The article summarizes the data on the clinical and economic evaluation of newborn screening programs for inborn errors of metabolism (IEM). Various approaches to the clinical and economic evaluation of the effectiveness of newborn screening programs, the impact of expanding screening programs by MS/MS on the budget are discussed.

In this article we present the nosological spectrum of monogenic hereditary diseases (MHD) in three districts of the Republic of North Ossetia - Alania (RNOA) - Pravoberezhny, Ardonsky and Kirovsky, with a total population of 119,590 people. The entire population of the districts was examined according to the Protocol of genetic and epidemiological studies (developed by the Federal state budgetary Research Centre for Medical Genetics), 600 patients (from 418 families) with various NBS were identified and diagnosed. We identified 136 nosological forms of MHD - 65 with autosomal dominant type of inheritance (AD), 57 with autosomal recessive (AR) and 14 with X-linked (X-lin.). We determine the prevalence of diseases, frequent and rare nosological forms. The nosological spectrum and prevalence of individual MHD were compared with previously surveyed populations in the European part of Russia: Kirov, Kostroma, Arkhangelsk, Tver, Bryansk, Rostov regions, Krasnodar territory and the Republics of Karachay-Cherkessia, Adygea, Tatarstan, Bashkortostan, Mari El, Udmurtia and Chuvashia. Features of the MHD diversity are revealed. With higher prevalence values than in other populations of the Russian Federation, Ehlers-Danlo syndrome, myotonic dystrophy, non - syndromic mental retardation with various types of inheritance and various forms of retinitis pigmentosa, etc. A number of diseases that are frequent in the Russian Federation have shown on the contrary lower prevalence values - vulgar ichthyosis, neurofibromatosis, hereditary motor-sensory neuropathy and ichthyosiform erythroderemia.

Polymorphism of CAG repeats in exon 1 of the androgen receptor gene (AR/HUMARA) is associated with pathozoospermia and male sub-/infertility, but its effect on spermatogenesis and seminal fluid parameters is under evaluated. The article presents the results of a study of CAG repeats in AR gene on semen parameters in Russian male patients from infertile couples with pathozoospermia (n = 451), and in normozoospermic men, a control group (n = 131). The analysis of the groups revealed no dependence of the concentration indices, the total amount and amount (%) of progressively motile («PR»), morphologically normal and live spermatozoa from the number of CAG repeats of the AR gene. Teratozoospermic patients have statistically significantly higher number of CAG repeats, than men without teratozoospermia (22.37 ± 3.20 versus 22.15 ± 3.12; p = 0.02).

Genetic epidemiological studies have established that polymorphisms of the genes encoding antioxidant defense enzymes represent meaningful predictors for the risk and severity of ischemic stroke (IS). The aim of this study was to investigate associations of IS with three common single nucleotide polymorphisms (SNPs) such as rs38420, rs4270 and rs6462210 in gamma-glutamylcyclotransferase (GGCT) gene, a key enzyme of glutathione catabolism. DNA samples obtained from 1288 unrelated individuals of Slavic origin, including 600 patients with IS and 688 healthy volunteers were included in the study. Genotyping of the GGCT polymorphisms was done using an iPLEX-based technology by the MassARRAY-4 system. Functional annotation of SNPs was performed using numerous online bioinformatics tools and resources. We found an association between genotype T/T rs6462210 and a decreased risk of ischemic stroke (OR = 0.36 95% CI 0.15-0.85, p=0.01). The haplotype rs38420A-rs4270T-rs6462210C showed a clear tendency in association with decreased disease risk (p=0.057). Bioinformatics analysis showed that the phenotypic effects of the SNPs are characterized by a weak transcriptional activity of the GGCT gene mainly in blood cells and arteries as a result of chemical modifications of chromatin. For the rs4270 polymorphism, which is in close linkage disequilibrium with SNP rs6462210 (D’=0.966, p<0.01), we found a binding site for miRNA hsa-miR-1246 which is capable to block the GGCT expression, thereby reducing the formation of L-cysteine, a precursor of glutathione. The study showed for the first time that GGCT gene may contribute to the development of ischemic stroke. Experimental studies focusing on the regulatory potential of GGCT gene polymorphisms are required for the pathophysiological interpretation of the identified associations.

The continuing development of mass DNA extraction methods entails the need to set standardisation and quality verification reference points. A study has been conducted and standards set for one of the many methods of DNA extraction - the automated мagnetic beads-based extraction using QIAsymphony SP station. It was shown that the concentration of DNA in an individual sample is mainly determined by the leukocyte content in the initial blood sample (correlation of about 0.9). DNA concentration also depends on the measurement method. It allowed us to build linear regression models and derive formulae that accurately predict the concentration of DNA in the sample for the use of two widely used methods - spectrophotometric (Nanodrop) and fluorescence (Qubit). It was found that the latest Nanodrop OneC model, thanks to a built-in algorithm for identifying impurities and adjusting the concentration, provides an even more accurate concentration estimate than Qubit 4.0. For a quick but rough forecast of DNA concentration, instead of regression models, standards calculated by us for reference values of the white blood cell count can be used.

We report on a case of small supernumerary marker chromosome (sSMC) in a 3-year boy with facial anomalies and speech delay. The constitution of marker chromosome was designated by mFISH analysis as r(20)(p12q12). The problems of diagnostics of sSMC, containing the pericentromeric regions only, and genotype-phenotype correlations are discussied.

Psoriasis is a chronic inflammation skin disease with complex genetic architecture that affects approximately 2% of the world population. The condition is characterized by abnormal keratinocyte hyperproliferation and differentiation related to a dysregulated immune system governed by a pro-inflammatory cytokine network. The accumulating data of psoriasis associative studies reveals significant number of SNPs located in genome sites related with immune system. A review of sources available allowed the selection of potentially significant for psoriasis occurrence and development SNP set, includes 84 markers. SNP determination has been carried out by a combination of high-performance genotyping on Illumina microchips and computer imputing. The differences in three SNPs rs12307915, rs2227473 and rs744166 were found in patient groups with different apremilast therapy outcome, paving the way to the development of predictive psoriasis therapy approaches.

We studied mRNA and protein levels of serotonin receptor 2A (5-НТ2А) in lymphocytes of schizophrenia patients both before and after 28 days of antipsychotic therapy in order to estimate biomarkers of efficacy and safety of the treatment. We found lower mRNA and protein levels of 5-НТ2А in peripheral blood lymphocytes (PBL) of schizophrenia patients with alcohol addiction syndrome than in PBL of schizophrenia patients without addictions (р<0.001). Absence of common adverse side effects (antipsychotic-induced weight gain, parkinsonism, akathisia) during antipsychotic therapy was associated with reduction of 5-НТ2А protein level in PBL by 28th day of the treatment, while HTR2A mRNA level was not changed. Reduction of 5-НТ2А protein level in PBL by 28th day may be a potential biomarker of the antipsychotic therapy safety.

Аnxiety disorders are considered a serious problem of psychiatry being comorbid with other states. In this context investigation of factors responsible for unequal drug efficiency and safety in different patients is needed. Among these factors, genetics is considered to be one of the most important. This study assessed the role of CYP2D6 gene polymorphism 1846G>A in Lexotan efficiency and safety in patients with anxiety disorders comorbid with alcoholism.

The study of the effect of CYP2D6 gene polymorphism on the efficacy and safety of mirtazapine therapy in patients with depressive disorders comorbid with alcoholism was carried out. In a group of 106 patients with depressive disorders comorbid with alcohol dependence, the effect of the 1846G> A polymorphism of the CYP2D6 gene (rs3892097) on the safety profile of mirtazapine was demonstrated, but not on the effectiveness. At the same time, hsa-miR-370-3p remains a promising biomarker for assessing the level of CYP2D6 gene expression, since the level of its plasma concentration differed in carriers of different genotypes for the polymorphic marker 1846G> A, although no connection with clinical efficacy and safety was found.

CF clinical variability could be associated with interaction of modifier genes. Сlarification of the causes of treatment failure and adverse reactions, prediction of risk factors could improve the outcome of therapy. Association of 18 polymorphic variants of 10 genes of xenobiotic biotransformation: CYP2C9 (c.430C>T, c.1075A> C), CYP2C19 (c.681G>A), CYP2D6 (1846G>A), CYP3A4 (c-392C>T), GSTT1 (del), GSTM1 (del), GSTP1 (c.313A>C), GCLC (TVR GAG, c.-129C>T), GCLM (c.-588C>T), NAT2 (c.282C>T, c.341T>C, c.434A>C, c.481C>T, c.590G>A, c.845A>C, c.857G>A) with severity of clinical manifestations were analyzed in 333 CF patients.

The biosocialization of society is a complex of phenomenon, among which, in a philosophical and ethical aspect, the techno-scientific approach to knowledge, the increasing role of autonomy and the problem of reflection stand out. For biobanks, this complex of problems is realized as the complexity of developing informed consent. The issue of genuine informed consent is critical to the success of biobanking. If scientists consider informed consent as a formality, then biobank donors themselves, realizing that their biomaterials may not be used correctly in one of the many projects that are implemented on the basis of biobanks, may not feel a sense of fairness and agreement with the conditions that are offered to them within broad informed consent. Maintaining the idea of awareness is an important condition for the formation of a positive biobanking image.

The development of genetic technologies has contributed to the rapid biosocialization of modern society. Biosociality and bioidentity are phenomena that describe the most important global and local processes of development of modern biomedicine, which determine the interests of an increasing number of people. Creating groups on biosocial grounds is impossible without the principle of convergence of efforts. It works at different levels of social life, influencing the formation of scientific knowledge. The physicality of the patient can be considered as a hybrid form where organics, knowledge, technology and existential experience of a personal medical history are intertwined. The possibilities of legitimizing the future genetic technologies for human enhancement lay the foundation for the formation of new loci of biosociality and bioidentity.

The use of any new assisted reproductive technology related to the manipulation of human sex cells and embryos will inevitably be controversial from an ethical point of view. This technology is mitochondrial replacement, which allows a woman suffering from mitochondrial dysfunction to give birth to a healthy child.

The main ethical challenges of preimplantation genetic testing (PGT) are examined, the relationship between the ethical issues of IVF and PGT is revealed, the social aspects of the use of PGT are analyzed.

The article discusses the social changes resulting from the application of genetic technologies and examines how the genetic research affect the language of social sciences. The «meeting points» between genetic and social research are shown.

The Russian legal policy in the field of the medicine genetic technologies creation and application does not provide a proper balance between the system of human rights that guarantee the protection of its dignity and health, and the freedom of scientific creativity. The non-coordination of these human rights is manifested in the fact that in the absence of prohibitions on research using technologies of human genome inherited editing, the law deprives patentability of any technology for modifying the genetic integrity of human germline cells. A consistent legal approach involves the restrictions on the possibility of the germ line genomic editing and the prohibition of patenting the methods of such editing, which does not go beyond the given restrictions. It is advisable to take into account the experience of Great Britain.

The study determines the significance of ethical and legal norms for regulating the use of genetic technologies. This task is important for modern society, but it is no less relevant for determining the risks of applying genetic technologies to the rights of future generations. The material was scientific articles and electronic resources. The research methods are formal-logical, system, structural-functional and formal-dogmatic. The results show that the topic of caring for future generations should not be ignored when using genetic technologies. Legal instruments will be able to determine the limits of the use of genetic technologies, taking into account the interests of future generations.

The article considers a number of ethical and legal problems of commodification of biomaterials in the development of genomics and genomic medicine. It is shown that biomaterials in the modern world are considered as objects of property and patent law and become a source of profit. Often this leads to the appearance of incidents related to the protection of the rights of the individual, which is the source of origin of biomaterials. The thesis is put forward that the situation associated with the circulation of biomaterials is reflected in various modes of relations between the individual, science and society, with the articulation of the priority of a personal or public good characteristic of each of them.

Documents regulating the use of genomic samples in clinical trials of medicines are presented and discussed.

Genetic carrier screening for autosomal-recessive disorders is an important part of hereditary diseases prevention at the stage of family planning. Patients of the Bauman clinic (18-49 years old women and men older 18 years) were asked to read a brochure about carrier screening for autosomal-recessive disorders and fill out an anonymous questionnaire to identify their attitudes towards screening. The questionnaire showed a positive attitude of the participants towards genetic screening, as 73% of respondents expressed a desire to undergo screening, but 46% had concerns about its possible negative consequences. With the further implementation of carrier screening by the healthcare system, it is important to organize educational work that will inform the population about the role of screening and for eliminating undesirable consequences.

Trust is a prerequisite for the effective functioning of communities in various fields of human activity, but especially in medicine. The development of human embryo genome editing technologies, according to the developers, will provide the opportunity to create new forms of medical care for people suffering from severe genetically determined diseases. At the same time, there are serious risks of introducing into the genome random adverse changes that will be transmitted to descendants. It is assumed that the start of clinical trials of these technologies will be possible after proving their clinical relevance, safety and moral acceptability. Another necessary condition should be the attitude of trust towards experimenters, including transparency of research, public and legal accountability, responsibility to patients and their families for possible adverse consequences.

The moral status of human embryo is one of the key issues of modern national and international law. The study shows public opinion on the ethical and legal status of a human embryo according to the results of anonymous survey.

In this work, the main range of bioethical problems that may arise during the mass introduction of DNA testing for hereditary hearing disorders are defined.