[Diversity in autosomal-dominant diseases in the Russian population]. / Raznoobrazie autosomno-dominantnykh zabolevanii v rossiiskikh populiatsiiakh.

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 x 10(-6) per gamete per generation.

[Analysis of diversity of autosomal-recessive diseases in Russian populations]. / Analiz raznoobraziia autosomno-retsessivnykh zabolevanii v Rossiiskikh populiatsiiakh.

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.

[Burden of hereditary diseases in residents of the Mari El Republic]. / Gruz nasledstvennykh boleznei u naseleniia respubliki Marii El.

A summary of the medical genetic studies of the Marii El population is presented. A total of 276,900 people, 110,894 and 166,006 urban and rural inhabitants, respectively, were examined. Regarding the ethnic composition, the studied population was mostly Mari (61.96%) and Russian (32.04%). Medical genetic examination revealed 480 subjects from 260 families with autosomal dominant (AD) diseases, 234 subjects from 184 families with autosomal recessive (AR) diseases, and 49 subjects from 41 families with x-linked diseases. Segregation analysis revealed a good agreement between the expected and observed segregation frequencies for families with AR and AD diseases and allowed the frequency of hereditary diseases in the urban and rural, as well as the Russian and Mari, populations, to be estimated. The total frequency of AD diseases in Maris was approximately twice as high as in Russians (1.99 and 0.97%, respectively); substantial differences between district populations were found. The total frequency of AR diseases was also two times higher in Maris than in Russians (1.00 and 0.54%, respectively). The frequencies of AR and AD diseases in different districts were correlated with the levels of random and local inbreeding, population size, and the index of maximum selection.

[A medico-genetic description of inhabitants of two regions of the Kransnodar Krai]. / Mediko-geneticheskoe opisanie naseleniia dvukh raionov Krasnodarskogo kraia.

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.

[Diversity of hereditary pathology in the population of Marii El Republic and its differentiation with respect to gene frequencies for hereditary diseases]. / Raznoobrazie nasledstvennoi patologii u naseleniia respubliki Marii El i ee differentsitsiia po chastotam genov nasledstvennykh boleznei.

The diversity of Mendelian hereditary pathology was studied in Marii El Republic. In total, 276,900 subjects, including 171,151 Maris and 88,714 Russians, living in seven raions (districts) were studied. Fifty-five autosomal dominant disease entities were found, with more than ten diseases having a frequency of 1:50,000 people or higher. In Maris, autosomal recessive hypotrichosis was observed at a relatively high frequency (1:15,337); this disease was not revealed in the Russian population studied earlier. Conversely, no phenylketonuria (PKU) was found in Maris, while it was a relatively common autosomal recessive disease in Russians. Regarding autosomal dominant pathology, 76 disease entities were revealed, with 21 diseases being observed at a frequency of at least 1:50,000. Ten X-linked diseases were found. The numbers of both autosomal recessive and autosomal dominant diseases exhibited a linear relationship with the number of subjects examined. The genetic structure of the Mari population was studied on the basis of data on the genes of recessive diseases. A matrix of Nei's genetic distances was calculated from the frequencies of 45 recessive diseases found in the seven districts studied. The average genetic distance calculated for the 45 loci of autosomal recessive diseases was 0.006175 x 10(-3). Similarly, matrix of genetic distances for five Mari populations was obtained (Medvedevskii and Zvenigovskii raions were not included) based on a total of 32 allelic frequencies for ten polymorphic immune and biochemical loci. The average genetic distance calculated from the ten polymorphic loci was 0.001930, i.e., 2.5 orders of magnitude greater than the average genetic distance for recessive diseases. The matrices of genetic distances for the five Mari populations calculated from the gene frequencies for recessive diseases and for the ten polymorphic systems were largely similar to each other. Thus, the main elements of the genetic structure of the Mari population can be estimated on the basis of gene frequencies for hereditary diseases. In this case, the characteristics of individual populations, which are more or less isolated, and of their interaction are the same as in the case of studying genetic structure with the use of polymorphic biological markers.

[The spectrum of spinal muscular atrophies: a population study]. / Spektr spinal'nykh myshechnykh atrofii: populiatsionnoe issledovanie.

A population medical genetic study of spinal muscular atrophies (SMA) was carried out in 1800 individuals in 6 russian and 3 middle asian regions. 33 patients with SMA were ascertained including 29 with autosomal recessive childhood proximal SMA (SMA I-III) and 4 patients with rare SMA types. There were revealed either overlapping of diagnostic criteria of I-III types in some patients or interfamilial differences of types in 3 from 6 familial cases, (one of them with distant relatives affected as well as pronounced clinical genetic variability of rare forms of SMA (all sporadic cases).

[Medico-genetic study of residents of Marii El republic: burden of hereditary diseases in four regions of the republic]. / Mediko-geneticheskoe izuchenie naseleniia respubliki MariI El: gruz nasledstvennykh boleznei v chetyrekh rainakh respubliki.

A medical genetic study of Orshanskii, Morkinskii, Sovetskii, and Semurskii raions (districts) of the Marii El Republic was performed. The total number of subjects examined was 115,743. Meadow Maris and Russians accounted for the most part of the populations of the districts studied. A total of 147 families with presumably autosomal dominant (AD) pathology and 150 families with presumably autosomal recessive (AR) or X-linked pathology (270 and 169 affected persons, respectively) were revealed. Segregation analysis demonstrated a good agreement between the observed and expected segregation frequencies for both AR and AD diseases, as well as a considerable number of sporadic cases of presumably AD diseases. The incidence of hereditary diseases was estimated separately for different population groups. Significant differences in this incidence were revealed between the urban and rural, as well as between the Russian and Mari populations; the average incidence was 2.33 affected subjects per 1000 people. The incidence of AR diseases was significantly higher in Maris than in Russians (1.34 x 10(-3) and 0.82 x 10(-3), respectively). The populations studied exhibited a significant, high correlation between the incidence of AR diseases and the levels of random and local inbreeding. The incidence of X-linked recessive diseases was approximately the same as in Russian populations studied earlier. Its average value was 0.5 per 1000 men; the incidence in the Mari and Russian populations did not differ significantly. The higher AD incidence in the total population studied and the higher AR incidence in the Meadow Mari population compared to the populations studied earlier are discussed.

[Genetico-demographic characteristics of the population from three districts of the Bryansk region]. / Genetiko-demograficheskie osobennosti naseleniia trekh raionov Brianskoi oblasti.

Results of genetic demographic investigation of three nations located in west Bryanskaya oblast (Klintsovskii, Klimovskii, and Starodubskii nations) are presented. A comparison is made with respect to a number of demographic parameters of "southern" (Krasnodar) and "northern" (Kirov) Russian populations. A low level of the Crow index, which is associated with a differential mortality rate, Im = 0.07, was established in the population studied. This fact significantly distinguishes the population of Bryanskaya oblast from other studied Russian populations. With respect to sex and age structure and the Crow index, the Bryansk population is comparable to the southern Krasnodar population, while in terms of level of isolation and inbreeding, the Bryansk population is similar to the northern Kirov population. Moreover, it was found that the Chernobyl meltdown in 1986 did not lead to any change in the genetic demographic situation in the three studied nations.

[Genetic structure and the load of hereditary diseases in five populations of Arkhangel'skaia region]. / Geneticheskaia struktura i gruz nasledstvennykh boleznei v piati populiatsiiakh Arkhangel'skoi oblasti.

A population and medical genetic investigation was performed in a number of raions in the Arkhangel' skaya oblast. Random inbreeding coefficients were 0.000358 and 0.000361 in the Vinogradovskii and Krasnoborskii raions. Malecot's local inbreeding coefficients were 0.000565 and 0.000472, respectively. The endogamy indices were 0.37 and 0.54, respectively. In the urban population, the loads of autosomal dominant, autosomal recessive, and X-linked pathology were 1.01 and 0.98 per 1000 individuals, and 0.29 per 1000 men; in the rural population, they were 1.22, 1.55, and 1.08, respectively. In the populations studied, the hereditary pathology spectrum is described.

[Monogenic hereditary diseases in Gorno-Mariiskii district of Marii El republic]. / Monogennaia nasledstvennaia patologiia v Gorno-Mariiskogo raione respubliki Marii El.

The population of Gornomariiskii raion, Marii El Republic, primarily made up of mountain Marii, was subjected to medical genetic examination. The size of the entire population is 54853. Estimates of hereditary pathology in urban and rural populations of the raion were obtained. They were 0.68 and 1.11, respectively, for autosomal dominant pathology (AD); 0.55 and 0.81 for autosomal recessive pathology (AR); and 0.45 and 0.20 for X-linked pathology. Twenty-two, 25, and six nosologic forms of autosomal dominant, autosomal recessive, and X-linked diseases were revealed, respectively. We attempted to compare the sample under consideration with previously studied Russian and Finnish populations for rare pathologic recessive genes.

[Population genetics of spinal muscular atrophy]. / Populiatsionnaia genetika spinal'nykh myshechnykh atrofii.

A population genetic study of spinal amyotrophy (SMA) in six Russian and three Central Asian regions was carried out. In total, 29 patients with autosomal recessive (AR) infantile proximal SMA (SMA I-III) and four patients with rare SMA forms with an unspecified type of inheritance were revealed. In Russian populations, the prevalence of SMA I-III is similar (1.5-2.5/100000), it is one of the most common hereditary neurological diseases. A tendency toward nonuniform territorial SMA prevalence is observed in genetically subdivided populations. The lesser SMA I-III prevalence in Central Asian populations might be due in part to inbreeding depression. A segregation frequency of 0.21 is in accordance with AR inheritance; the proportion of sporadic cases is 3%. Clinical genealogical data support the genetic unity of forms I-III. The origin of pedigrees with SMA in distant relatives is discussed.

[Hereditary spastic paraplegias: a comparative study of Russian populations]. / Nasledstvennye spasticheskie paraplegii: svranitel'noe issledovanie rossiiskikh populiatsii.

15 families (27 patients) with hereditary spastic paraplegia (HSP) were found in the course of monogenic disorders investigation in 6 Russian populations. High HSP prevalence (7.21+1.61) x 10(-5) was found in Kirov Province [the frequency of the gene of autosomal-dominant form was (3.61 +/- 1.14) x 10(-5), autosomal-recessive-(64.5 +/- 9.74)- 10(-6)]. The pronounced interfamilial polymorphism of HSP was observed. Two families with rare autosomal-recessive variation of "clear" HSP as well as two families with HSP associated with peroneal amyotrophies were revealed. Accumulation of cases with unusual combination of autosomal-dominant HSP together with mental deficiency was remarkable in Kirov Province.

[Population sturcture of the Gorno-Mariiskii region of the Marii El Republic]. / Populiatsionnaia struktura Gorno-Mariiskogo raiona Respubliki Marii El.

The genetic structure of the population of the Gorno-Mariiskii raion, Marii El Republic, was studied. The population consists of two major groups, highland Mari and Russians. The former constitute the majority of the rural population, and the latter, the majority of the urban one. A marked ethnicity-related marriage assortation was found. The value of random inbreeding was estimated using frequencies of surnames. It varied from 0.00015 to 0.00069 (the weighted average was 0.00026). The local inbreeding (a) for Gorno-Mariiskii raion estimated according to Malecot was 0.00029. The local inbreeding for marriages between Mari (0.0022) was five times higher than for marriages between Russians. The indices of endogamy were 0.84 in the rural population and 0.14 in the urban population. The matrix of genetic distances and its image in the form of genetic landscape suggest a regularly distorted isolation by distance and realized panmixia.

[Comparison of several Russian populations by vital statistics and frequency of genes, causing hereditary diseases]. / Sravnenie riada Russkikh populiatsii po vital'nym statistikam i chastotam genov, vyzyvaiushchikh nasledstvennuiu patologiiu.

Distances computed from vital statistics using the Euclid formula and thus termed "vital" are proposed for use in population studies. An example of use of these statistics for comparison of four large geographically separated Russian populations is given.

[Use of an index of migration, indicators for surname diversity, entropy and redundancy for surname distribution in describing the population structure]. / Ispol'zovanie indeksa migratsii, pokazatelia raznoobraziia familii, éntropii i izbytochnosti raspredeleniia familii pri opisanii struktury populiatsii.

The index of migration, the parameter of surname diversity, and the values of entropy and redundancy of the distribution of surnames, proposed by Barrai et al. [1], were determined for populations of Kirovskaya and Kostromskaya oblasts. The relationship of these indices with previously used population characteristics, such as the Wright's F st parameter, the index of endogamy, and the burden of autosomal recessive and autosomal dominant Mendelian pathology, was determined. Further use of these parameters in population genetic research is considered.

[Genetic structure of populations and characteristics of geographic distribution of autosomal recessive diseases in the Kirov region]. / Geneticheskaia struktura populiatsii i osobennosti territorial'nogo raspredeleniia autosomno-retsessivnykh zabolevanii v Kirovskoi oblasti.

The genetic structure of human populations inhabiting Kirov region is described. The effect of genetic drift on geographical distribution of families with autosomal recessive diseases is analyzed. Genetic distances were calculated from frequencies of occurrence of certain family names and frequencies of autosomal recessive genes encoding hereditary diseases. Cluster analysis based on matrices of genetic distances showed that descriptions of the genetic structure obtained using these two methods are in good agreement with one another. It is shown that genetic drift is the principal factor determining the territorial distribution of autosomal recessive genes within population of Kirov region. This conclusion is based on local accumulation of families suffering from autosomal recessive diseases.

[Comparison of the population of the Krasnodar region with other Russian populations regarding genetic and demographic parameters]. / Sravnenie populiatsii Krasnodarskogo kraia s drugimi russkimi populiatsiiami po genetiko-demograficheskim parametram.

The estimates of some genetical and demographical parameters important for populational structure of the population of West part of Krasnodar province are presented. The differences in forming of population structure of districts was revealed. In general, the decrescent type of reproduction, active family planning (average family value is 2.10 +/- 0.07 when average pregnancy quantity is 6.31 +/- 0.32), significant migration activity approached rural populations of Krasnodar district to those of urban type. The migration processes was the main factor of structure population forming. When effort of natural selection was studied the decrease of index Crow was discovered in comparison with rural Russian populations Kirov and Kostroma regions. Population of Krasnodar district approaches to pan-mixture one by genetic and demographic parameters. It can be considered as a gene sample from all regions when Russian live.

[Population genetic study of hereditary motor and sensory neuropathy in the Kirov region]. / Populiatsionno-geneticheskoe issledovanie nasledstvennoi motorno-sensornoi nevropatii v kirovskoi oblasti.

All the cases of hereditary motor and sensory neuropathy (HMSN) in an eastern part of Kirov region (Russian north-east) were ascertained (N = 42 including 11 persons with pre/subclinical forms; m: f = 1). HMSN prevalence is 15.95 +/- 2.47.10(-5) being higher in rural than in urban populations. The distribution of HMSN families (total 16) in 9 districts of the region is uneven. HMSN is the most common of all hereditary muscular disorders in the region. Autosomal dominant inheritance was established in 12 families, AD gene frequency is 10.90 +/- 2.90.10(-5) gene penetrance being 90%. Sporadic cases were few (N = 4; 9.76%). No proven autosomal recessive or X-linked inheritance was found out.

[Structure and variability of hereditary disease in the Kirov Province]. / Struktura i raznoobrazie nasledstvennoi patologii v Kirovskoi oblasti.

The main purpose of this report is to present the nosological spectrum of hereditary diseases in 9 Districts of Kirov Province and to compare it with that studies earlier in other Russian populations. This comparison is undertaken in an attempt to define a "nucleus" of hereditary diseases in the Russian population studied. During this study 343 families with 546 affected were registered. The spectrum covered 55 different autosomal dominant, 14 autosomal recessive and 11 X-linked recessive hereditary disorders in the population under study. Some of these forms could be considered as common forms for the whole Russian population, because they were met in all Russian populations which were analysed. This conclusion is proved by the cluster analysis of genetic distances calculated on the basis of gene frequencies for autosomal recessive hereditary disorders.

[Prevalence of hereditary pathologies in residents of the Kirov Province]. / Otiagoshchennost' naseleniia kirovskoi oblasti nasledstvennoi patologiei.

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.