Abstract: Results of genetic epidemiological study in ethnically and ecologically diverse groups of Daghestan fenales are presented. These groups were selected from urban and rural environments; rural residents are living in highland, foothill and lowland regions. Results obtained indicated significant differences between ethnic groups, as well as between rural and urban residents in IDA affectation. Genetically homogeneous (lower heterozygosity) offspring of consanguineous marriages have higher rate of affectation in comparison with offspring of non-consanguineous marriages. Associations analysis with IDA has been performed using 10 DNk loci (Alu insertion polymorphism) and some traditional classic markers -ABO, Rh, SER, PTC. Results obtained demostrated significan for different ethnic groups association between IDA and ACE, COL3A1, HS4_32, HS4_65, SB19_3: affected subjects are charcterized by higher frequency of II genotype in comparison with control. Significant association found between SER, Rh- and pTC sensitivity with IDA as well. Clinical and pathogenic mechanisms of IDA related to the findings is described.

Abstract: Monograph describes a population approach to study of human psychophysiology genetics. In large families ascertained from 8 ethnically (Laks, Avars, Dargins, Botlihs, Tindals, Andians, Kumiks, Kubachians), ecologically (highlands, foothils and lowlands) and demographycally (from ancient, more than 200 generations, to youngest -less that 40 generation) diverse genetic isolates of Daghestan were studied a complex of psychophysiology parameters measured using methods of Pavlovian' CNS types (simple sensomotor reaction time, strength and weakness of CNS related to individual resisitence to an environmental stress, lability of CNS, physiological sensitivity), of intellectual and motor activity (cattel test and tapping-test), as well as immunological and physiological single gene markers (ABO, Rh, MN, PTC, SER, CVAN). Results obtained demonstrated that a coefficient of heritability decreases in any human populations from simple reaction time to intellectual activity measured by time of performing of Cattel non-verbal IQ test. Between populations differences were related with altitude and associations of genetic markers with quantitative psychophysiological traits.

Abstract: A single-nucleotide variant, C/T-13910, located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T-13910 variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8–H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T-13910 H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T-13910 H98 allele (∼5,000–12,000 years old) is relatively older than the other geographically restricted LP alleles (∼1,400–3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T-13910 allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.

Abstract: Genetic isolates are exceptional resources for the detection of susceptibility genes for complex diseases because of the potential reduction in genetic and clinical heterogeneity. However, the outcome of these mapping efforts is dependent upon the demographic history of a given isolated population, with the most significant factors being a constant population size, the number of generations since founding, and the pathogenic loci and their allele frequencies among founders. Here we employed a cross-isolate genome-wide multipoint linkage study design using uniform genetic and clinical methods in four Daghestan ethnically and demographically diverse isolates with an aggregation of schizophrenia. Our previous population-genetics study showed that Daghestan has an extremely high genetic diversity between ethnic populations and a low genetic diversity within them. The isolates selected for this study include some with more than 200 and some with fewer than 100 generations of demographical history since their founding. Updated clinical data using DSM-IV criteria showed between-isolate differences in aggregation of distinct types of schizophrenia: one of the isolates had a predominant aggregation of disorganized schizophrenia, while the other three had predominantly paranoid schizophrenia. The summarized cross-isolate results indicated prominent within and between-isolate differences in clinical and genetic heterogeneity: the most ancient isolates have roughly twofold fewer incidences of distinct clinical phenotypes and fewer linked genomic regions compared to the demographically younger isolates, which exhibit higher clinical and genetic heterogeneity. Affected individuals in the demographically ancient isolate of ethnic Dargins (No. 6022) who suffered from disorganized schizophrenia showed the highest linkage evidence at 17p11-p12 (LOD=3.73), while isolates with a predominant aggregation of paranoid schizophrenia (Nos. 6005, 6011, and 6034) showed the highest linkage evidence at 22q11 (LOD=3.0 and 4.4). The unified clinical, genomic, and statistical design we used enabled us to separate the linked and unlinked pedigrees in an unbiased fashion for each genomic location. Overall maximized heterogeneity lod scores for the combined pedigrees ranging from 3.5 to 8.7 were found at 2p24, 10q26, 11q23, 12q24, 17p11-p12, 22q11, and 22q13. The cross-isolate homogeneity in linkage patterns may be ascribed to an identical-by-descent "metahaplotype" block with pathogenic loci derived from the Daghestan ethnic groups' common ancestral metapopulation, while the cross-isolate differences may reflect differences in gene drift and recombination events in the history of local isolates. The results obtained support the notion that mapping genes of any complex disease (e.g., schizophrenia) in demographically older genetic isolates may be more time and cost effective in comparison with demographically younger isolates, especially in genetically heterogeneous outbred populations, due to higher clinical and genetic homogeneity of the primary isolates. A study at higher genotyping density across the regions of interest and fluorescence in situ hybridization analyses are currently underway.

Abstract: While the season-of-birth effect is one of the most consistent epidemiological features of schizophrenia, there is a lack of consistency with respect to the interaction between season of birth and family history of schizophrenia. Apart from family history, measures related to consanguinity can be used as proxy markers of genomic heterogeneity. Thus, these measures may provide an alternate, indirect index of genetic susceptibility. We had the opportunity to explore the interaction between season of birth and measure of consanguinity in well-described genetic isolates in Daghestan, some of which are known for their relatively high prevalence of schizophrenia. Our previous population-genetic study showed Daghestan has an extremely high genetic diversity between the ethnic populations and a low genetic diversity within them. The isolates selected for this study include some with more than 200 and some with less than 100 generations of demographical history since their founding. Based on pedigrees of multiply-affected families, we found that among individuals with schizophrenia, the measure of consanguinity was significantly higher in the parents of those born in winter/spring compared to those born in summer/autumn. Furthermore, compared to summer/autumn born, winter/spring born individuals with schizophrenia had an earlier age-of-onset, and more prominent auditory hallucinations. Our results suggest that the offspring of consanguineous marriages, and thus those with reduced allelic heterogeneity, may be more susceptible to the environmental factor(s) underpinning the season-of-the effect in schizophrenia.

Abstract: AIM: To assess genetic diversity and genetic distances among isolated populations from Dagestan. METHODS: A cross-population genetic epidemiology design was applied in ethnically and demographically diverse isolates from Dagestan, some with more than 200 and some with less than 100 generations of demographical history since their founding. RESULTS: The analysis of genetic diversity showed that Dagestan ethnic populations are clearly close to European ethnic populations. The genetic data support the view of them as ancient, highly isolated populations 85%-97% the rate of the endogamy and inbreeding coefficient F=0.010-0.015. Many Dagestan populations have very high prevalence of certain complex diseases such as cardiovascular illnesses, cancer, schizophrenia, mental retardation, and progressive muscular dystrophy. Lifetime morbid risk for schizophrenia in the isolates varied from 0 to 5%. Among the relatives, the number of men with chronic schizophrenia was at least twice as high as women. The average age of onset of schizophrenia was 21.2 years for offspring of consanguineous marriages and 17.4 years for offspring of non-consanguineous marriages (P=0.033). CONCLUSION: The results support the hypothesis that cross-population design provides unique opportunities for observing reliable ancestral haplotypes with disease predisposing loci, as well as population-specific linked loci.

Abstract: Autosomal short-tandem repeats (STRs) were typed in ethnic populations of Kubachians, Dargins, Avars, Lezgins, Kumiks, and Nogais of the Caucasus (Daghestan, Russia) at the University of Utah. Daghestan ethnic populations demonstrated differences in STR allele frequency distributions, but these differences were much lower among these ethnic groups compared to worldwide ethnic groups. The observed genetic diversity was low while F(ST) values were high, both of which provided supporting evidence for small population sizes and high levels of isolation among the ethnic groups. An analysis of genetic distance from the three major continents, encompassing Daghestan populations and groups, reveals three distinct clusters: all populations of African affiliation, European and Daghestan populations except the Nogais, and Asian populations with ethnic Nogais.

Abstract: Genetic isolates, which provide outstanding opportunities for identification of susceptibility genes for complex diseases, can be classified as primary (having an ancient demographic history in a stable environment) or secondary (having a younger demographic history) Neel [1992: Minority populations: Genetics, demography, and health, pp. 1-13]. Daghestan contains 26 out of 50 indigenous Caucasus ethnicities that have been in existence for hundreds of generations in the same highland region. The ethnic groups are subdivided into numerous primary isolates. The founder effect and gene drift in these primary isolates may have caused aggregation of specific haplotypes with limited numbers of pathogenic alleles and loci in some isolates relative to others. These are expressed as inter-population differences in lifetime prevalence and features of certain complex clinical phenotypes and in patterns of genetic linkage and linkage disequilibrium (LD). Stable highland and ethnic-cultural environments have led to increased penetrance and a reduced number of phenocopies, which typically hamper the identification of any susceptibility genes for complex diseases. Owing to these characteristics of the primary isolates, a comparative linkage study in the primary isolates allows us to define the number of susceptibility genes for any complex disease and to identify the source of variability and non-replication of linkage analysis results. As part of an ongoing study, seven extended schizophrenia and one nonspecific mental retardation kindreds have been ascertained from Daghestan isolates. Lifetime morbid risk for schizophrenia in the isolates varied from 0 to 5%. A genome scan with markers spaced 10 cM apart was carried out on these pedigrees and linkage analysis was performed using descent graph methods, as implemented in Simwalk2. To identify regions containing susceptibility genes within these kindreds, we followed up those regions with non-parametric and parametric linkage analyses, with the choice of genetic model guided by the results obtained in the NPL. While the analyses are ongoing, the most positive findings were made in different isolated pedigrees on chromosomes 17p11, 3q24, and 22q for schizophrenia and on chromosome 12q for nonspecific mental retardation.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: A unique inbred Avar family from an isolate of the Dagestan highland was studied. Unusual phenotypic expression of autosomal recessive progressive muscular dystrophy was revealed in 12 members of this family from three generations. Limb-girdle (proximal) muscular dystrophy (LGMD) was detected in nine patients, while the other three patients displayed typical distal myopathy (DM). Genetic linkage analysis with several candidate loci determining various forms of muscular dystrophy allowed a gene for this polymorphic syndrome to be assigned to chromosome 2p13. In spite of the difference in clinical manifestation, all patients appeared to be homozygous for a unique haplotype. This implies the founder effect and proves the same genetic basis of LGMD and DM in the family. Recombination analysis showed that the centromeric and telomeric ends of the gene region are marked with D2S2111 and D2S327, respectively (genetic distance < 1 cM). This region is overlapped by two larger regions in which the genes for LGMD type 2B (LGMD2B) and Miyoshi myopathy were recently mapped. Complex analysis of clinical and genetic data indicated that LGMD2B, Miyoshi myopathy, and the revealed polymorphic syndrome may represent allelic variants of 2p13-linked autosomal recessive muscular dystrophy.

Abstract: 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.

Abstract: A unique inbred Avar family from an isolate of the Dagestan highland was studied. Unusual phenotypic expression of autosomal recessive progressive muscular dystrophy was revealed in 12 members of this family from three generations. Limb-girdle (proximal) muscular dystrophy (LGMD) was detected in nine patients, while the other three patients displayed typical distal myopathy (DM). Genetic linkage analysis with several candidate loci determining various forms of muscular dystrophy allowed a gene for this polymorphic syndrome to be assigned to chromosome 2p13. In spite of the difference in clinical manifestation, all patients appeared to be homozygous for a unique haplotype. This implies the founder effect and proves the same genetic basis of LGMD and DM in the family. Recombination analysis showed that the centromeric and telomeric ends of the gene region are marked with D2S2111 and D2S327, respectively (genetic distance < 1 cM). This region is overlapped by two larger regions in which the genes for LGMD type 2B (LGMD2B) and Miyoshi myopathy were recently mapped. Complex analysis of clinical and genetic data indicated that LGMD2B, Miyoshi myopathy, and the revealed polymorphic syndrome may represent allelic variants of 2p13-linked autosomal recessive muscular dystrophy.

Abstract: We describe a unique six-generation, highly consanguineous family originating from an isolated mountainous village in the Russian province of Daghestan. Three separate clinical phenotypes of progressive muscular dystrophy were identified in this large family. Seven patients developed a classical limb-girdle variant of muscular dystrophy (LGMD), with disease onset at 15-30 years and loss of ambulation within a 25-year course. The second group included three patients with a slowly progressive distal myopathy first manifested in the late teens and confined to the tibial and calf muscles. Each of these two phenotypes segregated independently as an autosomal recessive trait, and muscle biopsies showed non-specific myopathic changes. Lastly, two male siblings exhibited an atypical variant of Duchenne muscular dystrophy confirmed by detection of a deletion in the dystrophin gene. To clarify the molecular basis of the polymorphic autosomal recessive form of muscular dystrophy in this kindred, we performed molecular genetic studies on 67 family members and obtained significant evidence for linkage to chromosome 2p. A maximum pairwise lod (logarithm of odds) score of 5.64 was achieved at the zero recombination fraction (i.e. at theta = 0.00) for locus D2S291; multipoint linkage analysis confirmed the most likely location of a mutant gene near D2S291. The patients with LGMD and those with the distal muscular dystrophy phenotype share a common affected homozygous haplotype associated with the same founder chromosome; key recombinants defined D2S286 and D2S292 to be the closest loci flanking the mutant gene. Remarkably, two clinically distinct forms of autosomal recessive muscular dystrophy, LGMD type 2B (LGMD2B) and Miyoshi myopathy, were recently mapped to the same locus. We suggest that all three chromosome 2p-linked conditions may represent allelic disorders, i.e. different phenotypic expressions of a single gene.

Abstract: 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.

Abstract: Hereditary factors of arterial hypertension were evaluated genetically and epidemiologically in the study of an isolated population of Dagestan with high inbreeding. High prevalence of arterial hypertension was found. Its highest morbidity was found in native population of Tukhums characterized also by the highest inbreeding.

Abstract: 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.

Abstract: A number of characteristics of morphological, neurodynamical, and psychodynamical levels of organization of individual personality was studied in five isolated different ethnical populations and two panmixic ones. The degree of heritability was found to decrease and that of variability to increase with the rise of organization level. Significant interpopulational differences were shown in the mean values of characteristics under study and their dispersions. The results obtained were discussed in connection with peculiarities of genetical and social structures of investigated human populations.

Abstract: 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.

Abstract: Daghestan contains many distinct populations characterized by different degrees of isolation, ethnic backgrounds and ecological conditions. This report introduces a large-scale family study conducted in seven Daghestan populations as well as in Moscow, using four categories of measures: (1) single gene polymorphisms, (2) anthropometric, (3) physiological, and (4) psychological quantitative traits. Such a study permits the analysis of both phenotypic and genetic variation within and between populations. The implications of such variation are discussed, especially in the context of the measures used. These derive from Soviet conceptualizations of the nervous system and related assessment of individual differences, and vary considerably from conventional Western approaches to behaviour. From the anthropometric through the physiological to the behavioural measures there was a clear trend towards increased phenotypic variation but reduced genetic variation. Possibly because the genetic variance was less on the more complex phenotypes, measures of generalized distance indicated much greater population similarity when based on phenotypic data on the genetic component of variation. Issues that arise when using behavioural traits to study human population diversity are discussed, particularly in relation to inbreeding and the specific cultural and linguistic practices in the Daghestan region.

Abstract: 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.

Abstract: 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.

Abstract:

Abstract: 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.

Abstract: Four groups of human characters (mendelian markers, anthropometry, neurodynamics and psychodynamics) were studied in eight human populations characterized by different degrees of isolation and different ethnic backgrounds, and located in different ecological conditions. The populations examined were proved to display phenotypic and genetic differentiation for the studied groups of characters which were compared with linguistic and geographical distances. The role of genetic factors and that of environmental factors was shown to diminish and to increase, respectively, as the degree of complexity of expression of the group of characters under study (from anthropometry to psychodynamics) goes up.

Abstract: The multivariate genetic factor analysis is used, as first attempt, to study genetic bases of correlation variability of neurodynamic and psychodynamic levels of individual organization among isolates of Daghestan. Closer similarity between factors described in templates of phenotypic correlations is explained by lower heritability of the parameters under study. Interpopulation differences revealed by the multivariate genetic analysis are the result of differences in the genetic structure of the populations.

Abstract: The paper demonstrates the expedience of the developed populational-genetic approach to studying the genetic bases of a complex of quantitative characters pertaining to different levels of human organization: anthropometry, neurodynamics and psychodynamics. The studies were carried out in eight human populations of different degree of isolation and ethnical background. It is shown that correlation phenotypic variability is higher for these characters, as compared to genotypic variability, the number of general genes responsible for this variability being decreased, respectively.

Abstract:

Abstract: A component analysis of human neurodynamic and psychodynamic characters in the norm was carried out in 8 human populations characterized by different degrees of isolation and ethnic origin. An increase in phenotypic variability and a decrease in heritability with increasing complexity of organization of the characters under study were demonstrated for all these populations. The additive effect plays the major role in genetic determination of neurodynamic and psychodynamic characters studied. For a number of neurodynamic parameters the effect of intralocus dominance indicative of the oligogenic determination system was observed. Data in favour of real contribution of the factors linked to X-chromosome were obtained for simple sensomotor reactions.

Abstract: In eight human populations with different extent of isolation and different ethnic belonging, four groups of cues have been studied: Mendel and anthropogenetic markers, anthropometry, neurodynamics and psychodynamics. Integral estimates are obtained of phenotypic and genetic correlation of groups of anthropometric, neurodynamic and psychodynamic cues in examined populations. Their values vary significantly in different populations; in isolates they are higher than in heterogeneous populations. Multidimensional dispersion analysis of the studied groups of cues allows to establish significantly higher intrapopulation variability than interpopulation one (about 14%). The revealed interpopulation differences are presented in the form of generalized values of phenotypic and genetic resemblance of examined populations by four groups of cues.

Abstract: Subdivision of some isolates and heterogenic populations in Daghestan is analysed by human gene and phen frequencies. Comparative population study of phenotypic variability of quantitative characters (anthropometric, neurodynamic and psychodynamic) is carried out. Common hierarchy of variability for all populations as well as an effect of inbreeding and panmixis on variability of the above-mentioned quantitative characters in different populations is demonstrated.

Abstract: The results of gene pool analysis of three Daghestan isolates for mendelian markers and multifactorial characters are presented. The neurodynamic status of persons with tt and T-phenotypes for sensitivity to phenylthiocarbamide is characterized.

Abstract: A number of characteristics of morphological, neurodynamical, and psychodynamical levels of organization of individual personality was studied in five isolated different ethnical populations and two panmixic ones. The degree of heritability was found to decrease and that of variability to increase with the rise of organization level. Significant interpopulational differences were shown in the mean values of characteristics under study and their dispersions. The results obtained were discussed in connection with peculiarities of genetical and social structures of investigated human populations.

Abstract: The first attempt at using multivariate genetic analysis to study the neurodynamic and psychodynamic levels of individual organization in Daghestan isolates is described. The absence of close similarity between dendrograms of templates of phenotypical and genotypical correlations is explained by lower heritability of the parameters under study. Interpopulation differences revealed by the multivariate genetic analysis are the result of differences in the genetic and social structures of the populations.

Abstract: The authors elaborate the population-genetic approach to study the genetic basis of individual psychological differences. Psychodynamic parameters characterized by a more complex organization tend to be more phenotypically variable and less hereditable, as compared with parameters of lower organization levels. The results obtained are interpreted in relation to the genetic and social structure of populations.

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Abstract: Morphological, sensory and motor, and cognitive measures were obtained on 203 Moscow schoolchildren and 23 families (both parents and one child). There was evidence for assortative mating for all traits measured. Within groups (girls, boys, fathers, mothers), coefficients of variation (CV) were greatest for cognitive, intermediate for sensory and motor, and smallest for morphological measures. The authors theorize the CV reflects the degree of biological and social determination of a trait and thus also its heritability.

Abstract: The Caucasus region provides a great opportunity to investigate the influence of geography and language on the genetic structure of human populations. About 50 ethnic groups speaking Caucasian, Indo-European and Turkic languages live in this region, while mountain ranges reaching over 5000 m represent strong geographic barriers to gene flows. In order to investigate the genetic variability and relationships of Caucasus populations, 17 YSTR loci were analyzed among seven ethnic groups. from Daghestan (Northern Caucasus).. Genomic DNA from unrelated informed donors (N=144) was PCR-amplified using the "AmpFlSTR®Y-filerT" kit (Applied Biosystems®). The length of PCR products was estimated with the ABI-PRISM 310 genetic analyzer using the GeneScan® (Applied Biosystems®) software. The assignment of YSTR haplotypes to binary states defining haplogroups was obtained by a Bayesian method (Athey, 2006) with output scores > 70. The basic parameters of molecular diversity and population genetic structure, including the concordance between geography, language and genetic structure was investigated by AMOVA and Mantel tests using the software Arlequin 3.0. The results showed that the seven Daghestan ethnic groups fall into the range of Y-STR and Y-SNP variability of Caucasian populations, However some peculiar characteristics make Daghestan region an outlier in the Caucasus genetic scene. The mean level of genetic differentiation (FST = 0.138; p = 0.0000) was high and significant. Private alleles were found at DYS458, DYS448 and DYS385 loci. Linguistic barriers didn’t appear the main determinants of the high between-population Y-chromosome variability observed in the Caucasus. Eventually, founder effect and long-term genetic drift caused by the rigid structuring of societies in groups of patrilineal descent remain the best explanation of the genetic divergence among Caucasian ethnics and of the presence of rare allelic variants.

Abstract: The Caucasus region provides a great opportunity to investigate the influence of geography and language on the genetic structure of human populations. Several ethnic groups, speaking Caucasian, Indo-European and Turkic languages, are spread over a territory with sharp relief variations. Three population samples from Daghestan, belonging to Indo-European (Tats, Mountain Jews) and North-Caucasian (Tabasarans) linguistic families, were analysed at 17 Y-STR loci and their variability studied in the wider context of Caucasus region. Private alleles and high levels of between-population differentiation (FST = 0,152; p = 0,00000) were observed. Contrary to continental Europe, a lack of correspondence between either geography or linguistics and Y chromosome variability was observed in the Caucasus.

Abstract: We investigate the effect of mating practices on genetic structure in Daghestan by comparing the frequency of 24 mitochondrial DNA (mtDNA) and 22 Y chromosome (NRY) haplotypedefining single nucleotide polymorphisms in three highland (Avar, Dargin, Kubachi) and two lowland (Kumik, Nogai) populations from Daghestan. AMOVA analysis reveals three times the amount of genetic structure in the NRY data than in the mtDNA data (mtDNA ΦST=10.3%, NRY ΦST=31.5%). The same comparison in a series of European and East Asian populations produces nearly-equal values for both sets of markers (mtDNAΦST=46.1%; NRY ΦST=42.9%). This is consistent with the ethnographic record of patrilocality among highland Daghestani populations. AMOVA between highland and lowland pooled populations (ΦST=42.7%, p<0.001) reveals NRY genetic structure nearly as great as that between European and East Asian populations posted above. The highland-lowland structure is not nearly as strong in the mtDNA data (ΦST= 3.9%, p<0.01), and weaker than that observed when all Daghestani populations are considered independently (ΦST=10.3%, p<0.001). Reduced NRY haplogroup diversity among highland populations (h: 0.00-0.47) when compared to lowland populations (h: 0.82-0.93) suggests drift caused by isolation and patrilocality. The pairwise ΦST between the Nogai and Europe (21.0%) exceeds that (13.2%) between the Nogai and East Asia, consistent with their Mongolian origin. This unique observation is opposite the relationship observed between the Nogai and Europe and East Asia in the NRY data (Europe ΦST=18.8%; East Asia ΦST=45.1%), even though they are the only Daghestani population to exhibit Asian Y haplogroups D and Z. These results demonstrate that population history, isolation, and patrilocality have all left distinctive signatures on the genetic structure of Daghestan’s populations. Supported by NIH Grant GM-59290 and NSFGrant BCS-0218370.