Dyslipidemia is one of the most common metabolic disorders, the dominant risk factor for diseases of the cardiovascular system. Timely diagnosis and correction of the lipid profile can significantly reduce morbidity and mortality from cardiovascular diseases. An extensive heterogeneous group of diseases leads to persistent changes in the lipid profile. This review includes a description of lipid metabolism, the molecular basis, and clinical characteristics of primary monogenic dyslipidemia. Mutations in twenty-five genes are responsible for most monogenic dyslipidemias. On the basis of changes in the lipid profile, five groups of phenotypes are distinguished with extreme deviation in the levels of lipid profile markers: with high and low levels of low density lipoproteins, with high and low levels of high density lipoproteins, with high levels of triglycerides. For each phenotype, the associated genes are indicated, the gene with the most frequently detected mutations is indicated. The molecular basis of the most common dyslipidemia, familial hypercholesterolemia, is described in detail. Genetic testing of patients with dyslipidemia makes it possible to make an accurate diagnosis, the possibility of cascade examination and counseling of the patient’s family members, the possibility of early diagnosis to prevent or later manifest complications.

Identification of the genetic cause of a hereditary disease is a necessary step in the differential diagnosis, because plays an important role in evaluation of genetic risk, and in some cases also helps to determine the method of treatment, for example, for some hereditary metabolic diseases. The subsequent choice of molecular genetic testing method can be very difficult due to the presence of a number of advantages and limitations for each of these approaches. Methods of molecular genetic testing in order to identify the genetic causes of a hereditary disease, first of all, differ in diagnostic efficiency, time and cost of the study. In addition, the characteristics of different methods can also vary significantly for different groups of genetic diseases. Using the wrong method can significantly increase the time and cost of diagnosis. Recently, several data indicate that one of the next generation sequencing (NGS) methods - exome sequencing - has high efficacy for identification of the genetic cause of certain groups of hereditary diseases. Exome sequencing provides information about changes in gene coding regions - exons. A trio exome sequencing in families further increases the effectiveness of such analysis. The article describes the examples of clinical and financial feasibility of exome sequencing to identify the genetic cause of a hereditary disease. Such cases include: rare genetic diseases, heterogeneous diseases in children 0-3 years old, recently established connection of a gene with a disease, testing after negative results of other studies, for prenatal diagnosis, for financial reasons.

Polycystic kidney disease is a heterogeneous group of autosomal dominant or autosomal recessive disorders with age of manifestation varying from prenatal period to adulthood. Autosomal recessive polycystic kidney disease is caused by mutations in the PKHD1 gene. Approximately 85% of all autosomal dominant polycystic kidney disease cases are caused by mutations in the PKD1 gene, and around 15% - by mutations in the PKD2 gene. All these genes are large, and mutations were found to be scattered throughout the genes without any clustering. Therefore, mutation detection requires a lot of time, money, and effort. Due to clinical and genetic diversity of polycystic kidney disease, the search for mutations has to be carried out in several genes. Mass parallel sequencing (MPS) allows to analyze several genes simultaneously regardless of their size. 254 families with polycystic kidney disease were examined using mass parallel sequencing with a gene panel that included PKHD1, PKD1, PKD2, HNF1B and GANAB. Two variants in PKHD1 were found in 49 families (19%), one variant - in 9 families (3.5%); in PKD1 62 variants were detected (24.5%), in PKD2 - 6 variants (2.5%), in HNF1B - 9 variants (3.5%). In 119 families (47%) there were no mutations in the target genes. Among 66 patients from families with autosomal dominant polycystic kidney disease, 39 patients (59%) had mutations in the PKD1 gene. Out of 59 sporadic cases, 10 patients (17%) had 2 variants in PНKD1, 12 patients (20%) - in PKD1. 38 patients (29.5%) out of 129 patients with unknown type of inheritance had 2 variants in PНKD1, 11 patients (8.5%) - in PKD1, 4 patients (3%) - in PKD2, 5 patients (4%) - in HNF1B. Mass parallel sequencing allows to carry out relatively rapid molecular genetic analysis of several genes simultaneously for patients with symptoms of polycystic kidney disease.

Atherosclerosis is a leader in morbidity and mortality among all cardiovascular pathologies both in Russia and around the world. Nowadays there are evidences that somatic mutations in addition to classical risk factors can play a role in the development of endothelial dysfunction - the initial stage of atherogenesis, and atherosclerotic plaques are characterized by increased level of various DNA adducts. At the same time, a fundamental base of the contribution of mutagenesis to atherogenesis is still unstudied thought it is important for industrial regions with high genotoxic risk The aim of this research was to study the secretion and gene expression of proatherosclerotic cytokines IL-6 and IL-8 by primary human coronary- and internal thoracic artery endothelial cells characterized by different sensitivity to atherogenesis and exposed to alkylating mutagen mitomycin C. Concentration of the studied cytokines in culture medium and mRNA level of the corresponding genes were measured using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay at two time points - immediately after 6 hours of cell incubation with mitomycin C and after 6 hours of cell incubation with mutagen followed by 24 hours incubation in the complete media without mitomycin C. It was found that at the first time point, a significant decrease in the secretion and gene expression of IL-8, as well as a decrease in the mRNA level of the IL-6 gene in the exposed culture was discovered. At the second time point, on the contrary, the concentration and mRNA level of IL-8, as well as expression of the IL6 gene sharply increased in cultures exposed to mitomycin C in comparison with control (p <0.01), and the coronary artery cells were more sensitive to mutagenic effects than the cells of the internal thoracic artery. Thus, for the first time in in vitro experiment, mutagen-induced changes in the secretion and gene expression of proatherosclerotic cytokines IL-6 and IL-8 in primary human endothelial cells derived from various arteries have been shown.

Long QT syndrome (LQTS) is the genetically determined disease characterized by the QT interval elongation at the electrocardiogram, a high risk of life-threatening arrhythmias and sudden cardiac death. This syndrome is determined by mutations in genes encoding ion channel proteins, as well as proteins indirectly associated with ion channels. 4.5-8% of patients with LQTS have more than one mutation in the genes associated with the development of channelopathies. Purpose of work: description of two clinical cases of patients with life-threatening arrhythmia in which a combination of rare mutant alleles in the genes associated with LQTS was detected. The clinical examination included 12-lead ECG, echocardiography, cardiac MRI with delayed contrast, and 24-hour ECG monitoring (SM ECG). Genetic testing was performed by next generation sequencing (NGS) using the TruSight ™ Cardio Sequencing Panel reagent kit (Illumina). Both patients with no burdened family history had malignant ventricular tachyarrhythmias, which required the implantation of a cardioverter defibrillator. The NGS method allowed to detect a combination of substitutions in the genes ANK2 (c.9161C>G, p.Ala3054Gly, rs139007578) and KCNE1 (c.253G>A, p.Asp85Asn, rs1805128) in a patient with idiopathic ventricular tachycardia. In the patient with idiopathic ventricular fibrillation, the allelic variant was also found in the gene ANK2 (c.1397C>T, p.Thr466Met, rs786205722) and an additional substitution in the gene SNTA1 (c.1877>T, (p.Ala263Ser), rs150576530). If patients have several genetic defects, a “cumulative effect” of mutations can be observed, phenotypically manifested by a severe course of the disease with unfavorable outcomes. It has been shown that when genotyping patients with idiopathic life-threatening tachyarrhythmias, the use of panels with a large number of genes associated with cardiovascular pathology is quite justified. A comprehensive study of genes can increase the diagnostic and prognostic value of genetic screening.

Hereditary hemoglobinopathies are part of a group of blood diseases called hemolytic anemias. In general, hemoglobinopathy is the synthesis of abnormal hemoglobin. Hemolytic anemias occur in approximately 12% of the world’s population. This article is devoted to the results of genetic screening among newborns in Baku in order to study the frequency of hemoglobinopathies. The study involved 267 newborns. Among them are 143 boys and 124 girls. The studies were carried out in 2018-2019. To determine hemoglobinopathies among newborns, we used the method of iso-electrofocusing. The article also details the results of molecular diagnostics of the β-thalassemia gene in newborns by high-temperature allele-specific amplification. In Baku, the presence of pathological genes of α- and β-thalassemias and structurally abnormal hemoglobins S and D was established. Types of β-thalassemia mutations have been identified.

Accurate quantification of DNA methylation in cancer is a prerequisite for epigenetic-based diagnostics as well as the mechanistic understanding of tumour development. Still, the results of DNA methylation analysis are often prone to experimental biases of different origin. Since that thorough optimisation of the experimental conditions - a possibility to prevent biases - has serious limitations, particularly if many loci are analysed in parallel, we have earlier developed a universal process for correcting biased DNA methylation data irrespective of the loci that are interrogated. Its implementation required multiple manual steps, for example, solving the respective equations by using electronic tables, thereby increasing the risk of introducing errors and necessitating automation. Here, we present web-applications BiasCorrector and MethCorrector that implement our algorithm in the open-source programming languages “R” or Ruby, respectively. The software offers a graphical user interface (GUI) to accommodate also researchers without prior programming skills. Three common technologies - bisulphite pyrosequencing and next generation sequencing as well as oligonucleotide microarrays - were used to comprehensively test the correct operation of the applications. We demonstrate the accuracy of BiasCorrector’s performance and reveal PCR- and post-PCR biases that contribute to the total experimental deviation in a technology-specific manner. Both programmes effectively eliminate biases regardless of their nature, locus, the number of interrogated methylation sites, and the detection method. They are of interest as user friendly tools for epigenetic studies and are freely available https://biascorrector.diz.uk-erlangen.de/ and http://approximation.herokuapp.com/

The expression of miRNAs is affected by different factors. This poses challenges when interpreting the results of the study. Pathological processes can influence both the functional activity of cells and the ratio of cell populations. A possible solution is to utilize the approaches of deconvolution. We have developed an algorithm to assess reference panel from the microRNA dataset on the example of artery walls. In this study, we have shown that existing deconvolution algorithms are suitable for miRNA data.

The processes of detection and quantification by real-time PCR in blood of mature microRNAs, including miR-21, should be standardized and validated. Our studies show that the specificity of PCR method for miR-21 in the blood of healthy donors can be demonstrated by the formation of a 67 bp amplicon product, precision under conditions of convergence and reproducibility, expressed using the coefficient of variation, is less than 2% and 3%, respectively, and the linearity of PCR method for miR-21 is confirmed by the correlation coefficient r≥0.99.

The spatial organization of chromatin is important for the normal functioning of the cell. Genome repeat cluster sizes can affect the chromatin spatial configuration and function. The 1q12 heterochromatin loci movement from the periphery to the center of the nucleus is the cells’ universal response to various types of stress. We hypothesized that a large 1q12 domain could affect chromatin movement, thereby inhibiting adaptive response (AR). Using the FISH method, we shown that in the control, 1q12 loci are located near the surface of the nucleus; in the lymphocyte nuclei of schizophrenic patients and irradiated control cells, 1q12 loci are located in the central regions of the nucleus. During prolonged cultivation, the irradiated cells with a large Large f-SatIII amount die and the population is enriched with the cells with low f-SatIII content. In intact SZ patients’ lymphocytes and in irradiated cells we found an increase in SATIII RNA levels. The size of heterochromatin 1q12 loci in human cells can affect to the proliferation and cells’ adaptive response to stress. Quantitative polymorphism of tandem genome repeats is one of the epigenetic mechanisms of genome expression’s regulation.

An increased level of abnormal epigenetic regulation of gene expression in the trophoblast of spontaneous miscarriages with trisomy 16 was found. Among the hypermethylated genes, the group of genes of secreted proteins was significantly enriched, and a significant number of genes encoded receptors and transcription factors. Hypermethylation of the identified genes is a potential cause of death of embryos with trisomy 16 in the early stages of development.

In recent years it has been convincingly demonstrated that genetic factors play an important role in progression of Parkinson’s disease (PD). Since the etiology of PD has not been elucidated completely yet, it is crucial to shift focus of the research to the broader areas - to dive into investigations of methylome and transcriptome. Epigenetic regulation of gene expression may take part in pathogenesis of PD. Changes in epigenome can be conveniently investigated in case of individuals with almost identical genetic makeup, and monozygotic twins discordant for PD may be such “model”. 3 pairs phenotypically and genotypically monozygous twins of Russian ancestry were enrolled in the study. PD was diagnosed in one of each pair. The disease duration was at least 7 years. Data on blood methylomes was analyzed. Points of variable methylation in blood methylomes were selected. With this approach, 8 differentially expressed genes were found that also may be differentially methylated. Changes in methylation level for some of this genes were found in monozygotic twins discordant for PD fibroblasts cell-lines between healthy and afflicted siblings. Acquired data might suggest participation of DNA-methylation in transcription regulation of PD pathogenesis-related candidate genes.

Genetic causes of decreased fertility in men are represented by changes in the genome both separate and combined. The aim of the study was to study the frequency of occurrence of genetic factors leading to impaired reproduction, their combination and phenotypic manifestations.

А survey-based study of two groups of Sechenov University students was conducted to evaluate the attitude to the career planning and the role of genetics in the professional and personal life of the respondents. The first group included 4th-year students of the general medicine faculty and the second group included participants of the medical genetics scientific club. A deeper understanding of terms related to modern genetic technologies was revealed among students attending the scientific club. The professional plans of this group of students also differ markedly from those of students who do not attend the scientific club.

The paper considers the issues of preparation for the primary specialized accreditation procedure in the laboratory genetics

New approach is proposed for genetic education of physicians, medical teachers and students based on differentiated training programs for different medical type specialists.

With the transition to personalized medicine and high-tech healthcare, mastering any clinical discipline in the system of higher medical education is unthinkable without knowledge of the basics and the latest achievements of medical genetics. The organization of a step-by-step study of medical genetics in the senior years of medical universities can provide an opportunity to train more qualified doctors who are ready to move from standardized to personalized medicine.

The article summarizes the experience of writing course works on cytogenetics and mastering the basic methods of cultivation, preparation and staining of chromosomal preparations by students at the Department of Biology, Medical Genetics and Ecology of KSMU

The development of genetics has an increasing influence on modern medicine. Based on the achievements in the field of structural, functional genomics and epigenetics, new most promising directions have been formed - targeted therapy, personalized and regenerative medicine. There are fundamentally new opportunities for the diagnosis, prediction, prevention and treatment of a wide range of diseases. The increasing role of genetics imposes fundamentally different requirements for its teaching in medical Schools using new pedagogical methods. Simply increasing the number of academic hours in the subject “Biology” is no longer enough to train specialists whose professional activities are directly related to genetics: oncologists, virologists, immunologists, and many others.

This article is about the features and experience of teaching medical genetics for students, residents and doctors of various specialties.

The purpose of this publication was to analyze the structure and content of educational programs and plans used in medical universities of the Russian Federation for teaching subject Medical Genetics. The article discusses the problems of modern medical education through the prism of the importance of teaching Medical Genetics integrating the modern achievements in omics technologies for understanding the etiology and pathogenesis of diseases with subsequent application of this knowledge to clinical practice of future doctors of various medical specialties.

To assess the attitude of different groups of the population to some problems of medical genetics, a questionnaire for anonymous survey was developed. It consists of 16 questions regarding various genetic aspects. The questionnaire passed a psychological and social expert assessment. In 2009 and 2019, a survey was conducted of first-year students of a medical university and one faculty of a pedagogical university, as well as in groups of specialists: clinical residents of different specialties in the first year of study, and teachers working with children with disabilities. A total of 816 and 964 questionnaires were analyzed in 2009 and 2019, respectively. Thanks to the expansion of the teaching of medical genetics at the medical university and extensive work with the media over the past 10 years, understanding of the problems associated with hereditary diseases has improved significantly. It is necessary to expand the professional training of specialists working with children with hereditary pathology to further improve the situation. Joint actions will make it possible to individualize corrective work and increase its effectiveness.