented in the current version of the IARC TP53 mutation database. Purpose of the study was to compare the frequency and spectrum of TP53 gene mutations in Novosibirsk patients with DLBCL with the data presented in IARC TP53 mutation database. Material and methods. The TP53 gene sequence from 5 to 10 exons of 74 tumor tissue samples of patients with newly diagnosed DLBCL was analyzed by Sanger direct sequencing. Results. In 24.3% of patients were identified a mutation in the coding sequence of exons 5-8 TP53 gene. Multiple mutations had 4% of patients. The cases of loss of heterozygosity in the TP53 gene in DLBCL tumor tissue were revealed. The spectrum of single-nucleotide substitutions in the TP53 in the study group did not significantly differ from the data presented in IARC TP53 mutation database, but we observed differences in localization of the «hot spot» mutations. In the analyzed group of patients with DLBCL «hot spots» mutations were in codons 275, 155, 272 and 212. Conclusions. Comparative analysis of the results of sequencing gene TP53 in tumor tissue of patients with DLBCL in Novosibirsk with the data presented in IARC TP53 mutation database is revealed differences in the spectrum of mutations. The frequency of mutations in the gene TP53 in the study group are consistent with the literature dates.

We aimed to estimate the influence of intratumor morphological heterogeneity of breast cancer on the chemotherapy response depending on clinical-pathological parameters and to identify the molecular mechanisms of the association, obtained here, by whole transcriptome profiling and PCR analysis. We found the significant association between the presence of alveolar and trabecular structures in breast tumors and chemoresistance and identified expression markers: NAT1 , ABCA12 , ABCC1 , ABCG1 , PIK3C3 , TXN2 , SLC23A2 , SLC25A13 , SLC1A3 , and UBE2S that may determine the differential contribution of morphological structures in breast cancer chemoresistance.

Atopic dermatitis (AD) - chronic inflammatory skin disease, which usually arise in early childhood and often precedes allergic diseases. To date several genome-wide analysis are conducted and they revealed some new polymorphic loci that are associated with atopic dermatitis development. We investigated polymorphic variants located in the 11q13.5 chromosomal region ( C11orf30 and LRRC32 genes), and SNPs in KIF3A, OVOL1 and ACTL9 genes as well. Association of rs2508755 polymorphism of the C11orf30 gene with atopic dermatitis in Tatars was shown.

The structure of the gene pool of the indigenous population of Dagestan belonging to Dido language group of Nakh-Dagestani language family using Y-chromosome markers was investigated. We used DNA population samples representing Dido, Gunzibs, Bezhtins and Ginukhs. J1 was identified the most frequent haplogroup in all populations. Most of the pairs of the compared samples demonstrated no statistically significant differences between the different population. In populations of Dido linguistic group extremely low genetic diversity was due to the predominance of haplogroup J1. In different populations strong effects of the founder were observed.

The distribution of ethanol biotransformation genes ADH1B*rs1229984, ALDH2*rs671, CYP2E1*rs3813867 were studied in populations of 7 Turkic peoples of Western Siberia. The study included 2 groups Tobol-Irtysh Tatars Tyumen-Turin subgroup of the Tyumen region (Bukhara-Tatar and Yalutorovsk Tatars) and 5 of the peoples of the Altai Krai and Altai Republic - Southern Altai (Altai-Kizhi, Telengits) and Northern Altai (Kumandins, Tubalars, Chelkans). The total sample size was 564 people. Ethnic and territorial specificity of the nature of the distribution of the studied genes were revealed. In groups of Tatars set of allelic variants of genes ADH1B*rs1229984, ALDH2*rs671, CYP2E1*rs3813867 appears to be more balanced in terms of the efficiency of ethanol metabolism than in populations of indigenous peoples of the Altai. A significant interpopulation subdivision within studied peoples (G ST = 9,4%) was observed. The maximum genetic distances were indicated in population of the Bukhara-Tatar (d ̅= 0.12).

Topicality. The search for the associations of functionally polymorphisms of gene cytokines as potential markers of the disease, which influence both immune response and inflammatory process, is an actual aim of studying immune genetic factors of atopic bronchial asthma (ABA). Aim. To study the associations of polymorphisms of IL5 (rs2069812), IL12B (rs3212227), TGFB1 (rs1800469), IFNG (rs2069705) with ABA in depends from the stage of the disease control. Methods. For genotyping we have used PCR-PLRF-analysis. Results. No statistically significant difference was found in the distribution of the IL5, IL12B, TGFB1, IFNG polymorphisms between ABA patients and controls in this case-control study. The distribution of the frequencies of gene variants corresponded to the Europeans. Conclusions. As a result of our research we didn’t find any associations between polymorphisms of IL5, IL12B, TGFB1, IFNG genes and ABA including the level of the disease control.

Actuality: A comparative analysis of the molecular karyotypes of extracellular DNA in intracavitary fluid, inner cell mass and trophectoderm allows registering the phenomenon of reciprocal aneuploidies. This makes it possible to determine the origin of numerical chromosome abnormalities and suggest mechanisms of their occurrence related to post-zygotic chromosome segregation errors. Objective: Evaluation of the frequency of reciprocal aneuploidy in human embryos at the blastocyst stage. Materials and Methods: CGH-analysis of 14 human embryos (day 5) with separation to inner cell mass, trophectoderm and intracavitary fluid. Results: By comparing the molecular karyotypes of DNA from blastocoel fluid, inner cell mass and trophectoderm was found that 64% of embryos had from 1 to 3 reciprocal aneuploidies (9/14). Reciprocal anomalies were formed involving chromosomes 19 (33%), 16 (27%), 17, 21 and 22 (13%). The frequency of reciprocal aneuploidies based on a pair of homologous chromosomes, obtained on the basis of comparative analysis of the molecular karyotype of extracellular DNA, the inner cell mass and trophectoderm was 24% (16/67). The frequency of reciprocal aneuploidies in a comparative analysis of extracellular DNA and the inner cell mass was 21% (14/67), extracellular DNA and trophectoderm - 3% (2/67), inner cell mass and trophectoderm - 10% (7/67). Conclusions: Using of extracellular DNA from the cavity of the blastocyst as a source of additional information about the chromosomal constitution of embryo can increase the probability of detecting of reciprocal aneuploidy by 56%. These anomalies reflect an intensity of mitotic chromosome segregation errors.

The aim of the study is investigation of the association between the MYH7 gene R249Q (rs3218713) mutation and sudden cardiac death (SCD). Materials and methods. The SCD group was formed using WHO criteria for sudden cardiac death (n = 379, mean age 53,2 ± 8,7 years, men - 70.9%, women - 29.1%), the control group was selected according to sex and age from the DNA bank of HAPIEE, MONICA (n = 377, mean age 53,1 ± 8,3 years, men - 68.3%, 31.7% of women). DNA was isolated by phenol-chloroform extraction of the myocardial tissue of persons who died of sudden cardiac death, and venous blood of the persons included in the control group. Genotyping was done by PCR followed by analysis of restriction fragment length polymorphism. Results. In the SCD and control groups were not found carriers of the rare allele A of the MYH7 gene R249Q mutation. Conclusions. The MYH7 gene R249Q mutation is not associated with the SCD in the sample suddenly deceased residents of Novosibirsk.

Introduction. One of the genetic causes of intellectual disabilities (ID) is copy number variation (CNV). Despite the fact that for some variations an association with known syndromes has been shown, most of them are rare. Usually CNVs involve extended regions, including several genes. In some cases CNVs include single genes, what enables to directly link a change of their dose with clinical abnormalities observed in a patient. Aim. This work aims to characterize structural genomic variation in patients with ID and map candidate genes. Materials and methods. Using Agilent 44K and 60K arrays the molecular karyotyping for 136 children of 3-17 years old with developmental delay, ID and dysmorphic features was performed. Results. Eighty-seven individuals (64%) had normal karyotype or benign CNVs. Known microdeletion or microduplication syndromes were identified in 18 patients (13%). In the remaining 31 children (23%) potentially pathogenic mutations were found. For 15q24 and 16p11.2 microdeletion syndromes, diagnosed in two and three patients, respectively, using the literature data the minimal deleted regions and candidate genes within them were identified. In two families the reciprocal microdeletion and miproduplication of single CNTN6 gene were found. This gene is expressed in the brain and, therefore, is a candidate for ID. Conclusions. aCGH-analysis is an effective method for genetic diagnosis, which, when mutations in single genes are detected, allows identification of new candidate genes for intellectual disability.

Timeliness. Renal cell carcinoma (RCC) is a malignant neoplasm of the kidney which accounts for about 3% of all cancers. Recent studies have shown the important role of miRNAs in the occurrence and progression of cancer. We hypothesized that genetic polymorphisms of microRNA binding sites may be associated with RCC risk. Aim of investigation. Search for associations of polymorphic variants of miRNA binding sites rs6773576 CDCP1 gene, rs10982724 DEC1 gene, rs10491534 TSC1 gene with the risk of renal cell carcinoma, and the severity of the disease. Methods. We studied 255 DNA samples from 255 RCC patients and 298 controls. Genotyping of polymorphic loci was performed by real time PCR using TaqMan-competing probes. Results. We found allele rs10491534*C to be a marker of severe renal cell carcinoma (p = 0.044; OR = 1.72 (CI = 1.012-2.911)). Genotype rs10491534*T/T (p = 0.044; OR = 0.55; (95% CI = 0.31-0.98)) - protective marker against severe RCC. The most significant association of rs10491534 in TSC1 gene with the severity of the disease was found in the dominant model: the combination of genotypes *C/T+*C/C vs *T/T (p = 0,03; OR = 1.82 (95% CI = 1.05-3.15)). Conclusions. The revealed markers of RCC severity may be promising for the prognosis of the RCC.