Relevance. Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies. In 95% of cases, the disease is associated with partial deletion of the array of the D4Z4 repeats on one of the alleles of the 4th chromosome. The existing diagnostic methods of Southern blotting and molecular combing are quite resource-and time-consuming. At the moment, molecular genetic diagnostic of FSHD is not provided on the territory of the Russian Federation. Aim: to find new approaches for molecular genetic diagnostic of FSHD acceptable for use in standard molecular genetic laboratories Materials and methods: DNA isolated in agarose plugs and treated by the EcoRI restriction enzyme. DNA fragments then were separated by pulse field gel electrophoresis (PFGE) in agarose gel. After PFGE, the agarose gel was fragmented and used as a matrix for PCR. The identity of the obtained PCR products to the sequence of the D4Z4 repeats of the 4th chromosome was confirmed by sequencing by Sanger. Results. The PFGE protocol is optimized in such a way that, after all stages, DNA in agarose gel is suitable for use as a matrix for PCR. We achieve a specific amplification of the control DNA matrices of the 4th chromosome and confirm belonging of the PCR products to the sequence of D4Z4 repeats of the 4th chromosome by the Senger sequencing. Conclusions. This paper shows the possibility of using DNA in agarose gel after PFGE as a matrix for detection of D4Z4 repeats by PCR. The presented PCR system specifically amplify sequence of the 4th chromosome D4Z4 repeats. Using this PCR system and genomic DNA of a patient with a known length of the D4Z4 repeats array, a successful diagnosis of FSHD was performed. Thus, we propose a new approach for FSHD diagnostic, acceptable for use in standard molecular genetic laboratories.

It is well known that the presence in the tumor cells of such a phenomenon as a deficiency of homologous recombination, caused mainly by a defect in the BRCA1/2 genes, is associated with a favorable treatment effect and prognosis of the disease. But it has been established that the presence of other alternative ways of DNA repair, such as activation of the NF-κB or PARP1 genes, may have an additional negative effect. Thus, the aim of the work was to assess the association of chromosomal aberrations of the BRCA1, NF-κB, PARP1 genes in tumor breast tissue with the effect of chemotherapy and the prognosis of the disease. Materials and methods. The study included 85 patients with stage IIA - IIIB breast cancer. DNA was isolated from biopsy specimens of tumor tissue using the QIAamp DNA mini Kit (Qiagen, Germany). A microarray was studied for all tumor samples on Affymetrix CytoScanTM HD Array high-density DNA chips. To estimate the aberrations of the number of DNA copies, the program Chromosome Analysis Suite 3.3 was used. Results. It was found that the highest frequency of deletions is observed in the BRCA1 gene (28%, 24 cases out of 85), and this is statistically significantly associated with an objective response to neoadjuvant chemotherapy (p=0.02). The frequency of amplification of PARP1 in the studied group of patients is 62%, which also determines the presence of a good response to neoadjuvant chemotherapy, regardless of the presence of chromosomal aberrations of other have study genes. When analyzing the prognostic significance of gene aberrations, it was shown that PARP1 amplification is an unfavorable marker of metastatic-free survival (log-rank test, p=0.02). Conclusion. Based on the data obtained, it can be assumed that the aberrant state of the BRCA1 and PARP1 genes in a breast cancer may also be a promising marker of the effectiveness of chemotherapy and disease prognosis, which confirms the undoubted relevance of the study, but also requires further detailed study.

Background. Long non-coding RNA (lncRNA) in thyroid cancer are poorly investigated; no lncRNAs common and specific for the follicular and classical variants of papillary cancer, as well as no lncRNAs aberrantly expressed in benign nodules or other subtypes of thyroid cancer are established. The objective of the study is to determine long noncoding RNAs aberrantly expressed in follicular adenoma (FA), follicular carcinoma (FTC), follicular and classical variants of papillary carcinoma (PTC), anaplastic carcinoma (ATC). Methods. lncRNA expression was analyzed in dataset of Microarray (8 independent experiments available in GEO) and RNA-seq studies (PRJEB11591 and TCGA-THCA). In total, 246 samples of normal thyroid tissue, 26 FAs, 30 FTCs, 181 follicular variant PTCs, 481 classic variant PTCs and 49 ATCs were examined. In silico validation was performed. Potential biological functions were assessed by enrichment analysis of coexpressed genes. Results. LncRNAs differentially expressed in FA, FTC, follicular, and classical variants of PTC, and ATC are identified. There are 8 lncRNAs common for all investigated thyroid nodules, 22 common for PTC, 32 specific for classical PTC, 1 specific for follicular variant of PTC, and 177 specific for ATC. No lncRNA significantly differentially expressed in FTC compared to FA is identified. The previously described oncogenic and suppressor lncRNAs NR2F1-AS1, LINC00511, SLC26A4-AS1, CRNDE, RMST are detected in thyroid carcinomas for the first time. Identified lncRNA are putatively involved in cell adhesion, extracellular matrix organization, endoderm formation, VEGF signaling pathway, WNT signaling pathway and cell polarity, cell cycle and mitosis. Conclusion. The general and specific patterns of lncRNA expression in benign and malignant thyroid nodules are established.

Aim: Evaluation of the role of TР53 (rs1042522), XRCC1 (rs25487, rs1799782) gene depending on the human papillomavirus (HPV), morphological parameters of the tumor and tumor markers of the blood among women with cervical cancer (CC) in Kyrgyz Republic. Methods. This was a case-control study of 205 women of Kyrgyz origin with morphologically verified CC (N=103) and 102 women without cancer and chronic diseases. Genotyping was performed by PCR-RFLP method. HPV 16 and 18 types, levels of squamous cell carcinoma (SCC) and сarcinoembryonic antigen (CEA) tumor markers were detected. Results. A relationship has been identified between the genetic and clinical and biochemical parameters: Pro/Pro и Arg/Pro for single-nucleotide polymorphism p.Arg72Pro of the ТР53 gene were associated with HPV 16 type - OR 1,98 (95% CI=[1,01-3,86]), p=0,04; Pro/Pro for p.Arg72Pro of the ТР53 - with HPV 18 type - OR =9,15 (95% CI=[1,78-46,96]), p=0,002. Among patients with tumor size of more than 4 cm are more common high levels of CEA and SCC tumor markers. High levels of CEA and SCC are associated mainly with type 16 HPV. Conclusions. The results of the present study suggest that the presence of the Pro allele (genotypes Pro/Pro and Pro/Arg) by SNP p.Arg72Pro (TP53 gene) among women with cervical cancer is associated with a positive status for highly oncogenic HPV 16 and 18 types.

It has been established that polymorphisms of inflammatory mediator genes, tissue matrix proteins and growth factors are involved in autoimmune and fibrotic processes in systemic scleroderma (SSc). CCL2 chemokine is a key inflammatory protein present in the circulating blood and in the lesions of the skin of patients with SSc. The purpose of this study was to study the association of the polymorphism -2518 A / G of the CCL2 gene with C-reactive protein (CRP) levels among patients with different clinical and serological phenotypes of SJS. In the general group of patients, carriers of the genotype -2518AA had a statistically significant higher average CRP level compared to carriers of the -2518G allele (AG + GG genotypes) (p = 0.032). Similar differences in CRP levels were obtained in patients with a diffuse form of SJS and in patients with positive antibody titers to topoisomerase I (p = 0.041 and p = 0.042, respectively). Conclusions: The carriage of the -2518AA genotype was significantly associated with a high level of CRP in patients with poor prognosis of SSc (presence of a diffuse form and seropositive autoantibody titers to topoisomerase I) compared with patients carrying the -2518G allele. Polymorphism -2518A / G of the CCL2 gene can be used as a genetic marker of severity and poor prognosis for SSc.

Introduction: Tetrasomy for the distal chromosome 15q is rare. Only 24 cases have been described in the literature to date. Tetrasomy for the distal portion of chromosome 15q can be due to a supernumerary analphoid marker chromosome consisting of an inverted duplication of the distal long arm of chromosome 15. We report on a molecular cytogenetic diagnosis of mosaic tetrasomy 15q25.3-qter in a patient with multiple congenital anomalies. Aim: Molecular cytogenetic diagnosis of mosaic case with inverted duplication for the distal portion of 15q25.3→qter in a patient with multiple congenital anomalies and review of the literature. Methods: The case of mosaic supernumerary marker chromosome was characterized by GTG-banding, chromosomal microarray analysis and FISH diagnosis. Results: The chromosome analysis of a child revealed a supernumerary marker chromosome in mosaicism: 47,ХХ,+mar[8]/46,XX[23]. Chromosomal microarray analysis detected a copy gain of 16.4 Mb from the distal long arm of chromosome 15. Further FISH analysis showed an inverted duplication of distal long arm of chromosome 15 with neocentromere. Conclusion: Identification of structure and origin supernumerical marker chromosomes at patients with multiple congenital anomalies is an important problem of cytogenetic diagnostics. Modern molecular -cytogenetic diagnostic methods of chromosomal anomalies allow identifying and characterizing any case of neocentromeres.