Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
BMC Genomics ; 19(Suppl 3): 0, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29504899

RESUMO

BACKGROUND: The progress of medicine, science, technology, education, and culture improves, year by year, quality of life and life expectancy of the populace. The modern human has a chance to further improve the quality and duration of his/her life and the lives of his/her loved ones by bringing their lifestyle in line with their sequenced individual genomes. With this in mind, one of genome-based developments at the junction of personalized medicine and bioinformatics will be considered in this work, where we used two Web services: (i) SNP_TATA_Comparator to search for alleles with a single nucleotide polymorphism (SNP) that alters the affinity of TATA-binding protein (TBP) for the TATA boxes of human gene promoters and (ii) PubMed to look for retrospective clinical reviews on changes in physiological indicators of reproductive potential in carriers of these alleles. RESULTS: A total of 126 SNP markers of female reproductive potential, capable of altering the affinity of TBP for gene promoters, were found using the two above-mentioned Web services. For example, 10 candidate SNP markers of thrombosis (e.g., rs563763767) can cause overproduction of coagulation inducers. In pregnant women, Hughes syndrome provokes thrombosis with a fatal outcome although this syndrome can be diagnosed and eliminated even at the earliest stages of its development. Thus, in women carrying any of the above SNPs, preventive treatment of this syndrome before a planned pregnancy can reduce the risk of death. Similarly, seven SNP markers predicted here (e.g., rs774688955) can elevate the risk of myocardial infarction. In line with Bowles' lifespan theory, women carrying any of these SNPs may modify their lifestyle to improve their longevity if they can take under advisement that risks of myocardial infarction increase with age of the mother, total number of pregnancies, in multiple pregnancies, pregnancies under the age of 20, hypertension, preeclampsia, menstrual cycle irregularity, and in women smokers. CONCLUSIONS: According to Bowles' lifespan theory-which links reproductive potential, quality of life, and life expectancy-the above information was compiled for those who would like to reduce risks of diseases corresponding to alleles in own sequenced genomes. Candidate SNP markers can focus the clinical analysis of unannotated SNPs, after which they may become useful for people who would like to bring their lifestyle in line with their sequenced individual genomes.


Assuntos
Marcadores Genéticos/genética , Genômica , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Reprodução/genética , Proteína de Ligação a TATA-Box/metabolismo , Linhagem Celular , Feminino , Humanos , Internet , Ligação Proteica
2.
J Integr Bioinform ; 14(3)2017 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-28918420

RESUMO

Here we present the analysis of alternative splicing events on an example of glioblastoma cell culture samples using a set of computer tools in combination with database integration. The gene expression profiles of glioblastoma were obtained from cell culture samples of primary glioblastoma which were isolated and processed for RNA extraction. Transcriptome profiling of normal brain samples and glioblastoma were done by Illumina sequencing. The significant differentially expressed exon-level probes and their corresponding genes were identified using a combination of the splicing index method. Previous studies indicated that tumor-specific alternative splicing is important in the regulation of gene expression and corresponding protein functions during cancer development. Multiple alternative splicing transcripts have been identified as progression markers, including generalized splicing abnormalities and tumor- and stage-specific events. We used a set of computer tools which were recently applied to analysis of gene expression in laboratory animals to study differential splicing events. We found 69 transcripts that are differentially alternatively spliced. Three cancer-associated genes were considered in detail, in particular: APP (amyloid beta precursor protein), CASC4 (cancer susceptibility candidate 4) and TP53. Such alternative splicing opens new perspectives for cancer research.


Assuntos
Processamento Alternativo , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Glioma/genética , Transcriptoma/genética , Precursor de Proteína beta-Amiloide/genética , Linhagem Celular Tumoral , Éxons/genética , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Proteína Supressora de Tumor p53/genética
3.
BMC Evol Biol ; 17(Suppl 1): 19, 2017 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-28251877

RESUMO

BACKGROUND: The studies on CpG islands (CGI) and Alu elements functions, evolution, and distribution in the genome started since the discovery in nineteen eighties (1981, 1986, correspondingly). Their highly skewed genome wide distribution implies the non-random retrotransposition pattern. Besides CGIs in gene promoters, CGIs clusters were observed in the homeobox gene regions and in the macrosatellites, but the whole picture of their distribution specifics was not grasped. Attempts to identify any causative features upon their (genome wide) distribution, such as the DNA context mediated preferred insertion sites of Alu repeats, have been made to ascribe their clusters location. METHODS: Recent emergence of high resolution 3D map of human genome allowed segregating the genome into the large scale chromatin domains of naturally observable nuclear subcompartments, or Topologically Associated Domains (TADs), designated by spatial chromatin distribution. We utilized the chromatin map to elucidate relations between large scale chromatin state and CpG rich elements landscape. In the course of analysis it was confirmed that genes, Alu and CGI clusters maintain obvious, albeit different in strength, preference for open chromatin. For the first time it was clearly shown that the clusters density of the Alu and CGIs monotonically depend on the chromatin accessibility rate. In particular, the highest density of these elements is found in A1 euchromatin regions characterized by a high density of small length genes replicating in the early S-phase. It implies that these elements mediate (CGIs) or are a side element (Alus) of chromatin accessibility. RESULTS: We elucidated that both methylated and non-methylated CGIs display the affinity to chromatin accessibility. As a part of comparative genomics section, we elucidated that the dog's genome non-canonical structure, outstanding in mammals for its high CGIs abundance compared to gene number, is explained by the presence of dense tandem CGI extended hotspots (500 kb on average) in subtelomeric and pericentromeric regions with highly skewed CG content, and not by CGIs global distribution pattern shift. CONCLUSIONS: The study underlines the close association of CG-rich elements distribution with the newly introduced large scale chromatin state map, proposing a refined standpoint on interrelation of aforementioned genome elements and the chromatin state. To our expertise, the TAD-associated partition model employed in the study is likely the most substantial one regarding CpG rich clusters distribution among the whole genome chromatin/isochores maps available.


Assuntos
Ilhas de CpG , Genoma Humano , Elementos Alu , Animais , Evolução Biológica , Cromatina , Metilação de DNA , Genômica , Heterocromatina , Humanos , Mamíferos/genética
4.
J Integr Bioinform ; 13(4): 292, 2016 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-28187408

RESUMO

Computer analysis of gene expression in the nervous system plays a fundamental role in biology, genetics, and neurosciences. We studied molecular and genetic mechanisms of enhanced aggressiveness in comparison with tolerant behaviour using experimental animal models developed at the Institute of Cytology and Genetics SB RAS. Grey rats (Rattus norvegicus) have been subjected to selection during several generations in two directions – friendly, tolerant behaviour towards man (tame grey rats) and increased aggressive behaviour. We used samples from hypothalamus, mesencephalic tegmentum and periaqueductum grey matter from brain areas of grey rats genetically selected by behaviour in many generations. The set of computer tools and data processing pipelines helped to find genes and gene regulation patterns related to behaviour patterns. RNA - profiling experiments revealed the lists of differentially expressed genes in the contrast samples as well as differentially spliced isoforms. The gene ontology categories of protein transport, phosphoproteins, and nucleotide binding are presented together with categories of transmission of nerve impulses and neuron development were identified. Differential alternative splicing events found in the brain areas studied are statistically significant. We discuss role of alternative splicing events for neurospecific genes in behaviour patterns as well as extension of brain transcriptomics profiling.


Assuntos
Animais de Laboratório , Encéfalo/metabolismo , Expressão Gênica , Análise de Sequência de RNA , Animais , Feminino , Masculino , Ratos
5.
BMC Genomics ; 17(Suppl 14): 995, 2016 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-28105927

RESUMO

BACKGROUND: Aggressiveness in humans is a hereditary behavioral trait that mobilizes all systems of the body-first of all, the nervous and endocrine systems, and then the respiratory, vascular, muscular, and others-e.g., for the defense of oneself, children, family, shelter, territory, and other possessions as well as personal interests. The level of aggressiveness of a person determines many other characteristics of quality of life and lifespan, acting as a stress factor. Aggressive behavior depends on many parameters such as age, gender, diseases and treatment, diet, and environmental conditions. Among them, genetic factors are believed to be the main parameters that are well-studied at the factual level, but in actuality, genome-wide studies of aggressive behavior appeared relatively recently. One of the biggest projects of the modern science-1000 Genomes-involves identification of single nucleotide polymorphisms (SNPs), i.e., differences of individual genomes from the reference genome. SNPs can be associated with hereditary diseases, their complications, comorbidities, and responses to stress or a drug. Clinical comparisons between cohorts of patients and healthy volunteers (as a control) allow for identifying SNPs whose allele frequencies significantly separate them from one another as markers of the above conditions. Computer-based preliminary analysis of millions of SNPs detected by the 1000 Genomes project can accelerate clinical search for SNP markers due to preliminary whole-genome search for the most meaningful candidate SNP markers and discarding of neutral and poorly substantiated SNPs. RESULTS: Here, we combine two computer-based search methods for SNPs (that alter gene expression) {i} Web service SNP_TATA_Comparator (DNA sequence analysis) and {ii} PubMed-based manual search for articles on aggressiveness using heuristic keywords. Near the known binding sites for TATA-binding protein (TBP) in human gene promoters, we found aggressiveness-related candidate SNP markers, including rs1143627 (associated with higher aggressiveness in patients undergoing cytokine immunotherapy), rs544850971 (higher aggressiveness in old women taking lipid-lowering medication), and rs10895068 (childhood aggressiveness-related obesity in adolescence with cardiovascular complications in adulthood). CONCLUSIONS: After validation of these candidate markers by clinical protocols, these SNPs may become useful for physicians (may help to improve treatment of patients) and for the general population (a lifestyle choice preventing aggressiveness-related complications).


Assuntos
Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/metabolismo , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Proteína de Ligação a TATA-Box/metabolismo , Alelos , Progressão da Doença , Feminino , Estudos de Associação Genética , Doenças Genéticas Inatas/complicações , Doenças Genéticas Inatas/patologia , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Masculino , Obesidade/complicações , Obesidade/genética , Fenótipo , Prognóstico , Ligação Proteica , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...