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T A Pavlova

Publications and source records attributed to T A Pavlova.

At least 19 recordsLinked to original sources
PubMed2004

[STR polymorphism in populations of indigenous Daghestan ethnic groups].

Genomic diversity of 21 STR loci has been studied in six ethnic populations of Daghestan (the Caucasus), namely, Avars, Dargins, Kubachians, Lezgins, and Nogais, and the results have been compared with these data for European, African, and East Asian ethnic groups. Daghestan is unique in its ethnic diversity, which is the greatest in the Caucasus: 26 out of approximately 50 autochthonous ethnic groups of the Caucasus live there. The genetic origin of this wide ethnic diversity of Daghestan and the Caucasus as a whole is still obscure. The genetic heterogeneity of Daghestan populations has been found to be lower than that of most other populations in the world. This is explained by a prolonged isolation and gene drift in their demographic history. Generalized genetic distances between ethnic groups calculated for the whole set of loci studied allow differentiating Asian populations from African ones, with European populations occupying intermediate positions. All Daghestan ethnic populations form a distinct common group together with some European populations (Finnish, Polish, and French). Nogais are genetically close to Southeast Asian populations. The genetic closeness and the apparently equal genetic diversity of Daghestan and European populations suggest that the ethnic differentiation of the ancestral populations of Daghestan and European ethnic groups occurred in the earliest populations of modern humans.

Ethnicity↗
PubMed2003

[Genetic subdivision of Dagestan ethnic populations].

Relationships between ethnic and genetic differentiation with respect to 54 microsatellites have been analyzed in five Daghestan ethnic groups. To detect the microsatellites, human chromosomes 3, 17, and 18 were screened with a step of 10 cM (Weber/CHLC 9.0 markers) at the Mammalian Genotyping Service (National Institute of Health, United States). Comparison of the polymorphism of these loci in Daghestan populations with average worldwide data has revealed generally low heterozygosity in Daghestan populations, which is accounted for by traditional endogamous and consanguineous marriages throughout the history of these populations. The inbreeding coefficient in Daghestan ethnic groups varies from 0.005 to 0.0134 and is close to the worldwide maximum known to date. For some DNA loci, significant differences between the offsprings of consanguineous and exogamous marriages with respect to allele sizes and their variance have been found. The Daghestan ethnic populations studied differ from one another in both the frequencies of common alleles and the presence of rare alleles that are unique for each ethnic group of Daghestan and have not been found in any other population in the world.

Alleles↗
PubMed2003

[Genetic and epidemiological studies in Dagestan highland isolates].

Interpopulation differences in the epidemiology and age of onset of complex diseases, as well as expression of some vital parameters, have been found. The relationship between these interpopulation differences and the genetic processes that have been occurring in the populations throughout their history has been demonstrated. The Daghestan genetic isolates studied are characterized by aggregation of certain complex diseases. In each genetic isolate, almost all affected subjects with homogeneous clinical phenotypes belong to the same large pedigree with a limited number of founders. There is evidence for a large variance of the population risk of schizophrenia (morbid risk) in Daghestan isolates (this parameter varies from 0 to 5%). Examination of 211 cases of schizophrenia earlier diagnosed in Daghestan psychiatric hospitals has shown that only 139 of them meet the DSM-IV criteria for schizophrenia. The remaining 72 subjects have, according to DSM-IV criteria, various schizoaffective and affective disorders; all of these subjects are close relatives of the schizophrenic patients. The age of onset of schizophrenia in the isolates studied varies from 14 to 40 years (20.84 +/- 0.568 years). Offspring of consanguineous marriages exhibit later age at onset and a higher risk of schizophrenia than offspring of exogamous marriages. The results of multivariate genetic analysis indicate that different gene complexes are involved in the pathogeneses of early-onset and late-onset forms of schizophrenia. An association of schizophrenia incidence, its age dependence, and reproductive parameters with polymorphisms of some microsatellite loci have been demonstrated.

Adolescent↗
PubMed2002

[Mapping genes of complex diseases in genetic isolates of Dagestan].

Original results of the analysis of genetic linkage between some genomic markers and two complex clinical phenotypes, schizophrenia and mental retardation, in pedigrees from Dagestan genetic isolates are described. Interpopulation differences in the epidemiology of the complex phenotypes were studied and in their genetic linkage was demonstrated. These differences are evidently related to the genetic structure of the isolates determined by their genetic history. The MR epidemiological index characterizing the lifetime morbid risk of schizophrenia varies in the Dagestan isolates studied from 0 to 4.95%, which is almost five times higher than the average worldwide population rate, 1%. Comparative genetic mapping permitted determination of the most probable genetic linkages and associations of loci from chromosomal regions 17p11.1-12, 3q13.3, and a locus from 22q with schizophrenia and locus 12q23 with mental retardation. There is evidence that this approach is effective for detailed study of the relationship between the genetic (allele and locus) and clinical heterogeneity of complex diseases, which favors successful identification of the genes determining them. The study of linkage disequilibrium (LD) in genetic isolates of Daghestan populations (which have a common genetic background) may be an effective methodological approach for revealing the numerous contradictory results of mapping of the same genes of complex disease performed by different researchers in different regions of the world.

Chromosome Mapping↗
PubMed2000

The ascertainment of multiplex schizophrenia pedigrees from Daghestan genetic isolates (Northern Caucasus, Russia).

This article describes the preliminary ascertainment of multiplex schizophrenia pedigrees from the isolated mountain region of Daghestan (Northern Caucasus, Russia). Daghestan has a population of two million people and contains 26 aboriginal ethnic groups. Many of the ethnic groups reside in remote mountain villages that can be classified as 'primary isolates'. Prolonged reproductive isolation and severe environmental conditions in the highlands have created diverse, genetically isolated ethnic populations in Daghestan. A number of the isolates in this region contain large extended multiplex schizophrenia pedigrees that are ideal for genetic analyses. During summer expeditions of 1996 and 1997, 14 separate large multiplex schizophrenia pedigrees were ascertained from 14 different mountain villages. Of the 14 kindreds, one had 50 schizophrenic cases available for ascertainment, one had 32, and another had 24. Seven of the remaining pedigrees had between 11 and 23 living cases. Within the kindreds, the number of males with chronic schizophrenia was at least twice that of females. The average age of onset of schizophrenia is 21.2 years for offspring of consanguineous marriages and 17.4 years for offspring of nonconsanguineous marriages (P = 0.033). Although the pedigrees ascertained from the remote mountain villages may not be representative of the general population, they are unique kindreds for mapping schizophrenia susceptibility genes.

Ethnicity↗
PubMed1997

[Genetic polymorphism in three indigenous ethnic populations of Dagestan].

Genetic, demographic, and biochemical studies of three isolated ethnic populations of Dagestan were performed. Two populations lived in their historical (highland and lowland) habitats, and one population migrated from highlands to lowlands, i.e., changed its environment. A substantial genetic differentiation with respect to eight biochemical systems and marital structure was found. Altitudinal variation was revealed in allelic frequencies of group-specific component (GC) and haptoglobin (HP). The frequency of allele GC * 1 decreased and that of allele HP * 1 increased as the altitude increased in the studied localities. The studied populations differed with respect to the average heterozygosity levels per locus. Both absolute heterozygosity levels and the pattern of interpopulation differences estimated for all of the eight biochemical markers considerably differed from those estimated for all markers except for GC and HP. These data indicate that the latter two biochemical systems are important for adaptation of the studied Dagestan populations. In surviving migrants from highlands to lowlands, the levels of inbreeding and genetic polymorphism were intermediate between these values for highlanders and native lowlanders. Earlier, the 30% selective mortality was revealed in migrants from highlands to lowlands during the first years of adaptation to new conditions. Those individuals who died had a higher inbreeding level, homozygosity, and physiological sensitivity. In this study, only surviving migrants were examined. Therefore, it may be suggested that the inadaptive (dying) part of migrants also differed from the adaptive (surviving) part in the higher HP * 1 and GC * 2 allelic frequencies.

Alleles↗
PubMed1997

[Comparative study of genetic adaptation of the Caucasian highlanders to historic and to the new urban environments].

Marriage structure and female reproductive characteristics in a highland isolate and an urban population from Dagestan were compared. The studied urban population could be divided into three groups according to ethnic, genetic, and demographic parameters. In the native, highland population, a steady selection occurred due to a high, uncontrolled birthrate and a high prereproductive mortality. The genetic structure of the urban population still remained at the stage of formation. Different ethnic groups of the female urban population differed both in the rate and directions of selection. The migration of highlanders to the city mainly affected their mortality and morbidity, but not fecundity. The subpopulation of migrants from the highlands who retained a traditional endogamous and inbred marriage structure exhibited a high infant mortality comparable to that in the highland population. The migrant subpopulation in which interpopulation and interethnic marriages were contracted exhibited an increased genetic load expressed as high pre- and perinatal mortalities. The results obtained are discussed in terms of the hypotheses on the adaptive gene complex and the genetic and physiological mechanisms of differential adaptation of highland isolates to environmental changes due to migration or environmental pollution.

Adaptation, Physiological↗
PubMed1996

[A genetic and demographic study of Dagestan highland populations and migrants to the lowlands. The relationship between levels of consanguinity, homozygosity and physiologic sensitivity].

This is a continuation of a series of papers devoted to studying the genetic mechanisms of adaptation in migrants from isolated highland populations of Dagestan to new ecological conditions (lowlands). This paper describes the main results of studying the relationship between levels of inbreeding, homozygosity, and physiological sensitivity. Earlier, we found that decreased resistance to changing environmental factors in migrants to lowlands from the Dagestan highlands was connected with their high level of homozygosity. The data obtained allow us to assume that missing links in this chain of events include, in addition to parameters of inbreeding level, parameters of neurophysiological sensitivity, including absolute and differential sensitivity of various analyzers sensory systems, which are from 65 to 75% genetically determined. Migrants from highland auls (villages) to lowlands exhibited a decreased rate of sensomotor reactions in response to light and sound of various intensities, as well as decreased differential color sensitivity in the long-, medium-, and short-wave ranges of the spectrum, compared to highlanders. The results suggest the selective mortality of migrants from highlands to lowlands during adaptation to new conditions. Those migrants who dies were characterized by specific gene complexes that determined the characteristic features of expression of a number of interrelated polymorphic and quantitative traits. Thus, the high levels of homozygosity and inbreeding were accompanied by a greater neurophysiological sensitivity and lower indices of body weight and height.

Adaptation, Physiological↗
PubMed1996

[Clinical and pathogenetic features of exposure of workers to antimonate ore].

A total of 100 miners exposed to antimonate dust concentrations considerably exceeding the MAC were examined, and 16% of the subjects appeared to have chronic bronchitis. No pneumoconioses were diagnosed. The chronic bronchitis was characterized by mild slow course with I degree of ventilation disturbances. Antimonate ore turned out to induce toxic effects and activate some protective mechanisms: phagocytosis, immune response, inhibition of proteases.

Adult↗
PubMed1995

[Genetic-demographic study of mountain populations from Dagestan and their migrants to the lowlands. Comparison of basic parameters of fitness].

Results of a total genetic demography study of females of postreproductive age from both parts of "splits" highland isolates of Dagestan, highlanders, and migrants to lowlands are described. The components of natural selection that were related to differential mortality and differential fertility were estimated in the highlanders and the migrants using Crow indices. Offsprings of female migrants were characterized by a higher prenatal (spontaneous abortions and still-births) and a lower prereproductive mortality. These differences may be accounted for by two mechanisms: (1) the effects of changing marital structure (female migrants are more exogamous) and (2) better medical care for the children of migrants compared to those living in highland auls (settlements), which are still difficult to access. It was demonstrated that mortality of probands' children before reproductive age, as well as the proportion of their close genetic relatives that died within five years after resettling, increased with an increase in the level of individual inbreeding in women examined (probands). These data allow us to suggest that the drastic increase revealed in mortality of the highlanders during the first years after resettling may be partially attributed to high levels of inbreeding and heterozygosity; these, in turn, decrease the individual's nonspecific resistance to new ecological factors. Fertility and prenatal mortality appeared to increase and decrease, respectively, with an increase in the inbreeding level.

Adaptation, Physiological↗
PubMed1995

[Genetic-demographic study of mountain populations of Daghestan and migrants from it to the lowlands. Study of genetic and marital structure].

The results of a genetic and demographic study of two "split" isolates of small native ethnic groups of Daghestan are described. Parts of these populations were resettled from habitual highland ecological conditions to radically new lowland conditions in the 1940s. These split isolates were compared with a population of native inhabitants of the Daghestan lowland. It was found that, since resettling, separated populations originating from split isolates became significantly different in both marriage and genetic structures. This is manifested in different phenotypic and allelic frequencies of a number of physiological and biochemical markers and in levels of their heterozygosity. To explain the differences revealed, a hypothesis was proposed about the relationship between levels of inbreeding, heterozygosity, and physiologic sensitivity that account for the differential adaptability of members of the isolated populations to changing environmental conditions. This is the first report of a series of papers describing the experimental testing of this hypothesis. While testing the validity of the hypothesis in this study, a positive linear correlation was found between inbreeding and homozygosity levels.

Consanguinity↗
PubMed1993

Behavior genetic differences within and between defined human populations.

The small populations of the Caucasus offer a unique opportunity to consider concepts, such as heritability, which are often considered properties of a trait but which are really properties of a population. A comprehensive strategy is outlined for studying intra- and interpopulation genetic structure across a wide range of traits and environments. A three-way association is demonstrated between 12 of 16 psychophysiological traits, attitude, and the t allele for PTC sensitivity. Differences between populations and traits are evaluated in theoretical terms for morphological, physiological, and psychological measures. While decreases in performance with inbreeding are often predicted, in these small, isolated populations the effects are minimal.

Adolescent↗
PubMed1993

Visual evoked potentials: phenotypic and genotypic variability.

Evoked potentials (EPs) provide a unique way of analyzing the relationship between genes and behavior. Individual differences in EPs, in response to light flashes of two intensities and pattern reversal, were studied in families from the isolated population Mechelta in the Northern Caucasus. While there were no age or sex differences in EP latency, or many age effects on amplitude, there were sex differences on the amplitude measures. Variation in the additive genetic determination of latency and amplitude measures is discussed. The largest estimates of additive genetic variation were found for the complexes of amplitude measures between the positive and negative waveforms.

Adult↗
PubMed1991

[An immunochemical analysis of the function of the hemato-encephalic barrier in acute fetal hypoxia and asphyxia neonatorum].

The neurospecific protein alpha 1-globulin has been assayed in serum in order to evaluate the blood-brain barrier in newborns with acute intrapartum hypoxia. The study involved 35 term newborns with birth asphyxia of variable severity. The alpha 1-globulin levels correlated with severity of condition at birth, duration of intrauterine exposure to hypoxia and the presence of obstetric complications and clinical severity of cerebral circulatory disorders. A normal early adaptation and effective therapy reduced serum alpha 1-globulin levels 4-8-fold on the 3rd postnatal day and 6-16-fold on the 5th day. Deterioration of neurological symptoms was parallelled by a significant increase in protein levels (to 6400 ng/ml) at day 5. This evidence may confirm the fact that permeability of the blood-brain barrier is impaired by intrapartum hypoxia.

Acute Disease↗
PubMed1991

[Structural and functional aspects of erythrocyte membrane in children, delivered with asphyxia].

Serum and red blood cell membrane lipid peroxidation (LPO), antioxidative activity (AOA) of the ceruloplasmin/transferrin (CP/TF) system, and biophysical parameters of the structure of a red blood cell membrane lipid bilayer were examined in fetuses experienced acute hypoxia at birth and in babies born to healthy mothers with uncomplicated pregnancy. The intensity of LPO product accumulation in mild asphyxia was ascertained to be proportional to the duration of hypoxic exposure of a fetus. In severe asphyxia accompanied by lower formation of primary LPO products, the levels of secondary LPO products showed a rise. A slight increase of AOA in the CP/TF system was unable to adequately compensate a high intensity of LPO processes, which provides strong evidence for altered structural parameters in the lipid bilayer. It was concluded that it was essential to correct hypoxic states in children with antioxidants immediately after birth.

Antioxidants↗
PubMed1990

Population-genetics approach to the genetics of human behaviour.

Invariant values of inheritance factors within and between different populations can show the existence of and measure the degree of genetic determination of behavioural characters. The absence of inbred depression of quantitative behavioural characters in isolated populations of highland inhabitants of Daghestan is demonstrated by means of comparative analysis of the mean population values of psychophysiological characters in outbred, moderately isolated, and extremely isolated (and inbred) populations. The absence of pronounced adverse effects of inbred marriages, known as the 'Daghestan phenomenon', is explained by the antiquity of the native populations and the severe ecological conditions under which these populations live which have led to elimination of carriers of hereditary diseases and other detrimental phenotypes.

Adolescent↗