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.     

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.     

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.     

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.     

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.     

Hereditary diseases of nervous system in the population of Vladimir province

The first population genetic study of hereditary disorders of the nervous system (HDNS) in Vladimir oblast was carried out. A total of 1,622,900 subjects, including 1,306,200 from the urban and 316,700 from the rural population, were tested. The population examined was characterized by virtually homogenous ethnic structure, with Russians constituting 95.76%. Pooled prevalence of HDNS in Vladimir oblast corresponded to the average prevalence for other Russian populations. Substantial differences between urban and rural populations in respect of the population load of HDNS and its nosological structure were not observed. A total of 22 nosological forms of HDNS were revealed, including thirteen autosomal dominant (193 families with 272 affected individuals), seven autosomal recessive (59 families with 66 affected individuals), and two X-linked (15 families with 17 affected individuals) diseases. The composition of the HDNS spectrum "nucleus" in Vladimir oblast displayed a number of differences from that in the majority of other populations examined. The HDNS in different regions of the area tested were characterized by different prevalence and spectrum. The data obtained may constitute a basis for regional registration of HDNS in Vladimir oblast.     

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 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.     

Hereditary Diseases of Nervous System in the Population of Vladimir Oblast

The first population genetic study of hereditary disorders of the nervous system (HDNS) in Vladimir oblast was carried out. A total of 1622900 subjects, including 1306200 from the urban and 316700 from the rural population, were tested. The population examined was characterized by virtually homogenous ethnic structure, with Russians constituting 95.76%. Pooled prevalence of HDNS in Vladimir oblast corresponded to the average prevalence for other Russian populations. Substantial differences between urban and rural populations in respect of the population load of HDNS and its nosological structure were not observed. A total of 22 nosological forms of HDNS were revealed, including thirteen autosomal dominant (193 families with 272 affected individuals), seven autosomal recessive (59 families with 66 affected individuals), and two X-linked (15 families with 17 affected individuals) diseases. The composition of the HDNS spectrum nucleus in Vladimir oblast displayed a number of differences from that in the majority of other populations examined. The HDNS in different regions of the area tested were characterized by different prevalence and spectrum. The data obtained may constitute a basis for regional registration of HDNS in Vladimir oblast.     

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. 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 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.     

Prevalence of hereditary pathology in Altai Republic

Medical genetic study of the population of Altai Republic (Russia) has been performed. The population sample comprises 203 148 subjects, including 59 196 Altaians, 134 972 Russians, and 8980 Kazakhs. For each nosological group, the loads of Mendelian pathology with different modes of inheritance and their prevalence rates in urban and rural populations have been determined. Thirty-six autosomal dominant (AD) diseases have been found in a total of 121 subjects, with hereditary syndromes being the most prevalent. Autosomal recessive (AR) pathology is represented by 24 diseases found in 158 subjects, with metabolic disorders being the most prevalent; and X-linked pathology, by four diseases in nine subjects. The prevalence rate has been calculated for each nosological form in the district where it has been found. The loads of AD, AR, and X-linked pathologies in the urban population were, respectively, 2.98 and 9.62 per 1000 people and 0.56 per 1000 men in Altaians; 0.86 and 0.94 per 1000 people and 0.23 per 1000 men in Russians; 0.34 and 1.16 per 1000 people in Kazakhs. In the rural population, the genetic load has been calculated for each district. The spectrum of hereditary pathology in the populations studied is described.     

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 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.     

Molecular Genetic Analysis of Hereditary Neurodegenerative Diseases

The review summarizes the results of a decade of molecular genetic studies of several high-incidence hereditary neurodegenerative diseases, including primary parkinsonism, various forms of hereditary dystonia and ataxia, polyglutamine disorders, hepatolenticular degeneration, essential tremor, etc. Various relevant mutations were studied. The character and frequencies of particular mutations and the corresponding genetic disorders were established for the Russian population. Particular genotypes were associated with various clinical variants of the diseases. Genetic loci were identified for several unique hereditary diseases of the nervous system (X-linked cerebellar hypoplasia, an atypical form of autosomal recessive muscular dystrophy, etc.). Nosological positions of the relevant clinical forms were clarified on the basis of the molecular genetic data. Protocols were developed for direct or indirect DNA diagnostics of the diseases under study to improve medical genetic counseling and prevention of new disease cases in affected families.     

Medical Genetic Study of Hereditary Diseases in Abazins of the Karachay-Cherkess Republic

This paper estimates the load and nosological spectrum of monogenic hereditary diseases (HDs) in Abazins of the Karachay-Cherkess Republic (KChR), identified in Cherkessk and ten districts, Abazinsky, Ust-Dzhegutinsky, Malokarachaevsky, Karachaevsky, Prikubansky, Khabezsky, Nogaysky, Adyge-Khablsky, Urupsky, and Zelenchuksky. The number of the investigated population was 387231 individuals (including 33264 Abazins). We detected 153 patients from 105 families with 45 nosological forms of HDs: 83 patients from 50 families with 23 AD diseases, 47 patients from 42 families with 15 AR diseases, and 23 patients from 13 families with 7 X-linked diseases. The total load of HDs in Abazins was 1: 218 individuals (in the rural population 1: 162, in the urban population 1: 305). Frequent and rare nosological forms of HDs and the accumulation of certain diseases in Abazins in comparison with the previously surveyed populations of Russia were determined. On the basis of the prevalence of AD and AR hereditary diseases, a principal component analysis was carried out, which determined the genogeographical position of Abazins among nine ethnic groups (13 populations) of Russian Federation: six Russian regions, Bashkirs of the Bashkortostan, Tatars of the Tatarstan, Chuvashes of the Chuvashia, Maris of the Mari El, Udmurts of the Udmurtia, Adygeans of the Adygea, and Circassians and Abazins of the KChR.     

Molecular genetic analysis of hereditary neurodegenerative diseases

The review summarizes the results of a decade of molecular genetic studies of several high-incidence hereditary neurodegenerative diseases, including primary parkinsonism, various forms of hereditary dystonia and ataxia, polyglutamine disorders, hepatolenticular degeneration, essential tremor, etc. Various relevant mutations were studied. The character and frequencies of particular mutations and the corresponding genetic disorders were established for the Russian population. Particular genotypes were associated with various clinical variants of the diseases. Genetic loci were identified for several unique hereditary diseases of the nervous system (X-linked cerebellar hypoplasia, an atypical form of autosomal recessive muscular dystrophy, etc.). Nosological positions of the relevant clinical forms were clarified on the basis of the molecular genetic data. Protocols were developed for direct or indirect DNA diagnostics of the diseases under study to improve medical genetic counseling and prevention of new disease cases in affected families.     

Nozological Spectrum of Hereditary Diseases of the Nervous System in the Cities of Volgograd and Volzhsky

A spectrum of hereditary diseases of the nervous system (HDNS) was studied in the cities of Volgograd and Volzhsky. The estimates were obtained for the prevalence of major HDNS groups and individual nosological forms. The populations examined differed in prevalence of this pathology and in contribution of individual diseases and their nosological forms into HDNS load formation. The effect of the population dynamics in Volgograd and Volzhsky on the HDNS prevalence is discussed.