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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.

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.

The underrepresentation of non-Europeans in human genetic studies so far has limited the diversity of individuals in genomic datasets and led to reduced medical relevance for a large proportion of the world’s population. Population-specific reference genome datasets as well as genome-wide association studies in diverse populations are needed to address this issue. Here we describe the pilot phase of the GenomeAsia 100K Project. This includes a whole-genome sequencing reference dataset from 1,739 individuals of 219 population groups and 64 countries across Asia. We catalogue genetic variation, population structure, disease associations and founder effects. We also explore the use of this dataset in imputation, to facilitate genetic studies in populations across Asia and worldwide., Using whole-genome sequencing data from 1,739 individuals, the GenomeAsia 100K Project catalogues genetic variation, population structure and disease associations to facilitate genetic studies in Asian populations and increase representation in genetics studies worldwide.

Populations of the indigenous ethnic groups of Northern Eurasia are of considerable interest for population genomics, both because they have been relatively poorly studied with the use of modern genomic technologies and owing to the specificity of their gene pools that developed in various genetic-demographic conditions. We used genotype data on 242 179 autosomal SNPs of 876 individuals to search for regions with runs of homozygosity of more than 1 Mb. For Siberian populations, the number of runs of homozygosity and their total length was higher than for other populations of Northern Eurasia.

We provide an overview of the recent achievements in psychiatric genetics research in the Russian Federation and present genotype-phenotype, population, epigenetic, cytogenetic, functional, ENIGMA, and pharmacogenetic studies, with an emphasis on genome-wide association studies. The genetic backgrounds of mental illnesses in the polyethnic and multicultural population of the Russian Federation are still understudied. Furthermore, genetic, genomic, and pharmacogenetic data from the Russian Federation are not adequately represented in the international scientific literature, are currently not available for meta-analyses and have never been compared with data from other populations. Most of these problems cannot be solved by individual centers working in isolation but warrant a truly collaborative effort that brings together all the major psychiatric genetic research centers in the Russian Federation in a national consortium. For this reason, we have established the Russian National Consortium for Psychiatric Genetics (RNCPG) with the aim to strengthen the power and rigor of psychiatric genetics research in the Russian Federation and enhance the international compatibility of this research.The consortium is set up as an open organization that will facilitate collaborations on complex biomedical research projects in human mental health in the Russian Federation and abroad. These projects will include genotyping, sequencing, transcriptome and epigenome analysis, metabolomics, and a wide array of other state-of-the-art analyses. Here, we discuss the challenges we face and the approaches we will take to unlock the huge potential that the Russian Federation holds for the worldwide psychiatric genetics community.

This study investigated whether common polymorphisms of cytochrome P450 2J2 (CYP2J2), a major enzyme that controls the biosynthesis of vasoactive epoxyeicosatrienoic acids, are collectively involved in the molecular basis of essential hypertension (EH). A total of 2314 unrelated Russian subjects from the Kursk (discovery sample: 913 EH patients and 645 controls) and Belgorod (replication sample: 345 EH patients and 411 controls) regions were recruited for this study. Eight single nucleotide polymorphisms (SNPs), including rs890293, rs11572182, rs10493270, rs1155002, rs2280275, rs7515289, rs11572325, and rs10889162, of CYP2J2 were genotyped using the MassARRAY 4 system and TaqMan-based assays. Significant associations were identified among the SNPs rs890293 (OR = 2.17, 95%CI 1.30-3.65), rs2280275 (OR = 1.59, 95%CI 1.10-2.37) and rs11572325 (OR = 1.89, 95%CI 1.22-2.95) and the risk of EH in females from the Kursk population. Sixteen CYP2J2 genotype combinations only showed significant associations with EH risk only in females. A common haplotype, T-T-G-C-C-C-T-A, increased the risk of EH in females. The bioinformatic analysis enabled identification of the SNPs that possess regulatory potential and/or are located within the binding sites for multiple transcription factors that play roles in the pathways involved in hypertension pathogenesis. Moreover, the polymorphisms rs890293, rs2280275, and rs11572325 were found to be significantly associated with hypertension risk in the Belgorod population. In conclusion, the rs2280275 and rs11572325 SNPs of CYP2J2 may be considered novel genetic markers of hypertension, at least in Russian women. However, sex-specific associations between CYP2J2 gene polymorphisms and hypertension require further investigation to clarify the specific genetic and/or environmental factors that are responsible for the increased disease susceptibility of women compared to that of men.

Background The history of human populations occupying the plains and mountain ridges separating Europe from Asia has been eventful, as these natural obstacles were crossed westward by multiple waves of Turkic and Uralic-speaking migrants as well as eastward by Europeans. Unfortunately, the material records of history of this region are not dense enough to reconstruct details of population history. These considerations stimulate growing interest to obtain a genetic picture of the demographic history of migrations and admixture in Northern Eurasia. Results We genotyped and analyzed 1076 individuals from 30 populations with geographical coverage spanning from Baltic Sea to Baikal Lake. Our dense sampling allowed us to describe in detail the population structure, provide insight into genomic history of numerous European and Asian populations, and significantly increase quantity of genetic data available for modern populations in region of North Eurasia. Our study doubles the amount of genome-wide profiles available for this region. We detected unusually high amount of shared identical-by-descent (IBD) genomic segments between several Siberian populations, such as Khanty and Ket, providing evidence of genetic relatedness across vast geographic distances and between speakers of different language families. Additionally, we observed excessive IBD sharing between Khanty and Bashkir, a group of Turkic speakers from Southern Urals region. While adding some weight to the “Finno-Ugric” origin of Bashkir, our studies highlighted that the Bashkir genepool lacks the main “core”, being a multi-layered amalgamation of Turkic, Ugric, Finnish and Indo-European contributions, which points at intricacy of genetic interface between Turkic and Uralic populations. Comparison of the genetic structure of Siberian ethnicities and the geography of the region they inhabit point at existence of the “Great Siberian Vortex” directing genetic exchanges in populations across the Siberian part of Asia. Slavic speakers of Eastern Europe are, in general, very similar in their genetic composition. Ukrainians, Belarusians and Russians have almost identical proportions of Caucasus and Northern European components and have virtually no Asian influence. We capitalized on wide geographic span of our sampling to address intriguing question about the place of origin of Russian Starovers, an enigmatic Eastern Orthodox Old Believers religious group relocated to Siberia in seventeenth century. A comparative reAdmix analysis, complemented by IBD sharing, placed their roots in the region of the Northern European Plain, occupied by North Russians and Finno-Ugric Komi and Karelian people. Russians from Novosibirsk and Russian Starover exhibit ancestral proportions close to that of European Eastern Slavs, however, they also include between five to 10 % of Central Siberian ancestry, not present at this level in their European counterparts. Conclusions Our project has patched the hole in the genetic map of Eurasia: we demonstrated complexity of genetic structure of Northern Eurasians, existence of East-West and North-South genetic gradients, and assessed different inputs of ancient populations into modern populations. Electronic supplementary material The online version of this article (10.1186/s12863-017-0578-3) contains supplementary material, which is available to authorized users.

Oculopharyngeal muscular dystrophy (OPMD) is a hereditary neuromuscular disease with autosomal dominant and rarely with autosomal recessive inheritance types. This study included 50 patients with a clinical diagnosis of OPMD, 23 asymptomatic carriers of the mutation from 45 unrelated families, and 56 healthy relatives, as well as population samples of four ethnic groups of Yakutia: Yakuts, Evens, Evenks, Yukaghirs. It was found that the cause of OPMD development in all investigated families is the same increase in GCN repeats to 14 copies in the PABPN1 gene. The molecular structure of the (GCN)14 mutant allele is (GCG)10(GCA)3GCG. The genetic variability of ten SNPs at the OPMD locus was studied in patient families and population samples. The haplotypes of OPMD were determined by a segregation analysis technique and using the EM algorithm in the groups of patients, mutation carriers, and population samples. Only one haplotype of four SNPs (ATCG) linked with the (GCN)14 mutant allele was found in Yakuts and Russian patients and OPMD mutation carriers. Probably, this indicates the accumulation of mutations as a result of the founder effect.

X chromosome genetic markers are widely used in basic population genetic research as well as in forensic genetics. In this paper we analyze the genetic diversity of 62 X chromosome SNPs in 4 populations using multiplex genotyping based on multi-locus PCR and MALDI-TOF mass spectrometry, and report forensic and population genetic features of the panel of X-linked SNPs (XSNPid). Studied populations represent Siberian (Buryat and Khakas), North Asian (Khanty) and Central Asian (Kazakh) native people. Khanty, Khakas and Kazakh population demonstrate average gene diversity over 0.45. Only East Siberian Buryat population is characterized by lower average heterozygosity (0.436). AMOVA analysis of genetic structure reveals a relatively low but significant level of genetic differentiation in a group of 4 population studied ( F ST =0.023, p =0.0000). The XSNPid panel provides a very high discriminating power in each population. The combined probability of discrimination in females (PDf) for XSNPid panel ranged between populations from 0.99999999999999999999999982 in Khakas to 0.9999999999999999999999963 in Buryats. The combined discriminating power in males (PDm) varies from 0.999999999999999792 to 0.9999999999999999819. The developed multiplex set of X chromosome SNPs can be a useful tool for population genetic studies and for forensic identity and kinship testing.

To estimate the association of rs11218343 in the sortilin-related receptor 1 (SORL1) gene with cognitive performance in the elderly and with Alzheimer's disease (AD) in the Russian population.A sample included 586 elderly people (mean age 70.9±5.7 years) without AD diagnosis and 100 patients with late-onset AD (mean age 72.1±7.8 years) from the Tomsk population. SORL1 rs11218343 was genotyped using PCR and MALDI-TOF mass spectrometry. Cognitive performance in the sample of elderly without AD was assessed by Montreal Cognitive Assessment (MoCA) test.Allele frequencies of the SORL1 polymorphism were not significantly different between the elderly without AD and AD patients. However mean MoCA score in the carriers of the rare allele (19.00±6.61) was significantly lower than in homozygotes for the common variant (22.25±3.89) (F=4.97; p=0.026).The rare variant in SORL1 gene previously associated with AD in genome-wide association studies and meta-analyses was associated with lower total МоСА scores in the random sample of elderly people that suggests declined cognitive functions in the carriers of this variant in elderly.Цель исследования. Изучение связи rs11218343 гена сортилинподобного рецептора 1 (SORL1) с показателями состояния когнитивных функций у пожилых людей из российской популяции с диагнозом 'болезнь Альцгеймера' (БА) и без такового. Материал и методы. Выборка включала 586 пожилых пациентов (средний возраст 70,9±5,7 года) без БА и 100 пациентов с поздним началом БА (средний возраст 72,1±7,8 года) из популяции Томска. Генотипирование rs11218343 гена SORL1 проводили с помощью ПЦР и масс-спектрометрии. Нейропсихологическое тестирование проводили по Монреальской шкале оценки когнитивных функций (МоСА). Результаты. Частота аллелей rs11218343 гена SORL1 в изученных группах обследованных не достигала степени статистической достоверности. Однако средние значения общего балла по МоСА в контрольной выборке пожилых пациентов (без БА) у носителей редких аллелей отличались (были ниже) от гомозигот с частыми их вариантами (19,00±6,61 и 22,25±3,89; р0,026). Заключение. Редкий вариант в гене SORL1 связан с низкими показателями МоСА, о чем свидетельствует снижение когнитивных функций у носителей редкого аллеля в пожилом возрасте.

The data on distribution of genetic diversity in gene polymorphisms associated with autoimmune and allergic diseases and with regulation of immunoglobulin E and cytokines levels in 26 populations of the Northern Eurasia is presented. Substantial correlation between the values of average expected heterozygosity by 44 gene polymorphisms with climatic and geographical factors has not been revealed. Clustering of population groups in correspondence with their geographic locations is observed. The degree of gene differentiation among populations and the selective neutrality of gene polymorphisms have been assessed. The results of our work evidence the substantial genetic diversity and differentiation of human populations by studied genes.

Recently, genetic markers rs10503253 and rs2616984 in the CUB and Sushi multiple domains-1 (CSMD1) gene have been reported to be associated with schizophrenia and cognitive functions in genome-wide association studies. We examined the associations of the above SNPs with cognitive performance evaluated by the Montreal Cognitive Assessment (MoCA) tool in a cohort of the normal elderly from the Russian population. Significant association of rs2616984 genotypes with the MoCA scores was found using nonparametric analysis. No association of rs10503253 with MoCA scores was observed using both parametric and nonparametric statistics. Significant combined effect of two-locus CSMD1 genotypes on MoCA scores was demonstrated by median test. Allele “A” and genotype “AA” of rs2616984 were significantly associated with the lower MoCA scores in comparison of 1st and 4th quartiles of MoCA total score distribution. The results suggest that genetic variants in CSMD1 gene are likely a part of genetic component of cognitive performance in the elderly.

A biological microchip (biochip) has been developed to study the genetic predisposition to sporadic form of Alzheimer’s disease (AD). The biochip allows of genotyping of ten genetic polymorphisms within APOE, TOMM40, APOJ, EXOC3L2, GAB2, A2M, CR1, BIN1, and PICALM genes. The assay includes the amplification of the loci of interest and subsequent allele-specific hybridization of the fluorescently labeled amplicons with oligonucleotides immobilized on the biochip. The genotyping of 166 patients and 128 controls revealed a significant association of APOE allele ɛ4 with susceptibility to AD (OR = 2.275, 95% CI 1.045–4.954, p = 0.034). Protective effects were observed for APOE allele ɛ2 and CLU (rs11136000) allele T (OR = 0.215, 59% CI 0.090–0.516, p = 0.001 and OR = 0.679, 95% CI 0.47–0.99, p = 0.042, respectively). A gene-gene interaction analysis revealed two AD-associated genotype combinations, APOE ɛ3/ɛ4 GAB2 G/G (OR = 2.49, 95% CI 1.43–4.32, p = 0.001) and APOE ɛ4/ɛ4 GAB2 G/G (OR = 3.55, 95% CI 1.23–10.24, p = 0.015). Based on the results of the combined multivariate analysis, an algorithm was developed to identify the individuals having a higher risk of AD.

Type-1recessive congenital methemoglobinemia (RCM) is a rare autosomal disease characterized by a deficiency of the soluble form of nicotineamide adenine dinucleotide (NADH)-cytochrome b5 reductase (b5R) and clinically manifests as cyanosis of skin and mucous membranes. In the Russian Federation, type-I RCM is widely disturbed in Yakutia due to the local founder effect. The molecular genetics cause of type-I RCM in Yakutia is mutation c.806C > T in the CYB5R3 gene. In this work we used 13 polymorphic markers, which flanking the CYB5R3 gene to establish the founder haplotype. The age of the mutation was estimated as about 285 +/- 135 years. In this work, we have evaluated the frequency of the c.806 C > T mutation in Yakutia, which averaged 55 : 1000 Yakuts. The calculated frequency of disease was 1: 1250 Yakuts.

Analysis of the genome-specific linkage disequilibrium patterns in certain populations is a highly promising approach to the identification of functional variants that underlie susceptibility to complex diseases. In the present study, the linkage disequilibrium patterns of the methylenetetrahydrofolate reductase gene (MTHFR) were examined in a group of patients with coronary atherosclerosis (coronary artery disease, CAD) and in a control sample from the Russian population. It was demonstrated that in the samples from one population, which were differentiated by the presence or absence of CAD, the MTHFR linkage disequilibrium patterns had similar features. Association of the MTHFR rs7533315 and rs2066462 polymorphisms with CAD was demonstrated. In addition, the evolution of the haplotypes and their role in the formation of CAD in the Russian population was reconstructed. The data on the association between genetic variability in the MTHFR locus and pathogenetically important indices of lipid metabolism were obtained. The high informativeness of the haplotype approach in case-control tests for associations with CAD was demonstrated.

The structure of Khakass gene pool has been investigated: Y-chromosome haplogroup compositions and frequencies were described in seven population samples of two basic subethnic groups, Sagai and Kachins, from three geographically separated regions of the Khakass Republic. Eight haplogroups were detected in the Khakass gene pool: C3, E, N*, N1b, N1c, R1a1a, and R1b1b1. The haplogroup spectra and the genetic diversity by haplogroups and YSTR haplotypes differed significantly between Sagai and Kachins. Kachins had a low level of gene diversity, whereas the diversity of Sagai was similar to that of other South-Siberian ethnic groups. Sagai samples from the Askizskii district were very similar to each other, and so were two Kachin samples from the Shirinskii district, while Sagai samples from the Tashtypskii district differed considerably from each other. The contribution of intergroup differences among ethnic groups was high, indicating significant genetic differentiation among native populations in Khakassia. The Khakass gene pool was strongly differentiated both by haplogroup frequencies and by YSTR haplotypes within the N1b haplogroup. The frequencies of YSTR haplotypes within the chromosome Y haplogroups N1b, N1c, and R1a1 were determined and their molecular phylogeny was investigated. Factor and cluster analysis, as well as AMOVA, suggest that the Khakass gene pool is structured by territory and subethnic groups.

This review discusses the progress of ethnic genetics, the genetics of common diseases, and the concepts of personalized medicine. We show the relationship between the structure of genetic diversity in human populations and the varying frequencies of Mendelian and multifactor diseases. We also examine the population basis of pharmacogenetics and evaluate the effectiveness of pharmacotherapy, along with a review of new achievements and prospects in personalized genomics.

The gene pool structure of aboriginal Siberian populations has been described based on the polymorphism of the ZFX gene located on the chromosome X. In the ten populations studied, 49 haplotypes were present, three of them with high frequencies. Comparison of the obtained results with the available data from the HapMap project revealed unique African haplotypes that occurred in the Yoruba with the frequency of 3–7% and were not found in other populations. The genetic differentiation coefficient of the Siberian ethnic groups studied was 0.0486. Correlation analysis using Mantel’s test did not detect significant correlations between the genetic distance matrix and the matrices of geographic, linguistic, and anthropological differences, although the correlation with the anthropological matrix was the highest. Phylogenetic analysis proved strong isolation of the African population from the other ethnic groups investigated. The Siberian populations were divided into two separate clusters: the first one included Yakuts, Buryats, and Kets, while the second cluster included Altaians, Tuvinians, and Khanty. Using the principal component analysis, the populations were combined into three groups clearly differing by manifestation of Caucasoid and Mongoloid components. The first group included residents of Europe and one of Khanty populations, the second group included populations of South Siberia and residents of China. Mongoloid populations of East Siberia, the Japanese, and Kets were combined into the third group. Barrier analysis revealed a similar structure of genetic differentiation of Siberian populations. Linkage disequilibrium structure was obtained for six ethnic groups of Siberia. In five of them (except for the Ket population), ten ZFX SNPs formed a single linkage block.

The gene pool structure of Teleuts was examined and Y-chromosomal haplogroups composition and frequencies were determined. In the gene pool of Teleuts, five haplogroups, C3×M77, N3a, R1b*, R1b3, and R1a1, were identified. Evaluation of the genetic differentiation of the samples examined using analysis of molecular variance (AMOVA) with two marker systems (frequencies of haplogroups and Y-chromosomal microsatellite haplotypes) showed that Bachat Teleuts were equally distant from Southern and Northern Altaians. In Siberian populations, the frequencies and molecular phylogeny of the YSTR haplotypes within Y-chromosomal haplogroup R1a1 were examined. It was demonstrated that Teleuts and Southern Altaians had very close and overlapping profiles of R1a1 haplotypes. Population cluster analysis of the R1a1 YSTR haplotypes showed that Teleuts and Southern Altaians were closer to one another than to all remaining Siberian ethnic groups. Phylogenetic analysis of N3a haplotypes suggested specificity of Teleut haplotypes and their closeness to those of Tomsk Tatars. Teleuts were characterized by extremely high frequency of haplogroup R1b*, distinguished for highly specific profile of YSTR haplotypes and high haplotype diversity. The results of the comparative analysis suggested that the gene pool of Bachat Teleuts was formed on the basis of at least two heterogeneous genetic components, probably associated with ancient Turkic and Samoyedic ethnic components.

Gene pool structure of Sakha Republic (Yakutia) native population has been studied: we defined composition and frequencies of Y-chromosome haplogroups for Yakuts. Six haplogroups: C3 x M77, C3c, N*, N2, N3a and R1a1 have been revealed in Yakut gene pool. A greater part of Y-chromosome in Yakut population belongs to N3a haplogroup (89%). All investigated Yakut population samples have low values of gene diversity, calculated based on haplogroup frequencies. Gene differentiation of the investigated samples estimated using the analysis of molecular variance (AMOVA) by two marker systems (haplogroup frequencies and microsatellite haplotypes of Y-chromosome) revealed a portion of interpopulation differences amounting to 0.24 and 2.85%, respectively. Frequencies and molecular phylogeny of YSTR-haplotypes were revealed for N3a haplogroup of Y-chromosome. Altogether forty haplotypes were found in Yakuts. Evenks and Yakuts are characterized by overlapping and very specific spectrum of N3a haplotypes, which is not typical for other Siberian ethnic groups. Cluster analysis of populations by N3a YSTR-haplotypes shows Yakut isolation from Turkic-speaking populations in the South Siberia. Genetic diversity generation time for a specific spectrum of Yakut haplotypes was estimated as 4.45 +/- 1.96 thousand years. As opposed to the data on mtDNA, the obtained results give an evidence for significant contribution of a local palaeolithic component into Y-chromosomal Yakut gene pool. Ethnogenetic reconstruction of the present picture of genetic diversity in N3a haplogroup in the territory of Siberia is under consideration.

The area between the Dniester and the eastern Carpathian mountain range is at a geographical crossroads between eastern Europe and the Balkans. Little is known about the genetics of the population of this region. We performed an analysis of 12 binary autosomal markers in samples from six Dniester-Carpathian populations: two Moldavian, one Romanian, one Ukrainian and two Gagauz populations. The results were compared with gene frequency data from culturally and linguistically related populations from Southeast Europe and Central Asia. Small genetic differences were found among southeastern European populations (in particular those of the Dniester-Carpathian region). The observed homogeneity suggests either a very recent common ancestry of all southeastern European populations or strong gene flow between them. Despite this low level of differentiation, tree reconstruction and principle component analyses allowed a distinction between Balkan-Carpathian (Macedonians, Romanians, Moldavians, Ukrainians and Gagauzes) and eastern Mediterranean (Turks, Greeks and Albanians) population groups. The genetic affinities among Dniester-Carpathian and southeastern European populations do not reflect their linguistic relationships. The results indicate that the ethnic and genetic differentiations occurred in these regions to a considerable extent independently of each other. In particular, Gagauzes, a Turkic-speaking population, show closer affinities to their geographical neighbors than to other Turkic populations.

The allele and genotype frequency distributions of four STRs (the LPL, vWA, FES/FPS, and F13B loci) commonly used in forensic medicine were studied with a sample of 200 ethnic Russians from Siberia. Genetic and molecular diversity of the four STRs was characterized in comparison with the American Caucasoid population. The set of the four STRs showed a high power of discrimination (PD = 0.99975). Comparison of the genetic variation at the four loci revealed a considerable difference between the Russian and American Caucasoid populations, precluding the use of data on allele frequencies in American Caucasoids for forensic testing in Russia. The results can be used as a reference in Siberia.

It has been often stated that the overall pattern of human maternal lineages in Europe is largely uniform. Yet this uniformity may also result from an insufficient depth and width of the phylogenetic analysis, in particular of the predominant western Eurasian haplogroup H that comprises nearly a half of the European mitochondrial DNA (mtDNA) pool. Making use of the coding sequence information from 267 mtDNA haplogroup (Hg) H sequences, we have analyzed 830 mtDNA genomes, from 11 European, Near and Middle Eastern, Central Asian and Altaian populations. In addition to the seven previously specified sub-haplogroups, we define fifteen novel sub-clades of Hg H present in the extant human populations of western Eurasia. The refinement of the phylogenetic resolution has allowed us to resolve a large number of homoplasies in phylogenetic trees of Hg H based on the first hypervariable segment (HVS-I) of mtDNA. As many as 50 out of 125 polymorphic positions in HVS-I were found to be mutated in more than one sub-cluster of Hg H. The phylogeographic analysis revealed that sub-Hgs H1(*), H1b, H1f, H2a, H3, H6a, H6b and H8 demonstrate distinct phylogeographic patterns. The monophyletic sub-haplogroups of Hg H provide means for further progress in the understanding of the (pre)historic movements of women in Eurasia and for the understanding of the present-day genetic diversity of western Eurasians in general.

Three Russian populations of Siberia were examined for allele and genotype frequency distributions of two alcohol dehydrogenase genes, ADH1B (exon 3 polymorphism A/G detectable with MslI) and ADH7 (intron 5 polymorphism G/C detectable with StyI). No interpopulation or sex difference in allele frequencies was revealed. Allele ADH1B*G (+ MslI, A2) was rare (3.6–7.5%); the frequency of the “mutant” ADH7 allele (–StyI, B2) was 46.02% in the total sample (N = 339). The genotype frequencies obeyed the Hardy–Weinberg equilibrium and the alleles were in linkage equilibrium in each population. Frequency of ADH7 allele B2 increased beyond 40 years of age in the total sample (by 11%, P = 0.001) and in the Tomsk population (by 9%, P= 0.017). The ADH1B and ADH7 polymorphisms had no effect on the antioxidant activity (AOA), which was inferred from the ability of serum to reduce the yield of thiobarbituric acid-reactive species in the Fe2+–lecithin system. In the Tomsk population, carriers of AHD1B allele A2 showed a significant increase in very low density lipoproteins (by 9.95%, P = 0.045) and a near significant increase in systolic pressure (by 6.8%, P = 0.068) and serum triglycerides (by 6.16%, P = 0.058).

Two tribal groups from southern India--the Chenchus and Koyas--were analyzed for variation in mitochondrial DNA (mtDNA), the Y chromosome, and one autosomal locus and were compared with six caste groups from different parts of India, as well as with western and central Asians. In mtDNA phylogenetic analyses, the Chenchus and Koyas coalesce at Indian-specific branches of haplogroups M and N that cover populations of different social rank from all over the subcontinent. Coalescence times suggest early late Pleistocene settlement of southern Asia and suggest that there has not been total replacement of these settlers by later migrations. H, L, and R2 are the major Indian Y-chromosomal haplogroups that occur both in castes and in tribal populations and are rarely found outside the subcontinent. Haplogroup R1a, previously associated with the putative Indo-Aryan invasion, was found at its highest frequency in Punjab but also at a relatively high frequency (26%) in the Chenchu tribe. This finding, together with the higher R1a-associated short tandem repeat diversity in India and Iran compared with Europe and central Asia, suggests that southern and western Asia might be the source of this haplogroup. Haplotype frequencies of the MX1 locus of chromosome 21 distinguish Koyas and Chenchus, along with Indian caste groups, from European and eastern Asian populations. Taken together, these results show that Indian tribal and caste populations derive largely from the same genetic heritage of Pleistocene southern and western Asians and have received limited gene flow from external regions since the Holocene. The phylogeography of the primal mtDNA and Y-chromosome founders suggests that these southern Asian Pleistocene coastal settlers from Africa would have provided the inocula for the subsequent differentiation of the distinctive eastern and western Eurasian gene pools.

The paper presents the results of analysis of the gene pools of several North Eurasian ethnic groups (Buryats, Evenks, Altaians, Russians, Kyrgyzes, Tuvinians, Tatars, and Ukrainians) examined using a panel of autosomal microsatellite markers (D4S397,D5S393, D7S640, D8S514, D9S161, D10S197, D11S1358, D12S364 and D13S173) mapped on different chromosomes and represented by the (CA)n dinucleotide repeats. In the group of populations examined the proportion of genetic variability at microsatellite loci explained by interpopulation differences was about 2.5%, while genetic differences between the individuals within a population accounted for 97.5% of this variability. Analysis of genetic relationships among the populations revealed substantial differences between the populations belonging to the Indo-European and Altaic linguistic families in gene diversity at microsatellite loci.

The autosomal gene pool of Yakuts was analyzed with a panel of polymorphic Alu insertions. The observed allele frequencies were typical for other Asian ethnic groups. Genetic differentiation of three Yakut populations was relatively high, 2%. East Siberian ethnic groups were shown to have a common gene pool and to experience no intense gene flow from other populations. Development of the Yakut gene pool was assumed to involve no substantial genetic effect of neighboring populations. The results fit both autochthonous and southern origin hypotheses.

The structure of female (mtDNA) and male (Y-chromosome haplotypes) lineages in the Yakut population was examined. To determine mtDNA haplotypes, sequencing of hypervariable segment I and typing of haplotype-specific point substitutions in the other parts of the mtDNA molecule were performed. Y haplogroups were identified through typing of biallelic polymorphisms in the nonrecombining part of the chromosome. Haplotypes within haplogroups were analyzed with seven microsatellite loci. Mitochondrial gene pool of Yakuts is mainly represented by the lineages of eastern Eurasian origin (haplogroups A, B, C, D, G, and F). In Yakuts haplogroups C and D showing the total frequency of almost 80% and consisting of 12 and 10 different haplopypes, respectively, were the most frequent and diverse. The total part of the lineages of western Eurasian origin (“Caucasoid”) was about 6% (4 haplotypes, haplogroups H, J, and U). Most of Y chromosomes in the Yakut population (87%) belonged to haplogroup N3 (HG16), delineated by the T–C substitution at the Tat locus. Chromosomes of haplogroup N3 displayed the presence of 19 microsatellite haplotypes, the most frequent of which encompassed 54% chromosomes of this haplogroup. Median network of haplogroup N3 in Yakuts demonstrated distinct “starlike phylogeny”. Male lineages of Yakuts were shown to be closest to those of Eastern Evenks.

The gene pool of five ethnic groups of the Central Asian population was characterized using nine human-specific polymorphic insertion/deletion loci (ACE, PLAT, APOA1, PV92, F13B, A25, B65, CD4, Mt-Nuc). It has been shown for the first time that at the CD4 locus, the frequency of Alu(–) is inversely related to the Mongoloid component of the population. For the Central Asian populations, the lowest and highest frequencies of the Alu deletion at locus CD4 were recorded respectively in Dungans (0.04), immigrants from China, and Tajiks (0.15). The coefficient of gene differentiation in the Central Asian populations for all the genes was 2.8%, which indicates a relatively low level of population genetic subdivision in this region. The unity of the gene pool of the Central Asian Caucasoids was shown.

Background Replicative analysis of genetic markers, previously identified in genome-wide association studies (GWAS) for neuropsychiatric diseases, in population of various origin may contribute to better understanding of genetic composition of the diseases. Methods In this study 50 SNPs found in GWAS for schizophrenia (SZ), Alzheimer’s diseases (AD) and cognitive endophenotypes were genotyped in patients and control samples from Russian and Kazakh populations. Genotyping was performed by TaqMan assays and MALDI-TOF mass-spectrometry. Results Eight polymorphic markers (SNPs in regions of genes for APOЕ, APOJ, CSMD1, CCDC60, SNX29, PICALM, NOTCH4 and NRIP1) were associated with AD in Russian population. Associations of 10 genetic markers with SZ in Russian populations (markers in regions of genes for NRGN, KCNB2, NRIP1, CCDC60, LSM1, LOC100129100 / LOC100509857, CSMD1, СPVL, POM121L2 and NDE1P1 / PRMT6) and 8 genetic markers in Kazakh population (VRK2, KCNB2, СPVL, BRD1, PVRL2, ARHGAP1, CD33 и GPR89P / TRV-AAC1-5) were replicated. Multidimensional reduction methods revealed epistatic interaction of several genetic loci in formation of susceptibility to SZ in populations of various ethnic origin. Discussion Overlapping fields of genetic associations for AD and SZ, demonstrating some similarity in inherited background for both diseases, were found. This interaction may be implemented through common unknown levels in pathogenesis of AD and SZ, mediated by cognitive endophenotypes. Bioinformatic analysis of biological functions of associated genes revealed that among primary biological processes enriched by genes under study are the processes of lipid metabolism, cellular interactions, various regulatory and transport processes in neural cells, processes of immune response regulation. Substantial part of investigated genes forms an interacting network, which consisted of distinct clusters corresponding to major biological processes, were genes under study are involved, and to basic molecular functions of their products. Data obtained in the project, extend the understanding of genetic component in neuro-psychiatric diseases, as well as the biological processes and functions, implemented in the manifestation of genetic susceptibility to AD and SZ.

The gene-pool structure of Tuvinians was examined in terms of the composition and frequency of Y-chromosome haplogroups in five geographically distanct populations. In the Tuvinian gene pool, a total of 22 haplogroups were identified with six of these, which were the most frequent (C3c, C3*, N1b, N1c1, Q1a3, and R1a1a). It was demonstrated that eastern regions of Tuva were most different from the other regions in haplotype frequencies. The evaluation of genetic diversity based on the frequencies of biallelic haplogroups and YSTR haplotypes revealed very high diversity values for all samples. In general, the genetic diversity values identified in Tuvinians were the highest for the indigenous ethnic groups of Siberia. The evaluation of the genetic differentiation of the samples examined using the analysis of molecular variance (AMOVA) showed that the gene pool of Tuvinians was relatively poorly differentiated with respect to haplogroup frequencies. Phylogenetic analysis within haplogroup N1b revealed strong founder effect, i.e., reduced diversity and star-like phylogeny of the median network of haplotypes, which formed a separate subcluster exclusive to Tuvinians. It was demonstrated that, in Tuvinians, haplogroup N1c1 was the most heterogeneous in haplotype profile and consisted of three different haplotype clusters, demonstrating considerable differences of western population from the rest of the Tuva populations. Phylogenetic analysis of haplogroups revealed common components for Tuvinians, Khakasses, Altaians, and Mongols.

Allele and genotype frequencies of the T174M polymorphism of the angiotensinogen gene were for the first time estimated in the West Siberian population. The polymorphism was tested for association with coronary atherosclerosis (CAS) and with several quantitative risk factors in patients with angiographically verified CAS, healthy individuals, and in a population sample nondifferentiated with respect to CAS.

Polymorphism of three populations of the Buryat Republic and a population from Aginskii Buryat Autonomous okrug of Chita oblast was examined using a set of five autosomal Aluinsertions at theACE, PLAT, PV92, APOA1,and F13Bloci. The allele frequency distribution patterns revealed in Buryat populations were typical to other Asian populations. Buryats were characterized by relatively low level of intrapopulation diversity (0.369 in the pooled population sample). Analysis of autosomal Aluinsertions suggests the uniformity of the Buryat gene pool. The coefficient of genetic differentiation in the four populations studied was 0.8%.

Allele frequencies for 15 STRs (CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, Penta D, Penta E, THO1, TPOX, and vWA) in the PowerPlex 16 System (Promega Corporation) were assessed in 386 individuals from five Russian urban populations. No significant between-population differences in frequencies and molecular variance of 15 microsatellites were revealed. For all 15 loci, the combined matching probability is 3.19 x 10(-18) and the power of exclusion is 99.99989%.

Summary Mitochondrial aldehyde dehydrogenase (ALDH2) is one of the most important enzymes in human alcohol metabolism. The oriental ALDH2*504Lys variant functions as a dominant negative, greatly reducing activity in heterozygotes and abolishing activity in homozygotes. This allele is associated with serious disorders such as alcohol liver disease, late onset Alzheimer disease, colorectal cancer, and esophageal cancer, and is best known for protection against alcoholism. Many hundreds of papers in various languages have been published on this variant, providing allele frequency data for many different populations. To develop a highly refined global geographic distribution of ALDH2*504Lys, we have collected new data on 4,091 individuals from 86 population samples and assembled published data on a total of 80,691 individuals from 366 population samples. The allele is essentially absent in all parts of the world except East Asia. The ALDH2*504Lys allele has its highest frequency in Southeast China, and occurs in most areas of China, Japan, Korea, Mongolia, and Indochina with frequencies gradually declining radially from Southeast China. As the indigenous populations in South China have much lower frequencies than the southern Han migrants from Central China, we conclude that ALDH2*504Lys was carried by Han Chinese as they spread throughout East Asia. Esophageal cancer, with its highest incidence in East Asia, may be associated with ALDH2*504Lys because of a toxic effect of increased acetaldehyde in the tissue where ingested ethanol has its highest concentration. While the distributions of esophageal cancer and ALDH2*504Lys do not precisely correlate, that does not disprove the hypothesis. In general the study of fine scale geographic distributions of ALDH2*504Lys and diseases may help in understanding the multiple relationships among genes, diseases, environments, and cultures.

Moldova has a rich historical and cultural heritage, which may be reflected in the current genetic makeup of its population. To date, no comprehensive studies exist about the population genetic structure of modern Moldavians. To bridge this gap with respect to paternal lineages, we analyzed 37 binary and 17 multiallelic (STRs) polymorphisms on the non-recombining portion of the Y chromosome in 125 Moldavian males. In addition, 53 Ukrainians from eastern Moldova and 54 Romanians from the neighboring eastern Romania were typed using the same set of markers. In Moldavians, 19 Y chromosome haplogroups were identified, the most common being I-M423 (20.8%), R-M17* (17.6%), R-M458 (12.8%), E-v13 (8.8%), R-M269* and R-M412* (both 7.2%). In Romanians, 14 haplogroups were found including I-M423 (40.7%), R-M17* (16.7%), R-M405 (7.4%), E-v13 and R-M412* (both 5.6%). In Ukrainians, 13 haplogroups were identified including R-M17 (34.0%), I-M423 (20.8%), R-M269* (9.4%), N-M178, R-M458 and R-M73 (each 5.7%). Our results show that a significant majority of the Moldavian paternal gene pool belongs to eastern/central European and Balkan/eastern Mediterranean Y lineages. Phylogenetic and AMOVA analyses based on Y-STR loci also revealed that Moldavians are close to both eastern/central European and Balkan-Carpathian populations. The data correlate well with historical accounts and geographical location of the region and thus allow to hypothesize that extant Moldavian paternal genetic lineages arose from extensive recent admixture between genetically autochthonous populations of the Balkan-Carpathian zone and neighboring Slavic groups.

Investigation of linkage disequilibrium block architecture in human genome is modern, intensely investigated field of molecular genetics. In the present study, genetic differentiation and linkage disequilibrium pattern in the methylenetetrahydrofolate reductase (MTHFR) locus was examined in the populations of Russians, Tuvinians, and Northern and Southern Kyrgyzes. Methylenetetrahydrofolate reductase is the key enzyme of folate cycle, responsible for reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Decreased enzymatic activity of this protein often caused by certain associations of MTHFR alleles results in the increased plasma homocysteine levels. In the population groups examined, genotype and allele frequencies at five polymorphic MTHFR loci: rs17037397, rs4846052, rs1801133, rs1801131, and rs1537516 were evaluated. Statistically significant genetic differences between the population group of Southern Kyrgyzes and the other groups, as well as between Russians and Tuvinians, were demonstrated. In the MTHFR gene from the population of Southern Kyrgyzes one block was revealed; in the populations of Russians, Tuvinians, and Northern Kyrgyzes two blocks were detected. Thus, the structure of linkage disequilibrium in the MTHFR locus demonstrated population-specific pattern.

Allele frequencies and genetic diversity in the population of Teleuts were assessed by the Alu repeat polymorphism at eight autosomal loci (ACE, APOA1, PLAT, F13, PV92, A25, CD4, D1). For comparison, the study included previously obtained data on the Alu polymorphism in 19 indigenous populations of Siberia. On the dendrogram of genetic distances, the Teleut population is located in the cluster of Siberian ethnic groups, which are similar in origin, geography, and cultural traditions.

The genetic variability of the DMPK locus has been studied in relation to six SNP markers (rs2070736, rs572634, rs1799894, rs527221, rs915915, and rs10415988) in Yakuts with myotonic dystrophy (MD) in the Yakut population and in populations of northern Eurasia. Significant differences were observed in the allele frequencies between patients and a population sample of Yakuts for three SNP loci (rs915915, rs1799894, and rs10415988) associated with a high chance of disease manifestation. The odds ratios (OR) of MD development in representatives of the Yakut population for these three loci were 2.59 (95% CI, p = 0,004), 4.99 (95% CI, p = 0.000), and 3.15 (95% CI, p = 0.01), respectively. Haplotype TTTCTC, which is associated with MD, and haplotype GTCCTT, which was observed only in Yakut MD patients (never in MD patients of non-Yakut origin), were revealed. A low level of variability in the locus of DMRK gene in Yakuts (H(e) = 0.283) compared with other examined populations was noted. An analysis of pairwise genetic relationships between populations revealed their significant differentiation for all the examined loci. In addition, a low level of differentiation in territorial groups of Yakut populations (F(ST) = 0.79%), which was related to the high subdivision of the northern Eurasian population (F(ST) = 11.83%), was observed.

The enzyme methylenetetrahydrofolate reductase (MTHFR) catalyzes synthesis of 5′-methylenehydrofolate, which is the methyl donor for the conversion of homocysteine to methionine. According to the numerous literature data, polymorphic variant of the MTHFR-encoding gene, C677T, is associated with hyperhomocysteinemia, vascular pathologies, neural tube defects, dementia, perinatal mortality, mental disorders, long-term neurodegenerative disorders, lens displacement, arachnodactyly, and venous thromboses. The present study was focused on the analysis of the C677T polymorphism (missence mutation leading to the replacement of cytosine by thymine at position 677) of the MTHFR gene in three indigenous populations of the Republic of Sakha (Yakutia), living in the settlements of Cheriktei, Byadi, and Dyupsya. Comparison of the genotype and allele frequencies revealed no substantial differences between the three Yakut populations, as well as between Yakuts and other Mongoloid ethnic groups.

The structure of the haplotypes and linkage disequilibrium (LD) of the methylenetetrahydrofolate reductase gene (MTHFR) in 9 population groups from Northern Eurasia and populations of the international HapMap project was investigated in the present study. The data suggest that the architecture of LD in the human genome is largely determined by the evolutionary history of populations; however, the results of phylogenetic and haplotype analyses seems to suggest that in fact there may be a common old mechanism for the formation of certain patterns of LD. Variability in the structure of LD and the level of diversity of MTHFR haplotypes cause a certain set of tagSNPs with an established prognostic significance for each population. In our opinion, the results obtained in the present study are of considerable interest for understanding multiple genetic phenomena: namely, the association of interpopulation differences in the patterns of LD with structures possessing a genetic susceptibility to complex diseases, and the functional significance of the pleiotropic MTHFR gene effect. Summarizing the results of this study, a conclusion can be made that the genetic variability analysis with emphasis on the structure of LD in human populations is a powerful tool that can make a significant contribution to such areas of biomedical science as human evolutionary biology, functional genomics, genetics of complex diseases, and pharmacogenomics.