RESUMO
There are two regulatory single nucleotide polymorphisms (rSNPs) at the beginning of the second intron of the mouse K-ras gene that are strongly associated with lung cancer susceptibility. We performed functional analysis of three SNPs (rs12228277: T greater than A, rs12226937: G greater than A, and rs61761074: T greater than G) located in the same region of human KRAS. We found that rs12228277 and rs61761074 result in differential binding patterns of lung nuclear proteins to oligonucleotide probes corresponding two alternative alleles; in both cases, the transcription factor NF-Y is involved. G greater than A substitution (rs12226937) had no effect on the binding of lung nuclear proteins. However, all the nucleotide substitutions under study showed functional effects in a luciferase reporter assay. Among them, rs61761074 demonstrated a significant correlation with allele frequency in non-small-cell lung cancer (NSCLC). Taken together, the results of our study suggest that a T greater than G substitution at nucleotide position 615 in the second intron of the KRAS gene (rs61761074) may represent a promising genetic marker of NSCLC.
Assuntos
Genes ras , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Adenocarcinoma/genética , Adenocarcinoma de Pulmão , Fator de Ligação a CCAAT/genética , Fator de Ligação a CCAAT/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Estudos de Casos e Controles , Fator de Transcrição GATA6/genética , Fator de Transcrição GATA6/metabolismo , Frequência do Gene , Marcadores Genéticos , Humanos , Íntrons , Neoplasias de Células Escamosas/genética , Sibéria , Proteínas ras/genética , Proteínas ras/metabolismoRESUMO
A method has been developed for constructing a tree source model for genetic text generation. Model visualisation in the form of suffix (context) trees provides a new way of context analysis of symbol sequences. Estimation of the stochastic complexity of the data in the frame of the model serves as a criterion for the model's ascertainment. The model and complexity values are used for analysis of genetic texts. The software realisation of this algorithm enables to reveal statistical properties of genetic sequences based on an information measure. The program developed is available via Internet at http://wwwmgs.bionet.nsc.ru/mgs/programs/complexity/.
Assuntos
Modelos Genéticos , DNA/genética , Cadeias de Markov , Proteínas/genética , Análise de Sequência de DNA , SoftwareRESUMO
This paper presents implementation of Data Mining and Knowledge Discovery techniques for searching for regularities in tables of context features of DNA sequences involved in regulation of transcription. The goal is to discover regularities that relate nucleotide sequences to the functional classes of these sequences. The search patterns for regularities have been constructed in the first-order logic augmented by probabilistic estimates. To this aim. the PC software system "Gene Discovery" has been designed. This system accepts molecular-genetical data retrieved from a database by using SQL queries. Nucleotide sequences of promoters of several functional systems were extracted from the TRRD database (http://wwwmgs.bionet.nsc.ru/mgs/gnw/trrd/) and analysed. The data include nucleotide sequences of erythroid-specific gene promoters, endocrine system gene promoters, promoter regions of the genes controlling cell cycle, promoter of genes regulating lipid metabolism, and muscle-specific gene promoters. Several regularities that relate the nucleotide sequences in the regulatory DNA and their location relative to the transcription start with each functional class have been found.
