Topicality and demand of the subject of dissertation. Bronchial asthma (BA) is one of the most common and serious diseases, which in the world suffer from 3 to 12% of the child population of the globe. Proportion of adolescents with asthma, is one third of all children with this disease. High prevalence of asthma in the numbers of teenagers, characteristics of the disease, age-related aspects of the functioning of the endocrine and immune systems of teenagers that cause difficulties which arise in the course of the diagnostic process, highlight the need to find innovative approaches to diagnosis and treatment of this disease.
It is known that the key immune mechanisms in the pathogenesis of the vast majority of AD cases is real and indisputable fact. Currently, considerable interest to researchers involved in the pathogenesis of positions of allergic diseases, especially asthma, along with IL-4 and IL-13 causes a number of other (IL-6, IL-8, IL-10, IL-5, INF-a and INF-y) immunoregulatory cytokines.
Genetic predisposition plays an important role in the development of allergic diseases. Currently available data on the relationship with asthma and associated with disease symptoms polymorphism approximately 150 genes. Important role as the main contender for the predisposition to asthma gene is a gene encoding flchain of high affinity receptor IgE. Interaction elevated levels of antigen-specific IgE with FceRip plays a central role in the pathogenesis of allergic asthma. Particularly attractive candidate gene asthma is also one of the enzyme genes biotransformation - GSTirl, encoding glutathione S-transferase and л1 express almost exclusively in the pulmonary tissue. This gene is located at the locus 11 ql 3, for which repeatedly shown clutch with atopic symptoms. Accumulated in the literature say about the relationship of gene polymorphism FceRI, GSTnl with different allergic diseases.
From this perspective, the study of immunological and genetic mechanisms of the pathogenesis of this disease for the construction of rational treatment and prevention emphasizes the relevance of this thesis research.
From the earliest days of independence, the country has successfully implemented state programs aimed at reforming the health care system. As a result, the targeted implementation of organizational health and research activities aimed at effective diagnosis, prevention and treatment of asthma among adolescents, with some success in the treatment of this disease in the country. However, now the problem of early diagnosis and the development of effective programs for treatment and prevention among adolescents with asthma remain one of the most important issues of modern health care. This research work was carried out in the framework of the tasks set by the Resolution of the Cabinet of Ministers of the Republic of Uzbekistan "On additional measures to improve the health of women and the younger generation," dated 25.01.2002 for the №32. In this regard, the need to deepen the information received about the state of cellular and humoral immunity among adolescents, asking pathogenetic informative immunogcnctic studies in asthma arc one of the important criteria demand the dissertation topic.
Purpose of research is study the immunological and genetic mechanisms of the pathogenesis of asthma in adolescents and form the basis of this plan rational diagnostic and therapeutic measures in this pathology.
In To achieve this goal the following tasks of research is solved:
to establish the clinical course of asthma in the population of adolescents living in the Samarkand region, in the early stages of the pathological process in the bronchopulmonary system.
explore the features of the state of cellular and humoral immunity, as well as activation markers in asthma in adolescence by determining the immunophenotype of lymphocytes in the peripheral blood.
to examine the level of production of immunorcgulatory cytokine interleukin-6 and interfcron-y and install them pathogenetic informative in asthma among adolescents.
to determine the features of distribution of allele and genotype frequencies of polymorphic variants of genes and FceRip GSTnl population Uzbek people with asthma, compared with the healthy part of the population.
examine the clinical and immunological aspects effectiveness of therapies using drugs and polioksidony tsikloferon in patients with asthma in adolescence.
on the basis of studies to develop a multivariate model of formation of bronchial asthma and develop an optimal algorithm for the diagnosis, treatment, prevention in adolescents with this pathological condition.
Scientific novelty of dissertational research consists in the following:
proposed introduction to the work of doctors teen clinics layered approach testing can significantly improve the detection rate of asthma in adolescence and optimize treatment and preventive measures in high-risk groups;
first defined the peculiar characteristics of the quantitative parameters of the immune status of patients with asthma in the cohort of adolescence and the corresponding proposed regulations and guidance documents for the healthy part of the adolescent population;
for the first time presents a comprehensive assessment of the cytokine profile of blood serum in bronchial asthma in adolescents. Specific features of products immunorcgulatory cytokines IL-6 and INF-y and their pathogenetic and regulatory information content in asthma among adolescents;
first analyzed the distribution of alleles and genotypes of polymorphic gene variants and gene FceRip GSTirl among patients with different phenotypic variants of AD and healthy individuals of Uzbek nationality, which resulted in the identified markers of increased risk or, conversely, resistance to the development of asthma in adolescents Uzbek ethnicity;
algorithms for phase diagnosis, treatment and prevention of asthma in adolescence in terms of disclosure of important moments of the pathogenesis of the disease, allowing to build a rational sequence of diagnostic search, aimed at verifying the diagnosis and expedient construction of preventive measures.
Conclusion
1. Set the frequency of occurrence of the disease and the structure of "asthma" in the arid zone among teens. Said pathology is recorded in 9,6% of the population surveyed adolescents, while the disease is more common among females. In the structure of the disease prevails periodical exposure and mild persistent form.
2. Identified by clinical features of asthma among adolescents living in the arid zone, indicate a high frequency of lesions of the bronchial tree association with allergic processes in other organs and tissues: in 73,9% of the AR, 53,7% with AK. 16,6% with BA and 14% with urticaria/angiocdcma.
3. Found that in the study population of patients with asthma adolescence occur expressed disturbances of the immune status, manifested deficit indicators as cell (CD3‘, CD4+, CD8 , CD16+), and humoral immunity (CD19 , IgA, IgG, IgM) and activation markers (CD23+, CD95). The immune status of patients with asthma in young people, adolescence has distinctive features, the depth of detected violations immunoreactivity was most pronounced in the younger age group.
4. In patients with bronchial asthma in adolescence revealed distinct changes in cell-cell interactions in the immune system: a significant increase in the content of Th2-cclls secreted IL-6 is a regulator of maturation of antibodies and immunoglobulin production itself, and vice versa reducing regulator activity of Th 1-cell cytokine INF-y.
5. It was found that the contents of cytokines IL-6, INF-y and in the peripheral blood is in communication with one pathogenic disease. It is shown that the lowest level of INF-y production in the scrum is characteristic of allergic clinical pathogenic variant asthma in adolescence. Adolescents suffering from predominantly infectious form of asthma, there is a sharp trend towards increased production of IL-6 in peripheral blood.
6. Revealed that markers of increased risk of allergic forms of asthma in adolescents Uzbek ethnicity arc genotype FceRip-109T/T allele FceRip-109T, low-risk markers - FcsRip-109C/C and allele Fc£Rip-109C. A high degree of cohesion genotype FcsRip-109T/T allele and FcsRip-109T with hereditary burden of asthma in the Uzbek population.
7. Among females ethnic Uzbek Association revealed lie-105 allele and genotype Ilc-105/Ilc-105 polymorphic gene locus GSTkI at high risk for asthma. Revealed that the genotype associated with the development Ilc-105/Ilc-105 allergic form of asthma in adolescents Uzbek population.
8. Complex therapy with adolescents’ patients with asthma ciklofcron and polyoxidonium, providing immunocorrective effect, enhances the clinical efficacy of basic therapy. In the study of prophylactic efficacy of immunomodulators positive indicators prevailed in the group of patients receiving polioksidony, necessitating its inclusion in the priority scheme of integrated treatment and prevention of asthma in adolescents.
Objective: to study the role of the rs1799883 polymorphism of the FABP2 gene in the pathogenesis of gallstone disease in combination with MS. Material and methods. Molecular genetic studies were carried out in the Department of Molecular Medicine and Cell Technologies of the RSNPMC Hematology.
The analysis of the associations of the rs1799883 polymorphisms of the FABP2 gene was carried out using a case-control model.
The main group consisted of 118 patients with cholelithiasis in combination with MS living in the Khorezm region.
Results: As a result of our research, we identified a significant association of the homozygous genotype for the Thr allele with the development of gallstone disease in combination with MS. The indicator of the ratio of the chances of developing gallstone disease in combination with MS in carriers of this genotype was OR = 2.9 at 95% CI: 1.122- 7.424. The relative risk of disease was RR = 2.5 with 95% CI: 1.11-5.76.
Conclusion: Our results allow us to conclude that the homozygous Thr/Thr genotype plays an important role in the formation of gallstone disease and obesity in people of Uzbek nationality.
Topicality and demand of the subject of dissertation. Researches of human population genomic variety and scenarios of its genetic pool formation arc one of perspective directions of modem genetics. Prompt progress in this field has allowed defining the basic routes of continents settlement. However the information about Central Asian (CA) populations even on «classical» genetic markers has accidental, fragmentary character, and requires additional large-scale investigations. Besides, according to historical, archeological, paleontological and some anthropogenetic studies, given region was playing certain role in ancient moving of modem human ancestors throughout Eurasian continent. Therefore it is extremely important to summarize and perform complex assessment of new and collected data on Central Asian populations as practically there arc no multivariate analyses studies of given region as a complex population system.
In studies of human population genetic structure arc usually used various approaches allowing understanding concept of populations subdivision and character of genetic relationships between them. Among these techniques the prominent place belongs to approaches based on an assessment of genetic distances between populations with their subsequent analysis by multivariate statistics methods. For even more compelling picture of the relationships between the populations on tree diagram we composed «the genetic landscape» of area, where the description of population genetic structure is presented by equally spaced figures consistently consolidating populations according to their genetic distances from each other and thus creating a genetic landscape. This approach is not only a tool for elementary population boundary detection, but also can be effectively used for identification of borders and sizes of population as naturalistic unit.
Multigcnctic landscape is a collection of different genetic systems which arc specific to the region and ethnic groups, which have their geographical areas, their geographical, historical and cultural boundaries. Gene flows arc run through these conventional boundaries, but they arc less intense than in the limits of area. These limits arc ambiguous and fluid, but it is real. You can identify them by studying, for example, the structure of marriage migration. Therefore anthropogenesis of different populations will inevitably differ from each other. Ethnogenetic composition tends to change over time, from generation to generation, and hence there is a need to understand the structure of the genepool, not only at a given time, but also in the study of genetic processes that form and reform the gcncpooL In this regard, the studying of multigcnctic landscapes is in close contact with the demographics, medical and genetic ecology, anthropology, ethnology, archeology and history of the peoples, that is, with a range of areas, not only natural, but also the humanities knowleges.
Study of genomic diversity is important not only to address questions of origin and genetic history of different ethnic groups, but is also the basis for molecular epidemiology of hereditary and multifactor diseases. Each region is characterized by a specific set of common genetically determined diseases. To understand the causes of the prevalence of disease in different regions, and to develop approaches to their early DNA diagnosis and effective prevention, initially it is necessary to conduct population-based studies, which determine the development of the disease.
Purpose of research is to implement a comprehensive description of the structure of indigenous Central Asian populations genetic pool, examine demographic, phylogenetic and evolutionary features of Central Asian populations through the analysis of genetic variety of mtDNA, Y-chromosomal (NRY), autosomal, X-chromosomal microsatcllites and immunogcnetic variants of Helicobacter pylori (H.pylori) and hepatitis В virus (HB V).
To achieve this goal the following tasks of research is solved:
specification of immunogcnetic variants of H.pylori and HBV, allocated at the patients in Central Asian region, with the subsequent comparative phylogenetic analysis of H.pylori and HBV regional versions with those in other regions of the world;
examination of genetic variety and degree of genetic differentiation of Central Asian populations according to classical population-genetic objects -polymorphisms of mtDNA, Y-chromosomal, autosomal and X- chromosomal STRs;
assessment of the Western and East-Eurasian lines of population inheritance contribution to Central Asian populations’ genetic pool at regional, ethnic, sub-cthnic levels and in a level of elementary populations;
reviewing of character of regional populations relationships by genetic variety of mtDNA, autosomal, X-chromosomal, Y-chromosomal STRs markers in view of ethnographic, social and linguistic data;
evaluation of sex-specific genetic structure and the social organization according to polymorphisms of mtDNA, autosomal, X-chromosomal, Y-chromosomal markers in the region;
determination of ancient ways of migrations and scripts of formation of Central Asian populations according to mtDNA, autosomal, X-chromosomal, Y-chromosomal STRs markers and immunogcnetic variants of H.pylori and HBV',
evaluation of ethnogenetic position of studied Central Asian populations in the system of genetic pools of Eurasia and the world in general through comparative analysis of all studied population-genetic parameters.
Scientific novelty of dissertational research consists in the following:
for the first time was performed a study of genetic pool structure of 26 Central Asian populations from 6 ethnic groups as complete population systems using a wide range of genetic objects;
for the first time was made an assessment of informativeness of each type of genetic subjects. For the first time was received detailed characteristic of genetic pool structure of indigenous Central Asian population on the basis of variability lines of the spectrum of genetical objects;
for the first time was defined the ratio of Westem-and the East-Eurasian lines in a genepool of Central Asian population and were made an assessments of genetic variety level and genetic differentiation degree of regional populations as a whole;
for the first time phylogenetic analysis of major haplogroups of investigated genetic subjects was conducted;
for the first time the position of Central Asian population in population genetic pool system of surrounding regions and Eurasia in the whole was studied;
for the first time the evolutionary-adaptable mechanisms, necessary in the forecast of formations of multigenic pathologies in region were studied at 6 ethnoses of Central Asian.
CONCLUSION
1. H.pylori from Central Asian territory is similar to Western Europe isolates, and shaped by two ancestral populations genotype Ancestral Europe 1 (dominant) and Ancestral Europe2 and for AE1-genotype Central Asian region probably is the source. H.pylori from the territory of Central Asia form a separate cluster group: close relationship of Tadjik, Uzbek strains and Iranian isolates from the north of Iran is established. Kirghiz isolates were found to be closer to populations from territory of Siberia.
2. High diversity of HBV genotypes in Central Asia was found -4 genotypes (A, C, D, and G). Phylogenetic analysis of Central Asian genotype HBV-with options for other regions of the world showed a close relationship between the dominant genotype D (0,78), the D1-subtype with variants of the virus in Europe, the Middle East and Africa.
3. The rates of genetic affinity for STR-NRY in Kazakhs, Turkmens, Karakalpaks Turtkul at the level of the same lineage were high: 0,58 (p<0,001); 0,34 (p<0,01) and 0,77 (p<0,001), respectively. The coefficients of relationship at the level of clan for Kazakhs, Turkmens, Uzbeks and Karakalpaks from Kungrad and Turtkul were lower: 0,30 (r<0,01); 0,21 (p<0,001) and 0,40 (r<0,001); 0,07 (p<0,05) and 0,09 (p<0,05), respectively. At the level of the tribe, the indicators were negative for all Turkic populations: -0,02 (r<0,05);-0,04 (r<0,001);-0,07 (p<0,01); -0,0011 (r<0,1) and -0,10 (r<0,01), respectively.
4. The analysis of mtDNA HVS-1 showed that total rate of differentiation level for all populations was low: FST=0,013; p<0,0001. Level of diversity between groups was 0,6% (p<0,001) of the total variability. Parameter of genetic differences between Turkic and Indo-Iranian populations made 0,55% (p<0,0283) of the total genetic variability. The rate of genetic differentiation on a sub-ethnic level was significantly expressed in Indo-Iranian group (FST=0,0197;r<0,001) than among the Turkic-speaking (0,3%; p=0,10). In all populations, in general, wasn‟t detected the correlation between genetic and geographic distances at the global level on mtDNA HVS-1: r=0,00682; p=0,502.
5. Analysis of STR-NRY showed that the level of the genetic differentiation between ethnic groups was 5,6% (p<0,02); general differentiation between populations made RST=0,186 (p<0,001). Combined analysis, taking into account the language and way of life of Turkic and Indo Iranian populations, showed the general differences between the two groups – 9,1% Value of genetic differentiation when comparing the ethnos-ethnos was slightly lower than the level within ethnos: 5,6% among ethnic groups, 18,6%, and 13,7%-between populations within the ethnic group.
6. Analysis of heterozygosity (H) and the average number of pairwise differences (p) of mtDNA, were high in nomadic populations (av.H=0,99; av.p=5,29) and farmer populations (av.H=0,99; av.p=5,32). Heterozygosity (H) on Y- chromosome was lower in nomadic groups than in the agrarian – 0,86 and 0,99,respectively (p<0,01). Nomadic populations exhibit a higher level of population differentiation (RST) in comparison with farmers - 0,19 and 0,06, respectively (p<0,01). Indicators of population growth (r) were lower in nomadic populations compared with farmers - 1,004 and 1,008, respectively (p=0,056).
7. The level of genetic differentiation in all ethnic groups was higher on the Y chromosome in comparison with mtDNA. The farming populations showed no significant difference in the genetic differentiation FST (Y)=0,069 and FST (mtDNA)=0,034, while among patrilineal nomadic population the level of genetic diversity was higher in the male line of inheritance - FST(Y)=0,177 and FST (mtDNA)=0,010. Genetic diversity of population structure in patrilineal nomads on autosomal and X-linked markers were: FST (A)=0,008 (0,006-0,010) and FST (X)=0,011 (0,001-0,004) (H0: FST(A)=FST(X); H1: FST(A)>FST(X); p=0,02). In bilinear farmer populations the differences of autosomal and X-chromosomal markers were insignificant: FST (A)=0,014 (0,012-0,016) and FST (X)=0,013 (0,008-0,018 at p=0,36).
8. Analysis of mtDNA indicated that the age of expansion on the territory of Eurasia (τw) declined significantly from East to West (r=0,72; p<0,001). The age of expansion had a pronounced tendency to decrease from 30 thousand years in China to 17 thousand years in Western Europe. Age of expansion in Central Asia amounted to 26 thousand years. Results of expansion analysis on NRY also show a decrease in genetic diversity from the East to the West of Eurasia (r=0,49; p<0,001). In Central Asia this age was 16 thousand yrs. According STRs-NRYBatwing analysis of the minimal age of Uzbek population origin was 1232,71 yrs old (Ne=14088 (6765-23942); α=0,0108 (0,0065-0,0155)).
9. The apportionment of multilocus genetic variations among ethnic and linguistic groups of Central Asian populations showed that more than 98% of all variations were within the population (p<0,0001). Evaluation of the ethnic and linguistic affiliations in the observed variations showed reliable conformity - FST=0,007; p<0,0001 and FST=0,011; p<0,0001, respectively. We didn‟t find evidence of geographical isolation within each of the Turkic and Indo Iranian groups of populations (p=0,363 and p=0,772, respectively).
10. Analysis of multilocus allelic diversity (AR) and heterozygosity (He) showed differences among the Central Asian and other populations in allelic variety (χ2 =105,29; d.f.=25; p<0,0001) and heterozygosity (χ2=67,98; d.f.=25; p<0,0001). Population differentiation at multilocus analysis at populations of Central Asia is more pronounced than in the other regions of Eurasia: in European and Middle Eastern groups pairwise estimation of FST ranged from 0,011 to 0,015 and -0,008-0,021, respectively; in East-Asian groups from -0,011 to 0,046; and finally, in Central Asia these rates ranged from -0,004 to 0,056. Heterozygosity was significantly higher in the group of the Indo-Iranian populations than among Turkic-speaking (He=0,818 and He=0,787, respectively; Z=-4, 55; p<0,0001). According to multilocus analysis all 26 Central Asian populations slightly but significantly differed (FST=0,015; CI99%=0,011-0,018; p<0,01).
Viral hepatitis C (HCV) is one of the most important problems of modern medicine. According to WHO statistics, there are between 500 and 700 million HCV carriers worldwide. The aim of the study was to study the clinical and immunological features of the course of chronic viral hepatitis C, depending on the genotype of the virus, and to assess the diagnostic and prognostic value of immunological disorders. The clinical and laboratory features of the course of chronic viral hepatitis C depending on the genotype of the virus, the immunological features of the course of chronic viral hepatitis C depending on the genotype of the virus were studied, the diagnostic and prognostic value of immunological indicators as objective criteria for assessing the severity of the disease and the prognosis of the disease was determined. We examined 83 patients with chronic viral hepatitis, 35-50 years old with chronic viral hepatitis C, and 20 practically healthy individuals of the same age and gender.
Early diagnosis of Myeloproliferative diseases (MPD) is one of the serious problems of oncohematological practice. MPD efers to multifactorial diseases, the development of which is influenced by both environmental factors and genetic predisposition. The study studied the association of the carriage of the genotype for the polymorphic marker encoding glycoprotein-P and the development of MPD. The homozygous T / T genotype of the rs1045642 polymorphism of the MDR1 gene is a significant determinant of the increased risk of developing MPD in Uzbekistan (P<0.05). Conclusion. Genotype association the rs1045642 polymorphism of the MDR1 gene is associated with the risk of developing MPD.
Topicality and demand of the subject of dissertation. Various techniques of hybridization arc used in crop breeding, including cotton to produce a wide variability in agronomical valuable traits and develop new forms.
Regardless of its implementation hybridization process leads heredity decoding which allow the new plastic genotypes formation with an ability to change and adapt to the new conditions. Hybridization and selection arc considered as a main synthetic method of new varieties development and a success in this largely depends on the choice of crosses method and genotypes of initial forms. Therefore, there is given a special attention for studying the genetic basis and improving of hybridization methods. However, based on the most widely used of hybridization methods arc not always possible to develop varieties having high parameters of composite agronomical traits. Many developed varieties as a result of breeding methods arc genetically become homogeneous, which leads to a reduction of genetic variation and increasing of risk of cpiphytoty outbreaks and decreasing of total productivity (Boroycvich, 1981). Therefore, it is necessary to increase the genetic variability of crops’ agronomic traits by involving of original forms, as well as wild relatives of crops with genetic resistance to various stress factors, diseases and pests.
In increase cotton production through the creation of early maturing, high-yielding having good fiber yield and quality, resistant to various diseases, pests and stress factors, as well as with low level or toxic gossypol in cotton seeds still remain as critical problem in cotton production.
To overcome these problems there need to improving of genetic basis for assessment of existing donors and through the use of various hybridization methods to create new enriched genotypes, promoting positive recombination of polygene in hybrid’ organism for use in applied cotton breeding. Based on the above stated, the study of the genetic aspects of various methods of remote composite intraspecific and interspecific hybridization, based on the comparative evaluation of the effectiveness in order to isolate valuable recombinants and transgressive forms having new genetic variability of traits arc important both scientific and practical point of view.
The dissertation meets the objectives as set out in the Lows of Uzbekistan «On Seed Production» of December by 21, 2007 and «On Breeding achievements» by August 21, 2002 directed to developing and introduction of high-yielding cotton varieties, with a good yield and fiber quality, tolerance to various factors, as well as improving seed production.
Purpose of researches is comparative study of effectiveness of the various methods of intraspecific composite, convergent and inter-specific (3 to 5 species) hybridization revealing the nature of inheritance, form shaping and transgressive variation of traits, total and (+)-gossypol in creation of genetically enriched breeding material and for using in the applied cotton breeding.
Scientific novelty of the dissertation research is follows:
in the system of topcrosscs there used genetic evaluation for combining ability of main agronomic traits cotton varieties with different origins for further using in intraspecific composite and convergent hybridizations;
there established principally dominant inheritance and overdominance type of inheritance (with deviation toward the initial forms with the high agronomic traits) in F| at composite intra-and interspecific hybridization which genetically distinct accessions from the local and foreign selection and wide transgressive variability in F2-F3, facilitating to efficient selection of valuable recombinants;
first identified the inheritance nature and variability of total and (+)-gossypol in the cotton hybrids’ generative parts, developed by involving of American accessions with high (+)- gossypol and local varieties, as well as their correlation with some agronomical valuable traits;
first there held comparative study of economic traits at the different forms of amphidiploid G.thurheri x G.raimondii K-58 (hirsutum type) and K-59 (type harhadense) for free reproduction and after crossing the cultural forms of G.hirsutum L. species, it was established a wide range of variation of agronomic traits at mutant form of K-59 and composite hybrids, derived from it’s participation as compared to K-58 amphidiploid and it’s composite hybrids. It was found out those two types (type G.hirsutum K-58 and type G.harhadense K-59) of amphidiploid G.thurheri x G.raimondii at the free reproduction exhibits similarities with the both cultural tctraploid species; G.hirsutum L. and G.harhadense L., respectively. When they crossed with the cultivated G.hirsutum L. species these amphidiploid forms also behave as natural tctraploids;
it is revealed that, at the composite hybrids produced with the participation of the both forms of amphidiploid (K-58 and K-59) G.thurheri Tod. x G.raimondii Ulhr., as a result of transgressive variation, there is a disturbance of negative correlations between such traits as yield and fiber length, fineness and boll numbers conducive to positive recombinants emergence and increase donor opportunities of amphidiploids;
by comparative study of different methods of remote intra-and interspecific hybridization revealed the genetic nature of inheritance nature and variation degree of the main agronomic traits in composite hybrids, as well as their effectiveness in allocating recombinants having a new genetic variability of traits;
it is revealed that the possibility of breaking some negatively correlated traits by different methods of composite intra-and interspecific hybridization and selection of recombinants combining early maturity and high productivity, high fiber output with its quality and 1000 seed weight, etc.;
it is confirmed that the effectiveness of used methods such as a composite intraspecific and interspecific crosses, to increase positive transgressive variation and segregation genetically enriched recombinants having new combination of high levels of positive parameters of agronomic traits that were recommended and used to develop valuable initial material and new cotton varieties;
the obtained theoretical data on inheritance nature, hcritability and agronomic traits morphogenesis, levels of total and (+)-gossypol and their correlation with other agronomical valuable traits at developed hybrids could be successfully used in the field of fundamental research, and created unique hybrids, forms, progenies, lines and varieties could be used in applied cotton breeding.
Conclusion
1. There obtained and identified on comparative study base of intraspecific composed and converged hybrids with participation of six registered medium staple cotton cultivars in topcross system and high effects of GCA on the following traits:
«50%-cmcrgcncy-50 % flowering» Yulduz (-0.71); Tashkent-6 (-0.39) and in S-9070 (-0.38); “50% cmcrgcncy-50% maturing” S-9070 (-1.43), and in
Tashkent- 6 (-0.91); one boll weight S-6532 (+ 0.11); 1000 seeds weight S-9070 (+0.51); on productivity Tashkent-6 (+5,28), S-4911 (+4,04) and S-9070 (+2 24); fiber output S-6532 (+1,29); fiber length S-4911 (+0,70) and S-6532 (+0,48); fiber strength S-6532 (+1,57) and S-4911 (+0,91); micronairc S-6532 (+0,24) and Ak-Darya-6 (+0.24). These donors of high valuable traits were used by us for improving of the recurrent varieties by composite and convcrcgcnt hybridization. It was found that involvement of the varieties with a high GCA in convergent hybridization allows improving of the recurrent varieties and developing of a new initial material for cotton breeding:
inheritance nature and variability degree of agronomic traits at intraspecific composite and convergent cotton hybrids revealed the relative efficiency of the studied hybridization techniques during elaboration of new initial material with enriched genotypes of agronomic traits, and recommended to use in geneticselection process;
convergent hybrids F i dominated by early maturity, in terms of productivity and fiber output occurcd overall effect of overdominance, and F2-F3 appeared as positive transgressive forms;
significant effect of the genotype of the parental forms involved in hybridization on the inheritance nature of fiber quality (length, micronairc, strength) had convergent hybrids Fj, as well as their level of recombination in F2-F3 indicating the need for breeding of recombinants on these traits in early generations, taking into account genotype of initial forms;
the inheritance of the wilt tolcrancccs bccamcs not only depending on the pathogen load in soil fungus infections, but also depends on the used hybridization methods. Thus, most high resistance, i.c. negative superdominance on wilt tolerance observed in convergent hybrids F, and F2;
the direction and strength of correlation between the studied traits in intraspecific composite and convergent hybrids varied in depending on crosses type and from genotype of recurrent varieties. At present ease, the greatest number of recombinants with positive combination of high indicator traits which determining fiber quality, as well as its output, length, observed with with composite, particularly with convergent hybridization.
2. For the first time, on the basis of studies on determination the percentage of (+)- gossypol in seeds of genetically different cultivars of Uzbek cotton selection and analysis of variability, inheritance degree of total and (+)-gossypol in the environmentally and genetically remote hybrids and their correlations with economically valuable traits was proved:
the cultivars S-6524, S-6530 and S-6532 which were elaborated involving subspccic of G.ssp.punctatum had the highest level of (+)- gossypol and the «Turon» cultivar which was developed by composite hybridization has a low indicator of the current trait and relatively high level of total gossypol in seeds;
It was determined intermediate inheritance level of (+)- gossypol in the petals and seeds in F| hybrids and wide positive and negative transgressive variability in Ғ2-Ғ3. It was proved that the efficiency of plant selection with high (+)- gossypol in seeds since F2, that confirmed with segregation of constant progenies and lines on trait basis in F4 hybrids;
as a result of research the cross-correlation total and ( +)- gossypol and some agranomically valuable traits was found that between the ( +)- gossypol in the petals and seed exists a weak correlation. The data on correlations of studied traits showed an independent genetic control of (+)-gossypol in the generative organs and independent inheritance of them at cco- geographically and genetically remote hybridization.
3. For the first time, based on comparative study of agronomic traits of amphidiploid G.thurheri Tod. x G.raimondii Ulbr. two forms (hirsitum type -K-58 and harhadense type -K-59) and hybrids derived from G.hirsutum L. varieties revealed:
both studied forms of hirsutum type and harhadense type of amphidiploid G.thurheri Tod. x G.raimondii Ulbr., being functional diploids provided wide combinative variability in the progeny from the free reproduction and crossing with the cultivars of tetrapioid G.hirsutum L., and showed their similarity to G.hirsutum L. and G.harhadense L. tctraploid species, respectively;
as a result of the research a group of unique composite hybrids (F\G.thurherii Tod. x G.raimondii Ulbr.) x G.hirsutum L. confirmed unlimited transgressive variation as the basis of a new form revealing, new gene pool developing for use in applied cotton breeding. Herewith, at bud mutant K-59 observed emergence of phenotypes with higher variability for most agronomic traits compared to K-58;
it was found out that in composite hybrids which obtained by crossing of studied forms of G. thurberi Tod. x G. raimondii Ulbr. amphidiploids (2n=52) and with G.hirsutum L. cultivars were observed relatively rapid improvement on productivity and its components in comparison with freely propagated amphidiploids offspring. Herewith, composite hybrids involving K-58 on boll number in all generations was slower comparied to hybrids derived from K-59;
composite hybrids F, obtained involving two cultivars of cultivated forms on fiber output and length were observed deviation toward the parent with the best expression of the trait. It was revealed that the fiber output and length of the studied composite hybrids susceptible to less variability compared in terms productivity and its components. Relatively high variation was manifested on fiber output in F2, and on fiber length in F2-F3. In freely multiplying offspring of K-59 and its hybrids with varieties in F3 was observed the derivations of more long staple plants compared with hybrids, developed involving K- 58;
free propagating amphidiploids’ offsprings and composite hybrids selected by using of cultural forms showed the least wilt susceptibility compared with the control. Wilt resistance of barbadense type K-59 progenies from the free breeding was higher as compared than offspring of K-58, and higher in composite hybrids F2-F4, obtained involving K-59.
4. Under the general principle of correlation relationships among the studied hybrids were found that composite hybrids F2 amphidiploids’ G.thurberi Tod x G.raimondii Ulbr., both types (K-58 and K-59) with a G.hirsutum L. type Acala sj-5 cultivar showed mainly low positive and negative correlation coefficient values, which in most eases were none significant. In hybrid combination of K-58 x Andijan-60 fiber output and length correlated positively;
5. Based on comparative study of inheritance and variation of agronomic traits in developed 4 genomic [(G.thurberi Tod. X G.raimondii Ulbr.) X G.arhoreum L.] x G.hirsutum L., 5 - genome [(F|K-28 x S-6524 ) x G.harhadense L. hybrids and their backcross hybrids were proved:
the possibility of broad transgress variation and creation genetically enriched recombinants on unique traits;
efficiency of backcrosscs among the composite interspecific earlier generation hybrids for rapid improvement and stabilization of eultuvated forms of cotton;
wide transgress variability presence in 4 and 5 species composite hybrids and their backcross hybrids on productivity and its components starting with F|. In particular, it was confirmed the effectiveness of five species hybridization to increase the boll numbers per plant, boll weight and weight of 1000 seeds at 4 and 5 species and backcrosscs hybridization.
by obtaining recombinants having fiber output 43,1-45,0%, fiber length - 40 mm and above, micronairc of fiber 3.9-4.5 and wilt tolerance it was confirmed the effectiveness of introgressive and transgressive breeding at composite 4-5 species hybridization and their backcross hybrids.
6. As a result of studies of correlations in composite 4-5 species and backcrosscs hybridization of F2 hybrids it was revealed the effectiveness of used methods in interruption of such negatively correlated traits as «fiber output» and «fiber length» from medium positive (r=+0,39) up to high positive (r=+0,62), «fiber length» and «micronairc» -medium positive (r=+0,55), as well as «fiber length» and «fiber strength» -medium positive (r =+0,56 and r=+0.50).
7. Based on intraspecific composite and convergent, eco-geographically and genetically remote and 3-4-5 species and backcrosscs hybridizations were developed the following new breeding progenies, lines and varieties of upland cotton:
by composite and convergent hybridization way-L-7966, L-214/05; CC-896/05; CC-896/28; CC-991/05; CC-991/09; KC-1/05; КС-1/08; КС-1/18; KC-1/35; KC-1/51; KC-1/77, S-231-233/07, L-234-235/07, L-236-237/07, L-242-243/07, L-244-245/07, L-482-483/07, L-484-485/07, L-666-667/07, L-397-398/07, L-802-803/07, L-814-815/07, L-230/05;
cco- geographically and genetically distant hybridization - cultivar S-7300, S-7301, the progenies S-5344, S-5361. HPG-1;
composite 3 - specific hybridization -cultivar «Sulton», «Jarkurgan», S-7276, S-7277, as well as a number of lines;
8. Using the remote intra-and interspecific hybridization it was elaborated unique introgression hybrids, genetically enriched cotton recombinants, progenies, lines, and varieties «Sulton», «Jarkurgan», S-7276, S-7277, S-7300, S-7301 having positive combination of high agronomic traits. Cultivar «Sulton» was included in the State register from 2011 and for the period from 2008 up to 2014 it was sown on the area of over than 275,5 thousand hectares.
9. The following rcccomcndations were given for practize and future studies:
use of method convergent hybridization, allowing improving of agronomic valuable traits of recurrent parent and registered medium staple cotton cultivars and receiving a positive transgressive variability;
as an initial source in convergent crosses use cotton varieties with high General combination ability (GCA) on the following: on early maturity- Tashkent-6 and S-9070; boll weight - S-6532; weight of 1000 seeds S- 9070; on productivity -Tashkent-6, S-4911 and S-9070; fiber output -S-6532; fiber length - S-4911 and S-6532; fiber strength - S-6532 and S-4911; and for micronairc - S-6532 and Ak-Darya-6.
for use as an initial source in cotton genetics and breeding research such new cotton selection progenies as well as the lines: KS-1/05; K.S-1/08; K.S-1/18; KS-1/35; KS-1/51; and KS-1/77, L-7966, L-214/05, S-214/05, SS-896/05; SS-896/28; SS-991/05 and SS-991/09 with early maturity, productivity, wilt tolerance, fiber output and quality.
to use in cotton genetics and breeding researches both USA accessions BC3S,-47-8-l-17, BC3S|-l-3-6-15 with 95% of (+)-gossypol level in seeds and lines HPG-1 and others with 90% of (+)-gossypol level, as donors on this trait. Since 2012, developed and studied in the competitive variety testing of Institute the following lines: L-404-05 and L-6970 with high (+)- gossypol level were recommended for testing on ground control of the State Inspection Commission for Agriculture crops variety testing.
widespread use of various forms of synthetic tetrapioids G.thurheri Tod. x G.raimondii Ulbr., 4-5 species composite hybrids [(G. thurheri Tod. x G. raimondii Ulbr.) x G.arhoreum L.] x G.hirsutum L. and [(F t K- 28 x C-6524 ) x G.harhadense L., as well as their backcrosscs for achievement the broad transgress variation, elaboration genetically enriched recombinants on economically valuable traits and their use in practical cotton breeding;
to extend the areas in of early maturing commercialised cotton cultivar «Sulton» and perspective one «Jarkurgan» as well broad testing of such as new varieties S-7277, S-7300 and S-7301 in the republic.
Our results confirm the hypothesis that the presence of an unfavorable genotypic variant of the IL4 gene can lead to a violation of the synthesis (expression) of anti-inflammatory cytokines-interleukins, a decrease in the body's resistance to infectious diseases, and an increase in the risk of developing CPRS. In addition, these data emphasize the prognostic significance of the C/C genotype of the IL4 gene polymorphism in the development of CPRS. The relative risk of developing CPRS in carriers of these genotypes is more than 3 times higher than in carriers of other genotypic variants of IL4 gene polymorphism.
It was established, that the studied lines and families have a high adaptive ability. Significant differences in most of the studied traits between the lines were not noted, but there was a slight excess in the number of boxes in L-51 and the height of the main stem in line L-52.
At present, the issues of identifying and creating adaptive forms characterized by the stability of the main economically valuable traits have acquired particular importance. One of the important indicators characterizing the resistance of plants to the influence of unfavorable environmental factors is homeostasis, which is a universal property in the system of the relationship between the genotype and the external environment. Homeostasis is nothing more than the ability of the genotype to minimize the effects of exposure to adverse external conditions.
Selection and seed production of agricultural plants are an integral part of adaptive crop production, and they play a leading role in the biologization and greening of intensification processes.
The frequency distribution of alleles and genotypes of polymorphism RS1800497 of the DRD2 gene in the studied samples is statistically significantly different (χ2> 3.8; P <0.05), which indicates the presence of a pathogenetic connection between this genetic polymorphism and the formation of AdHd in children. Genotypes containing an unfavorable «T» allele (C / T and T / T or A1 / A2 and A1 / A1 genotypes, respectively) are independent genetic markers predicting an increased risk of developing AdHd in children. The genotype of C / C (A2 / A2) has a protective effect in the formation of the sign of the syndrome.
To accurately assess the role of the rs1800471 polymorphism of the TGFb1 gene in the formation of nasal respiratory disorders and the development of rhinopathy, we believe that it is necessary to conduct additional and in depth studies with an increase in the number of patients and individuals in the control group. According to the results of the study, population genetic data turned out to be representative in relatively healthy groups of patients with rhinopathy and control, which allows us to continue working in the following process.
The present study reports for the first time the genotypic distribution of PPARG Pro12Ala polymorphism in group of Uzbek athletes. The human peroxisome proliferator-activated receptor gamma (PPARγ) is involved in lipid storage, glucose homeostasis and adipocyte differentiation. Pro-allele contributes to the development of high physical performance in sports where you need extra physical stamina, and Ala-allele - in sports based on the strength and speed. An analysis of the distribution frequency of genotypes of the PPARG gene, based on the general model of inheritance, in the group of athletes involved in football, was statistically significant compare to control (p =0.004). These results suggest that the presence of PPARG Ala allele, which increases the sensitivity of muscle tissue to insulin, and thus enhancing its anabolic effect on skeletal muscle, predisposes the development and display of speed-power qualities. In addition, we are studied frequencies of Pro/Ala genotypes in Uzbek population in comparison with Russian, Ukrainian, Italian, Bosnian and Herzegovinian, and Ethiopian samples. In conclusion, the present data seem to suggest that some selective factors such as climate could have influenced the present distribution of the Ala allele.
The purpose of the study is to determine the significance of genetic factors in the development of chronic nephritic syndrome in children and to clarify the features of the clinical course
The оbject of research were 129 children aged 4-15 years who were treated for chronic nephritis in the nephrology department of the Samarkand Regional Multidisciplinary Paediatric Medical Centre.
The scientific novelty of the study is as follows:it has been established that the severity of chronic nephritic syndrome in children is associated with clinical manifestations (gradual development, dyspepsia, abdominal pain) and an increase in the amount of Cystatin C in the blood;for the first time, it was revealed that the development of sclerotic lesions due to increased proliferation in patients with the presence of the MMP-9 (A-8202G) rs 11697325 genotypes in chronic nephritic syndrome leads to a worsening of the clinical course of the disease; established early diagnostic marker MMP-9 (A-8202G) rs 11697325 and its tissue inhibitor TIMP-2 (C536T) rs 11551797 in chronic nephritic syndrome in children in the diagnosis of the disease; for the first time, the prognostic value of the alleles of the MMP-9 (A-8202G) rs 11697325 genes and the homozygous G/G genotype in determining the risk of developing the disease in children with chronic nephritic syndrome has been proven.
Implementation of the research results. Based on scientific results of evaluation of the role of polymorphic genes of matrix metalloproteinase and its tissue inhibitors in chronic nephritic syndrome in children: methodological recommendation “The role of polymorphic genes of matrix metalloproteinase and its genetic inhibitors in the development of chronic nephritic syndrome in children” was developed and approved (reference of the Ministry of Health of the Republic of Uzbekistan No. 8n-r / 554 of 30.02.2022).
This methodological recommendation made it possible to predict the development of chronic nephritic syndrome in children and improve preventive measures; approved and developed on the basis of scientific results of research on early diagnosis and prognosis of chronic nephritic syndrome “Dynamics of clinical and laboratory parameters in nephritic syndrome in children”, (reference of the Ministry of Health of the Republic of Uzbekistan No. 8n-r / 555 of 30.02.2022).
This methodological recommendation made it possible to optimize the diagnosis and treatment tactics for various forms of nephritic syndrome in children;
The results obtained were implemented in the practice of health care, in particular, in the Republican Children's National Medical Center, in the 1st clinic of the Samarkand State Medical University, in the Samarkand Regional Children's Multidisciplinary Medical Center (conclusion No. 8 n-r/324 of 21.06.2022 of the Ministry of Health of Uzbekistan).
The application of the obtained results to practice has made it possible to reduce the frequency of recurrence of the disease in children, prevent complications of the disease, improve the quality of life of patients, diagnose and prevent the disease.
The structure and scope of the dissertation. The dissertation consists of an introduction, 4 chapters, conclusions, practical recommendations. The volume of the dissertation is 120 pages.
Maqolada olmos va kumushsimon rangbaranglikdagi sur qorakoʻl qoʻzilarida gullarning joylashish rasmi va mustahkamligi, gullarning ahamiyati yoritilgan