For the senior generations of Moscow and Novosibirsk, no significant differences by the dis-tribution of haplogroups of Y-chromosome (typical for the Russian gene pool [1, 2]) were re-vealed, excluding those by «Southern by origin» haplogroups, penetrating into gene pool by migration, that indicates necessity of development separate reference databases for each meg-alopolis.

In the sample of male residents of St. Petersburg, Y-chromosome haplogroups were determined by genotyping 18 STR Y-chromosome (DYS389I, DYS389II, DYS390, DYS19, DYS385A, DYS385B, DYS456, DYS437, DYS438, DYS447, DYS448, DYS449, DYS391, DYS392, DYS393, DYS439, DYS635 and DYS576) and data on genetic demography were collected by means of a questionnaire. The distribution of Y-chromosome haplogroups in St. Petersburg residents generally corresponds to the published data on Russian gene pool, with the most frequent haplogroups R1a, R1b, E1b1b1, N, T, I1, I2, J1 and J2, and with the predominance of haplogroup R1a. The presence of “southern by origin” haplogroups (C3, G2a, G2c, J1, J2, L, O2, O3, Q, R2 and T) entering the megalopolis with a flow of migrants, with a total frequency of 16% (in Moscow – 18.1%) was noted. A comparative analysis of the frequency distributions of Y-chromosome haplogroups in residents of St. Petersburg and Moscow revealed statistically significant differences in the frequency of haplogroup E1b1b1, and differences in the ratio of I1 and I2, determined by geographic position. Based on the survey data, a sample of Russian men who had no ancestors of another ethnicity in the male line in the two previous generations was formed. Significant differences in the frequency of “southern-origin” haplogroups were established between the initial sample of residents of St. Petersburg (16%) and the sample of men with Russian ancestors in two previous generations (4.1%). The obtained result confirms the spectrum of haplogroups of “southern origin” as penetrating into the gene pool of the population of a megalopolis with migrant flows and indicates the need for genetic and demographic questionnaires when forming reference databases for a megalopolis, as well as for their timely updating due to changes in the gene pool under the influence of migration.

Based on the analysis of the data of the 2010 All-Russia’s Population census and the demographic statistics of Rosstat Agency, the genetic-demographic parameters of temporal and interethnic variability of natural reproduction parameters and selection parameters (Crow’s indices) were calculated for the most numerous ethnic groups of Moscow and St. Petersburg. The selection component due to differential prereproductive mortality was shown to decrease to the lowest possible values (index Im < 0.01). In both megacities, interethnic differences were revealed in the parameters of natural reproduction and the selection component due to differential fertility, while the birth rate in both capitals for all ethnic groups, except for Uzbeks in St. Petersburg, is lower than required even for simple reproduction of the population, and hence stable reproduction of the gene pool. This indicates the unfavorable nature of the genetic- demographic processes in all the represented nationalities of the megacities. The If index ranges from 0.2 to 0.5. The temporal dynamics of the average number of offspring and its variance, as well as the If index, traced according to the data on the age cohorts of women born in the 1940s–1960s, is weakly expressed; a tendency to selection relaxation is not observed for all the studied ethnic groups. It is shown that the intensity of intergroup selection, due to interethnic differences in fertility, in the population of St. Petersburg increases from older age cohorts to younger ones, while in the population of Moscow it did not change significantly, and the temporal dynamics of this indicator, calculated on the base of the data in the 2002 All-Russia’s Population census for cohorts born in 1930s–1950s have the opposite direction. The genetic-demographic consequences of the revealed tendencies are discussed.

On the basis of demographic statistics from the Rosstat Agency and population censuses, a statistical analysis of the temporal and interethnic variability of natural reproduction indicators and selection parameters (Crow’s indices) in the population of the USSR and the Russian Federation was carried out. A multiple decrease over a one-hundred-year period in the selection component due to differential mortality (index Im) was shown. A significant temporal dynamics in the selection component due to differential fertility (index If) was revealed, and fundamental differences in the nature of this dynamics in different ethnic groups were demonstrated: several groups demonstrate relaxation of this selection component, while in most groups the dynamics is absent or the If index increases over time. It has been shown that the intensity of intergroup selection based on interethnic differences in fertility increased over half a century in the USSR nationwide and was an order of magnitude higher than in modern Russia nationwide. The genetic and demographic consequences of the revealed trends are discussed.

In three generations, peculiarities of changes in the profile of Y-chromosome haplotypes were studied. Genetic demographic questionnaire collecting and genotyping by 18 STR of Y-chro-mosome were performed, haplogroups of Y-chromosome were detected. In generations of megalopolis population, specific peculiarities of the frequency profiles of Y-chromosome hap-logroups were detected, due to migration of population to megapolis. In the youngest genera-tion, in comparison with two previous generations statistically significant accumulation in the gene pool of megalopolis population “southern” by origin haplogroups bringing to megapolis with migrant flows. Obtained results are in good agreement with ethnic contents of migrants to Moscow detected by questionnaire data.

In three samples from the Moscow population representing three conditional generations, genotyping was carried out for 18 STR of the Y-chromosome and data on genetic demography were collected by means of a questionnaire. Comparative statistical analysis revealed spectra and frequency profiles of Y-chromosome haplogroups characteristic for each generation and demonstrated significant differences between the two older generations and the younger generation of Moscow residents, in particular, in the frequency of haplogroup N. In the younger generation, statistically significant accumulation of haplogroups of “southern origin” brought with the flows of migrants was shown. In the three generations of Muscovites, features of the Y‑chromosome haplogroup frequency distribution are in good agreement with the parameters of migration flows to Moscow during recent decades and with survey data on the migrant places of origin and ethnic composition. The results of the study indicate the necessity of permanent updating and actualization of population reference databases for the purposes of DNA-based identification in megacities, as well as the necessity of accomplishing molecular genetic analysis by the data on genetic demography obtained by questionnaire survey.

In children of Krasnodar krai ( N = 159), association of VNTR polymorphisms of two cytokine genes, antagonist of receptor of interleukin 1 ( IL1RN ) rs2234663 and interleukin 4 ( IL4 ) rs8179190 , with dental caries was studied. In three groups of children with DFC (decompensated form of caries), with SFC (subcompensated form of caries), and with CFC (compensated form of caries) and in healthy children, statistically significant differences were observed between groups by the presence of two “long” alleles L / L of rs2234663 , including found alleles A1 and A4 , between groups of children with CFC and DFC and between SFC and DFC using statistical analysis: OR = 0.33, p = 0.014; 95% CI 0.13–0.87 and OR = 0.35, p = 0.035; 95% CI 0.12–1.00, respectively. The genotypes with two “long” alleles L / L (500 and 410 bp) in genotype were demonstrated mediating resistance to a highly active form of caries, and compound two-locus genotypes by rs2234663 and by rs8179190 ( A1 / A2 P2 / P2 and A2 / A2 P2 / P2 ) and genotypes including at least one allele P2 and one allele A2 (“short”) mediating susceptibility. The group of children with SFC analogous to the group of children with CFC (and healthy) statistically significantly differs from DFC in the same spectrum of the studied VNTR markers of two cytokine genes, which supposes a special role of the studied markers of two cytokine genes in the development of a highly active form of caries.

Adequate levels offolate are crucial for human development. MTHFR (Methylene tetrahydrofolate reductase) is involved in the metabolism of folic acid and other B vitamins. The aim of this work is to examine the allele frequency and haplotype distribution of MTHFR-C677T and MTHFR-A1298C polymorphisms in two independent samples (North-East Spanish and North-Western Siberia). The degree of population differentiation and signatures of positive selection were also examined in 18 world populations. The samples comprised 623 Spanish individuals and 172 Ob-Ugric people (Khanty and Mansi). The Spanish sample showed 44% individuals with 30% reduced enzyme activity, and 16% people with 70% reduced activity; whereas the Khanty sample revealed only 3% people with 70% reduced activity. In the 18 populations screened, we found significant South to North clines for SNPs and haplotypes. Overall, we failed to detect any traces of positive selection. The high frequency of people with reduced MTHFR enzyme activity in Spain highlights the need for diets rich in folate and folic acid supplementation in some groups. The low frequency of individuals with reduced enzymatic activity among the Khanty together with their traditional diet indicates a protective combination against pathologies related to folic acid deficiencies.

Estimation of the main genetic-demographic parameters of migration processes significant for studying the structure of the gene pool of the Moscow population is based on the analysis of demographic statistics, All-Russia population censuses, and data from a sample survey of two groups of Moscow residents differing in age characteristics: “older” group, mean year of birth 1948; “younger” group, mean year of birth 1987. A significant increase in the intensity and distance of migration to Moscow over the past 40 years was demonstrated. The migration coefficient calculated according to the survey data of the “older” group of Muscovites is 0.413 for men and 0.517 for women; the average migration radius is 1008 km; according to the survey data of the “younger” group, the migration coefficient is 0.636 for men and 0.657 for women; the average migration radius is 1782 km. Gender peculiarities of migration processes in Moscow were detected; they cause significant differences in age and sex composition of urban residents of different nationalities (a numerical predominance of men among the members of “young” ethnic diasporas). Data on the sources of formation of the gene pool of the Moscow population at the present stage demonstrate that the portion of those born in Russia in the “older” age group (89%) is much higher than in the “younger” group (76%). In the first case, the gene pool is formed by 3/4 owing to the population of the Central Federal District (CFD); the contribution of the Volga Federal District and Ukraine is noticeable; in the second case, only half of the respondents were born in the CFD; there are many natives of the Volga, North Caucasus, Southern, and Siberian districts, the republics of Central Asia, Ukraine, and Armenia. The survey data are confirmed by the analysis of data on migration statistics of Rosstat Agency about the composition of migrants to Moscow by country of exit. Differences in migration parameters in the two age groups indicate the possibility of dynamics of the ethnoterritorial composition of the Moscow population in subsequent generations, which will certainly cause a change in the frequencies of many genetic markers, including frequency profiles of DNA-based identification markers. The peculiarities of migration processes in Moscow identified in this study indicate the need for timely renewal and updating of genetic databases for DNA-based identification purposes in a megalopolis.

In children with mixed bite from Krasnodarskii krai, investigation of association of VNTR-polymorphisms of two cytokine genes – gene of antagonist of interleukine 1 receptor gene (IL1RN) rs2234663 and interleukine 4 (IL4) rs8179190 with dental caries revealed, that markers studied are associated with highly active form of caries: genotypes with two “long” alleles L/L by IL1RN were found as mediating resistance to highly active form of caries and genotypes A1/A2 P2/P2 and A2/A2 P2/P2 mediating susceptibility. Key words: children, caries, IL1RN (rs2234663), IL4 (rs8179190), VNTR, cytokine genes

In this study, we investigated VNTR polymorphisms in intron 2 of the IL1RN gene (rs2234663) and intron 3 of the IL4 gene (rs8179190) related to the development of caries in school children (N = 196) with mixed bite dentition from Krasnodarskii Krai. The genotypes A1/A1 and L/L (L-“long” alleles) (rs2234663) provided resistance to the most intensive form of dental caries. The groups of children with DFC (decompensated form of caries) were significantly different from the pooled group SFC (subcompensated form of caries) and CFC (compensated form of caries) (and healthy children) for two genotypes: A1/A1 (OR = 0.37, p = 0.015, 95% CI: 0.17-0.84) and L/L (OR = 0.38. p = 0.020, 95% CI: 0.17-0.88). In locus rs8179190 (IL4), a rare allele with a single repeat (70 bp)-P3 (113 bp) was observed. For VNTR polymorphisms of rs8179190, association with the most intensive form of caries was found only for two-locus genotypes with rs2234663. The results suggested that the studied cytokine markers and the ratio of the pro-inflammatory to anti-inflammatory cytokines might be involved in the development of the most intensive form of caries.

Association of VNTR polymorphisms of two cytokine genes – antagonist of receptor of interleikine 1 (IL1RN) rs2234663 and interleikine 4 (IL4) rs8179190 with dental caries was studied in three groups of chidren with DFC (decompensated form of caries) with average age 10.19±0.54, with SFC (subcompensated form of caries) (11.66±0.46) and with CFC (compensated form of caries) and healthy (12.08±0.38). The genotypes with two “long” alleles L/L by IL1RN were demonstrated mediating resistance to highly active form of caries, and genotypes: A1/A2 P2/P2 and A2/A2 P2/P2 - susceptibility.

On the basis of the materials of the 2010 All-Russian Population Census in Moscow, an analysis of the unevenness of the settlement of ethnic groups in the urban area is carried out. Maps reflecting the “ethnic topography” of the megalopolis have been constructed. Using the attribute “nationality” as a “quasi-genetic” marker, estimates of the level of territorial subdivision of the megalopolis population have been obtained for two levels of the population structure: for the level of large administrative-territorial units F st = 0.129 × 10 –2 ; for the level of small administrative-territorial units F st = 0.742 × 10 –2 . Areas of the city characterized by the greatest ethnic diversity have been identified. The analysis of changes in the ethnic topography of Moscow for more than a century is carried out. The results of the study should be taken into account when forming genetic databases for the purposes of DNA identification in the Moscow population.

Association of the A66G SNP in the MTRR gene with dental caries was studied in children with congenital anomalies of the maxillofacial region (CA of MFR), i.e., with congenital cleft lip with or without cleft palate (CL, CP, and CLP) and in children without congenital anomalies. Comparison of samples of children with CL, CP, and CLP and children without congenital anomalies revealed association of the A66G SNP of the MTRR gene with the considered anomalies, which made it impossible to establish probable association of this marker with caries (for the G/G genotype, an association with the increased risk for developing CA of MFR was observed: OR = 2.16; P = 0.046; 95% CI (1.00–4.67). In children without pathology, an association of the A66G SNP of the MTRR gene with early caries was revealed. In carriers of the A/A genotype among children with primary and mixed bite (N = 91) and the mean age of 6.51 ± 0.2 years, the risk for developing more severe form of caries was higher: OR = 4.91; P = 0.006; 95% CI (1.53–15.78); and among children with primary bite (N = 53) and the mean age of 4.71 ± 0.18 years, OR = 10.53; P = 0.024; 95% CI (1.19–485.29). In children with heterozygous A/G genotype, the resistance to more severe form of caries was observed. Therefore, the A66G SNP of the MTRR gene can be considered as a marker of early caries in children without congenital anomalies.

The principal genetic demographic parameters that describe migration processes affecting the structure of the St. Petersburg population gene pool were determined on the basis of the demographic statistics obtained from the Petrostat Agency, All-Russian population censuses, and a sample survey of St. Petersburg residents. The migration coefficient was 0.36 according to the survey data, 0.42 according to the 2002 census, 0.44 according to the 2010 census, and 0.69 according to the 1897 census. The estimated average migration distance was 1746 km from the survey data, 1526 km according to the 2002 census, and 1652 km according to the 2010 census. The sources of the St. Petersburg population gene pool in different periods are discussed: in the 18th and 19th centuries, the main source was the population of the Upper Volga and Northwestern provinces of the Russian Empire, as well as foreign immigrants, whereas currently three quarters of the population gene pool originates from the Northwestern Federal District, 10% comes from natives of foreign countries, and only 6–9% is due to the population of the Central Federal District of the Russian Federation. An analysis of the Rosstat migration statistics showed that the composition of migrants by countries of exit varied over time. For instance, the share of migrants who arrived in St. Petersburg from Russia in the last five years ranged from 74 to 87%. In 2013–2014, most international migrants came from Uzbekistan (10% of all arrivals) and Tajikistan (3–4%), while in 2017, the countries with the highest number of migrants ranked as follows: Kyrgyzstan (almost 4%), Ukraine (about 2%), Belarus (1.5%), Kazakhstan (1.25%), and Armenia (1%). Migration processes determine the dynamics of the ethnic composition of the population. Gender differences in migration flows are manifested in different age structure and in unequal sex ratio within particular ethnic groups (e.g., predominance of men in the “young” ethnic diasporas: Armenians, Azerbaijani, and Uzbeks). The described features of migration processes in St. Petersburg should be taken into account when forming genetic marker databases for the purposes of DNA-based identification. The areas of migration attraction of St. Petersburg and Moscow overlap only partially, which predetermines the need to create separate databases for each megacity.