Dmitry A. Verbenko

Y-Chromosome distribution within the geo-linguistic landscape of northwestern Russia

Populations of northeastern Europe and the Uralic mountain range are found in close geographic proximity, but they have been subject to different demographic histories. The current study attempts to better understand the genetic paternal relationships of ethnic groups residing in these regions. We have performed high-resolution haplotyping of 236 Y-chromosomes from populations in northwestern Russia and the Uralic mountains, and compared them to relevant previously published data. Haplotype variation and age estimation analyses using 15 Y-STR loci were conducted for samples within the N1b, N1c1 and R1a1 single-nucleotide polymorphism backgrounds. Our results suggest that although most genetic relationships throughout Eurasia are dependent on geographic proximity, members of the Uralic and Slavic linguistic families and subfamilies, yield significant correlations at both levels of comparison making it difficult to denote either linguistics or geographic proximity as the basis for their genetic substrata. Expansion times for haplogroup R1a1 date approximately to 18 000 YBP, and age estimates along with Network topology of populations found at opposite poles of its range (Eastern Europe and South Asia) indicate that two separate haplotypic foci exist within this haplogroup. Data based on haplogroup N1b challenge earlier findings and suggest that the mutation may have occurred in the Uralic range rather than in Siberia and much earlier than has been proposed (12.9±4.1 instead of 5.2±2.7 kya). In addition, age and variance estimates for haplogroup N1c1 suggest that populations from the western Urals may have been genetically influenced by a dispersal from northeastern Europe (eg, eastern Slavs) rather than the converse.

Variability of the 3′ApoB Minisatellite Locus in Eastern Slavonic Populations

Objective: To describe and compare the 3′ apolipoprotein (Apo) B minisatellite allele frequency distributions of Eastern Slavonic populations and their Uralic, Altaic, and Caucasian speaking neighbors. Methods: Healthy individuals of 10 populations among Russians, Byelorussians, Komis and Bashkirs were studied for variable number tandem repeats (VNTRs) in the 3′ApoB minisatellite region. Data were analyzed with other results reported for this polymorphism in eastern Europeans and Siberians. Results: Allele frequency spectra in Eastern Slavonic, Northern Caucasian and Finno-Ugric speaking populations are bimodal with the main peak in alleles 34–36 and a secondary mode around allele 48, whereas Altaic speaking populations have a unimodal allele frequency distribution with a peak of around 34–36 VNTRs. Population relationships were revealed using both multidimensional scaling analysis (based on Nei’s genetic distance estimate) and testing for genetic heterogeneity. Eastern Slavonic populations (Russians, Ukrainians, Byelorussians) were most closely related to each other and formed a separate tight clusterwhen plotted. Testing for genetic heterogeneity among the Eastern Slavonic ethnic groups revealed maximum diversity among Byelorussians, followed by Russians, then Ukrainians.The 3′ApoB minisatellite variability reveals little heterogeneityamong the Eastern Slavonic ethnic groups, whereas there wassignificant heterogeneity for Northern Caucasian and Altaic speakers. Conclusion: For this 3′ApoB polymorphism the Eastern Slavonic populations, despite their wide geographical distribution, appear to be much more homogenous than other ethnic groups of the region. Multidimensional scaling analysis of these data allowed for differentiation between individual populations from an ethnic group even if there is little heterogeneity.

Apolipoprotein B 3'-VNTR polymorphism in Eastern European populations

Apolipoprotein B 3′ (3′ ApoB) minisatellite polymorphism was studied in healthy unrelated individuals from the Russian Federation and the Republic of Belarus, in 10 populations from five ethnic groups: Russians, Byelorussians, Adygeis, Kalmyks and Yakuts. The analysis was carried out using PCR and electrophoresis followed by silver staining. Overall, 25 alleles of the 3′ ApoB minisatellite, ranging from 25 to 55 repeats, were detected. Heterozygosity indices were high and varied from 0.73 to 0.84. The distributions of alleles of this minisatellite in the Caucasoid populations (Russians, Byelorussians and Adygeis) had a bimodal character, whereas that for Mongoloid populations (Kalmyks and Yakuts) had a unimodal distribution. Neis genetic distances between the populations studied and some reference populations of Europe and Asia were estimated. Despite their allele distribution homogeneity, different East Slavonic ethnic groups were clearly resolved by multidimensional analyses. The East Slavonic and Adygei populations revealed a high similarity with European Caucasoids. The Mongoloid populations (Kalmyks and Yakuts) were considerably different from those of the European Caucasoid populations, but were similar to other Asian Mongoloid populations. The results demonstrate the variability of 3′ ApoB minisatellite polymorphism not only in distant populations but also, to a certain extent, in genetically relative ones.

Polymorphisms at locus D1S80 and other hypervariable regions in the analysis of Eastern European ethnic group relationships

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 Neis 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.

Allele frequencies for D1S80 (pMCT118) locus in some East European populations.

The Byelorussian populations are from three regions of the Republic of Belarus (Grodno, Bobruisk, and Mjadel areas); the Russians are from the Kholmogory town of the Russian Federation (Arkhangelsk district); and the Ukrainian populations are from the Kiev and L’vov areas of Ukraine. The Mordva-Moksha (StaroShaiginsk and Romodanovsk areas of Mordva Republic), the Bashkirs (Ilishevsky, Abzelilovsky, Sterlibashevsky, Arkhangelsky, and Beloretsky districts of Bashkir Republic), the Komi-Zyrjan (Sysolsky district of Komi Republic), the Tartar (Almetyevsk town of Tartar Republic), and the Mari (Zvenigovsk area of Mari Republic) populations present distinct ethnic groups of the region between the Volga River and the Ural Mountains in Russia. Eastern Slavonic populations (Russians, Byelorussians, Ukrainians) are Caucasoids; other populations were considered as admixture populations with different levels of a Mongoloid component. Blood samples were collected in EDTA vacutainer tubes from healthy unrelated volunteers belonging to a native ethnic group of the regions studied. DNA was isolated by phenol-chloroform ex

Specificity of genetic diversity in D1S80 revealed by SNP–VNTR haplotyping

Background: The allele frequency patterns of the D1S80 variable number tandem repeat (VNTR) locus have been shown to be multimodal in many different human populations. Aim: To explore the complex allele distribution of the D1S80 polymorphic locus in different populations comparing the derived single nucleotide polymorphism (SNP) rs16824398–D1S80 haplotype frequencies in samples of European (Russians), Asian (Yakuts) and sub-Saharan African origin. Subjects and methods: The D1S80 locus together with its 5′-flanking region including SNP rs16824398 was amplified using allele-specific polymerase chain reaction (PCR). Results: Haplotype phase determination sub-divided the total D1S80 allele spectrum into two allele sets marked by the corresponding SNP rs16824398 alleles. In non-African samples, the most frequent D1S80 alleles had 24 and 18 repeats that were associated with different SNP backgrounds (T and G alleles, respectively). Both combinations also occurred in Africans, but these samples exhibited an expanded spectrum of VNTR alleles on both SNP backgrounds. Conclusions: The sub-division of the D1S80 allele spectrum shape on the linked SNP background is indicative of populations of the main human groups. The reported differences in D1S80 allele spectra between populations of different ethnic origins can be explained by the ratios of chromosomes with T and G alleles.

East European lowland as an area of long-time interaction between Caucasoid and Mongoloid peoples

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.

Minisatellite DNA Markers in Population Studies

The discovery of an anonymous multiallelic locus in 1980 demonstrated for the first time that the human DNA contains hypervariable regions (Wyman & White, 1980). Eight alleles of a polymorphic locus that was not associated with any known gene were identified during the blot hybridization of total human genomic DNA treated with the restrictase EcoRI with a human DNA fragment (16 tbp in length) isolated from a phage genomic library. The multiallelic nature of the polymorphism at this locus did not stem from a variation in restriction sites; rather, it originated from a variable number of tandem repeats in the short core DNA sequence. Later, other similar polymorphic sites were detected near the 5 end of the insulin gene (Bell et al., 1982), in the Harvey ras oncogene (Capon et al., 1983), in the globin pseudogene (Proudfoot et al., 1982), and within the -globin cluster (Weller et al., 1984). In 1985, Jeffreys et al. published the results of their research, in which they described a fourfold repeat of 33 nucleotides in one of the introns of the human myoglobin gene (Jeffreys et al., 1985). These polymorphic regions consisted of tandem repeats of a short sequence (11–60 bp) and were termed variable number tandem repeats (VNTRs) (Kendrew & Lawrence, 1994).

DNA diversity in modern East European human populations in view of demographic history and adaptation

The interaction of the human genome with the changing environment moulds the genetic structure of human populations. The variability of autosomal loci and the haplotype diversity was studied in geographically diverse populations from Russia and neighboring countries. Basic tendencies in variability were investigated concerning specific types of polymorphism. The results reveal marked differences between East European populations and those from the Asian part of Russia. The possible effects of climatic-geographic factors on the allele and haplotype frequencies have been studied for some loci. The existences of these correlations provide evidence of possible effect of both adaptation to natural environmental factors and large-scale population movements on the specificity and diversity of gene pool.