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.     

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).     

The marriage migration characteristics of the Rostov oblast population

Marriage records have been used to study the marriage migration structure of five raions of the Rostov oblast. The mean ethnic marriage assortativeness in the Russian and Ukrainian rural populations are 1.16 and 1.6, respectively. The endogamy index of the urban population varies from 0.19 to 0.34; and that of the rural population, from 0.21 to 0.54. Malecot's isolation by distance parameters have been calculated. Genetic landscapes have been constructed.     

Integrated population genetic and medical genetic study of two raions of the Tver oblast

An integrated medical genetic an population genetic study has been performed in two raions (administrative districts) of the Tver oblast (region) of Russia: the Udomlya raion located in the zone affected by the Kalininskaya Nuclear Power Plant and the Ostashkov raion, which served as a control district. No significant differences has been found with respect to the genetic parameters studied. The values of these parameters in the populations of the town of Udomlya, the town of Ostashkov, the Udomlya raion, and the Ostashkov raion, respectively, are the following: random inbreeding, 0.00006, 0.00011, 0.000167, and 0.000366; endogamy index, 0.05, 0.43, 0.30, and 0.42; local inbreeding, 0.0003, 0.00045, 0.0009, and 0.0011; the degree of isolation by distance, 0.0003, 0.00045, 0.0009, and 0.0005; sigma, 2098, 1338, 1473, and 1189; the load of autosomal dominant (AD) diseases, 0.71, 0.92, 0.92, and 1.37; the load of autosomal recessive (AR) diseases, 0.68, 0.69, 0.67, and 0.82; and the load of X-linked diseases, 0.18, 0.64, 0.83, and 0.27.     

Medical genetic study of the Rostov oblast population: analysis of surname distribution in seven districts

Data on the surname frequency distribution in seven districts (districts) of the Rostov oblast (region) have been used to calculate random inbreeding varying from 0.000064 to 0.000186 in the Volgodonsk and Millerovo districts, respectively. Schematic surname landscapes have been constructed for six districts. The observed spectrum of frequent surnames is compared with that of the complete register of surnames in Russia.     

Medical genetic study of the Rostov oblast population: Analysis of surname distribution in seven districts

Data on the surname frequency distribution in seven raions (districts) of the Rostov oblast (region) have been used to calculate random inbreeding varying from 0.000064 to 0.000186 in the Volgodonsk and Millerovo districts, respectively. Schematic surname landscapes have been constructed for six districts. The observed spectrum of frequent surnames is compared with that of the complete register of surnames in Russia.     

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.     

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.     

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).     

The chemistry and control of hereditary lipid diseases

Direct inlet mass spectrometry has been performed on different derivatives of a hematoside (a triglycosylceramide of a tumour) and the major monosialoganglioside of brain (a pentaglycosyl-ceramide). As a confirmation of earlier results it was shown that trimethylsilyl derivatives gave information on ceramide structure (fatty acids and long-chain bases) but no specific information on carbohydrate structure. Fully methylated derivatives on the other hand, not analyzed before, gave in addition to ceramide fragments, specific ions for the sialic acid as well as carbohydrate sequence and branching. Using these derivatives molecular ions were not obtained for the brain ganglioside. However, by reduction of the methylated derivatives with LiA1H₄ (amide groups of ceramide and amino sugars were reduced to the corresponding amines) and trimethylsilylation of the converted sialic acid ester group, molecular weight ions were obtained for both gangliosides. In addition very strong peaks were found for the complete carbohydrate plus the fatty acid, of importance for the determination of the type and exact ratio of sugars, and also the fatty acid composition of the molecules. Ions were also obtained for a conclusive information on carbohydrate sequence and branching. It is concluded that a combined mass spectrometric use of methylated and methylated plus reduced ganglioside derivatives affords structural information on the complete molecules, which will be of considerable help in the characterization of gangliosides on a microscale.     

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 epidemiological study of monogenic hereditary diseases in the Republic of Tatarstan: Population dynamic factors determining the differentiation of the load of hereditary diseases in five districts

A genetic epidemiological study has been performed in five districts of the Republic of Tatarstan, Russia: Arsky, Atninsky, Kukmorsky, Buinsky and Drozhzhanovsky raions. The total size of the population surveyed is 188397 people. Tatars accounted for 77.13% of the population analyzed (145466 people) and were represented by two main ethnic groups: Kazan Tatars and Mishars. The medical genetic study encompassed the total population of the districts, irrespective of ethnicity, and was carried out according to the standard protocol developed in the Laboratory of Genetic Epidemiology of the Research Center for Medical Genetics of the Russian Academy of Medical Sciences. After segregation analysis, the prevalence rates of the main types of monogenic hereditary disorders (MHDs), i.e., autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases, have been calculated for the total population of the five districts and for Tatars alone. The prevalence rates of AD, AR, and X-linked diseases considerably vary in different subpopulations. The largest difference in the MHD prevalence rate has been found between the rural and urban populations. The overall prevalence rate of MHDs was one patient per 293 urban residents and populations and one patient per 134 rural residents, with a wide variation between subpopulations, from 1: 83 people in the rural population of Atninsky raion to 1: 351 people in the town of Kukmor. Comparison of the MHD prevalence rate in Tatars with those in populations surveyed earlier has shown that the characteristics of the load of MHDs in the Tatar population are similar to those in some districts of the republics of Bashkortostan, Udmurtia, Mari El, and Chuvachia. In Russian populations of European Russia, the MHD prevalence rates are substantially lower. Correlation analysis has shown high (r = 0.5?C0.9) significant correlations between the local inbreeding (a), the im index, the random inbreeding (F _ST), and the AD and AR prevalence rates in the Tatar population. This analysis has demonstrated that genetic drift is the main population dynamic factor determining the MHD load in the Tatar population.     

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.     

The genetic heterogeneity of hereditary human diseases]

The paper deals with the probability regularities of mutations arising in the same locus (or nucleotide) in human populations. It is shown that in a population of constant size the number of such recurrent mutations tends to an equilibrium value. It is demonstrated that dynamics of this number of recurrent mutations depends on the population structure essentially. This phenomenon is illustrated by comparing non-subdivided and hierarchy populations of the same size.     

The emerging genetic diversity of hereditary spastic paraplegia in Korean patients

Hereditary Spastic Paraplegias (HSP) are a group of rare inherited neurological disorders characterized by progressive loss of corticospinal motor-tract function. Numerous patients with HSP remain undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel genetic variations related to HSP is needed. In this study, we identified 88 genetic variants in 54 genes from whole-exome data of 82 clinically well-defined Korean HSP families. Fifty-six percent were known HSP genes, and 44% were composed of putative candidate HSP genes involved in the HSPome and originally reported neuron-related genes, not previously diagnosed in HSP patients. Their inheritance modes were 39, de novo; 33, autosomal dominant; and 10, autosomal recessive. Notably, ALDH18A1 showed the second highest frequency. Fourteen known HSP genes were firstly reported in Koreans, with some of their variants being predictive of HSP-causing protein malfunction. SPAST and REEP1 mutants with unknown function induced neurite abnormality. Further, 54 HSP-related genes were closely linked to the HSP progression-related network. Additionally, the genetic spectrum and variation of known HSP genes differed across ethnic groups. These results expand the genetic spectrum for HSP and may contribute to the accurate diagnosis and treatment for rare HSP.     

Virus load and antigenic diversity

In this paper, we analyse mathematical models for the interaction between virus replication and immune responses. We show that the immune system can provide selection pressure for or against viral diversity. The paper provides new insights into the relationship between virus load (=the abundance of virus in an infected individual) and antigenic diversity. Antigenic variation can increase virus load during infections, but the correlation between load and diversity in comparisons among different infected individuals can be positive or negative, depending on whether individuals differ in their cross-reactive or strain-specific immune responses. We derive two models: our first model applies to any replicating parasite that can escape from immune responses; our second model includes immune function impairment, and specifically describes infections with the human immunodeficiency virus (HIV).     

Analysis of population genetic structure of ten district populations of the Rostov oblast by means of an extended isonymic method of Barrai and colleagues

Parameters suggested by Barrai et al. (1992), including the random isonymy (I _r), surname diversity (α), migration index (v), and entropy (H) and redundancy (R) of surname distribution have been estimated in ten district populations of the Rostov oblast. Their weighted mean values are the following: I _r = 0.000813, v = 0.048, α = 1334.9, H = 11.30, R = 22.52.     

Analysis of population genetic structure of ten district populations of the Rostov oblast by means of an extended isonymic method of Barrai and colleagues

Parameters suggested by Barrai et al. (1992), including the random isonymy (I(r)), surname diversity (alpha), migration index (nu), and entropy (H) and redundancy (R) of surname distribution have been estimated in ten district populations of the Rostov oblast. Their weighted mean values are the following: I(r) = 0.000813, nu = 0.048, alpha = 1334.9, H = 11.30, R = 22.52.