There are populations that have kept apart for many centuries, show less genetic variability and they differ in their genetic structure from representatives of other groups - genetic isolates. The high degree of isolation of small human populations for many generations has created good conditions for gene drift. Due to population mechanisms, such as the founder effect or the bottleneck effect there is a genetic burden of hereditary diseases, which observed in isolated populations, that negatively affects both social and economic level, as well as the quality of life. This review provides information about hereditary diseases in genetically isolated populations, existing carrier’s screening programs and the feasibility of its implementation.

This work is devoted to the study of the role of one of the most important cytokines in the human organism, interleukin-6 (IL-6). The structure and functioning of IL-6 molecule, the relationship of its level in blood plasma with diseases are considered. Data on genetic polymorphism of IL-6 gene, IL6 G(-174)C, its distribution in human populations and its association with various diseases are also described in detail. The study of this cytokine and its genetic polymorphism is relevant to population genetics and personalized medicine as well as preventive medicine aimed at taking preventive measures and preventing the development of serious diseases.

Aim: to determine the population frequency of abdominal wall malformation - gastroschisis, to analyze its dynamics from 2011 to 2019, to identify risk factors according to the regional registers of congenital malformations of the Russian Federation. Methods. We used data from registers of congenital malformations in 22 constituent entities of the Russian Federation for 2011-2019. Cases of gastroschisis in newborns and in fetuses eliminated due to the detection of a defect in the prenatal period were taken into account. The frequency of the defect was calculated per 10 000 births. Results. During the analyzed period of time 896 cases of gastroschisis were registered. The majority of cases recorded in fetuses (56.6;%), 40.4% - cases of gastroschisis in livebirths and 3.0% - in stillborns. The sex ratio among the affected is 1.3M:1F. The population frequency of the defect was 2.24 (95% CI 2.10-2.40) per 10,000 births. The frequency of the defect did not change over the years of the study. Gastroschisis is more common as an isolated defect (79.1%). In 20.9%, there was a combination with other malformations. It was shown that the frequency of the defect is higher among children of mothers under the age of 20 years (frequency 8.67, 95% CI 7.38 ÷ 10.17) and less often among the offspring of women older than 35 years (1.24, 95% CI 0.97 ÷1.58). Conclusions. As a result of the study, the frequency of gastroschisis in the regions of the Russian Federation was determined, which does not change over a 9-year period. It is shown that the young age of the mother is a risk factor for the defect occurrence. The identification of such risk factors is important to improve the effectiveness of preventive measures.

Background. The method of multiplex methylation sensitive quantitative real-time PCR (MS-qPCR) is used for the first time in the format of a multiplex system with TaqMan probes. The previously described approaches to MSRE-qPCR are insufficient for the implementation of the technique in studies of large samples of patients, which is due to the lack of a multiplex reaction format and internal controls. We propose an MS-qPCR method with the possibility of multiplexing and the presence of internal PCR controls. Aim: to characterize the analytical properties of the developed multiplex MS-qPCR method. Methods. DNA from lymphocytes from healthy donors was used as a material for the study. We have postulated that DNA undigested with methylation sensitive restriction enzyme is a model methylated template (undigested), while hydrolyzed DNA is a model unmethylated template. To determine the analytical sensitivity, mixtures of digested and undigested DNA were used. Development of the MS-qPCR panel was carried out taking into account the design requirements developed by the team: the inclusion of a positive internal control of the PCR efficiency and a control of digestion of genomic DNA by the methylation sensitive restriction enzyme. For the kinetic curves of the studied loci in all samples, Cy0 values were obtained using the qPCR package of the R programming language, and on the basis of these data, methylation levels were calculated, and box plots were presented. The analytical sensitivity of the method was determined by finding the Limit of Blank (LoB) and Limit of Detection (LoD) values. Results. The coefficient of determination (R2) for the normally non-methylated locus is 0.98, and for the locus with normal monoallelic methylation, 0.77. Analytical sensitivity of the MS-qPCR method is 5%; the relative error was 11.38%. Conclusions. Based on the results obtained, the analytical sensitivity of the MS-qPCR method is higher than that of the direct Sanger bisulfite sequencing, and comparable to bisulfite pyrosequencing. The use of TaqMan probes allows multiplexing of several target loci in one reaction, which is a fine solution to the problem of a small amount of available biological material.

Disorders of mitochondrial beta-oxidation of fatty acids - a group of rare hereditary metabolic disorders. Deficiency of long-chain 3-hydroxyacyl CoA dehydrogenase of fatty acids (LCHADD) is one of the most frequent in Europe inherited metabolic disorders from the group of defects of mitochondrial beta-oxidation of fatty acids. This disease is characterized by pathology of the liver, heart and skeletal muscle, frequent metabolic crises, and high mortality in infancy. This article discusses the basic principles of diet therapy for long-chain fatty acid oxidation disorders and the experience of using the specialized therapeutic food product «Lipano» (Kanso, Italy) in children with a confirmed hereditary disorder of mitochondrial beta-oxidation of fatty acids.

Background. The birth incidence of inherited metabolic disorders (IMDs) according to foreign literature data is about 1:5000. In some countries of the world and in most regions of the Russian Federation, newborns are screened for only 5 diseases, although the spectrum of hereditary diseases for which treatments have been developed is much wider. A new stage in neonatal screening was initiated with the advent of tandem mass spectrometry (TMS), a technology that significantly improves screening and expands the list of detectable disorders that are treatable and previously undiagnosable by screening programs. Aim: to evaluate the results of newborn screening by TMS for 37 IMD and to estimate the incidence of IMDs in Primorsky Krai. Methods. Extended neonatal screening in Primorsky Krai for 37 IMDs was performed using TMS in the period 2017-2021. 68481 newborns were examined. All detected cases were confirmed by molecular genetic methods in Research Centre for Medical Genetics (RCMG). Results. As a result of the examination of more than 68,000 newborns, various IMDs were identified in 8 children with phenylketonuria, 4 patients with very long-chain acyl-CoA fatty acid dehydrogenase deficiency, 2 patients with homocystinuria, 2 patients with glutaric aciduria, 1 patient with leucinosis, 1 patient with deficiency of trifunctional mitochondrial protein. Additionally, 12 children are currently under dynamic observation, and among them, there is a high probability of detecting IMD. All disorders from the group of other diseases were confirmed by specialists of RCMG. The incidence of confirmed IMD was 1:3805 newborns. The actual incidence was assumed to be higher for a variety of technical, organizational, and social reasons. Conclusions. The results convincingly demonstrate that newborn screening by the TMS method is an effective and extremely necessary element of clinical practice to reduce morbidity, disability and mortality from IMDs.