Medico-genetic study of the population of Uzbekistan. VII. Variability of hereditary pathology in 4 regions of Khorezm province

Medical-genetic study was carried out in the population of Khorezm province (population size above 200 000 persons). Hereditary pathology was ascertained among families having two or more members affected with chronic non-infectious diseases. 155 families with 348 members affected with hereditary diseases were registered. The most frequent were autosomal recessive diseases (55 nosological forms in 104 families with 271 affected), then followed the autosomal dominant conditions (10 nosological forms in 21 families with 53 affected). The less frequent was X-linked recessive pathology (6 forms in 12 families with 20 affected). The main part of cases of autosomal recessive pathology were found in separate families and were not observed during previous medical-genetic studies in Uzbekistan. Three autosomal recessive conditions are probably new forms of hereditary pathology. The important role of assortative matings in manifestation of rare autosomal recessive genes in Uzbek population is discussed.     

Medico-genetic study of the Uzbekistan population. X. Hereditary forms of hearing impairment in the Khorezm and Samarkand regions

Medical-genetic study in some populations of Khorezm (about 200,000) and Samarkand (about 56,000) provinces was performed with the view of identification of all family cases of deafness and deaf-mutism. 53 families with 140 affected patients were registered, in total. 8 nozological forms were found in this study, the most frequent being autosomal-recessive ones (6 nozological forms, 48 families, 122 patients). The autosomal-dominant forms were represented by 2 nozological forms (5 families with 18 patients). The reason for predominance of autosomal-recessive deafness in Uzbek population is discussed.     

Medico-genetic study of isolates in Uzbekistan. IV. Clinico-biochemical diagnosis of hereditary diseases]

An exhaustive clinico-biochemical examination of the population of two kishlaks of the Samarkand Region, viz. Karakent (210 persons) and Ishan (248 persons) was carried out. The program of this examination permitted to exclude over 160 forms of hereditary pathology. A total of 45 persons affected with diseases belonging to 12 nosological forms were revealed in the course of the examination. Among the diseases observed only 5 are hereditary sensu stricto, viz. myoclonus-epilepsy, Bonevi-Ulrich's syndrome, imperfect osteogenesis, pigment choreoretinite and Down's syndrome, others belong to diseases with a pronounced hereditary predisposition. The main part of this group comprises neuro-psychic diseases, such as non-differentiated olygophreny (5.0%), epilepsy (1.3%), schizophreny; many of these cases have a familial character, particularly in Karakent. Besides the persons suffering from diseases, 20 heterozygous carriers of beta-thalassemia and 17 heterozygous carriers of G6PD-deficiency were discovered in the kishlaks examined. On the whole the frequency of the diseases revealed did not exceed the level in the general population. Despite the different degree of isolation of the kishlaks examined (Karakent is isolated on a religious basis, F = 0.0064; while Ishan is a desintagrated isolate, F = = 0.0014), no substantial differences between them in the distribution of pathological phenomena were observed. On the basis of the experience of this expedition recomendations are proposed concerning the origination and accomplishment of medico-genetic expeditions. A scheme is proposed for the performance of medico-genetic examination through several stages. The first stage in the composition of tentative maps of the distribution of hereditary diseases within a region on the basis of the information obtained from the medical personnel and from the examination of the documents of district and regional hospitals. Subsequently the primary information is specified, the regions to be examined are determined, as well as concrete tasks and the staff of the expedition. The conclusive stage is the medico-genetic examination proper, including clinical, biochemical, immunological and cytogenetic diagnoses of hereditary pathological phenomena. The place of the disposition is a village or a district hospital. More complicated laboratory studies should be performed on the basis of the institution by which the expedition is formed. The results obtained by such expeditions would be important for the investigation of the problems of genogeography, for the discovery of new forms of mutant alleles, for the investigation of the causes and the conditions of the formation of the definite populational structure, of clinical polymorphism of human hereditary diseases.     

Medico-genetic study of the population of Uzbekistan. I. Incidence and variety of hereditary pathology]

In district of the Samarkand province the screening for families burdened with multiple cases of non-infectious diseases was performed. The principles of the applied screening procedure are described in the present paper. In the course of clinical examination 98 families were detected, 55 of which included more than one person suffering presumably with Mendelian diseases and 43--with multifactorial disorders. Over 30 nosological forms were found, among which orthopaedic and neurological forms were the most frequent. As a rule, identical cases were detected in one or two families. The role of certain genetic processes in the distribution of hereditary diseases in the Uzbek population is discussed.     

Medico-genetical study of the Uzbekistan population. IX. Variability of hereditary pathology, territorial distribution of hereditary diseases and hereditary disease load in the population of the Urgut district of the Samarkand region

Medical-genetic study was carried out in the population of Samarkand province (the population size about 150 000). Hereditary pathology was ascertained among families with two or more affected members with chronic diseases. 110 families with 210 patients were registered. The most frequent were autosomal-recessive disorders (42 nozological forms). 15 nozological forms are probably "new" conditions in this province, because they were absent in our previous medical-genetic study of this province. A tendency to local accumulation of families with the same disorder in small populations was observed. The load of autosomal-recessive disorders comprised 2.2 X 10(-3) affected, that of autosomal-dominant disorders being 0.51 X 10(-3) and of X-linked disorders being 0.25 X 10(-3) males. The importance of assortative maitings in manifestation of rare autosomal-recessive genes in Uzbek population is discussed.     

Medico-genetic study of the population of Kostroma Province. VII. Approaches to the study of the hereditary pathology load in the population of Kostroma

Complex medical-genetic study was performed in the center of Kostroma Province with the population of about 250 thousands. A method for ascertainment of patients was developed and the information value of different sources of a registration system available is given. The complete algorithm of calculation of both the segregation frequency and the fraction of sporadic cases for autosomal recessive diseases is presented.     

Medico-genetic studies of the Kostroma oblast population. X. Load of hereditary diseases in the population of Kostroma

Medical-genetic study of the population of Kostroma (the total size of the population analysed approx. 250,000) was carried on. The load of hereditary diseases in the population (per 1000) was 0.75 for autosomal dominant, 0.49 for autosomal recessive and 0.17 for X-linked recessive disorders. Significant differences in the prevalence of autosomal recessive hereditary disorders between rural populations and the population of Kostroma were observed. The dependence of the load of autosomal recessive pathology on random inbreeding was shown for the whole Kostroma province.     

Medico-genetic study of the population of Uzbekistan. VI. Hereditary pathology among the populations of 4 regions of the Kashkadarinskaia area]

The screening for families burdened with multiple cases of non-infectious diseases, the diagnostic of those diseases and the investigation of relations between the population structure and the distribution of hereditary diseases in 4 districts of the Kashkadarja province were carried out. On the basis of the data obtained the load of excessive hereditary diseases was calculated and nosological spectrum was described; it included more than 30 different diseases. The study of spatial distribution of recessive diseases has shown that the load of hereditary diseases may be accounted for the positive assortative matings. The high level of interpopulation migration prevents from the local accumulation of a certain hereditary disease.     

Medico-genetic study of the population of Uzbekistan. IV. Medico-genetic description of the population of 4 villages of the Urgut district of the Samarkand region]

The data about the incidence of hereditary diseases and those with genetic predispositions which received after subtotal medico-genetical examination of the inhabitants of 4 villages in the Urgut district of the Samarkand province are presented. 848 inhabitants (348 adults and 464 children aged 7--16 years) are examined. The nosological profile of the morbidity and spectrum of the Mendelian diseases in the population is evaluated. The integrative estimate of load of the detrimental (non-lethal) genes is about 0.166 per individual.     

Medico-genetic study of the population of Kostroma Province. I. The population burden of hereditary pathology

Data on the prevalence of hereditary diseases in five regions of the Kostroma province were obtained and analysed. It was shown that the ascertainment was close to the truncate selection for the rural population and to the single selection for the urban population. Segregational analysis proved the rightness of the material subdivision, according to the type of inheritance. The load of hereditary diseases (for the registered forms) in the population was: 0.78 +/- 0.08 X 10(-3) for autosomal dominant, 0.75 +/- 0.08 X 10(-3) for autosomal-recessive and 0.54 +/- 0.1 X 10(-3) for X-linked recessive disorders. The dynamics of the load of hereditary diseases in the populations with different structure is discussed.     

Medico-genetic study of the residents of the Kostroma province. XI. Diversity of hereditary pathology in Kostroma

The diversity of hereditary pathology in Kostroma was studied. An attempt was made to classify all isolated cases by genetic and clinical analysis. 57 nosological forms of autosomal dominants, 41 autosomal recessive and 14 X-linked recessive disorders were found. The analysis of marriage distances in the whole population and in the families of the probands was carried out. The spectra of hereditary pathology in Kostroma and Kostroma Province were compared. The sources of the load of hereditary pathology in Kostroma are discussed.     

Medical genetic study of the population of Turkmenia. II. Study of the distribution of hereditary pathology in 5 regions of Tashauz Province

The large-scale screening for hereditary diseases in five regions of the Tashauz province was carried out. More than 50 families represented by persons with different nosological forms of hereditary diseases, were found. The role of drift in rare mutant gene dynamics was shown. The load of hereditary diseases was mainly connected with autosomal recessive forms and shown to vary between the regions from 0,34 to 1,29 pro mille.     

Medico-genetic study of the Kostroma Region population. VIII. Genetic structure of large subdivided populations and its relation with the incidence of autosomal-recessive pathology

FST was estimated for 67 communities and 6 small towns of Kostroma province. The mean FST value for rural and urban populations was (0.83 +/- 0.08).10(-3) and (0.29 +/- 0.07).10(-3), respectively. The connection between FST values and the load of autosomal-recessive disorders was established; the coefficient of correlation (by Chuprov) was 0.34 (chi 2 = 8.45; P less than 0.05). The matrices of genetic distances for two groups of districts of Kostroma province, based on surnames frequencies, were calculated. Dendrogramms were constructed using genetic distances, which reflect the degree of genetical similarity of the populations. The conclusion drawn from the analysis of these dendrogramms is that there is distinct isolation by distance in populations of Kostroma province. It is shown that genetical subdivision of populations is dependent on geographical and some other factors and on the load of autosomal-recessive pathology in the population.     

Medico-genetic study of the population of Uzbekistan. III. Phenotypical assortativity as a factor in population structure (using palmoplantar hyperkeratosis and vitiligo as examples)]

The article comprises the examples of homophenogamic marriages between persons with a rare hereditary dominant character, hand-palm and foot-sole hyperkeratosis, leading to the increase of inbreeding intensity in the population. On the contrary, homophenogamic marriages between persons with vitiligo, a considerably more widespread character, lead to the decrease of the degree of inbreeding in a population, since they take place between partners coming from different districts of the region.     

Medico-genetic study of the population of Turkmenistan. I. Hereditary diseases in 5 districts of the Ashkabad region

Medico-genetic characteristics of the Ashkhabad province of Turkemenia are given. 23 nosological forms of hereditary diseases were found. The population load estimated per 1000 of autosomal-recessive (AR) diseases was 0.7, autosomal-dominant (AD) - 0.4, X-linked - 0.5. Inbreeding coefficient for the families with AR pathology was 0.03529, with AD - 0.01172. The study of territorial distribution of hereditary disease detected slightly marked local accumulation of certain forms of hereditary diseases.     

Genetic epidemiological study of Bashkortostan Republic: The effect of genetic structure of population on the load of monogenic hereditary diseases

Here we present the data obtained during medical genetic examination of the population of five districts of Bashkortostan Republic (Burzyanskii, Baimakskii, Abzelilovskii, Salavatskii, and Arkhangelskii) populated with 168050 persons including 135748 Bashkirs. The study involved all the population of the districts including each ethnic group and was conducted according to standard protocol developed in the Laboratory of Genetic Epidemiology, Medical Genetic Research Center, Russian Academy of Medical Sciences. Based on segregation analysis, the values of prevalence rates of the major types of Mendelian pathology (AD, AR, and X-linked diseases) was calculated in five regions of the Republic as well as for Bashkirs alone. Significant differences in the prevalence rates of AD and AR pathologies between individual districts, in particular upon division in rural and urban population, was observed. The prevalence rates comparison of monogenic hereditary pathology among Bashkirs compared to other previously examined populations have shown that the patterns of the hereditary disease load in the inspected districts of Bashkortostan were similar to that observed in the population of some districts in Udmurtia, Marii El and Chuvashiya. Russian European populations have shown significantly lower load of hereditary diseases. Correlation analysis of local inbreeding, endogamy and prevalence rates of AD and AR pathologies has shown that development of hereditary diseases load is significantly affected by gene drift.     

The load and diversity of hereditary diseases in four raions of Rostov oblast

The results of a medical genetic survey of the population of four raions (176535 individuals) of Rostov oblast (Dubovsky, Zimovnikovsky, Myasnikovsky, and Krasnosulinsky raions) are presented. The load of autosomal dominant (AD), autosomal recessive (AR), and X-linked hereditary diseases for urban and rural population was calculated, and the diversity of monogenic hereditary diseases (MHD) was reviewed. The nosological spectrum of MHD constituted 117 diseases (63 diseases with AD inheritance; 38, with AR inheritance; and 16, with X-linked inheritance). The analysis showed that the incidence of MHD among the population of Rostov oblast was 1: 336. Considerable differentiation in the prevalence rates of MHD (AD, AR, and X-linked pathologies) among certain raions was revealed.     

Medico-genetic study of the population of Turkmenia. IV. The population geography of hemoglobinopathies

Large-scale screening for hereditary haemoglobinopathies in five districts and among main Turkmen tribes was carried out. The frequencies of ABO and HP pheno- and genotypes were determined in the same populations. The different kinds of haemoglobinopathies genes were discovered (beta +, beta 0-thalassemia, alpha beta-thalassemia, alpha-thalassemia, HPFH, haemoglobins D and E). The geographic and ethnic differentiation of Turkmen population for beta-thalassemia géne was discovered. The FST values were found to be the same for ABO, Hp and beta-thal gene systems. The role of genetic drift in differentiation of Turkmen population is discussed.     

Correction for the estimated load of hereditary diseases in the population of the Krasnodarsk district

Medico-genetical examination of children from 6 invalid houses, 2 asylum houses, 3 internate schools and 1 house for deaf and feeble-hearing children as well as from the internate school for children with poor vision was undertaken in Krasnodar district. 10.6% of the children were found to have chromosomal abnormality, 26.5%--multifactorial pathology and 62.9% of children were affected by monogenic diseases. The spectrum of diseases covers 20 forms, 8 of them being autosomal-dominant, 10--autosomal-recessive and 2--X-linked forms. A "selective" method presented in this article for revealing patients affected by genetical diseases in specialised institutions permitted to evaluate a portion of the patients having been not identified when using the "survey" expeditional method of population--epidemiological study of the district population. This portion constitutes 19%. The more accurate values of genetic load in populations of Krasnodar district were obtained, being 1.06-0.06 for autosomal-dominant, 0.78-0.05 for autosomal-recessive and 0.38-0.05 for X-linked diseases per thousand.     

Medico-genetic study of the population of Turkmenia. V. A population and demographic description of the Nokhur isolate

The paper deals with demographic, genealogical and genetic characterization of one Turkmenian isolate--"Nochur". The data on its load of hereditary diseases were published previously. The Turkmenian "Nochurly" tribe consists of 19 large and small clanes. 600 nuclear families live in a small mountain valley of the same name. The share of prereproductive age class is 60%, of reproductive class--29%, this value for postreproductive class being 11%. The average number of children per family, when the families have completed their reproductive period, is 6.84. The average duration of generation (the mean parental age to the birth time of a mean newborn) is 37.7 and 31 years for a man and woman, respectively. Immigration into Nochur is practically absent, there is a flow of emigrants to the capital of the Republic, Ashkhabad. A very high level of assortative mating has been noted, the minimal estimation of inbreeding coefficient being 0.033 (the pedigree) and the maximal--0.0529 (isonimy). Diminishing of the number of lethal equivalents between 1940-1965 and 1966-1980 was discovered. This can be explained by a decrease in natural selection pressure. The data on distribution of genetic markers of the ABO, MN, Rh, Hp and Pp systems within this isolated population are presented.