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Hemophilia B is a monogenic X-linked recessive disorder associated with blood clotting reduction caused by mutations in the clotting factor IX gene (F9). An unusual form of this disorder, hemophilia B Leyden, caused by mutations in the promoter region of the F9 gene, is described. This form of hemophilia B is characterized by a significant, within norm, increase in factor IX in the patient’s plasma after puberty. Mutations in the promoter are grouped in discrete regions of transcription factor binding sites and alter the F9 gene expression during the ontogeny in different ways. This disorder demonstrates how single-nucleotide pathogenic variants in cis-regulatory regions can have a dramatic impact on gene expression. In this article, we present the current data on the F9 gene promoter structure and the results of examining three patients with hemophilia B Leyden who underwent genetic testing in the DNA-diagnostics laboratory of the Bochkov Research Centre for Medical Genetics.

On the basis of the data from the archive of the Laboratory of Genetic Epidemiology of the Research Centre for Medical Genetics, marriage records are selected for three large cities of the North Caucasus with a significant proportion of Russians: Vladikavkaz (25% Russians), Mozdok (59%), and Cherkessk (54%). In the selected marriage records, one or both spouses are Russian. The places of birth of migrants are analyzed at the level of federal districts. It is shown that three quarters of the Russian population of North Caucasian cities are natives of the North Caucasian Federal District. The majority of Russian migrants are natives of Ukraine and Kazakhstan.

The results of the study of genetic load and diversity of monogenic forms of hereditary pathology (MHP) among the child population from 11 districts of Kirov region (KR) obtained during genetic and epidemiological study of the region are presented. The total size of surveyed population is 286 616 individuals (including 37 348 children—13.03%), mainly Russians (88.1%). MHP included 91 diseases (287 patients from 255 families): 50 with autosomal dominant (AD) inheritance (153 patients from 129 families), 33 with autosomal recessive (AR) (107 patients from 104 families), and 8 nosologies with X-linked inheritance (27 patients from 22 families). All diseases were found in previously surveyed populations of the Russian Federation. Nine forms of MHP were detected with a prevalence higher than 1 : 5000: hereditary motor-sensory neuropathy (21.42/100 000), AD ichthyosis vulgaris (83.00/100 000), AD congenital ptosis (24.10/100 000), AD congenital cataract (29.45/100 000), AD syndactyly, type 1 (24.10/100 000), AR undifferentiated mental retardation (26.76/100 000), AR microcephaly with mental retardation (50.87/100 000), AR congenital cataract (26.78/100 000), and AR nonsyndromic sensorineural hearing loss (58.91/100 000). The average prevalence of MHP among the child population of KR was 1 : 130 children, with variation from 1 : 236 children in Vyatskopolyansky district to 1 : 51 children in Sunsky district. On the basis of the correlation analysis between load estimations and Fst values carried out, the reasons for revealed differentiation between districts are assumed.

A cartographic analysis of the values of random inbreeding obtained by the isonymy method, as well as the Barrai parameters considered as an extension of the isonymy method, was carried out. In North Ossetia, two opposite extremes with different degrees of expressiveness—in the Mozdoksky and Irafsky districts—were revealed.

Based on 28 359 marriage records for 1990–2000 throughout the Republic of North Ossetia-Alania, endogamy indices were calculated for different categories of the population of the republic: for the entire population in each district, for the urban and rural population, for the main ethnic groups. The cartographic analysis showed a reduction of endogamy in the direction of west to east. The obtained values of endogamy positively correlate with the values of random inbreeding. It is shown that the Republic of North Ossetia–Alania is not a population of the highest hierarchical level; the Ossetian people live on the territory of two republics, North and South Ossetia, without losing family ties, despite the presence of borders.

Malecot’s model of isolation by distance was used to describe the population structure of the population of North Ossetia-Alania based on 12 308 marriage records for a population of the rank of “republic.” A number of positive correlations were obtained with the results of previous studies. The difference between the Mozdoksky district and other districts of the republic is confirmed.

The results of genetic and epidemiological study of monogenic hereditary diseases (HD) among children of the Karachay-Cherkess Republics are presented. The surveyed population comprised 410 368 individuals (Cherkessk and ten rural areas), including 90 739 children (22.11%). The examination was performed following the original protocol for genetic-epidemiological studies (developed by the Research Centre for Medical Genetics) making it possible to register not less than 3500 HD and syndromes. One hundred eighty-three nosological forms of HD (922 patients from 764 families) were registered in the child population, including 100 patients with AD (459 patients from 366 families), 60 patients with AR (372 patients from 326 families), and 23 patients with X-linked inheritance (91 patients from 72 families). The structure of diversity is determined, and frequent HDs are described in accordance with the main classification by organ and systemic types of disease: neurological, ophthalmic, genodermatoses, skeletal, hereditary syndromes, and other pathology. There were 55 frequent HDs (30.05%)—the number of patients in this group was 739 (80.15% of sick children). The load of AD, AR, and X-linked pathology for urban and rural child population was calculated. Differences in HD load were identified. On the basis of correlations between the load and FST, the causes of the observed differentiation of subpopulations were proposed.

This paper carries out a comparative analysis of standard population-genetic parameters based on the distribution of surnames and marriage migrations in the Digorsky and Ardonsky districts. The positive and significant correlation of all the considered parameters allowed concluding that it is possible to use Ossetian surnames (of both Irons and Digors) as a biological marker in population-genetic studies.

The generalized results of the genetic and epidemiological study of the genetic structure of various ethnic groups of the Karachay-Cherkess Republic (KChR) through various genetic systems are presented: by the genes causing AD, AR, and X-linked hereditary diseases and by nonbiological parameters estimated by the methods of population statistics (random inbreeding FST, Malecot’s isolation-by-distance parameters, migration index, and Crow index and its components). The total size of the investigated population was 410 367 individuals (city of Cherkessk, Ust-Dzhegutinsky, Karachayevsky, Malokarachayevsky, Prikubansky, Khabezsky, Nogaysky, Adyge-Khablsky, Urupsky, and Zelenchuksky districts). On the basis of the study of correlations between different characteristics of the population genetic structure, it is assumed that the main cause of genetic differentiation of KChR subpopulations in terms of diversity and load of hereditary diseases (AD, AR, and X-linked) is genetic drift and migration under decreased influence of natural selection and mutational process.

The PAX6 gene encodes one of the key embryonic transcription factors and serves as a master regulator of eye and central nervous system morphogenesis in all species of bilaterian animals. The PAX6 protein contains two DNA binding domains: paired and homeobox. To ensure specific regulation of target genes, the domains are able to bind different DNA motifs either independently or in cooperation or even antagonizing in different cell contexts. PAX6 has a complex temporal and tissue-specific expression pattern. Abnormal levels of its expression, either excessive or insufficient, as well as a misbalanced ratio of expressed transcript variants, lead to the disturbance of embryogenesis. Compound heterozygous mutations in the PAX6 gene are lethal. Most heterozygous mutations lead to the loss of function of mutated PAX6 allele (haploinsufficiency). PAX6 function deficiency results in several phenotypes. The most frequent one is congenital aniridia (>90%), which is characterized by damage to various eye structures often accompanied by morphological and functional disorders of other organs and systems. The reasons for the varying expressiveness of mutant alleles of the PAX6 gene and the development of various phenotypes are still poorly understood. This review deals with the analysis of the current state of knowledge about the normal structure and functions of the PAX6 gene and its encoded protein, as well as the phenotypes associated with various mutations of this gene in humans.

The diversity and prevalence of hereditary diseases (HDs) among Nogais of the Karachay-Cherkess Republic (KChR) are described. The size of the surveyed KChR population was 387231 individuals, including 3.81% Nogais (14741 individuals). We revealed 36 nosological forms of HDs (110 patients from 81 families): 22 with autosomal dominant (AD) inheritance, 10 with autosomal recessive (AR) inheritance, and 4 with X-linked inheritance. The prevalence of HDs in Nogais was 1: 134. The features of HD diversity in Nogais were determined in comparison with the previously surveyed populations of Russia. The accumulation of Ehlers–Danlos syndrome (1: 388), AD amelogenesis imperfecta (1: 3685), AD ichthyosis (1: 4914), AR nonsyndromic mental retardation (1: 1340), AR Gilbert syndrome (1: 4914), and X-linked inherited deficit of glucose-6-dehydrogenase (1: 1774 males) was established. The analysis of heterozygous carriage of mutations “major” for Russia in the genes of the four following AR diseases in 118 unrelated clinically healthy Nogais (236 analyzed chromosomes) was performed: cystic fibrosis (13 mutations in the CFTR gene: CFTRdele2,3 (21 kb), F508del, I507del, 1677delTA, 2184insA, 2143delT, 2183AA>G, 2184delA, 394delTT, 3821delT, L138ins, E92K, W1282X); phenylketonuria (six frequent mutations in the PAH gene: R261X, R408W, R413P, F331S, P211T, P211L); nonsyndromic sensorineural hearing loss (35delG mutation in the GJB2 gene); and Gilbert syndrome (an increase in the number of TA repeats in the UGT1A1 gene). Allelic specificity for all studied genes in the Nogai people was revealed.

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.

The paper aims to review the diversity of monogenic hereditary disorders (MHD) in the Circassians of the Karachay-Cherkess Republic (KCR). In total, 50817 Circassians were investigated. The populations of eight districts (Ust-Dzhegutinsky, Karachayevsky, Malokarachayevsky, Prikubansky, Khabezsky, Abazinsky, Nogaysky, and Adyge-Khablsky) and of the city of Cherkessk were studied. Two hundred fifty patients from 167 families were registered. The prevalence of MHD in Circassians happens to be 1: 214. The nosological spectrum of MHD in Circassians includes 70 disorders: 34 with autosomal dominant, 25 with autosomal recessive, and 11 with X-linked inheritance patterns. Confirmatory DNA diagnostics was performed in 56 patients. Accumulation of particular diseases in the Circassian population was revealed in comparison with the previously surveyed ethnic groups/populations of Russia. The cluster analysis was performed on the basis of the prevalence of AD and AR disorders and determined the genogeographic position of the Circassians among eight ethnic groups of Russia (13 populations in total). The total size of the surveyed populations was over 3.5 million people: six Russian regions, Tatars of the Tatarstan, Bashkirs of the Bashkortostan, Chuvashs of the Chuvash Republic, Maris of the Mari El Republic, Udmurts of the Udmurt Republic, Adygeans of the Republic of Adygea, and Circassians of the Karachay-Cherkess Republic. The general pattern for AD and AR diseases was similar: six Russian populations group within a single cluster, being remote from people of the Volga-Ural region and the North Caucasus (Adyghe: Adygeans and Circassians).

This paper presents analysis of 28879 marriage records from 1990–2000 (total sample). Ethnic marriage assortative mating is positive in all ethnic groups significantly represented in Karachay-Cherkessia; the lowest values are characteristic of the more numerous ethnic groups (Karachays and Russians). The rate of metisation of the urban population is 21.6%; the rate for the rural population is 16%; the values vary significantly for different ethnic groups, reaching 98% for urban Ukrainians. With this rate of gene exchange, half of the urban population becomes interbred after three generations, and half of the rural population after four.

According to the neonatal screening conducted during the last nine years in Karachay-Cherkessia, the frequency of hyperphenylalaninemia (including PKU) was 1: 850 newborns, which significantly exceeded the average frequency of 1: 7000 in Russia. Analysis of DNA obtained from 25 patients with a diagnosis of “hyperphenylalaninemia” (HPA) from the Karachay-Cherkess Republic was performed to search for mutations in the PAH gene. Mutations were identified on 90% of the studied chromosomes, while at least one mutation in the PAH gene was observed in all patients. The allele frequency of a major mutation R261X was 32.5%. A correlation between genotype and phenotype was confirmed in patients with HPA.

To date, the efficacy of the phenylalanine hydroxylase (PAH) cofactor is proved for the treatment of both BH4-dependent hyperphenylalaninemia and phenylketonuria patients with mutations in the PAH gene. Since the patient’s response depends on the presence of residual PAH enzyme activity, it is advisable to search for mutations in the PAH gene to identify the potential responders and nonresponders to therapy. Four hundred thirty-five phenylketonuria patients from 13 regions of the Russian Federation were genotyped in order to identify responders and nonresponders to tetrahydrobiopterin (BH4) therapy. According to the results of this study, the number of probable nonresponders to the BH4 treatment exceeds 50% owing to a higher overall allelic frequency of “severe” PAH gene mutations. Responder patients with two “mild” mutations in the PAH gene were identified (1.6%).

To describe the population-genetic structure of the Russian population of Karachay-Cherkessia, the database of Compulsory Medical Insurance and marriage records for 1990–2000 were used. The Russian population is characterized by a low birth rate, low endogamy, low inbreeding, and a high level of miscegenation.

A comprehensive population and medical-genetic study was carried out in ten districts and two cities in the Karachay-Cherkess Republic (Russia). As a result, 57 patients with phenylketonuria were revealed. PAH gene genotypes for 40 probands and their diseased and healthy relatives were determined. The mutation spectrum of the PAH gene in the Karachay-Cherkess Republic was investigated. The major mutation in this region is R261X with allelic frequency of 68.4%. We elaborated a convenient system for detection of six PAH gene mutations common in the Karachay-Cherkess Republic, with the total information content of the system being 89.9%. As a result of processing the clinical data, association of the diet and phenylalanine levels in the blood was verified. Genophenotypic analysis confirms the association of the residual activity of phenylalanine hydroxylase and the severity of the disease. It is shown that common mutation R261X is severe and that patients who are homozygous for this mutation have classical phenylketonuria (PKU).

As part of systematic research carried out by the Laboratory of Genetic Epidemiology of the Research Center for Medical Genetics, the marriage and migratory structure of the urban population of Karachay-Cherkessia was studied. Numerical estimates of the population-genetic parameters were obtained from 11346 marriage records for 1990–2000. The endogamy, ethnic assortativeness, miscegenation and local inbreeding intensities, and mean-square migration for the four cities Cherkessk, Karachayevsk, UstDzheguta, and Teberda were estimated. It is shown that the autochthonic urban population is highly miscegenated, despite the traditional preference for monoethnic marriages. Half of the Russian urban population is migrant; the autochthonic urban population is substantially formed of Karachay-Cherkessia natives of.

Within the framework of a complex medical population genetic study of the population of Karachay-Cherkessia, the standard population genetic characteristics for Abazins were calculated and analyzed: the endogamy index (no more than 0.60), Barrai's parameters (l(r) = 0.0070, v = 0.0131, α = 143.5, H = 8.09, R = 39.65), ethnic assortativeness A (from 0.84 in the Kubina aul to 3.58 in Cherkessk), estimates of Maleco's isolation by distance parameters, and values of random inbreeding (0.0018).

This paper analyzes 2052 marriage records for 1990–2000 in the Khabezsky district of KarachayCherkessia. The main marriage and migration characteristics of Circassians are studied: index of endogamy, ethnic marriage assortivity, intensity of metisation, and Malecot’s parameters of isolation by distance.

Using data on the distribution of frequent surnames, the Crow index and its components, and nine polymorphic DNA loci, it was shown that the Tatar population of the Republic of Tatarstan is divided into subethnic groups (Mishars, Teptyars, and Kazan Tatars). No subdivision within each of these groups was found.

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.

On the basis of 1212 questionnaires filled up by women of postreproductive age living in five districts of the Republic of Tatarstan (Arsky, Atninsky, Kukmorsky, Buinsky, and Drozhzhanovsky), the basic reproductive characteristics and Crow’s index and its components have been calculated. The rural population is characterized by expanded reproduction with a mean sibship size of 2.68; in district administrative centers, there is only simple reproduction. Crow’s index and its components for the rural Tatar population are Im = 0.026, If = 0.172, Itot = 0.202. Graphic analysis of the mutual positions of some populations studied has been carried out.

The results of integrated study of the genetic structure and prevalence of monogenic hereditary diseases (MHDs) in the child population of three republics of Russia are summarized. Eight raions (districts) of the Republic of Bashkortostan and six districts of each Republic of Chuvashia and Republic of Udmurtia has been surveyed. The total population surveyed was 782184 people, with children accounting for 24.67% of them (192 992 children). The loads of autosomal dominant (AD), autosomal recessive (AR), and X-linked MHDs have been calculated separately for urban and rural populations; differences between individual populations in the MHD load have been found. The differentiation of subpopulations with respect to MHD prevalence is explained by differences in the degree of subdivision. The MHD spectrum in the child population of the three republics comprises 222 disease entities, including 121 AD, 83 AR, and 18 X-linked diseases. Group of highly prevalent MHDs in regional child populations have been determined. The mean fitness of MHD patients in Bashkortostan has been calculated; it is 0.87, 0.04 and 0.16 for AD, AR, and X-linked diseases, respectively. Analysis has demonstrated that the prevalence rates of MHDs in the child populations of the republics of Chuvashia, Udmurtia, and Bashkortostan are 1, 1.2, and 1.4%, respectively.

Genetic analysis of hereditary deafness (HD) has been performed in the city of Kirov and ten rural districts of Kirov oblast (administrative region). The analysis employed the methods used in audiology, medical genetic counseling, and DNA diagnosis. Deafness has been established to be hereditary in 143 children from 100 unrelated families. The incidence rates of isolated and syndromic HDs in the period studied (1995–2001) have been estimated at 1.25 and 0.36 per 1000 newborns, respectively, the total incidence rate of all HD forms being 1.61 per 1000 newborns (1 case per 621 newborns). DNA analysis for the detection of seven frequent mutations in the genes GJB2 (the 35delG, 167delT, 235delC, and M34T mutations), GJB6 (the del(GJB6-D13S1854) and del(GJB6-D13S1830) mutations), and TMC1 (the R34X mutation) has been performed in families with isolated neurosensory deafness. Molecular genetic analysis has detected mutations in 51 children (48.6%); in 54 children (51.4%), no mutations have been found. The following genotypes have been identified in children with HD: 35delG/35delG in 32 probands (30.5%), 35delG/+ in 16 probands (15.2%), 35delG/235delC in 1 proband (0.95%), M34T/+ in 1 proband (0.95%), and M34T/35delG in 1 proband (0.95%). The 167delT mutation has not been found. The frequency of the 35delG mutation in the GJB2 gene has been estimated to be 39.05%. In the group with a family history of HD, mutations have been found in 66.7% of patients; in the group without a family history of HD, in 37.5% of patients. No mutation has been found in the GJB6 or TMC1 gene. Molecular genetic analysis has been performed in a family with clinically diagnosed Treacher Collins-Franceschetti syndrome. Sequencing has been used to find the 748–69C>T polymorphism in intron 6 (in the homozygous state) and the 3635C>G mutation in exon 23 leading to the substitution of glycine for alanine at position 1176 of the amino acid sequence (Ala1176Gly, in the heterozygous state), which have not been described before.

The results of a genetic epidemiological study of hereditary deafness (HD) in ten raions (districts) of Kirov oblast (administrative region), Russia, are presented. A total of 122 075 people have been examined. Segregation analysis of all families with diagnosed HD has demonstrated a good fit to either the autosomal dominant (AD) or autosomal recessive (AR) mode of inheritance. The total prevalence rates of AD and AR HDs, as well as the specific prevalence rates of nonsyndromic and syndromic forms of HD, have been calculated for the population of ten raions. The HD prevalence rate in Kirov oblast has been found to be 1: 1043 people (1: 1453 and 1: 3699 for the nonsyndromic and syndromic forms, respectively). This value has been found to vary in different raions, which is explained by differences in the genetic subdivision levels of the populations studied; the correlation coefficient between the HD load and random inbreeding (FST) in district populations is r = 0.81 ± 0.22. The diversity of syndromic hearing disorders is described.

A total sample of 31 837 marriage records made in 13 raions (districts) of Tatarstan in 1990–2000 have been used to determine the endogamy index and parameters of Malecot’s isolation by distance model. The endogamy index varied from 0.45 in Pestrechinsky raion to 0.74 in Aktynashsky raion. The parameters of Malecot’s isolation by distance model varied in Tatars as follows: random inbreeding, from 0.00014 to 0.00076; root mean square migration, from 46 to 110 km.

The distribution of surnames in for populations of the district rank in Kirov oblast has been used to calculate Barrai’s parameters, which are the following: Ir, 0.0008–0.0208; H, 6.80-211.57; ν, 0.003–0.058; α, 47.35–1191.39; R, 23.03–50.07. The results have been compared with data on the 1980s; no substantial changes in the studied parameters during a generation have been found.

The results of two studies on the population genetic structure of Afanas’evo raion of Kirov oblast are compared. The changes that have occurred during two decades are insignificant.

Data on surname distribution in 24 raions of Kirov oblast with a total adult population of more than 785000 people were used to calculate the random inbreeding values for populations of the district and rural municipality levels and analyze the geographic distributions of these values. The data have been compared with the results of studies carried out in the 1980s.

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 marriage migration structure of the populations of six districts of Bashkortostan Republic has been studied. The rates of assortative marriages in Bashkirs, Tatars, and Russians are 1.02–2.71, 1.30–5.99, and 2.14–7.50, respectively; the endogamy indices are 0.58–0.97, 0.90, and 0.68, respectively. Malecot’s isolation-by-distance parameters in Bashkirs, Tatars, and Russians, respectively, are the following: σ is 6.7–83.0, 40.3–106.1, and 69.9; a is 0.00012–0.00074, 0.00170–0.0029, and 0.00096; and b is 0.0087–0.0467, 0.0038–0.0208, and 0.0129. Changes in these parameters with time have been traced.

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 structure of Southern and Northern ethnographic groups of the Udmurt population from six regions of the Republic of Udmurtia has been studied. All the samples were examined using ten polymorphic DNA loci: VNTR/PAH, VNTR/ApoB, VNTR/DATI, VNTR/eNOS, ACE, CCR5 Δ32, KM19, IVS6a, THOI, and FABP2. Allelic and genotype frequencies were estimated for each of the six populations. The average heterozygosity for these ten polymorphic loci varied from 0.47 in Udmurts from Glazovskii region to 0.53 in Udmurts from Malopurginskii region. The level of genetic variation (F ST) between populations of Udmurts was 0.0048. Ethnographic subdivision of the population into Northern and Southern Udmurts is in good agreement with the values of genetic distances and phylogenetic analysis.

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.

A genetic epidemiological study of hereditary diseases of the nervous system (HDNS) was conducted in the cities of Volgograd and Volzhsky for the first time. In total, 1 323 500 individuals were examined including the populations of Volgograd and Volzhsky (1 012 800 and 310 700 persons, respectively). The prevalence of neurological diseases with autosomal dominant (AD), autosomal recessive (AR), and X-linked recessive inheritance was estimated. These data were compared with the estimates previously obtained for different population of the Russian Federation. A decrease was found in general HDNS load in Volgograd and Volzhsky. The compared populations were shown to differ in a contribution of AD, AR, and X-linked recessive diseases into the HDNS load formation. The possible effect of population dynamics factors on the HDNS load structure is discussed.

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; σ, 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.

Based on the data from 569 questionnaires collected in Udomlya and Ostashkov raions of Tver oblast and 436 questionnaires collected in Tsimlyansk and Dubovsk raions of Rostov oblast, genetic demographic characteristics and Crow's index for urban and rural populations of these regions were calculated. The data obtained were compared with those for other Russian populations obtained earlier.

Genetic demographic characteristics were calculated for Chuvash and Russian inhabitants of the Republic of Chuvashia. The generation lengths were 27.09 and 26.4 years and the sibship sizes were 2.54 and 1.82 for Chuvashes and Russians, respectively. Crow's indices and their components were as follows: Im = 0.05, If = 0.31, and Itot = 0.37 for Chuvashes and Im = 0.03, If = 0.43, and Itot = 0.46 for Russians. The genetic demographic characteristics obtained were compared with those for Highland and Meadow Maris.

Population genetic characteristics were estimated in the Alatyr' raion (administrative district) of the Republic of Chuvashia, which has long been populated by three ethnic groups. The ethnic assortativeness values in the town of Alatyr' and the rural area of the district were 1.17 and 1.21, respectively, for Russians; 1.14 and 4.82, respectively, for Chuvashes; and 1.33 and 2.45, respectively, for Mordovians. Wright's statistics were as follows: Fst = 0.00358, Fit = 0.00178, and Fis = 0.00134. The migration indices were 0.0264 for Alatyr' and 0.0178 for the district. The endogamy indices for the total and the Russian populations of Alatyr' were 0.47 and 0.53, respectively. The parameters of isolation by distance were a = 0.000189 and b = 0.009591 for the urban and a = 0.000318 and b = 0.00919 for the rural area. Schemes of the genetic landscape were constructed. The influence of the polyethnic composition on the genetic structure of the population is discussed.

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 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 : 50000 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 : 877483). 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.

Results of 20-year studies on the diversity of autosomal dominant (AD) diseases are summarized. The studies were carried out in six regions of Russia: Kirov, Kostroma, and Bryansk oblasts; Krasnodar krai; and Adygea and Marii El republics. A total of 1.5 million subjects from 44 raions (districts) were studied. In the populations studied, 144 AD diseases were found; the total number of affected persons was 1723. The prevalence rate in the region where the disease was found and the average prevalence rate in the total population studied were calculated for each disease. Only 11 AD diseases had prevalence rates of 1 : 50 000 or higher. About half of AD diseases (64) had a very low prevalence rate (1 : 861 408). However, most cases (about 70% of the affected persons) were accounted for by more frequent diseases. Forty-six diseases exhibited local accumulation. The AD mutation rate was estimated by direct calculation. This rate was 0.542 × 10–6per gamete per generation.

Comprehensive population genetic and medical genetic studies were performed in three raions (districts) of Chuvashia. The population of these districts is more than 90% Chuvash. About 70% of the families that completed reproduction had two or three children. The proportion of families with four or more children was 18%. The duration of generation was 27.6 years. The differential fertility and differential mortality indices in the Chuvash population were estimated at 0.33 and 0.076, respectively. The total index of differential selection was 0.403, which is typical of modern urbanized populations. Mean values of local inbreeding calculated from Malecot's model of isolation by distance were 0.00124 and 0.00377 for the urban and rural populations, respectively, of the districts studied. The prevalence rates of autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases were found to be 0.47, 0.52, and 0.35 per 1000, respectively, in the urban population and 1.62, 1.14, and 0.31 per 1000, respectively, in the rural population. Significant correlation between the local inbreeding and prevalence rates of AD and AR diseases was found. A total of 43 AD and 43 AR diseases were identified. Some of them were not found in previous studies on other populations.

Based on marriage records for 1950–1959, 1970–1979, and 1990–1999, ethnic assortativeness of Chuvash and Russian inhabitants of Tsivil'sk raion of the Chuvash Republic was calculated. It was shown that in half a century ethnic assortativeness of Chuvashes did not change (1.18, 1.15, and 1.15), while in Russians a clear downward trend was observed (4.20, 2.18, and 1.28). The data on ethnic assortativeness obtained were compared with those for the same populations from other regions of the Chuvashia examined earlier.