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.     

Medical genetics study of the population of Kostroma Province. II. The diversity of hereditary pathology in 5 districts of the province

The diversity of hereditary pathology in 5 regions of Kostroma district was studied. 32 nosological forms of autosomal dominant, 30 autosomal recessive and 7 X-linked recessive disorders were found. The most frequent autosomal dominant disorders were: neurofibromatosis, pigmentary degeneration of retina, hypochondroplasia, ichtiosis, idiopathic scoliosis. The most frequent among the autosomal recessive disorders were: oligophrenia, pigmentary degeneration of retina, muscular atrophy of juvenile Kugelberg--Welander type, congenital cataract. The most frequent X-linked disorders were: muscular Duchenne type dystrophy and hemophilia A. Analysis of mutant gene distribution over the territory by the study of birthplaces of probands and their parents was carried out.     

Medico-genetical study of the population of the Kostroma Region. IV. Genetic load and diversity of hereditary pathology in 5 districts

Data on the prevalence of hereditary diseases in five regions of the Kostroma province were obtained and analysed. 28 autosomal recessive, 25 autosomal dominant and 4 X-linked recessive disorders were found. Segregation analysis proved the rightness of the material subdivision, according to the type of inheritance. The load of hereditary diseases in five regions was: 0.86 +/- 0.09 X 10(3) for autosomal recessive, 0.97 +/- 0.1 X 10(3) for autosomal dominant and 0.36 +/- 0.09 X 10(3) for X-linked recessive disorders. The problems of prevalence of hereditary diseases connected with population structure is discussed.     

Medical genetic study of the population of Kostroma Province. V. The hereditary pathology burden of urban and rural populations

Medical genetic study was carried out in the urban and rural populations of Kostroma Province. Urban populations were shown to have lower frequencies of "rare" forms of autosomal recessive diseases, in comparison with those in the rural populations. Analysis of interrelationship between genetical structure of populations and prevalencies of hereditary diseases in the populations revealed clear relations between the load of autosomal recessive diseases and the level of inbreeding in the populations.     

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 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.     

Spectrum and territorial distribution of hereditary diseases in the population of the Krasnodar Krai]

The analysis of the spectrum of hereditary diseases in the population of the Krasnodar province is performed and the influence of the population dynamics factors on the spectrum is discussed. More than 130 nosological forms were discovered in the population of approx. 200,000. Among these, there are 63 autosomal dominant, 49 autosomal recessive and 17 X-linked recessive forms. Of the most frequent autosomal dominant diseases (more than 1 per 50,000) autosomal recessive and X-linked recessive disorders 13, 7 and 7 forms, respectively, were picked up. The coefficient of diversity of hereditary diseases (the number of nosological forms per 10 inhabitants) with different types of inheritance is higher in the Krasnodar population, as compared with the Kostroma population. The problem of similarity of the "nucleus" of autosomal-recessive disorders in Russian populations is discussed.     

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.     

Prevalence of hereditary pathologies in residents of the Kirov Province]

Medical-genetic study was carried out in the population of Kirov Province (population size about 120.000). 203 families with 334 affected with hereditary disorders were registered. The correctness of pathology classification for the inheritance type was confirmed by segregational analysis. The load of hereditary diseases in the population was: 1.25 +/- 0.06 for autosomal dominant, 1.37 +/- 0.07 for autosomal recessive and 0.22 +/- 0.06 for X-linked recessive disorders. It is suggested that variability in the values of the load of autosomal recessive disorders is determined to the large extent by genetic structure of the population.     

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.     

Epidemiology of monogenic hereditary diseases in Rostov oblast: Population dynamic factors determining the differentiation of the load of hereditary diseases in eight districts

Analysis of the diversity of monogenic hereditary diseases in eight raions (districts) of Rostov oblast (region) of Russia (Tsimlyansk, Volgodonskoi, Tselina, Egorlykskaya, Millerovo, Tarasovskaya, Rodionovo-Nesvetaiskaya, and Matveevo-Kurgan raions) has been summarized. The total sample size was 320925 subjects. The spectrum of hereditary diseases detected in the eight districts comprises 187 diseases, including 99 autosomal dominant (AD), 72 autosomal recessive (AR), and 16 X-linked diseases. The mean prevalence rate of each disease in the total population has been calculated. Accumulation of individual diseases in different regions of Rostov oblast has been calculated; the disease accumulation has been compared with that in some populations of Russia examined earlier. Cluster analysis using the data on the frequencies of genes of hereditary diseases has shown the gene geographic position of the Rostov oblast population among the following ethnic populations of Russia: Russians (Kostroma, Kirov, and Rostov oblasts and Krasnodar krai), Chuvashes (Chuvashia), Adygeans (Adygea), Maris (Marii El), and Udmurts (Udmurtia).     

A medico-genetic description of inhabitants of two regions of the Kransnodar Krai]

The spectrum and prevalence rate of hereditary pathology in Kanevskii and Bryukhovetskii raions (districts) of Krasnodar krai (territory) were analyzed. The total size of the studied population was 145,937. The prevalence rate of monogenic hereditary pathology was estimated. This value was 1.08 +/- 0.08, 0.72 +/- 0.07, and 0.20 +/- 0.06 per 1000 people for autosomal dominant (AD), autosomal recessive (AR), and X-linked (XL) recessive diseases, respectively. Forty-two AD (158 affected persons in 82 families), 32 AR (105 affected persons in 82 families), and 6 XL disease entities (13 affected persons in 8 families) were found. A slight genetic subdivision was found in the populations of Kanevskii and Bryukhovetskii raions. However, it was not found to affect the prevalence of hereditary pathology.     

Medico-genetic study of the population of Kostroma Province. VI. The parameters of isolation by distance in the populations of the Bui and Shar'ya Districts of Kostroma Province

A model of isolation by distance proposed by Malécot and developed by Morton is applied to the data on marriage distances collected in two regions of Kostroma Province. There is good agreement between the estimates of local inbreeding when using the isonymy method and the model of isolation by distance. Interpopulation kinship approaches 0 at the distance 700 km. The mean coefficient of kinship for parents in the families with autosomal-recessive pathology is 20 times higher than mean coefficient of kinship in the population.     

Genetic epidemiological study of Bashkortostan Republic: The diversity of monogenic hereditary diseases in five districts

The diversity of monogenic hereditary diseases (HDs) (autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases) has been studied in five districts of Bashkortostan Republic: Burzyanskii, Abzelilovskii, Baimak, Salavatskii, and Arkhangel’skoe raions. The spectrum of HDs comprised 144 diseases, including 83, 48, and 13 AD, AR, and X-linked diseases. Most of them were found earlier during studies in ten other regions of Russia (Kirov, Kostroma, Tver’, Bryansk, and Rostov oblasts, and Krasnodar krai, and the republics of Adygea, Marii El, Udmurtia, and Chuvashia). Foci of local accumulation of some AD, AR, and X-linked diseases have been found in individual districts. Data on the gene frequencies for the HDs have been used for cluster analysis, which has shown the gene geographic position of Bashkirs among nine ethnic populations of Russia: Russians (Kostroma, Kirov, and Rostov oblasts and Krasnodar krai), Chuvashes (Chuvashia), Adygeans (Adygea), Maris (Marii El), Udmurts (Udmurtia), and Bashkirs (Bashkortostan).     

Characteristics of the Gd- alleles discovered in a population check of pupils in the city of Kostroma

The population study of distribution of G-6-PD alleles among normal Russian school-children of Kostroma town was carried out. In total, 952 children were examined, 429 girls and 523 boys (from 7 to 18 years old). The frequency of Gd- alleles is 0.36%. Two Gd- alleles discovered in this study belong to the III class. One of them was characterized according to the WHO programme. This allele designated "Kostroma" has not been described earlier.     

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 population of Uzbekistan. VIII. Territorial distribution of hereditary diseases in the population of four regions of the Khorezm province and its genetic load

The load of hereditary diseases was estimated on the basis of data obtained during medical-genetic study of the population of four districts of Khorezm province. The load of autosomal recessive disorders comprised 2-3 X 10(-3) affected, that of autosomal dominant disorders - 0.4-0.5 X 10(-3) and that of X-linked disorders - 0.2-0.4 X 10(-3) males. The main part of patients with autosomal recessive disorders belonged to separate families randomly spread over the populations. A trend for local accumulation of families with the same disorder was observed in small populations. It was shown that overall frequency of autosomal recessive genes per individual increased with the increase in the population size.     

Windthrows in forests of Kostroma oblast and neighboring lands in 1984–2011

A retrospective analysis of windthrows in southern taiga forests (Kostroma oblast and neighboring lands) is performed. The main traits of massive windthrows are calculated. The dominant spatial forms of windthrows are identified. The average annual rates of the forest-cover damage from clearcuts, forest fires, and windblows are compared. The topographical effect on the spatial distribution of fragments of massive windthrows is analyzed.     

Medical genetic study of the population of Turkmenia. III. Hereditary pathology in Turkmen Nokhurlis

Medical-genetic investigations were carried out in isolated population of Nokhurlis inhabiting some villages of Ashkhabad and Krasnovodsk provinces. A high coefficient of inbreeding, high endogamy, and low coefficients of migration were found for this population. Two hereditary disorders are relatively frequent among the Nokhurlis and lacking in neighboring populations. The frequency of the autosomal dominant gene for congenital cataract is 0.26% and that of the autosomal recessive gene for a peculiar form of obesity is 2.47%. In both cases, the main factor affecting gene accumulation appears to be the result of genetical drift effect. The total load of hereditary diseases of higher in Nokhurlis than in other Turkmen populations. The connection between the population structure of Nokhurlis and the accumulation of hereditary disorders is discussed.     

Analysis of diversity of autosomal-recessive diseases in Russian populations]

The diversity of autosomal recessive (AR) diseases was studied in six Russian regions: the Kirov, Kostroma, and Bryansk oblasts; Adygea Republic; Krasnodar krai, and Marii El Republic (in the latter region, the Mari and Russian ethnic groups were studied separately). In total, more than 1.5 million people were studied. The spectrum of the AR diseases included 101 nosological forms; the total number of the affected subjects was 942. For all diseases, the prevalence rate in the region where they were found and the mean prevalence rate in the total population studied were calculated. Only seven AR diseases had prevalence rates of 1:50,000 or higher; however, this group contained about 50% of the patients. About half of the AR diseases (66) had an extremely low prevalence rate (1:877,483). Eleven diseases exhibit local accumulation. Accumulation of some or other diseases was only observed in four out of seven populations studied (Marii El, Adygea, and the Kirov and Bryansk oblasts). To determine the cause of the local accumulation of some diseases in populations, correlation analysis of the dependence of accumulation of hereditary diseases on the genetic structure of the populations studied was performed. The accumulation coefficients for AR and autosomal dominant (AD) diseases and the mean values of random inbreeding (Fst) in individual districts were calculated for all populations studied. The coefficients of the Spearman rank correlation between the accumulation coefficient and random inbreeding (Fst) were 0.68 and 0.86 for the AD and AR diseases, respectively. The correlation between the accumulation of AD and AR diseases was 0.86. The relationships found indicate that the diversity of AD and AR diseases, as well as the genetic load, distinctly depended on the population genetic structure and were largely determined by genetic drift.