Prevalences of hereditary diseases in various populations in Russia

The geographic distribution of hereditary diseases (HDs) in different populations and ethnic groups of Russia has been studied. The main patterns of the formation of the prevalence and spectrum of HDs in five ethnic groups (Russians from six regions, Mari, Chuvashes, Udmurts, and Adygeans) from a total of ten regions of Russia have been analyzed. Analysis of correlations suggests that genetic drift is the main factor of the genetic differentiation of populations with respect to the prevalence of HDs. Accumulation of HDs in individual populations and ethnic groups has been analyzed. Hereditary diseases characterized by locally high prevalence rates in individual populations or ethnic groups have been detected. The main patterns of the accumulation of individual diseases and differences between populations and ethnic groups in this respect have been studied with the use of principal component analysis, which describes these patterns more graphically. It has been demonstrated that the genes of HDs are a promising tool for characterizing ethnogenetic processes in populations.     

Prevalences of hereditary diseases in different populations of Russia

The geographic distribution of hereditary diseases (HDs) in different populations and ethnic groups of Russia has been studied. The main patterns of the formation of the prevalence and spectrum of HDs in five ethnic groups (Russians from six regions, Mari, Chuvashes, Udmurts, and Adygeans) from a total of ten regions of Russia have been analyzed. Analysis of correlations suggests that genetic drift is the main factor of the genetic differentiation of populations with respect to the prevalence of HDs. Accumulation of HDs in individual populations and ethnic groups has been analyzed. Hereditary diseases characterized by locally high prevalence rates in individual populations or ethnic groups have been detected. The main patterns of the accumulation of individual diseases and differences between populations and ethnic groups in this respect have been studied with the use of principal component analysis, which describes these patterns more graphically. It has been demonstrated that the genes of HDs are a promising tool for characterizing ethnogenetic processes in populations.     

Genetic load of hereditary diseases in populations of the Krasnodar Krai]

Medico-genetical study of populations living in Krasnodar district was carried out. The mean value of genetic load contributed by autosomal dominant diseases composed 0.92 +/- 0.06, this value being 0.56 +/- 0.04 for autosomal recessive and 0.36 +/- 0.05 for X-linked recessive disorders per one thousand. Comparative analysis of genetical load in urban and rural populations demonstrated that they had no differences in relation to genetical load contributed by autosomal recessive and X-linked recessive disorders. At the same time, significant differences were noted between the populations concerning genetic load contributed by autosomal-dominant disorders.     

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.     

Genetic-demographic structure of the Adyg population]

The results of comparative analysis of series of genetical and demographical parameters in two ethnically distinct populations coexisting in Adyg autonomous region of the Krasnodar district are presented. The parameters of population structure in Russians and Adygs were determined, such as sex and age distribution, ethnical marital assortativity, vital statistics and selection pressure. The analysis revealed that the populations only differ in the level of ethnical marital assortment: the coefficient of assortativity H is 2.54 and 1.55 for Adygs and Russians, respectively.     

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-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.     

Leukocyte cell populations in hereditary muscular dystrophic chickens

Adult hereditary muscular dystrophic (MD) chickens were compared with normal chickens for properties of the reticuloendothelial and lymphoid systems. Storrs strain MD chickens exhibited elevated levels of blood heterophils with reduced lymphocytes compared with normal Hyline SC strain chickens. Of the lymphocytes, MD chickens possessed a greater incidence of E-rosette forming cells than were present in SC adults. Similarly, MD spleens possessed more adherent cells with a greater incidence of heterophils than were found in SC chickens. This difference also extended to the peritoneal cavity. Recruitment of peritoneal exudate cells into the cavity with Sephadex stimulation led to a greater incidence of heterophils at the expense of macrophages in MD compared with SC chickens. These findings are discussed in light of the recent detection of a specialized adherent suppressor cell population in MD chickens, and with reference to the muscle disease.     

遗传病的生物治疗

遗传病尤其是单基因遗传病是儿童致畸致残的主要原因之一,给家庭、社会带来沉重的经济、心理负担。目前绝大多数遗传病临床治疗以对症治疗为主,尚缺乏有效的治疗方法。随着生命与医学科学的发展,近年来以靶向致病分子或其相关信号通路、靶分子的外源物质补充、转基因、RNA干扰、基因组编辑等生物学技术为代表的生物学治疗措施开始应用于遗传病的治疗,并取得了一定的疗效。但目前大多数遗传病的生物学治疗仍局限于动物实验研究,今后在继续研发基于致病机制的新治疗策略的同时,将关注如何开展临床试验,为最终安全、有效应用于临床患者奠定基础。     

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).     

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

A genetic epidemiological study has been carried out in eight raions (districts) of Rostov oblast (region) of Russia: Tsimlyansk, Volgodonskoi, Tselina, Egorlykskaya, Millerovo, Tarasovskaya, Rodionovo-Nesvetaiskaya, and Matveevo-Kurgan raions. The population structure (the parameters of the isolation by distance model, ethnic assortative marriage, random inbreeding (F _ST), endogamy index, and ie) and the genetic demographic characteristics of the regional population (vital statistics, Crow’s index, and its components) have been analyzed. The total sample size was 320 925 subjects (including 114 106 and 206 816 urban and rural residents, respectively). The load of the main types of Mendelian diseases (autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases) has been calculated for the total sample from eight districts and separately for the urban and rural populations. Substantial differences between individual districts in the AD and AR genetic loads have been found, especially upon separation into urban and rural samples. The results of correlation analysis suggest that migration and genetic drift are the main factors of genetic differentiation of populations with respect to the prevalence of hereditary diseases.     

Marital and migration structure and inbreeding in the Adyg population]

Endogamy and gametic indices for both Russian and Adyg populations living in the Adyg autonomous region of Krasnodar district were determined on different levels of territorial units: village, rural, community (a group of villagers) and rural region. Inbreeding coefficient was estimated for Adyg population and its structure analysed: a random component contributes mostly to the inbreeding coefficient (Fst = 0.00991), non-random component of the inbreeding coefficient being Fis = 0.010009, which testifies to negative marital assortativity among Adygs. Local inbreeding "a" and decline in the inbreeding "phi" coefficient at a distance from 0 to 500 km were calculated using the Malecot's formula: the coefficient "a" was found to be 0.00397, which is in good accordance with the Fst.     

Balanced hereditary polymorphism and the mortality from cardiovascular diseases in the populations of 17 countries of Europe. I. A correlation analysis

The correlation analysis of ratios between six polymorphic genetic systems (ABO, MNSs, Rh, Hp, Gm, HLA) and mortality from ishemic heart disease, brain vascular lesions, and hypertensive disease in 17 European populations has been made. A statistically significant correlation has been established between the populational frequency of most of the 50 phenotypes and genes under study, and mortality. The qualitative structure of correlations and their quantitative expression depend on the cause of death, age and sex. The possible mechanisms of relationship between the genetic populational differences and mortality from cardiovascular diseases are discussed.