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Information × Registration Number 0210U007469, 0105U005341 , R & D reports Title Molecular genetic researches of the factors,that cause reproductive losses and disability popup.stage_title Head Livshits Ludmila, Registration Date 30-12-2010 Organization Institute of molecular biology & genetics popup.description2 Data of spectrum, nature and origin of genes' mutations which are involved in pathogenesis of the investigated monogenic pathologies with the dominant type of inheritance (РМР22, Сх32, ІТ15, TGFBI) and also association of mutant variants of genes with different clinical phenotypes of these diseases have been got. The high level of genome reorganization of 17р11.2 area, and also high-frequency of de novo origin of these alterations in families of patients with inherited type 1 polyneuropathy (CМТ1) from Ukraine. The recurrent origin of expanded of АG-allelic variants ІТ15 gene is well-proven in the group of patients with Huntington's Disease from Ukraine. Stability of inheritance of mutant alleles with CAG expansion of IT15 gene is depend on sex of patient's parent which the mutation is inherited from. Reverse correlation is set between onset age of Huntington's Disease and amount of CAG-repeats in expanded allele of ІТ15 gene, the presence of three nucleotide deletion in 58th exon of ІТ15 gene and also presence in patient-s genotype the С677Т mutation in a MTHFR gene. Data about the spectrum of mutations of TGFBI gene are first got. It has been shown, that these mutations have a recurrent origin. The new mutation of Leu558Pro of gene of TGFBI is identified in group of patients with atypical corneal dystrophy which has originated from one ancestor-founder. The analysis of association of polymorphic variants of several genes-candidates with oogenesis (INHa, FSHR, FMR1), spermatogenesis (CFTR and AR) and early embriogenesis (CYP1A1, GSTT1, GSTM1, GSTP1, NAT2, F2 and F5, MTHFR) disturbances next data have been done. The associations of heterozygous replacement 769G-A (variant of Ala257Thr) in 2th exon of INHa gene, homozygous genotype Ala307 - Ser680/Ala307 - Ser680 of 10th exon of FSHR gene and high risk alleles (40 - 47 CGG-repeats) of FMR1 gene with pathogenesis of ovaries dysfunctions and with a poor response for an exogenous gonadotropin stimulation have been set. It has been also obtained data about allelic variants of CAG-polymorphism of first exon of AR gene (less than 18 or more than 28 CAG-repeats), and also IVS8 - 5T allelic variant of СFTR gene involving in the processes of differentiation of androgen-responsible tissues and alterations of the different stages of spermatogenesis. It has been set that females with genotypes homozygote on 481Т variant of NAT2gene and even one of polymorphic alleles 313G and 6235C of GSTP1 and CYP1A1 genes accordingly have a high risk of the inherited predisposition to the pregnancy losses on the different stages of ealy implantation period. Methodical recommendations are worked out and the information letters of IMBG NASU (№109/127-13 №109/126-13 №109/1019-13) are inculcated in 12 establishments of the system of health protection of Ukraine that is confirmed by the corresponding acts of introduction. Prognostic suppositions to development of research object are search of new mutations in genes-determinates and genes-modifiers, involved in pathogenesis of the inherited diseases, search of genetic factors of the inherited predisposition to development of multifactor diseases, development of prototypes of test-systems for DNA-diagnostics Product Description popup.authors Грищенко Наталія Володимирівна Кравченко Сергій Афанасійович Лівшиць Ганна Борисівна Пампуха Володимир Миколайович Соловйов Олександр Олександрович Татарський Павло Феліксович Фесай Ольга Анатоліївна Чернушин Сергій Юрійович popup.nrat_date 2020-04-02 Close