[Hereditary thrombophilia in children: current views of etiology and pathogenesis].

This review is focused on the role of genetic factors in etiology and pathogenesis of thrombophilia in adults and children. Their knowledge permits to elucidate the main causes of this pathology and choose adequate measures for its prevention.

[Genetic counseling in the Mental Health Research Center of the Russian Academy of Medical Sciences]. / Opyt mediko-geneticheskogo konsul'tirovaniia v Nauchnom tsentre psikhicheskogo zdorov'ia RAMN.

Current concepts on the role of genetic factors in the development of schizophrenia and on the relative risk for this disease and spectrum disorders are reviewed. An analysis of the results of genetic counseling of 120 subjects revealed that, comparing to other mental disorders, patients with schizophrenia or relatives, mostly those having a schizophrenic parent (40%) or spouse (25%), referred more frequently for a consultation. Most of the referrals (70%) had a high educational level. As it was found out during the counseling, up to 20% of the relatives met a diagnosis of psychiatric disorders, mostly personality disorder (9%) and depressive state (7%). Psychological testing with personality inventories revealed a high level of personality abnormalities (schizoid--22%, hyperthymic--16% and obsessive-anxiety--4%) in 43% close relatives of patients seeking medicogenetic advice. The genetic counseling featured by the use of the comprehensive approach, basing on all obtained data (psychiatric, psychological, neurophysiologic etc.), that increases its accuracy and may assist families in taking a reasonable decision in birth planning.

[Polymorphism of serotonin receptor gene 5-HTR2A and schizotypic traits in mentally healthy subjects]. / Polimorfizm gena serotoninovogo retseptora 5-HTR2A i shizotipiceskie cherty lichnosti u psikhicheski zdorovykh lits.

Serotonin receptor type 2 (5-HTR2A) polymorphism was consistently reported to be related to schizophrenia and some clinical presentations of the disease. The present study aimed at searching for association between 5-HTR2A polymorphism and schizotypic personality traits being considered as recognized phenotype predisposing to schizophrenia. Relationship between these features measured by SPQ-74 and two 5-HTR2A polymorphic loci has been studied in mentally healthy community sample (n = 64). Significant difference was found between AG and GG genotype carriers on No-close-friends scale (t = 2.3; p = 0.03), with GG scoring higher on this item. Also, a trend towards higher scores on this scale (p = 0.08) was observed in women, but not in men, with A2A2 genotype. To a certain extent, the results confirm a hypothesis articulated in the study of G-allele and A2-allele relation to interpersonal relationship factor of SPQ-74.

[Immuno-modulating properties of a macrolide antibiotic "Z-factor"]. / Immunomoduliruiushchie svoistva makrolidnogo antibiotika "Zi-faktor".

Zi-Factor is a trade mark of azithromycin made in Russia by ZAO Veropharm. The in vitro modulating action of Zi-Factor (ZF) on neutrophil functional activity and production of immunity mediators was studied. The direct modulating effect of ZF in a concentration of 50 mcg/ml corresponding to the single therapeutic dose of 500 mg/70 kg body weight on the neutrophil oxidase activity evident from increased production of active oxygen and higher myeloperoxidase activity was shown. The immunomodulating effect of ZF on modulation of intracellular oxidative metabolism depended on the initial state of the phagocyte system (secondary insufficiency or activation). When the neutrophil oxidase system is exhausted and there is no response to the antigen stimulus, it is advisable to combine the use of ZF with immunomodulating therapy.

[Retrospective estimation of the frequency of heterozygous beta-thalassemia in the Crimean Tartar population. Formulation of the problem. Estimation of the gametic contribution to a mixed population from frequencies of the ABO blood group genes]. / Retrospektivnaia otsenka chastoty geterozigotnoi beta-talassemii v populiatsii krymskikh tatar. Postanovka problemy. Otsenka velichiny gametnogo vklada v smeshannuiu populiatsiiu po chastotam grupp krovi sistemy ABO.

Polymorphism of the beta-thalassemia gene frequency in non-indigenous populations of Central Asia, especially Crimean Tartars, is often explained by inter-ethnic marriages. The frequencies of these marriages, however, are not sufficient to produce the observed gene frequencies. Because of this, an estimation of the extent of Uzbek gametic contribution to the ethnic group of Crimean Tartar origin was conducted using data on the frequencies of ABO blood group genes. The maximum-likelihood estimate obtained (0.325) was used to determine the heterozygous beta-thalassemia frequency of the ancestral Crimean Tartar population.

[Retrospective estimation of the frequency of heterozygous beta-thalassemia in the Crimean Tatar population. Estimation of gene frequency in the ancestral population based on mixed population data with a known admixture rate]. / Retrospektivnaia otsenka chastoty geterozigotnoi beta-talassemii v populiatsii krymskikh tatar. Otsenka chastoty gena v predkovoi populiatsii po dannym smeshannoi populiatsii pri izvestnoi dole smesheniia.

Results of the maximum-likelihood estimation of heterozygous beta-thalassemia frequency in the Crimean Tartar ancestral population obtained by evaluating the gametic contribution of Uzbeks to the Crimean Tartar ethnic group are presented. The computing algorithm is given, and reliability of the obtained results is discussed.

[A case of prenatal diagnosis of beta-thalassemia by polymerase chain reaction]. / Sluchai prenatal'noi diagnostiki po povodu beta-talassemii na osnove tekhniki polimeraznoi tsepnoi reaktsii.

The prenatal diagnosis of beta-thalassemia in the Udin family, where the parents were the carriers of 2 bp deletion in the codon 8 (-AA) was undertaken using PCR. Five polymorphic restriction endonuclease sites in the beta-globin gene region were tested. They are: 2 HindIII sites in the gamma G and gamma A genes, 2 HincII sites located in the pseudogene and in its 3'-flanking region, and the AvaIII site in the second exon of the beta-globin gene. The heteroduplex analysis was also performed. Two HindIII polymorphic sites were informative and the HincII site in the pseudogene and the AvaII site in the beta-globin gene were partially informative. According to the results of the RFLP analysis, the embryo was heterozygous. The similar result was obtained by heteroduplex analysis.

[Molecular nature of beta-thalassemia in Tajikistan: a four base pair deletion in codons 41-42 of the beta-globin gene]. / Molekuliarnaia priroda beta-talassemii v Tadzhikistane: deletsiia chetyrekh par osnovanii v kodonakh 41-42 beta-globinobogo gena.

Thirty tajiks, whose relatives had beta-thalassemia traits (revealed in previous investigations by determination of the HbA-2 and HbF levels) were selected to screen beta-thalassemia mutations. DNA samples from each individual were subjected to the PCR (polymerase chain reaction) to amplify the 635 bp beta-globin gene fragment. One additional band was detected in three samples after the amplified fragment underwent electrophoresis in 2% agarose gel and the EtBr was stained, and two additional ones were revealed by 6% PAAGE and staining of the EtBr. All additional bands migrated more slowly than appropriate 635 bp fragment. It is supposed that additional bands are heteroduplexes formed from the wild type chains and mutated chains carrying a deletion or insertion. The 4 bp deletion of the 41-42 (-tctt) was detected after the direct sequencing of the amplified fragments. This mutation is common among Chinese but it was not revealed in the Middle Asia populations. The mutation can be easily screened using the PCR and electrophoresis in 2% agarose gel or PAAG of the amplified beta-globin gene fragments.

[Medico-genetic study of the residents of Krasnodar territory. Incidence of hemoglobinopathies]. / Mediko-geneticheskoe izuchenie naseleniia krasnodarskogo kraia. Rasprostranenie gemoglobinopatii.

Data on distribution of various types of hemoglobinopathies in the Krasnodar region are presented. This region was unfavourable, due to malaria in the past. The results obtained allow to conclude that the territory needs more attention as a possible focus of beta-thalassemia in our country.

[Population genetics study of hemoglobinopathies in Uzbekistan. II. Population dynamics of hemoglobinopathies]. / Populiatsionno-geneticheskie issledovaniia gemoglobinopatii v Uzbekistane. Soobshchenie II. Populiatsionnaia dinamika gemoglobinopatii.

It was shown that on comparing variability of selective neutral genetic marker systems with that of the beta-thalassemia system for the populations of different hierarchical level, the relative importance of selection and genetic drift could be evaluated. The genetic differentiation of the beta-thalassemia gene frequencies in elementary populations (villages) could be solely explained by genetic drift. On the other hand, the differentiation of district populations (the sizes of the populations being 10(6] for beta-thalassemia gene frequencies could be explained by selection forces. This is supported by the fact that the genetic distances and FST values are only significant for the beta-thalassemia gene and not for the neutral genetic systems, when the district populations are compared.

[Medico-genetic study of the population of Turkmenia. V. A population and demographic description of the Nokhur isolate]. / Mediko-geneticheskoe izuchenie naseleniia Turkmenii. Soobshchenie V. Populiatsionno-demograficheskoe opisanie izoliata Nokhur.

The paper deals with demographic, genealogical and genetic characterization of one Turkmenian isolate--"Nochur". The data on its load of hereditary diseases were published previously. The Turkmenian "Nochurly" tribe consists of 19 large and small clanes. 600 nuclear families live in a small mountain valley of the same name. The share of prereproductive age class is 60%, of reproductive class--29%, this value for postreproductive class being 11%. The average number of children per family, when the families have completed their reproductive period, is 6.84. The average duration of generation (the mean parental age to the birth time of a mean newborn) is 37.7 and 31 years for a man and woman, respectively. Immigration into Nochur is practically absent, there is a flow of emigrants to the capital of the Republic, Ashkhabad. A very high level of assortative mating has been noted, the minimal estimation of inbreeding coefficient being 0.033 (the pedigree) and the maximal--0.0529 (isonimy). Diminishing of the number of lethal equivalents between 1940-1965 and 1966-1980 was discovered. This can be explained by a decrease in natural selection pressure. The data on distribution of genetic markers of the ABO, MN, Rh, Hp and Pp systems within this isolated population are presented.

[Frequencies of ABO system blood groups and haptoglobins in Uzbekistan. The problems of sampling studies]. / Chastoty grupp krovi sistemy ABO i gaptoglobinov v Uzbekistane. Nekotorye problemy vyborochnykh issledovanii.

The results of the analysis of the distribution of blood group gene frequencies of ABO and haptoglobins (Hp) systems for four regions of Uzbek SSR are presented. Three sources were used for sampling: 1) subtotal population samples in 6 villages (the total of 1839 specimens were assayed for ABO and 1729 for Hp); 2) unselected sampling among school children from some districts (2662 specimens assayed for ABO and 3582 for Hp systems); 3) sampling in 18 955 random philanthropic donors from various districts of Uzbekistan. Estimations of blood group gene frequencies were obtained: for the first source--IO = 0.5291; IA = 0.2529; IB = 0.2180; HpI = 0.2510. For the second source--IO = 0.5549; IA = 0.2434; IB = 0.2017; HpI = 0.2783. For the third source--IO = 0.5614; IA = 0.2404; IB = 0.1982. It was established that the frequencies of O(1) blood group of ABO system were permanently increasing, from the values obtained in subtotally investigated villages (kishlaks) toward sampling among school children and reaching the highest value obtained from the sampling in random philanthropic donors (0.5291 leads to 0.5549 leads to 0.5614). The differences are statistically significant. There is strong evidence that it is important for the sampling to be corresponding to the sex-age distribution of populations studied.

[Population analysis of minor hemoglobin fractions. I. Hemoglobin A2]. / Populiatsionnyi analiz malykh gemoglobinovykh fraktsii. Soobshchenie I. Gemoglobin A2.

The inhabitants of 7 isolated villages (of different nationalities) and of 5 panmictic populations were studied. Populational and segregation analyses of Hb A2 in 3036 normal and 150 heterozygous individuals for beta- and delta beta-thalassemia were carried out. The Hb A2 levels in some populations are established to deviate from the normal distribution. Bimodal dependency of the levels of Hb A2 distribution is demonstrated, which suggests the existance of heterogenous subpopulations by the Hb A2 level. The segregation analysis has revealed distinct genetic determination of Hb A2 levels. There was a good correlation between Hb A2 and Hb F values (r=-0.82).

[Medical genetic study of the population of Uzbekistan. V. The frequency of heterozygous beta-thalassemia in 4 kishlaks of Urgut District, Samarkand Province]. / Mediko-geneticheskoe izuchenie naseleniia Uzbekistana. Soobshchenie V. Chastota geterozigotnoi beta-talassemii v chetyrekh kishlakakh Ugutskogo raiona Samarkandskoi oblasti.

A subject of this investigation is the results of the subtotal examination of 4 villages for the detection of heterozygous beta-thalassemic carriers. 848 persons (55.5% of the registered population) have been examined. The mean frequency of the beta-Th gene was 0.0159, FST-Wahlund--0.00975. Statistically significant differences in the gene frequencies between villages have been revealed (p less than 0.01). The study of genetic distances (by Edwards) has revealed no intertribe differences in gene frequencies. The comparison of findings of the present study with other similar investigations enabled to account for the detected differences in the frequencies of beta-thalassemia as a result of the genetic drift. The importance of choosing populations for the study and methods for detection heterozygous beta-thalassemia are discussed.

[Medico-genetic study of the population of the Samarkand region. II. Population-genetic description of 4 kishlaks of the Urgut district]. / Mediko-geneticheskoe izuchenie naseleniia Samarkandskoi oblasti. Soobshchenie II. Populiatsionno-geneticheskoe opisanie chetyrekh kishlakov Urgutskogo raiona.

This report is a second one in a series of works devoted to the medico-genetical screening of Uzbekistan populations. The paper comprises the results of the analysis of the populational structure of one of the village councils (soviets) of the Urgut District of the Samarkand Region. The main parameters of the population studied were as follows: total number 1529 persons, the average number of inhabitants of one village--328. The proportion of the inhabitants studied--56%, the average number of persons per family--5.22; the average period between subsequent generations--30-35 years, the gametic index--0.8, the inbreeding coefficient inferred from pedigrees--0.018899--0.00781, Fst = 0.03577, the average genetic distanse according to Edwards--0.0231-0.0671. The distribution of Mendelian markers (ABO, Rh, Hp and Ptc) was studied. The observed ratio between a high degree of inbreeding and a relatively low extent of isolation of populations permits to explain satisfactorily the distribution and frequencies of hereditary pathology in the Urgut District of the Samarkand Region pointed out in the previous report.