The effects of the demographic history of mankind have led to the fact that the indigenous peoples of Dagestan and Siberia are inferior in terms of genetic diversity to the populations of Europe, which affects the level of identification informativeness of standard forensic autosomal markers in these populations. In our study, we evaluated the effectiveness of two standard sets of autosomal STRs (13 CODIS, 20 CODIS, Combined DNA Index System) for the genetic testing of parent-child relatedness in four highly inbred populations of the Russian Federation and the Russian population, using two types of reference frequencies. The results of the study confirmed the assumption that the level of identification informativity of standard autosomal markers in highly inbred populations of Siberia and Dagestan is lower than in the Russian population. The total information content of markers of the new CODIS standard exceeds the threshold values required in the order of the Ministry of Health and Social Development of the Russian Federation (No. 346n). At the same time, the probability of a false positive result increases with an increase in the inbreeding coefficient in the population.

The effects of the demographic history of mankind have led to the fact that the indigenous peoples of Dagestan and Siberia are inferior in terms of genetic diversity to the populations of Europe, which affects the level of identification informativeness of standard forensic autosomal markers in these populations. In our study, we evaluated the effectiveness of two standard sets of autosomal STRs (13 CODIS, 20 CODIS, Combined DNA Index System) for the genetic examination of parent–child relationship in four highly inbred populations of the Russian Federation and the Russian population, using two types of reference frequencies. The results of the study confirmed the assumption that the level of identification informativity of standard autosomal markers in highly inbred populations of Siberia and Dagestan is lower than in the Russian population. The total information content of markers of the new CODIS standard exceeds the threshold values required in the order of the Ministry of Health and Social Development of the Russian Federation (no. 346n). At the same time, the probability of a false positive result increases with an increase in the inbreeding coefficient in the population.

The gene pool of the indigenous population of Siberia is a unique system for studying population and evolutionary genetic processes, analyzing genetic diversity, and reconstructing the genetic history of populations. High ethnic diversity is a feature of Siberia, as one of the regions of the peripheral settlement of modern human. The vast expanses of this region and the small number of aboriginal populations contributed to the formation of significant territorial and genetic subdivision. About 40 indigenous peoples are settled on the territory of the Siberian historical and ethnographic province. Within the framework of this work, a large-scale population study of the gene pool of the indigenous peoples of Siberia was carried out for the first time at the level of high-density biochips. This makes it possible to fill in a significant gap in the genogeographic picture of the Eurasian population. For this, DNA fragments were analyzed, which had been inherited without recombination by each pair of individuals from their recent common ancestor, that is, segments (blocks) identical by descent (IBD). The distribution of IBD blocks in the populations of Siberia is in good agreement with the geographical proximity of the populations and their linguistic affiliation. Among the Siberian populations, the Chukchi, Koryaks, and Nivkhs form a separate cluster from the main Siberian group, with the Chukchi and Koryaks being more closely related. Separate subclusters of Evenks and Yakuts, Kets and Chulyms are formed within the Siberian cluster. Analysis of SNPs that fell into more IBD segments of the analyzed populations made it possible to compile a list of 5358 genes. According to the calculation results, biological processes enriched with these genes are associated with the detection of a chemical stimulus involved in the sensory perception of smell. Enriched for the genes found, molecular pathways are associated with the metabolism of linoleic, arachidonic, tyrosic acids and by olfactory transduction. At the same time, an analysis of the literature data showed that some of the selected genes, which were found in a larger number of IBD blocks in several populations at once, can play a role in genetic adaptation to environmental factors.

Проведена оценка уровня генетического разнообразия, вероятности дискриминации неродственных индивидов (PD, power of discrimination) и исключающей способности (PE, power of exclusion) 43 аутосомных STR (D3S1358, TH01, D12S391, D5S818, TPOX, D13S317, FGA, D22S1045, D18S51, D16S539, D8S1179, CSF1PO, D6S1043, vWA, D21S11, SE33, D10S1248, D1S1656, D19S433, D2S1338, D20S1082, D6S474, D12ATA63, D4S2666, D1S1677, D11S4463, D9S1122, D2S1776, D10S1435, D3S3053, D5S2500, D1S1627, D3S4529, D2S1360, D17S974, D3S1744, D9S2157, D17S1301, D8S1132, Penta D, D21S2050, D7S1517, Penta E) в популяциях аварцев из трех районов Дагестана: Шамильского, Тляратинского, Унцукульского. Полученные результаты показали, что для проведения генетической экспертизы в Дагестане, при выборе референсной группы, необходимо учитывать не только этническую принадлежность индивида, но и географическую локализацию. We assessed the level of genetic diversity, power of discrimination, power of exclusion of 43 autosomal STRs (D3S1358, TH01, D12S391, D5S818, TPOX, D13S317, FGA, D22S1045, D18S51, D16S539 , D8S1179, CSF1PO, D6S1043, vWA, D21S11, SE33, D10S1248, D1S1656, D19S433, D2S1338, D20S1082, D6S474, D12ATA63, D4S2666, D1S1677, D11S4463, D9S1 122, D2S1776, D10S1435, D3S3053, D5S2500, D1S1627, D3S4529, D2S1360, D17S974 , D3S1744, D9S2157, D17S1301, D8S1132, Penta D, D21S2050, D7S1517, Penta E) in Avar populations from three regions of Dagestan: Shamilsky district, Tlyaratinsky district, Untsukulsky district. The results emphasized the need to take into account the geographic origin of the individual, and not just his nationality, when choosing reference data during genetic examination in the populations of Dagestan.

For the first time, genetic characteristics of 15 local populations of eight ethnic groups of Eastern Europe were obtained using an expanded panel that included 21 autosomal STR markers used in forensic practice for DNA identification and kinship establishment. The assessment of polymorphism of markers in the Russian, Belarusian, and Moldovan populations was carried out, and the levels of intra- and interpopulation genetic differentiation of the studied population groups were characterized. The parameters of the informational significance of the system of autosomal microsatellites for expert DNA identification and establishment of kinship were estimated. A database of allele frequencies of autosomal STR loci has been developed, which can be used to carry out probabilistic and statistical calculations when assessing the level of reliability of an expert study in the countries of the Union State. It was shown that population genetic structure should be taking into account in forensic DNA analysis.

A replicative analysis of associations with obesity of 53 polymorphic markers associated with the results of genome-wide studies with variability of the body mass index and/or obesity was performed. For the first time in the Russian population, an association with obesity of polymorphic markers rs3810291 of the ZC3H4 gene, rs12940622 of the RPTOR locus, rs1800437 of the GIPR gene, and rs13021737 located in the intergenic region of the genome is shown. Possible molecular mechanisms for the involvement of the studied genes in the pathogenesis of the disease are discussed.

Genetic diversity of a large number of populations is analyzed using various Y-chromosome markers. Genotyping of a wide range of novel highly informative SNP and YSTR markers shows that most of the Y-chromosome haplogroups can be divided not only into ethnically specific lineages but also into narrower sublineages and clusters of haplotypes. A significant extent of population and interethnic genetic differentiation is revealed. Most ethnic gene pools are characterized by the predominance or even complete dominance of specific SNPs across all major haplogroups, that is highly promising for the application in ethnic identification of biological samples of males.

Актуальным является поиск генетических вариантов связывающих снижение различных сфер мыслительных процессов с возрастом и болезнью Альцгеймера. Цель исследования - поиск взаимосвязи белковых гаплотипов двух полиморфных вариантов гена APOE с вариабельностью восьми доменов когнитивных функций пожилых людей, определяемых по баллам батареи тестов Монреальской шкалы оценки когнитивных функций (МоСА). Две наиболее высоко статистически значимые ассоциации выявлены для генотипа ε3/ε3 в сравнении с носителями аллеля ε4. Это домены памяти (р=0,002) и зрительно конструктивных навыков (р=0,007). Не обнаружено статистически значимых ассоциаций для когнитивных сфер: внимание и концентрация, исполнительные функции, язык, абстрактное мышление, счет и ориентация. Возможно, обнаруженные ассоциации обуславливают общую генетическую природу наследования болезни Альцгеймера, психических расстройств, деменции и интеллекта у пожилых людей. The search for genetic variants linking the decline in various areas of cognitive processes with age and Alzheimer’s disease is relevant. The aim was to search for the relationship of protein haplotypes of two polymorphic variants in the APOE gene with the eight cognitive function domains variability in f the elderly. Domains were determined by the battery score of the Montreal Cognitive Assessmnet (MoCA). The two most highly statistically significant associations were identified for the ε3/ε3 genotype in comparison with carriers of the ε4 allele. These are memory (p = 0.002) and visuospatial abilities (p = 0.007) domains. No statistically significant associations were revealed for cognitive domains: attention and concentration, executive functions, language, abstraction, calculations and orientation. Possibly, the identified associations determine the general genetic baseline of inheritance of Alzheimer’s disease, mental disorders, dementia and intelligence in the elderly.

Haplotype associations of 894 DNA samples of elderly people from the Russian population of Tomsk were analyzed using 49 SNPs (single nucleotide polymorphisms). As the analyzed markers, SNPs were selected that showed an association with Alzheimer's disease or variability of cognitive abilities in genome-wide association studies. As a result of the analysis, blocks on chromosomes 1, 2, 6, 8, 11, 19, and 20 were identified. Significant associations were shown, taking into account 50 000 permutations, for haplotypes localized on chromosomes 1 and 19 in the genesCR1andAPOE,APOC1, respectively. Our results confirm the role of theAPOEandCR1genes in the pathogenesis of Alzheimer's disease in the Russian population.

Obesity is one of the major challenges in modern society. More than a third of the world's population suffers froms overweight. This phenotype affects the quality of life and is associated with cardiovascular diseases, diabetes, cancer and reproductive disorders. The population variability of allele frequencies of 26 single nucleotide polymorphisms, in association with obesity and body mass index, according to data from genome-wide association studies (GWASs) is discussed in this study. Genetic variability was analyzed in populations of Northern Eurasia and populations from the human genome diversity project (HGDP). The population samples are characterized by high genetic diversity that correlates with climatic and geographical parameters. The results of the test for searching for natural selection signals revealed a selection effect for rs1167827 of the HIP1 gene, rs7138803 and rs7164727 located in the intergenic region, rs7141420 of the NRXN3 gene, rs7498665 of the SH2B1 gene, and rs7903146 of the TCF7L2 gene.

Obesity is one of the main risk factor for the development of socially important diseases, determining the life quality and human longevity. According to the World Health Organization (WHO) overweight and obesity are dramatically increased all over the world. This problem is particularly acute in industrialized countries, where it is becoming a non-infectious pandemic. Thus, it is critically important to focus our research efforts on studying of the genetic basis of the obesity spread in modern human populations. Genetic markers that are related to obesity and quantitative characters as body mass index (BMI), blood lipid levels and others have been identified as a result of number of studies. In the present study the variability of the GWAS-identified SNP allele frequencies associated with BMI and obesity was studied. The results of our study were compared with data on 20 populations from the international project "1000 Genomes". Genetic markers that make the greatest contribution to the genetic differentiation of populations were identified.

Obesity is one of the global health problems resulting in significant economic and social damage in both developed and developing countries. Overweight and obesity are key risk factors of diabetes and cardiovascular and oncological diseases that cause high morbidity and mortality. In the present paper, the method of multiplex genotyping of polymorphic variants of genes associated with obesity and variability of body mass index (BMI) was developed on the basis of multilocus PCR and MALDI-TOF mass spectrometry of DNA molecules. The frequencies of 51 single-nucleotide polymorphisms of obesity candidate genes in a population sample of Russians in Kemerovo were characterized. The results obtained were compared with the data for populations from the 1000 Genomes project. The association of markers rs12446632 of the LOC105371116 locus and rs16851483 of the RASA2 gene with BMI variability in the Russian population of Kemerovo was shown.

Human adaptation to extreme climatic and geographic conditions mediated by natural selection may be one of the major factors for formation of genetic structure in North Eurasian populations. Using data on a genome-wide set of single nucleotide polymorphisms (SNPs), we searched for the signals of positive selection in five populations of Siberia and the Russian European North. From 113 to 185 genomic regions with extended homozygous haplotypes blocks containing altogether 771 genes were found in each of the populations. Cross-population search of the selection targets resulted in about 150 genomic regions, 57 of which overlap with the results of haplotype analysis in individual populations. Genomic loci with the most profound signals of positive selection in northern populations include regions of SLC30A9, CACNA1C, KCNQ5, ABCA1, ALDH1A2, CSMD1, RBFOX1, and WWOX, as well as some other genes. Bioinformatics analysis demonstrated that major biological processes where selection targets are implicated are those conferring the response to external stimuli, including proteins, nutrients, and glucose, and defense reactions, including inflammatory immune response. The network of protein-protein interactions of genes under positive selection forms distinct clusters related to a number of biological processes indicated above. Results of the study indicate that non-neutral microevolution mechanisms may play a substantial role in genetic structuring of the human populations during long-term adaptation to unfavorable environmental conditions.

A developed method of multiplex genotyping of polymorphic markers of genes associated with cognitive abilities and neuropsychiatric diseases is based on multilocus PCR and MALDI-TOF mass spectrometry of DNA molecules. The frequencies of 32 single-nucleotide markers localized in 24 genes are analyzed in a sample of elderly people from the Russian population of Tomsk. The data obtained are compared with data for populations from the 1000 Genomes Project.