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.     

Prevalence and molecular-genetic typing of nonsyndromal neurosensory deafness in the Chuvash Republic

Summarized genetic epidemiological characteristics of nonsyndromic sensorineural deafness in six raions of Chuvash Republic (Cheboksary, Kanash, Morgaushi, Tsivil'sk, Mariinski Posad, and Alatyr') are presented. A total of 264,419 individuals were examined. Forty-five families (60 affected individuals) with autosomal recessive (AR) and 8 families (18 affected individuals) with autosomal dominant (AD) nonsyndromic sensorineural deafness (NSSD) were identified. The load of AD and AR NSSD in the raions examined was estimated. A correlation between the distribution of AR NSSD and genetic drift was demonstrated. Furthermore, the load of AR NSSD was substantially higher in the regions with higher differentiation level. The Spearman's correlation coefficient value was 0.87. Typing of the 35delG mutation in the gene for connexion 26 was carried out in 34 patients from 26 families with AR NSSD. Comparative estimates of the NSSD prevalence in a number of Russian populations were performed.     

Genogenography of the aboriginal population of Marii El (from data on immunobiochemical polymorphism)

The geographic distribution of the frequencies of genes related to the immunological and biochemical polymorphism was studied in the Maris, who are the indigenous population of the Marii El Republic. Data on the frequencies of 33 alleles of 10 loci (ABO, TF, GC, PI, HP, AHS, F13B, ACP1, PGM1, and GLO1) in five raions (districts) of Marii El were obtained. Computer interpolation maps were constructed for all alleles. The maps allows to predict the distribution of the alleles throughout Marii El. A map of the reliability of the cartographic prediction was drawn. For the first time, the reliability of predicted gene frequencies were taken into account in constructing and interpreting the maps of gene frequencies. For the entire set of the studied genes, parameters of heterozygosity (HS) and gene diversity (GST) were estimated. Cartographic correlation analysis was performed to reveal the relationship between gene frequencies and geographic coordinates. It was found that 42% of the studied genes predominantly correlated with latitude and 9% with longitude. It was assumed that the genetic structure of Mari populations had been mainly determined by latitude-related factors. A map of Nei's genetic distances between the overall Mari gene pool and the local populations revealed a central core, which was close to the "average Mari" gene pool, and a periphery, which was genetically distant from it. Suggestions on the microevolution of the Mari gene pool were advanced. Maps of the genes with the most characteristic genetic relief (ABO*B, ACP*A, TF*D, GC*1F, PI*M2, HP*1F, and F13B*3) are shown. These maps exhibit a high correlation with the maps of principal components.     

Genetic Epidemiological Study of Three District Populations in Chuvashia

Comprehensive population genetic and medical genetic studies were performed in three raions (districts) of Chuvashia. The population of these districts is more than 90% Chuvash. About 70% of the families that completed reproduction had two or three children. The proportion of families with four or more children was 18%. The duration of generation was 27.6 years. The differential fertility and differential mortality indices in the Chuvash population were estimated at 0.33 and 0.076, respectively. The total index of differential selection was 0.403, which is typical of modern urbanized populations. Mean values of local inbreeding calculated from Malecot's model of isolation by distance were 0.00124 and 0.00377 for the urban and rural populations, respectively, of the districts studied. The prevalence rates of autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases were found to be 0.47, 0.52, and 0.35 per 1000, respectively, in the urban population and 1.62, 1.14, and 0.31 per 1000, respectively, in the rural population. Significant correlation between the local inbreeding and prevalence rates of AD and AR diseases was found. A total of 43 AD and 43 AR diseases were identified. Some of them were not found in previous studies on other populations.     

Genetic epidemiological study of populations in three regions of Chuvashia Republic

Comprehensive population genetic and medical genetic studies were performed in three raions (districts) of Chuvashia. The population of these districts is more than 90% Chuvash. About 70% of the families that completed reproduction had two or three children. The proportion of families with four or more children was 18%. The duration of generation was 27.6 years. The differential fertility and differential mortality indices in the Chuvash population were estimated at 0.33 and 0.076, respectively. The total index of differential selection was 0.403, which is typical of modern urbanized populations. Mean values of local inbreeding calculated from Malecot's model of isolation by distance were 0.00124 and 0.00377 for the urban and rural populations, respectively, of the districts studied. The prevalence rates of autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases were found to be 0.47, 0.52, and 0.35 per 1000, respectively, in the urban population and 1.62, 1.14, and 0.31 per 1000, respectively, in the rural population. Significant correlation between the local inbreeding and prevalence rates of AD and AR diseases was found. A total of 43 AD and 43 AR diseases were identified. Some of them were not found in previous studies on other populations.     

Apolipoprotein B 3'-VNTR polymorphism in the Udmurt population

An analysis of a highly polymorphic region of the apolipoprotein B gene 3'-end DNA (Apo B 3'-VNTR), represented by 10 alleles, was carried out using the polymerase chain reaction. Data inferred from the principal component analysis indicate that the Udmurts occupy an isolated position among the populations constituting the northern branch of Caucasoid peoples.     

Prevalence and Molecular Genetic Typing of Nonsyndromic Sensorineural Deafness in Chuvash Republic

Summarized genetic epidemiological characteristics of nonsyndromic sensorineural deafness in six raions of Chuvash Republic (Cheboksary, Kanash, Morgaushi, Tsivil'sk, Mariinski Posad, and Alatyr') are presented. A total of 264419 individuals were examined. Forty-five families (60 affected individuals) with autosomal recessive (AR) and 8 families (18 affected individuals) with autosomal dominant (AD) nonsyndromic sensorineural deafness (NSSD) were identified. The load of AD and AR NSSD in the raions examined was estimated. A correlation between the distribution of AR NSSD and genetic drift was demonstrated. Furthermore, the load of AR NSSD was substantially higher in the regions with higher differentiation level. The Spearman's correlation coefficient value was 0.87. Typing of the 35delG mutation in the gene for connexion 26 was carried out in 34 patients from 26 families with AR NSSD. Comparative estimates of the NSSD prevalence in a number of Russian populations were performed.     

Selective structure of the gene pool. IV. Estimation from the selection intensity index Rs

A new approach for investigating the selective structure of the gene pool reflecting the type and intensity of selection is proposed. Selection pressure is estimated on the basis of interpopulation gene diversity with the use of the selection intensity index: RS(i) = NeS(i) = 1/4(1/FST(i)-1/Fe). Distributions of RS(i) in gene pools of indigenous populations from all continents and five subregions of the northeastern Eurasia were examined. It was shown that, of all theoretical distributions, only beta-distributions provide a good approximation of RS(i) estimates. Based on the confidence intervals of RS obtained from beta-distributions, genes can be grouped into the three following classes according to their selective structure: LOWER DIFF, NEUTRAL, and SUPER DIFF. These classes, respectively, include genes subjected mainly to stabilizing selection (RS(i) > 0; LOWER DIFF), genes subjected mainly to differentiating selection (RS(i) < 0; SUPER DIFF), and arbitrarily selectively neutral genes (RS(i) approximately 0; NEUTRAL). Simulation of gene pool sampling (10(6) samples from 50 markers for each gene pool) allowed us to characterize the selective structure by determining markers that fall into the same selective class irrespective of the variant for the sampling process. The selective structure of gene pools from six continents (Europe, Asia, Africa, Australia, America, and southeastern Eurasia) and five subregions of northeastern Eurasia was characterized. It was shown that approximately one-third of genes is subjected to selection irrespective of the hierarchical level of the region. In gene pools of Europe, northeastern Eurasia, and European and Ural subregions, the proportion of genes under stabilizing selection was higher, the proportion of selectively neutral genes, lower. Debatable issues of tests for selective neutrality based on heterogeneity of interpopulation gene diversity are considered. These issues include the effect on FST of the hierarchical population structure, sample size, number of subpopulations, and other factors that shift estimates of gene selective values.     

"Synthetic" maps of the Mari gene pool (from immunobiochemical polymorphism data)]

Models of geographic distribution of 33 alleles of 10 loci (AB0, TF, GC, PI, HP, AHS, F13B, ACP1, PGM1, GLO1) in the indigenous population of five raions (districts) of Marii El Republic were analyzed by cartographic statistical methods. Based on 33 maps for individual alleles, synthetic maps were constructed; they reflected the general characteristics of the spatial variability of the Mari gene pool. A map of reliability of the synthetic maps was also obtained. This study was the first to use estimates of the reliability of the gene-geographic prognosis for constructing and interpreting the maps of principal components. Synthetic maps of principal components reveal the geography of the main factors that determine the genetic diversity of the Maris. In the map of the first principal component (accounting for 25.5% of the total variation of the Mari gene pool), isolines clearly ran in the latitudinal direction; i.e., the variability exhibited a north-south gradient. The direction of changes reflects the characteristic features of the microevolution of the Mari gene pool, because it differs from the direction of the principal components of in the total Ural gene pool. The second principal component (24.3% of variation) also exhibited a latitudinal gradient in the western part of Marii El. In the eastern part of the republic, isolines drastically change their direction and display a marked west-east gradient. This longitudinal orientation of principal components is characteristic of the Maris in the synthetic maps of the Ural region. Contributions of individual genes in the variation of principal components were analyzed. In proceeding from the geographic space to the space of principal components, it was found that Highland Maris are separated from Meadow Maris not only geographically, but also genetically.     

Mutation C3256T of Mitochondrial Genome in White Blood Cells: Novel Genetic Marker of Atherosclerosis and Coronary Heart Disease

This study was undertaken to examine the association between the level of heteroplasmy for the mutation C3256T in human white blood cells and the extent of carotid atherosclerosis, as well as the presence of coronary heart disease (CHD), the major clinical manifestation of atherosclerosis. Totally, 191 participants (84 men, 107 women) aged 65.0 years (SD 9.4) were recruited in the study; 45 (24%) of them had CHD. High-resolution B-mode ultrasonography of carotids was used to estimate the extent of carotid atherosclerosis by measuring of the carotid intima-media thickness (cIMT). DNA samples were obtained from whole venous blood, and then PCR and pyrosequencing were carried out. On the basis of pyrosequencing data, the levels of C3256T heteroplasmy in DNA samples were calculated. The presence of the mutant allele was detected in all study participants; the level of C3256T heteroplasmy in white blood cells ranged from 5% to 74%. The highly significant relationship between C3256T heteroplasmy level and predisposition to atherosclerosis was revealed. In individuals with low predisposition to atherosclerosis the mean level of C3256T heteroplasmy was 16.8%, as compared to 23.8% in moderately predisposed subjects, and further to 25.2% and 28.3% in significantly and highly predisposed subjects, respectively. The level of C3256T heteroplasmy of mitochondrial genome in human white blood cells is a biomarker of mitochondrial dysfunction and risk factor for atherosclerosis; therefore, it can be used as an informative marker of genetic susceptibility to atherosclerosis, coronary heart disease and myocardial infarction.