Analysis of Y-chromosomal diallelic loci polymorphism in populations of the Volga-Ural region

Three diallelic polymorphisms of human Y chromosome, DYS287 (Y Alu polymorphism, YAP), T/C transition at the RBF5 locus (Tat), and G/A transition at the LLY22 locus, were studied in eight ethnic populations of the Volga-Ural region, representing Turkic (Bashkirs, Tatars, and Chuvashes) and Finno-Ugric (Maris, Mordovians, Udmurts, Komi-Zyryans, and Komi-Permyaks) branches of the Uralic linguistic family, and in the group of Slavic migrants, belonging to the Indo-European linguistic family (Russians). Ethnic populations of the Volga-Ural region were characterized by a low frequency of the Y chromosome Alu insertion. Examination of an association between the Alu polymorphism and Tat mutation revealed absolute C/YAP linkage. Analysis of the haplotype frequency distribution patterns constructed from the data on the DYS287 and RBF5 polymorphisms revealed substantial differences between Udmurts and the other ethnic populations. The differences were also observed between Komi-Zyryans and the populations of Bashkirs, Mordovians, Komi-Permyaks, and Russians. Analysis of the degree of genetic differentiation pointed to high level of genetic differentiation of the male lineages of the Finno-Ugric ethnic groups. The data on the linkage between mutations of the RBF5 and the LLY22 loci indicated the common origin of the Tat mutation in Bashkirs, Mordovians, Udmurts, and Komi-Zyryans, and of a number of ancestral C allele-bearing chromosomes in Tatars, Maris, and Chuvashes.     

Polymorphism of Y-Chromosomal Diallelic Loci in Populations of the Volga–Ural Region

Three diallelic polymorphisms of human Y chromosome (DYS287(Y Alupolymorphism, YAP), T/C transition at the RBF5locus (Tat), and G/A transition at the LLY22locus) were studied in eight ethnic populations of the Volga–Ural region, representing Turkic branch of the Altai (Bashkirs, Tatars, and Chuvashes) and Finno-Ugric branch of the Uralic linguistic family (Maris, Mordovians, Udmurts, Komi-Zyryans, and Komi-Permyaks), and in the group of Slavic migrants, belonging to the Indo-European linguistic family (Russians). The Volga–Ural populations were characterized by a low frequency of the Y chromosome Aluinsertion. Examination of an association between the Alupolymorphism and Tatmutation revealed absolute YAP–/C linkage. Analysis of the haplotype frequency distribution patterns constructed from the data on the DYS287and RBF5polymorphisms revealed substantial differences between Udmurts and other populations. The differences were also observed between Komi-Zyryans and the populations of Bashkirs, Mordovians, Komi-Permyaks, and Russians. Analysis of the degree of genetic differentiation pointed to high level of genetic differentiation of the male lineages of the Finno–Ugric ethnic groups. The data on the linkage between the RBF5locus and the LLY22locus mutations indicated the common origin of the Tatmutationin Bashkirs, Mordovians, Udmurts, and Komi-Zyryans, and of a number of ancestralCallele-bearing Y chromosomes in Tatars, Maris, and Chuvashes.     

Investigation of monoamine oxidase gene restriction polymorphism in male populations of the Volga-Ural region

Restriction polymorphism at the monoamine oxidase A (MAO A) gene was typed in eight male populations of the Volga-Ural region (Bashkirs, Chuvashes, Tatars, Udmurts, Maris, Mordovians, Komis, and Russians inhabiting the Republic of Bashkortostan). Analysis of the MAO A alleles frequency distribution patterns did not reveal statistically significant differences between the Volga-Ural populations examined. The results obtained suggest genetic homogeneity of the populations described in respect of the polymorphic locus examined.     

Analysis of polymorphism of CTG repetitive sequences in the gene of myotonic dystrophy in human populations of the Volga-Ural region]

Distribution of CTG repetitive sequences in the myotonic dystrophy (MD) gene was analyzed in ten populations of the Volga-Ural region, including Tatars, Chuvashes, Maris, Udmurts, Mordovians, Komis, and four ethnogeographical groups of Bashkirs. A total of 25 alleles were found (9 to 14 in individual populations), with each allele containing 5 to 34 trinucleotide repeats. The allele frequency distribution had two peaks corresponding to alleles with 5 and 11-14 CTG repeats. The frequency of the (CTG)5 allele varied from 0.23 to 0.47 in Maris and Mordovians, respectively. Regarding the (CTG)11-14 alleles, those containing 13 and 12 trinucleotides were most frequent in all populations; their frequencies varied from 0.15 in Mordovians to 0.24 in Maris and Bashkirs from the Abzelilovskii raion (district). Alleles with large numbers of repeats (more than 30) were only found in Tatars and Bashkirs from the Abzelilovskii raion, where their frequency was 0.01. The data obtained were compared with those on other human populations from various regions of the world. In general, the populations of the Volga-Ural region took an intermediate position between European and Asian populations (although were somewhat more similar to the latter ones) with respect to the distribution of allelic frequencies of the CTG repetitive sequences. In individual populations, the number of genotypes varied from 13 to 27 in Mordovians and Bashkirs from the Ilishevskii raion, respectively. The observed heterozygosity was the highest (91%) in Udmurts and the lowest (58%) in Mordovians; the average heterozygosity was 81%. Such a high heterozygosity, as well as the revealed differentiation of the populations with respect to the distribution of the allelic frequencies of CTG repetitive sequences in the MD gene, allow this polymorphic DNA locus to be considered a highly informative genetic marker of populations.     

Molecular genetic analysis of polymorphism of the HindII and (CA)-repeat of the factor VIII gene loci in people of the Volgo-Ural region

Molecular genetic analysis of polymorphism of the factor VIII gene at loci HindIII (intron 19) and (CA)-repeats (intron 13) was performed in seven ethnic groups of the Volga-Ural region (Bashkirs, Tatars, Chuvashes, Maris, Mordovians, Udmurts, and Komis). The allelic frequency of the HindIII locus was shown to be similar in these ethnic groups. The ethnic groups were more heterogeneous with regard to the genotype and allele frequencies of (CA)-repeats, which indicates that this polymorphic system can be used to characterize the genetic structure of the Volga-Ural human populations.     

Molecular-genetic analysis of polymorphism of the DXS532 locus in people from the Volga-Ural region]

The DXS52 polymorphic locus mapping to the 5'-region of the blood-clotting factor VIII gene on the X chromosome was genotyped in seven Volga-Ural ethnic groups (Bashkirs, Tatars, Chuvashes, Maris, Mordovians, Udmurts, and Komis). A total of 47 different genotypes and 15 allelic variants of this locus were described. Substantial intra- and interpopulation heterogeneity of the ethnic groups studied in respect to frequency and distribution of the DXS52 alleles and genotypes was demonstrated. The unimodal DXS52 allele frequency distribution pattern with the peak at 1690 bp was typical to Mordovians and Komis. Chuvashes and Maris, as well as Udmurts, were characterized by bimodal frequency distribution patterns, with the peaks at 1690 and 670 bp, and 1690 and 1390 bp, respectively. Moreover, Bashkirs and Tatars displayed trimodal DXS52 allele frequency distribution patterns with the peaks at 1690, 1390, and 670 bp. The DXS52 allele frequency distribution patterns described in populations of the Volga-Ural region were found to be remarkably different from those established for the mixed Moscow population and the population of Western Europe. These data indicate that the DXS52 locus is highly informative, and this polymorphic system can serve as a molecular marker for population genetic studies.     

Evaluation of the relative contribution of Caucasoid and Mongoloid components in the formation of ethnic groups of the Volga-Ural region according to data of DNA polymorphism]

For the first time, an attempt was made to quantitatively estimate the relative contributions of major racial components to populations of the Volga-Ural region based on the data on allelic polymorphisms of nine loci of the mitochondrial and nuclear genomes. Comparison of the proportions of Caucasoid and Mongoloid characteristics in the gene pools of Bashkirs, Tatars, Chuvashes, Maris, Mordovians, Udmurts, and Komi revealed a heterogeneous pattern. Data on the proportions of major racial components in the nuclear genome indicated that the Caucasoid component was maximum in Mordovians, Komis, and Udmurts. Mongoloid characters were most prevalent in Bashkirs, Maris, Tatars, and Chuvashes. Data on restriction-deletion polymorphism of mitochondrial DNA (mtDNA) also indicated an increased Caucasoid contribution to Mordovian, Udmurt, and Komi gene pools and an increased Mongoloid component in Chuvashes and Tatars. In general, the results obtained agree with ethnic anthropological data indicating the greatest Caucasoid contribution to the Mordovian and Komi gene pools and an increased Mongoloid component in Turkic populations of the Volga-Ural region (Bashkirs, Tatars, and Chuvashes).     

Analysis of polymorphism of the glutathione S-transferase gene in populations of the Volga-Ural region

The frequency of the GSTM1 gene deletion homozygotes in eight populations of the Volga-Ural region belonging according to linguistic classification to Turkic (Bashkirs, Tatars, and Chuvashs), Finno-Ugric (Maris, Komis, Mordovians, and Udmurts), and Eastern-Slavic (Russians) ethnic groups, was examined by means of PCR technique. The frequency of the deletion homozygotes varied from 41.4% in Bashkirs to 61.3% in Mordovians. The mean deletion frequency comprised 50.1%, which was consistent with the data for European populations (chi 2 = 0.009).     

Polymorphism of the serotonin 2A receptor gene in populations from the Volga-Ural region]

The MspI restriction polymorphism of the serotonin 2A receptor gene (5HT2A) was typed in populations of the Volga-Ural region (Bashkirs, Chuvashes, Tatars, Udmurts, Maris, Mordovians, Komis, and Russians inhabiting the Republic of Bashkortostan). Population-specific patterns of the main polymorphism indices distribution were established. Specific trends in the changes of genotype and allele frequency of the 5HT2A gene depending on the ethnicity of the population were revealed.     

Analysis of the genetic differentiation of Bashkirs and peoples from the Volgo-Ural region from data on polymorphic markers of the nuclear genome]

Nei's coefficient of genetic differentiation (Gst) was used to estimate the intergroup differentiation of four ethnic geographic groups of Bashkirs and the interethnic differentiation of seven ethnoses (Bashkirs, Tatars, Chuvashes, Udmurts, Maris, Komis, and Mordovians) from the Volga-Ural region. The coefficient of genetic differentiation calculated from data on four polymorphic loci (MET, D7S23, PKU, and apoB) and classical biochemical markers (AB0, MN, Rh, Hp, and AcP) of the nuclear genome was similar in all tested populations. The genetic difference between the ethnoses from the Volga-Ural region (Gst = 1.91%) was intermediate between that in European (Gst = 1.18%) and Siberian (Gst = 5.84%) ethnoses.     

Polymorphism of the dopamine D2 receptor gene in populations from the Volga-Ural region

The PCR technique was used to analyze the TaqIA- and NcoI-polymorphisms at the dopamine D2 receptor gene (DRD2) in eight populations of the Volga-Ural region belonging to Turkic (Bashkirs, Tatars, and Chuvashes), Finno-Ugric (Maris, Komis, Mordovians, and Udmurts), and Eastern-Slavic (Russians) ethnic groups. Population-specific patterns of the main TaqIA- and NcoI-polymorphisms distribution were established. Specific trends in changes of genotype and allele frequency of the dopamine D2 receptor gene depending on the ethnicity of the population were revealed.     

Molecular-genetic analysis of VNTR polymorphism in alleles of the phenylalanine hydroxylase gene in inhabitants of the Volga-Urals region

Molecular genetic analysis of the VNTR alleles at the phenylalanine hydroxylase (PAH) gene was carried out in seven Volga-Ural ethnic groups (Bashkirs, Tatars, Chuvashes, Maris, Mordovians, Udmurts, and Komis). The PCR fragments revealed included alleles of 380, 440, 470, 500, 530, 560, and 650 bp, containing 3, 5, 6, 7, 8, 9, and 12 repeat copies, respectively. Substantial heterogeneity of the populations in respect to the distribution and frequency of the VNTR alleles and genotypes was demonstrated. The indices of observed and theoretical heterozygosity of the PAH VNTR alleles were calculated. The mean heterozygosity index was 70.02%. This high index value along with the established differentiation of the populations in respect to the frequency distribution of the VNTR alleles and PAH genotypes permitted the conclusion that the given polymorphic locus can serve as a highly informative marker for examination of the genetic structure of the Volga-Ural populations.     

Polymorphism of the serotonin transporter gene in populations of the Volga-Ural region

Polymorphism of the serotonin transporter gene (hSERT) was studied in eight human populations of the Volga-Ural region by means of polymerase chain reaction (PCR). The populations studied belonged to Turkic (Bashkirs, Tatars, and Chuvashes), Finno-Ugric (Maris, Komis, Mordovians, and Udmurts), and Eastern Slavic (Russians) ethnic groups. Comparison of the hSERT polymorphisms in these populations established the population-specific distribution patterns of the main component of this polymorphic system in the region studied and revealed the interethnic differences in hSERT allelic and genotypic frequencies.     

Analysis of the angiotensinogen gene T174M polymorphism in populations of the Volga-Ural region

The method of polymerase chain reaction was used to analyze T174M polymorphism at the angiotensinogen (AGT) gene in a number of populations of the Volga-Ural region, belonging to Finno-Ugric (Komi-Permyaks, Maris, Mordovians, and Udmurts), Turkic (Chuvashes, Tatars, and Bashkirs), and Eastern-Slavic (Russians) ethnic groups. Population-specific patterns of the polymorphic alleles and genotypes frequency distribution were established. Comparison of the results with the literature data on the AGT gene polymorphism in different world populations provided identification of specific trends in the changes of genotype frequency of the AGT gene depending on the ethnicity of the populations.     

Insertion-deletion polymorphism of the angiotensin-converting enzyme gene in populations of the Volga-Ural region

Insertion-deletion polymorphism at the angiotensin I-converting enzyme (ACE) gene in populations of the Volga-Ural region was examined by means of polymerase chain reaction. The populations studied belong to the Finno-Ugric (Komis, Maris, Mordovians, and Udmurts), Turkic (Chuvashes, Tatars, and Bashkirs), and Eastern-Slavic (Russians) ethnic groups. Distribution patterns of allele and genotype frequencies of this polymorphic system in the examined region were characterized. Comparison of the obtained results with the literature data on the ACE gene polymorphism in other Caucasoid and Mongoloid populations revealed some trends in the ACE genotype frequency dynamics depending on the ethnicity of the populations.     

Investigation of Monoamine Oxidase Gene Restriction Polymorphism in Male Populations of the Volga–Ural Region

Restriction polymorphism at the monoamine oxidase A (MAO A) gene was typed in eight male populations of the Volga– Ural region (Bashkirs, Chuvashes, Tatars, Udmurts, Maris, Mordovians, Komis, and Russians inhabiting the Republic of Bashkortostan). Analysis of the MAO A alleles frequency distribution patterns did not reveal statistically significant differences between the Volga–Ural populations examined. The results obtained suggest genetic homogeneity of the populations described in respect of the polymorphic locus examined.     

Molecular Genetic Analysis of the DXS52Polymorphism in Populations of the Volga–Ural Region

The DXS52polymorphic locus mapping to the 5"-region of the blood-clotting factor VIII gene on the X chromosome was genotyped in seven Volga–Ural ethnic groups (Bashkirs, Tatars, Chuvashes, Maris, Mordovians, Udmurts, and Komis). A total of 47 different genotypes and 15 allelic variants of this locus were described. Substantial intra- and interpopulation heterogeneity of the ethnic groups studied in respect to frequency and distribution of the DXS52alleles and genotypes was demonstrated. The unimodal DXS52allele frequency distribution pattern with the peak at 1690 bp was typical to Mordovians and Komis. Chuvashes and Maris, as well as Udmurts, were characterized by bimodal frequency distribution patterns, with the peaks at 1690 and 670 bp, and 1690 and 1390 bp, respectively. Moreover, Bashkirs and Tatars displayed trimodal DXS52allele frequency distribution patterns with the peaks at 1690, 1390, and 670 bp. The DXS52allele frequency distribution patterns described in populations of the Volga– Ural region were found to be remarkably different from those established for the mixed Moscow population and the population of Western Europe. These data indicate that the DXS52locus is highly informative, and this polymorphic system can serve as a molecular marker for population genetic studies.     

Analysis of polymorphic loci of Huntington genes in peoples from the Volga-Ural region

Eleven populations of the Volga-Ural region were analyzed with respect to three intragenic polymorphisms of the Huntington disease gene (IT15), including highly polymorphic (CAG)n and moderately polymorphic (CCG)n of exon 1 and neutral del2642 of exon 58. In the case of (CAG)n, 101 genotypes were observed, with genotype number varying from 15 in Southeastern Bashkirs to 34 in Mari. Allele diversity RS ranged from 9.70 in Southeastern Bashkirs to 18.00 in Chuvash, averaging 13.79 +/- 2.12. The (CAG)n allele frequency distribution was unimodal and had a maximum at (CAG)17. In the case of (CCG)n, six alleles with 6-10 or 12 repeats were observed. RS was 4.13 +/- 0.44, ranging from 3.73 in Udmurts to 4.99 in Tatars. In the case of del2642, allele del- was detected at a frequency 0.830 in Mari to 0.932 in Udmurts. Of all Volga-Ural ethnic populations, Finno-Ugric ones proved to be most heterogeneous with respect to the three polymorphisms, whereas Turkic populations and, in particular, Bashkirs were homogeneous. Micro-differentiation of the Volga-Ural populations corresponded to the European type.     

Genetic structure of people from the Volga-Ural region and Central Asia from data of Alu-polymorphism

Nine Alu loci (Ya5NBC5, Ya5NBC27, Ya5NBC148, Ya5NBC182, YA5NBC361, ACE, ApoA1, PV92, TPA25) were analyzed in six ethnic populations (Trans-Ural Bashkirs, Tatars-Mishars, Mordovians-Moksha, Mountain Maris, Udmurts, and Komi-Permyaks) of the Volga-Ural region and in three Central Asian populations (Uzbeks, Kazakhs, and Uigurs). All Alu insertions analyzed appeared to be polymorphic in all populations examined. The frequency of insertion varied from 0.110 in Mountain Maris at the Ya5NBC5 locus to 0.914 in Tatars at the ApoA1 locus. The data on the allele frequency distribution at nine loci point to the existence of substantial genetic diversity in the populations examined. The value of the observed heterozygosity averaged over nine Alu insertions varied from 0.326 in Mountain Maris to 0.445 in Kazakhs and Uigurs. The level of the interpopulation genetic differences for the Volga-Ural population (Fst = 0.061) was higher than for the populations of Central Asia (Fst = 0.024), Europe (Fst = 0.02), and Southeastern Asia (Fst = 0.018). The populations examined were highly differentiated both in respect of linguistic characteristics and the geographical position. The data obtained confirmed the effectiveness of the marker system used for the assessment of genetic differentiation and the relationships between the ethnic groups.     

Analysis of polymorphism of the HLA-DRB1 gene in populations from the Volga-Ural region

Polymorphism at the HLA-DRB1 locus in six Turkic (Bashkirs, Tatars, and Chuvashes) and Finno-Ugric (Udmurts, Maris, and Komis) populations of the Volga--Ural region was studied by PCR. A total of 12 DRB1 specificities displaying population-specific frequency distribution patterns were described. The most frequently observed specificities in Bashkirs and Udmurts were DRB1*07 (25 and 34%, respectively) and *15 (by 15%). In Tatars the prevalence of *04 (18%), *01 (17%), *07 (16%) and *15 (13%) specificities was observed, while in Chuvashes these were *04 (28%), *11 (18%), *01 (16%), and *07 (16%). High frequencies of *11 (21%), *04 (17%), *01 (13%), and *04 (11%) specificities were characteristic of Komis, whereas Maris were distinguished by high frequencies of *01 (23%), *11 (14%), *07 (13%), and *04 (11%). In general, the pattern of DRB1 allelic polymorphism in populations of the Volga-Ural region, occupying the intermediate position between the Caucasoid- and Mongoloid-specific allelic frequency distribution patterns, was consistent with their anthropological type rather than with their linguistic affiliation.