Tetranucleotide Tandem Repeat Polymorphism of the CFTR Intron 6B in Populations of the Volga–Ural Region

The allele and genotype frequencies of the tetranucleotide tandem repeat (TTR) of CFTR intron 6B were analyzed in eight ethnic populations of the Volga–Ural region, including Bashkir, Tatar, Chuvash, Mari, Mordvinian, Udmurt, Komi-Permyak, and Russian. The most common TTR allele 7 varied in frequency from 0.636 in Chuvash to 0.805 in Mordvinians. The frequency of the second common allele 7 ranged from 0.188 in Mordvinians to 0.333 in Chuvash. Allele 8 was found in about 8% of Udmurts and Mari; occurred in a few Bashkirs, Tatars, Mordvinians, and Komi-Permyaks; and was not observed in Russians. The genetic diversity coefficient was minimal in Mordvinians (0.496) and in Tatars (0.505), indicating their low heterogeneity in TTR. The observed heterozygosity was maximal in Udmurts (0.532) and Komi-Permyaks (0.560) and minimal in Mordvinians (0.297). In total, the populations proved to be heterogeneous in TTR allele frequency distribution, the interpopulation difference being significant in most cases.     

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.     

Analysis of Polymorphisms of the Huntington Disease Gene in Ethnic Populations of 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 R_S 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 6–12 repeats were observed. R_S 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. Microdifferentiation of the Volga–Ural populations corresponded to the European type.     

A study of polymorphism of the D2 dopamine receptor gene in the population of the Volga-Ural Region

Using polymerase chain reaction (PCR), TaqI polymorphism for the D2 dopamine receptor gene (DRD2) was studied in eight populations of the Volga-Ural region that belong to the Turkic (Bashkirs, Tatars, and Chuvashes), Finno-Ugric (Maris, Komis, Mordvinians, and Udmurts), and Eastern-Slavonic (Russians) ethnic groups. Significant differences in the distribution of genotype frequencies were found between the Tatar population belonging to the Turkic branch of the Altaic linguistic family and the Mari and Mordvinian populations belonging to the Finno-Ugric branch of the Ural family and between the Tatar and Bashkir populations belonging to the Turkic ethnic group.     

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.     

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.     

Polymorphism of microsatellite loci DYS19, DYS393, and frequency of the T-C transition of the RBF5 locus on the Y-chromosome in inhabitants of the Volga-Ural region

Polymorphism of the DYS19 and DYS393 microsatellite loci and T-C transition at the RBF5 locus of the Y chromosome were analyzed in Volga-Ural populations of Bashkirs, Tatars, Chuvashes, Maris, Mordovians, Udmurts, and Komis. For the DYS19 locus, statistically significant differences were observed between Trans-Ural and Northeastern Bashkirs; between Trans-Ural Bashkirs and Tatars; and between Udmurts and other populations of the Volga-Ural region, excluding Trans-Ural Bashkirs. The DYS393 locus allele frequency distribution patterns were similar in all populations studied. The highest and the lowest frequencies of T-C transition at the RBF5 locus was detected in Udmurts (0.68) and in Mordovians (0.09), respectively. Association of C-alleles with the DYS19/DYS393 microsatellite haplotypes was investigated. The major haplotypes specific to the Turkic- and Finno-Ugric populations were revealed.     

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.     

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.     

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 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.     

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.     

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.     

Genetic Structure of the Volga–Ural and Central Asian Populations Inferred from the Data on Alu Polymorphism

NineAlu 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 (F _st = 0.061) was higher than for the populations of Central Asia (F _st = 0.024), Europe (F _st = 0.02), and Southeastern Asia (F _st = 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.     

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.     

Hereditary Disorders in Circassians of the Karachay-Cherkess Republic

The paper aims to review the diversity of monogenic hereditary disorders (MHD) in the Circassians of the Karachay-Cherkess Republic (KCR). In total, 50817 Circassians were investigated. The populations of eight districts (Ust-Dzhegutinsky, Karachayevsky, Malokarachayevsky, Prikubansky, Khabezsky, Abazinsky, Nogaysky, and Adyge-Khablsky) and of the city of Cherkessk were studied. Two hundred fifty patients from 167 families were registered. The prevalence of MHD in Circassians happens to be 1: 214. The nosological spectrum of MHD in Circassians includes 70 disorders: 34 with autosomal dominant, 25 with autosomal recessive, and 11 with X-linked inheritance patterns. Confirmatory DNA diagnostics was performed in 56 patients. Accumulation of particular diseases in the Circassian population was revealed in comparison with the previously surveyed ethnic groups/populations of Russia. The cluster analysis was performed on the basis of the prevalence of AD and AR disorders and determined the genogeographic position of the Circassians among eight ethnic groups of Russia (13 populations in total). The total size of the surveyed populations was over 3.5 million people: six Russian regions, Tatars of the Tatarstan, Bashkirs of the Bashkortostan, Chuvashs of the Chuvash Republic, Maris of the Mari El Republic, Udmurts of the Udmurt Republic, Adygeans of the Republic of Adygea, and Circassians of the Karachay-Cherkess Republic. The general pattern for AD and AR diseases was similar: six Russian populations group within a single cluster, being remote from people of the Volga-Ural region and the North Caucasus (Adyghe: Adygeans and Circassians).     

Restriction polymorphism of the major non-decoding region of mitochondrial DNA in human populations from the Volga-Ural region]

The restriction fragment length polymorphism (RFLP) of the major noncoding region of mitochondrial DNA (mtDNA) was studied in the Bashkir (N = 217), Tatar (N = 57), Chuvash (N = 44), Mari (N = 52), Mordovian (N = 55), Udmurt (N = 62), and Komi (N = 45) populations. Of seven polymorphic AvaII, BamHI, EcoRV, KpnI, and RsaI restriction sites, five were found in Bashkirs and Tatars, and four were found in each of the other populations. In total, 13 mitotypes were detected, and only three of them were common to all populations from the Volga-Ural region. The parameters of gene diversity were calculated with respect to the polymorphic sites and mitotypes. Comparison with published data revealed both Mongoloid and Caucasoid components in the gene pool of the modern populations from the Volga-Ural region. The Mongoloid component was prevalent in the mitochondrial gene pool, which is consistent with historical, anthropological, and ethnographic data.     

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.     

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.     

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.