ABSTRACT
BACKGROUND: Prostate cancer is one of the most common male cancers in Western countries and takes the third place in morbidity in Ukraine. It is a highly heterogeneous disease. AIM: To analyze relative expression levels of the TGFB1, IL1B, FOS, EFNA5, TAGLN, PLAU, and EPDR1 genes in malignant and non-malignant prostate tissues. MATERIALS AND METHODS: Total RNA was isolated from 16 prostate adenomas, 37 prostate adenocarcinomas, and 29 conventionally normal prostate tissues. To analyze relative gene expression levels the quantitative real-time polymerase chain reaction was performed. RESULTS: The significant alterations in the relative expression levels were found in all analyzed sample groups for 4 genes: FOS, EFNA5, IL1B, and TGFB1. We have found that FOS and EFNA5 were more frequently overexpressed in carcinomas with Gleason score ≤ 7, compared with adenomas. On contrary, PLAU expression levels were decreased more frequently in prostate cancers, compared with conventionally normal tissues. Noteworthy, we found positive correlation between IL1B expression level and PSA (for patients with slight PSA increase, no more than 20.0 ng/ml). CONCLUSION: The EFNA5, FOS, IL1B, PLAU, and TGFB1 genes that showed significant expression alterations in prostate tumors, compared with conventionally normal prostate tissue, may play role in prostate cancer development and should be further investigated.
Subject(s)
Cell Transformation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic , Oncogenes , Prostatic Neoplasms/genetics , Biomarkers, Tumor , Gene Expression Profiling , Humans , Male , Mutation , Neoplasm Grading , Neoplasm Staging , Polymerase Chain Reaction , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathologyABSTRACT
The results of clinical, genealogical, cytogenetic and molecular genetic studies of 113 patients from 96 families with different forms of mental retardation from Ukraine are presented. This study was held as part of the CHERISH project of the 7-th Framework Program. The aim of the project is to improve diagnostics of mental retardation in children in Eastern Europe and Central Asia through detailed analysis of known chromosomal and gene's aberrations and to find the new gene-candidates that cause mental retardation. All patients have normal chromosome number (46XY or 46XX). The cases with fragile-X syndrome were eliminated using molecular genetic methods. Genome rearrangements were found among 28 patients using cytogenetic analysis, multiplex ligation-dependent probe amplification (MLPA analysis) ofsubtelomeric regions and array-based comparative genomic hybridisation (array CGH screening). In 10 cases known pathogenic CNV's were identified, 11 cases are unknown aberrations; their pathogenicity is being determined. The rest cases are known nonpathogenic gene rearrangements. Obtained results show the strong genetic heterogeneity of hereditary forms of mental retardation. The further studies will allow to identificate genes candidates and certain mutations in these genes that may be associated with this pathology.
Subject(s)
Chromosome Aberrations , Gene Deletion , Intellectual Disability/genetics , Genome , Humans , Intellectual Disability/epidemiology , Sequence Analysis, DNA , Ukraine/epidemiologyABSTRACT
Direct molecular-genetic analysis of CAG- and CCG-polymorphism has been carried out in 37 patients with Huntington disease (HD) clinical diagnosis. Heterozygote expanded HD alleles were found in 33 patients, in 4 cases DNA-analysis did not confirm the preliminary clinic diagnosis. Twenty asymptomatic high risk carriers were analyzed, 11 individuals inherited HD chromosome. Linkage disequilibrium between expanded CAG-alleles and the (CGG)10-allele of IT15gene in the group of HD-patients from Ukraine has been displayed. The significant differences in CAG-repeat sex-determined instability inheritance have been revealed. The genetic factors associated with the HD age of onset have been analyzed.
Subject(s)
Huntington Disease/genetics , Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Trinucleotide Repeat Expansion/genetics , Adult , Age of Onset , DNA/genetics , Gene Frequency , Genotype , Heterozygote , Humans , Huntingtin Protein , Huntington Disease/epidemiology , Middle Aged , Pedigree , Phenotype , Polymerase Chain Reaction , Ukraine/epidemiologyABSTRACT
Two intercomplementary methods of 17p11.2 duplication/deletion identification have been elaborated: STR allelic variants analysis and direct PMP22 gene dosage measuring by means of quantitative Real- Time PCR. It has been carried out detection and analysis of 17p11.2 chromosome region rearrangements in CMT1 patients from Ukraine. It has been registered the high level of de novo cases with 17p11.2-duplication. It has been shown the 17p11.2 chromosome region duplication/deletion association with CMT1A and HNPP clinical phenotypes which may be used in differential diagnosis of this type of CMT polyneuropathy.
Subject(s)
Charcot-Marie-Tooth Disease/genetics , Chromosome Aberrations , Chromosomes, Human, Pair 17/genetics , Case-Control Studies , Charcot-Marie-Tooth Disease/blood , Chromosome Deletion , Cytogenetic Analysis , DNA/genetics , Diagnosis, Differential , Gene Dosage , Gene Duplication , Gene Rearrangement , Hereditary Sensory and Motor Neuropathy/genetics , Humans , Leukocytes/metabolism , Myelin Proteins/genetics , Pedigree , Reverse Transcriptase Polymerase Chain Reaction , UkraineABSTRACT
Methods of DNA-analysis of 769G --> A mutations in INHalpha1 gene and CGG-repeats polymorphism in FMRI gene have been developed for creating test-systems for genetically caused forms of premature ovarian failure (POF) diagnostics. The frequency of 769G --> A mutation among women population in Ukraine was established and, by preliminary calculations, makes up 2.8%. Results of analysis of CGG-repeats numbers in FMRI gene in the group of 215 women (oocyte donors) revealed five persons with CGG-repeats numbers, that exceeds the normal one (42 copies). Thus the frequency of persons with allels with high risk of premutation in FMRI gene is 2.3%. The results of our research confirm the actuality of genetic tests of mutations in INHalpha1 and FMR1 genes among the women of reproductive age with the purpose of POF prognosis and prevention the birth of children with fragile X syndrome.
Subject(s)
DNA/analysis , Fragile X Syndrome/diagnosis , Inhibins/genetics , Nerve Tissue Proteins/genetics , Primary Ovarian Insufficiency/diagnosis , RNA-Binding Proteins/genetics , DNA Mutational Analysis , Female , Fragile X Mental Retardation Protein , Fragile X Syndrome/genetics , Genetic Testing , Humans , Mutation , Polymorphism, Restriction Fragment Length , Primary Ovarian Insufficiency/genetics , Trinucleotide Repeat ExpansionABSTRACT
Charcot-Marie-Tooth neuropathy (CMT) is one of the most common hereditary disorders, affecting 1:2500 individuals. The major mutation--microduplication of 1.4 megabases in 17p11.2 region, which is responsible for 68-90 % of cases of CMT1, results in CMT1A. In the present article we provide the population genetic study in 52 unrelated non-CMT volunteers from population of Ukraine in three STRs (D17S921, D17S1358 and D17S122) from the 17p11.2 chromosomal region to determine their ability for the CMT1A-duplication detection using STR-PCR method in Ukraine. The informativity for the CMT1A detection in current use STR panel is calculated to be 93,6%. It has been shown that current use STR panel analysis is important for CMT1A duplication detection, early differential diagnosis of CMT including prenatal diagnosis and genetic consulting in high risk families.
Subject(s)
Charcot-Marie-Tooth Disease/genetics , Gene Duplication , Genetics, Population , Microsatellite Repeats , Polymerase Chain Reaction , Alleles , Blood Donors , Charcot-Marie-Tooth Disease/diagnosis , Charcot-Marie-Tooth Disease/epidemiology , Chromosomes, Human, Pair 17 , Gene Frequency , Genes, Dominant , Haplotypes , Heterozygote , Humans , Models, Genetic , Physical Chromosome Mapping , Recombination, Genetic , Ukraine/epidemiologyABSTRACT
Charcot-Marie-Tooth neuropathy (CMT) is one of the most common hereditary disorders, affecting 1:2500 individuals. CMT is a heterogeneous group of disorders characterized by chronic peripheral motor and sensory neuropathy. We have performed the detection of 1.5 Mb CMT1A tandem duplication in 17p11.2-12 chromosome region for autosome-dominant CMT1 patients and their relatives using the analysis of two (CA)n polymorphic microsatellite loci: 17S921 and 17S1358 localised in the duplication region. CMT1A duplication was found in three of five autosome-dominant CMT1 families. It has been shown that CMT1A duplication analysis is important for early differential diagnosis of CMT including prenatal diagnosis and genetic consulting in high risk families.
