[Genetic and epidemiological studies in Dagestan highland isolates]. / Genetiko-épidemiologicheskie issledovaniia v gornykh izoliatakh Dagestana.

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.

[Mapping genes of complex diseases in genetic isolates of Dagestan]. / Kartirovanie genov kompleksnykh zabolevanii v geneticheskikh izoliatakh Dagestana.

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.

[Genetic subdivision of Dagestan ethnic populations]. / Geneticheskaia podrazdelennost' étnicheskikh populiatsii Dagestana.

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.