Изучение наследственных факторов в детерминации долголетия представляется весьма актуальным в связи с ростом средней продолжительности жизни, поиском возможностей продления «здорового» периода в позднем отногенезе. Феномен высокой продолжительности жизни всегда вызывал особый интерес исследователей, а его изучение представляется наиболее перспективным в популяциях с достаточно большой долей долгожителей. С давних времен известны случаи ярко выраженного активного долголетия в регионе Кавказа. У долгожителей Абхазии темпы соматического развития, уровень обменных процессов и меньшая интенсивность возрастной инволюции скелета указывали на относительно «здоровый» тип старения. Среди генетических факторов, которые потенциально могли бы играть важную роль в достижении долголетия, особенно перспективным представляется изучение плейотропных генов, действие которых проявляется во множественных эффектах и обладающих высокой функциональной значимостью. Среди них особый интерес представляют те, которые определяют эффективность функционирования сердечно-сосудистой системы, а также особенности, влияющие на темп созревания и старения организма. К числу таких генов можно отнести ген ангиотензин-превращающего фермента (ACE) и ген множественной лекарственной устойчивости (ABCC11). Целью исследования был поиск закономерностей в характере распределения полиморфных вариантов плеойтропных генов ABCC11 и ACE в популяции абхазов в связи с возрастом обследуемых и наличием долгожителей в выборке. В качестве материала исследования были собраны образцы клеток буккального эпителия от коренных жителей Абхазии, подразделенных на две группы: старшего возраста (75-101 год, 79 человек) и контрольную ( 97 индивидов в возрасте от 16 до 33 лет ). Анализ распределений частот генотипов и аллелей полиморфизма 538G>A (rs17822931) гена ABCC11 показал, что группы старшего возраста и контроля очень сходны между собой и достоверные различия между выборками отсутствуют. Генотипирование по инсерционно-делеционному полиморфизму гена ACE (rs1799752) осуществлялось методом ПЦР-ПДАФ. Для контрольной группы абхазов установлены следующие частоты генотипов: II = 0,186; ID = 0,412; DD = 0,402, частоты аллелей I и D оказались равны 0,392 и 0,608 соответственно. Группа старшего возраста по частотам генотипов существенно не отличалась от контроля, генотипы II/ID/DD были распределены в соотношении 0,088/0,380/0,532, а частоты аллелей I и D оказались равны 0,278 и 0,722 соответственно. В результате исследования выявлено, что частота аллеля делеции по инсерционно-делеционному полиморфизму в гене ACE в старшей возрастной группе абхазов достоверно повышена по сравнению с контрольной группой. The study of the phenomenon of longevity is the most promising in populations with a fairly large proportion of centenarians. Since old times cases of pronounced active longevity have been widely known in the Caucasus region. The complexity of age-related processes of aging assumes the involvement of multiple complex factors that have affect on life expectancy. Therefore the study of the pleiotropic genes with their multiple effects and functions could be helpful in that case. The angiotensin I-converting enzyme (ACE) gene and the multiple drug resistance gene ( ABCC11) are of great interest because of their high importance for essential vital functions. The aim of the study was the search for correlations in the frequencies distribution of polymorphic variants of pleoitropic genes ABCC11 and ACE in the population of Abkhazians with the longevity. The material included the DNA samples from indigenous residents of Abkhazia. They were divided into two groups: older age (N = 79) and control (N = 97). The differences in the frequencies distribution of 538G>A genotypes and alleles of the gene ABCC11 in the older group and control were not significant. ACE gene insertion-deletion polymorphism ( rs1799752) genotyping was performed by PCR-AFLP. The genotype frequencies were : II = 0.186; ID = 0.412; DD = 0.402, allele frequencies I and D were equal to 0.392 and 0.608 for the control group of Abkhazians. The older group did not differ significantly from the control in genotype frequencies, the ratio for II/ID/DD genotypes were as 0.088/0.380/0.532, and the frequencies of alleles I and D corresponded to 0.278 and 0.722. The obtained results revealed that the ACE gene deletion allele frequency was significantly increased in the older group of Abkhazians.

Proteins of the ATP-binding cassette superfamily have important biological functions for active transmembrane transport of compounds, ion channels modulation in cells. Mutations in genes of this superfamily are responsible for the pool of hereditary diseases and cause the effect of multiple drug resistance response to chemotherapy as well. The frequency distribution of this functionally significant mutation in the multidrug resistance gene was analyzed in the present study. This is the first case of finding carriers of the ABCC11 gene 27-bp deletion in the ethnic groups of Russia. The revealed deletion allele frequency corresponds to 4.44% for the Aleuts and to 0.36% for the Kalmyks. The rest studied populations - Russians, Khants, Nivkhs, Mongols, Altaians were monomorphic for the absense of this (rs387906296) mutation. This study genotyping data were compared to the worldwide frequency distribution of the 27bp-deletion in the ABCC11 gene.

A short review represents comprehensive information in ABCC11 gene polymorphism including our own data about the distribution genotypes and alleles frequencies of ABCC11 (rs17822931) in some ethnic groups of Russia. The protein encoded by ABCC11 gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. Non-synonymous single nucleotide polymorphisms (SNP) 538G >A (rs17822931; Gly180Arg) in the ABCC11 gene determines the type of earwax in individuals has shed light on the novel function of this ABC transporter in apocrine glands. The wild-type (Gly180) of ABCC11 gene associated with wet-type earwax, axillary osmidrosis, and colostrums secretion from mammary gland as well as the potential risk of mastopathy. The SNP (538G>A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy. The aim of this work is to study the genotypes and alleles distribution in the ethnical groups of Russia by molecular genetics methods. In the results data on the ABCC11 (rs17822931) polymorphism in three small ethnic group of Russia are represented in this study. The frequencies of ABCC11 (rs17822931) alleles (*G and *A) which determine wet and dry types of ear wax are equal were in khants population to 0,3291 and 0,6709; in nenets 0,3172 and 0,6828 (Western Siberia) and in kalmyks of the Lower Volga to 0,1620 and 0,8380 accordingly.

Analysis of DNA samples from buccal epithelium of Abkhazian residents was submitted for APOE polymorphism. The material was collected in 2013 and it was grouped according to the genetic research into two samples: a) persons of oldest age group (from 75 to 101 year); b) a control group of an average age cohort persons (from 16 to 33 years). APOE polymorphism (OMIM +107241) associated with effect of life duration in other world populations were investigated. Among many diseases which are associated with certain APOE genotypes, carriers of APOE* 4 allele are characterized by the increased risk of development of cardiovascular pathology. APOE*3 and APOE*4 allele frequencies demonstrated for Abkhazian long-livers were 0,9359 and 0,0128 respectively, while in control group these frequencies were 0,8315 and 0,0815 respectively. Distinctions between the compared cohorts concerning alleles APOE*3 and APOE*4 frequencies were significant (at x 2 > 10 and 8 respectively and P<0 ,05 ). Distinctions between the compared groups concerning genotype frequencies were also significant (x 2 = 10,072; d.f. = 5; P < 0 ,05 ). Frequencies of APOE* 2 allele were statistically similar for both samples. So the ApOe 4-4 genotype and APOE* 4 allele seem to be unfavorable for the oldest age group. On the contrary, APOE* 3 allelomorph and genotypes connected with APOE*3 are favorable factors. Our results confirmed previous observation that frequency of the «wild» genetic factors increases to the maximum in the oldest age group.

Results of the molecular-genetic polymorphism study (ACE, CHIT1, SIRT1, NOS3 and PON1 genes) in a group of patients suffering from vibration syndrome (VS) are presented. The findings were compared with those obtained from a control group mainly of Russian nationality. Similarities in the frequencies of ACE, CHIT1 and NOS3 factors were determined between group with VS and cardiovascular pathology patients. We observed significant differences in frequencies of the ACE and NOS3 genetic markers between VS and the control group. A distinctive character of CHIT1 genotype distribution was observed in patients with VS. The previously described connection between VS and SIRT1 genotypes frequencies was not confirmed.

The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (~3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago.

Serological and biochemical polymorphisms in marker genes of the AB0, MN, RH, FY, HP, TF, ACP1, PGM1, ESD, and GLO1 systems were studied in the combined sample of 369 individuals of Chuvash ethnicity from Morgaushskii, Mariinsko-Posadskii and Yadrinskii districts of the Chuvash Republic. We have compared our results with the data obtained in previous studies by other authors. A linear relationship has been established between genetic and geographical distances by examining 11 ethnoterritorial groups in Northeastern Europe and Western Siberia.

BACKGROUND:It was demonstrated previously that the three-locus RFLP haplotype, TaqI B-TaqI D-TaqI A (B-D-A), at the DRD2 locus constitutes a powerful genetic marker and probably reflects the most ancient dispersal of anatomically modern humans.RESULTS:We investigated TaqI B, BclI, MboI, TaqI D, and TaqI A RFLPs in 17 contemporary populations of the East European Plain and Siberia. Most of these populations belong to the Indo-European or Uralic language families. We identified three common haplotypes, which occurred in more than 90% of chromosomes investigated. The frequencies of the haplotypes differed according to linguistic and geographical affiliation.CONCLUSION:Populations in the northwestern (Byelorussians from Mjadel'), northern (Russians from Mezen' and Oshevensk), and eastern (Russians from Puchezh) parts of the East European Plain had relatively high frequencies of haplotype B2-D2-A2, which may reflect admixture with Uralic-speaking populations that inhabited all of these regions in the Early Middle Ages.

The mtDNA variation of 198 Aleuts, as well as North American and Asian populations drawn from the literature, were analyzed to reconstruct the Aleuts' genetic prehistory and to investigate their role in the peopling of the Circumarctic region. From median-joining network analysis, three star-like clusters were identified in the Aleuts within the following subhaplogroups: A3, A7 (an Aleut-specific subclade of A3), and D2. Mismatch analyses, neutrality test scores, and coalescent time estimates for these three components provided evidence of two expansion events, one occurring at approximately 19,900 B.P. and the other at 5,400 B.P. Based on these findings and evidence from the archaeological data, four general models for the genetic prehistory of the Aleutian Island chain are proposed: 1) biological continuity involving a kin-structured peopling of the archipelago; 2) intrusion and expansion of a non-native biface-producing population dominated by subhaplogroup D2; 3) amalgamation of Arctic Small Tool tradition peoples characterized by D2 with an older Anangula substratum; and 4) biological continuity with significant gene flow from neighboring populations of the Alaskan mainland and Kodiak Island. The Aleut mtDNAs are consistent with the Circumarctic pattern by the fixation of A3 and D2, and the exhibition of depressed diversity levels relative to Amerind and Siberian groups. The results of this study indicate a broad postglacial reexpansion of Na-Dene and Esko-Aleuts from reduced populations within northern North America, with D2 representing a later infusion of Siberian mtDNAs into the Beringian gene pool.

Background: It has been hypothesized that, whereas many loci are used to generate phylogenetic relationships, the utilization of those that yield the most information could increase the accuracy of any multilocus phylogenetic reconstruction. Among these is the D1S80 hypervariable minisatellite region, which has been shown to be highly polymorphic globally, and it was of interest to compare the nearest neighbours and distant populations of Eastern Europe using the D1S80 polymorphism.Aim: The study evaluated the capacity of the D1S80 locus to discriminate between populations from different ethnic groups in Russia and the Republic of Belarus, revealing the polymorphism parameters of the populations studied.Subjects and methods: Hypervariable D1S80 minisatellite polymorphism was studied in 15 populations, belonging to six distinct ethnic groups from the Russian Federation (Russians, Komis, Maris, Udmurts, Kalmyks, and Yakuts) and the Republic of Belarus (Byelorussians). The data were analysed with other results reported for D1S80 polymorphism among Eastern Europeans, and were analysed together with those previously reported for Eastern European populations for the 3'ApoB, DMPK, DRPLA, and SCA1 hypervariable loci. Genetic diversity analysis was carried out using multidimensional scaling (MDS) of Nei's genetic distances.Results: The Eastern Slavonic populations (Russians, Ukrainians, and Byelorussians) are closely associated, and outermost from populations of Asian origin (Kalmyks and Yakuts). The populations that inhabit the Volga-Ural region (Udmurt, Komi, Mari, and Bashkir ethnic groups) revealed intermediate characteristics.Conclusion: The clustering of populations demonstrated here using D1S80 alone coincides with the analysis of five hypervariable region (HVR) loci, and is consistent with linguistic, geographic, and ethnohistorical data. These results are in agreement with most studies of mtDNA, Y-chromosomal, and autosomal DNA diversity in Eastern Europe. The D1S80 locus is convenient for population analyses, and may be used as part of a set of similar markers, which should allow the easy resolution of small differences in population structures.

The rapid social and cultural changes introduced by the collapse of the Soviet Union have resulted in important differences in cardiovascular health for indigenous Siberians. This study investigated diet and lifestyle determinants of plasma lipids in the Yakut, an indigenous Siberian herding population. The study used a cross-sectional design with data on 201 subjects in three urbanized towns and three rural communities in northeastern Siberia. Data on sociodemographic characteristics, dietary intake, and material lifestyle were collected, and lipids were analyzed from venous whole blood. Diet was analyzed using patterns of dietary intake based on principal components analysis of a dietary intake (food frequency) questionnaire. We identified three diet patterns: a traditional subsistence diet, a market foods diet, and a mixed diet. The effect of lifestyle on cardiovascular risk factors was measured using an ethnographically defined lifestyle index, with two orthogonal dimensions: subsistence lifestyle and modern lifestyle. Total cholesterol (TC) and low-density lipoprotein (LDL) were significantly higher among those consuming a traditional subsistence diet of meat and dairy products. A modern lifestyle was associated with lower TC and LDL but higher adiposity and higher risk of obesity. LDL and TC were higher in rural communities and lower in urbanized towns. The significantly higher lipid levels associated with a subsistence diet and indirectly with a subsistence lifestyle indicate the emergence of a significant health problem associated with the social and cultural changes occurring in Yakutia today. These findings underscore the need for dietary modification and promotion of physical activity among those most at risk for cardiovascular disease (CVD). Moreover, these results differ from those commonly seen in "modernizing" populations, in that elements of subsistence lifestyle are associated with an elevated rather than reduced risk of CVD. Such variable responses to lifestyle change emphasize the need to better understand the distinct social and historical events that may influence health changes among populations in transition.

Mitochondrial DNA (mtDNA) variation was studied in population of Oroks (N = 61), the indigenous inhabitants of Eastern Siberia. Most of the mtDNA types examined fell into five haplogroups (C, D, G, M10, and Y) typical of Eastern Eurasian populations. For three haplogroups (D, C, and M10), the founder effect was established. In one individual, a unique lineage belonging to haplogroup HV and typical of Caucasoids was detected.

Four different polymorphisms in the human p53 gene (a 16-bp duplication in intron 3, and three RFLPs: for Bsh1236I at codon 72, for MspI in intron 6 and for BamHI in the 3' flanking region) and extended haplotypes were studied in nine geographically diverse populations from Russia and Belarus. The Yakuts differed from all other populations, as they had a significantly higher frequency of the BamHI A1 allele. Most populations did not differ significantly from each other in the frequency of the Bsh1236I polymorphism. The 16-bp duplication A1 allele and MspI A2 allele frequencies were significantly higher in the Yakut and Khant populations. Linkage disequilibrium values (D') between BamHI and other polymorphic sites were not significant in many cases; for this reason we have used the 16 bp-Bsh1236I-MspI haplotype frequencies only. Of eight possible haplotypes, five were observed in the populations investigated. Haplotype 1-2-2 was the most frequent in all populations. The next most common haplotype, 1-1-2, was present at very similar frequencies among the Byelorussians and Russians from Smolensk, but was more frequent in other populations. The frequency of haplotype 2-1-1 showed a nearly continuous decrease from West to East (from 17.857% among the Byelorussians to 0.685% in the Yakuts from the Verkhoyansk) and correlated with longitude (Spearman's r = -0.8667, P = 0.0025), which may be due to natural selection and adaptation. The relationships among populations were evaluated by means of Nei's D(A) distances for the 16 bp-Bsh1236I-MspI haplotype frequencies. Based on the multidimensional scaling analysis a correlation between p53 haplotype frequencies and ethnicity is supposed.

A complex anthropological survey based on population-genetic methods and a study of a wide spectrum of genetic systems (43 alleles from 17 independent loci) was undertaken among 450 Buryat women of post-reproductive age. The results obtained showed the influence of particular genetic markers and their complex on the formation of peculiarities in the reproduction structure of the Buryat population.A sharp increase in phenotype GC 2-2 frequency and the corresponding GC*2 allele of the group-specific component (GC) was established for women groups with burdened obstetric records. These groups are characterized also by a considerable decrease in the observed geterozygosity (Ho) as compared to its expected value (He). Samples including women with multiple pregnancies in the recorded obstetric anamnesis are characterized by a significant increase in the frequency of the rare alleles TF*C3 of the transferrin system and those of PI*Z belonging to the proteinase inhibitor system (a1-antitrypsin) as compared to the control group.The results obtained widened current knowledge about the influence of genetic and environmental components on reproduction processes in human populations.

Most of the population of Eastern Europe inhabit an area of great anthropological interest, because of the contact between Caucasoid and Mongoloid anthropological types. We have analyzed normal variability in minisatellite and microsatellite loci in some East European population. Different synthetic maps were constructed using reliability theory to evaluate the degree of accuracy. Comparison of the synthetic maps for DNA with classical markers has revealed a high level of correlation. All the data obtained show the diverse influence of both anthropological types in forming the gene pool of the Eastern European peoples.

The frequencies of three alleles, CCR5delta32 , CCR2-64I , and SDF1-3′A , known to decrease the risk of AIDS onset and the rate of the disease progression in HIV-infected individuals were determined in three native population samples from Russia, Ukraine, and Belarus. The frequencies of the alleles were 0.15, 0.12, 0.21; 0.12, 0.07, 0.20; and 0.12, 0.08, 0.26 for Russians, Ukrainians, and Belarussians, respectively. The proportion of the individuals without any of three protective alleles among Russians, Ukrainians, and Belarussians constituted 49, 65, and 61%, respectively. The genotype frequencies for the three loci studied were in Hardy–Weinberg equilibrium. Based on the three-locus genotype frequencies, the relative hazards of AIDS onset in HIV-infected individuals in each population were calculated as ranging from 0.79 to 0.88. In the samples of Eastern Slavs analyzed the estimated frequencies of the AIDS-protective alleles tested, as well as the frequencies of the corresponding genotypes and the relative hazards of AIDS onset were within the range of these parameters for the other European populations. The data on the allele frequencies and the relative hazard values in Russians, Ukrainians, and Belarussians can be used as the predictors of AIDS onset and progression rate in HIV-1-infected individuals from the populations studied.