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Article in Chinese | WPRIM | ID: wpr-878958


Based on the characteristics and ISSR molecular marker technology, the study is aimed to compare and perform genetic diversity analysis on Sparganium stoloniferum from 7 regions. Molecular identification method was established for S. stoloniferum from Hunan province. Differences among Sparganii Rhizoma samples from seven habitats were analyzed via measuring weight, length, width and thickness of them. Genetic diversity of S. stoloniferum from 7 regions was analyzed by screening out primers amplifying clear band and showing rich polymorphism, then a cultivars dendrogram was built. The target primer was screened out, and the specific band was sequenced. Nine ISSR primers were selected to amplified clear band, rich polymorphism. A total of 73 bands were amplified by nine ISSR primers selected from 27 ISSR primers. On average, each primer produced 8.0 bands. A total of 38 bands were polymorphic, which occupied 52.8% of all bands. The cultivars dendrogram showed the genetic similarity was 0.54-0.94. Genetic similarity coefficient of S. stoloniferum from Jiangsu province, Anhui province and Jiangxi province was big, indicating the differences among them were slight on genetic level. S. stoloniferum from Hunan province is quite different from samples from the other six habitats on appea-rance and genetic level. A specific band(327 bp) in S. stoloniferum from Hunan province was obtained via ISSR-857 primer, and was sequenced. According BLASTn database, there were few sequences similar to the gene fragment and had little correlation with the growth process of plant. ISSR molecular marker technology provides a new idea for the identification of S. stoloniferum. This result confirmed the particularity of S. stoloniferum from ancient Jingzhou.

China , Drugs, Chinese Herbal , Genetic Markers/genetics , Genetic Variation , Microsatellite Repeats , Phylogeny , Polymorphism, Genetic
Rev. cuba. invest. bioméd ; 39(1): e336, ene.-mar. 2020. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1126572


Introducción: El género Brucella está incluido en la familia Brucellaceae que pertenece al orden Rhizobiales y es reconocido por su alto grado de patogenicidad. Las bacterias de este género son responsables de la brucelosis, enfermedad que ha sido reportada como una de las zoonosis más importantes a nivel mundial por su incidencia en el ganado y el hombre. Los estudios previos para la clasificación taxonómica del género, se han basado fundamentalmente en el análisis del gen 16S ARNr. Sin embargo, pocas investigaciones se han dirigido a la identificación de marcadores moleculares que distingan a sus miembros de otros grupos de bacterias. Objetivo: Identificar inserciones en secuencias de proteínas conservadas, que pudieran ser utilizados como marcadores moleculares para la taxonomía y diagnóstico de especies del género Brucella. Métodos: Las secuencias homólogas de las proteínas analizadas fueron obtenidas de bases de datos internacionales y, posteriormente, alineadas con el programa ClustalX2, para ello fueron considerados los parámetros sugeridos en la literatura. Resultados: Se identificaron inserciones en las proteínas oxoglutarato deshidrogenasa (componente E1) y ADN ligasa A específicas del género Brucella. Conclusiones: Las inserciones halladas pueden ser empleadas como complemento a los métodos tradicionales de clasificación taxonómica y para el diagnóstico molecular de bacterias incluidas en el género Brucella(AU)

Introduction: Brucella is a genus from the Brucellaceae family, Rhizobiales order. This genus is recognized for its high pathogenicity. Brucella bacteria cause brucellosis, a disease reported as one of the most important zoonoses worldwide due to its incidence in cattle and people. Previous studies on taxonomic classification of the genus have been mainly based on the analysis of gene 16S rDNA. However, few studies have been aimed at identification of molecular markers distinguishing its members from other groups of bacteria. Objective: Identify insertions in preserved protein sequences which could be used as molecular markers for the taxonomy and diagnosis of species from the Brucella genus. Methods: The homologous sequences for the proteins analyzed were obtained from international databases and aligned with the software ClustalX2, considering the parameters suggested in the literature. Results: Insertions were identified in the proteins oxoglutarate dehydrogenase (component E1) and DNA ligase A, specific of the genus Brucella. Conclusions: The insertions found may be used as complements to the traditional methods for taxonomic classification and for the molecular diagnosis of bacteria from the genus Brucella(AU)

Humans , Sequence Homology , Ketoglutarate Dehydrogenase Complex , Brucella/pathogenicity , Genetic Markers/genetics
Mem. Inst. Oswaldo Cruz ; 115: e190407, 2020. tab
Article in English | LILACS | ID: biblio-1101275


BACKGROUND Early diagnosis of tuberculosis (TB) and identification of strains of Mycobacterium tuberculosis resistant to anti-TB drugs are considered the main factors for disease control. OBJECTIVES To standardise a real-time polymerase chain reaction (qPCR) assay technique and apply it to identify mutations involved in M. tuberculosis resistance to Isoniazid (INH) directly in Ziehl-Neelsen (ZN) stained slides. METHODS Were analysed 55 independent DNA samples extracted from clinical isolates of M. tuberculosis by sequencing. For application in TB diagnosis resistance, 59 ZN-stained slides were used. The sensitivity, specificity and Kappa index, with a 95% confidence interval (CI95%), were determined. FINDINGS The agreement between the tests was, for the katG target, the Kappa index of 0.89 (CI95%: 0.7-1.0). The sensitivity and specificity were 97.6% (CI95%: 87.7-99.9) and 91.7% (CI95%: 61.5-99.5), respectively. For inhA, the Kappa index was 0.92 (CI95%: 0.8-1.0), the sensitivity and specificity were 94.4% (CI95%: 72.7-99.8) and 97.3% (CI95%: 85.8-99.9), respectively. The use of ZN-stained slides for drug-resistant TB detection showed significant results when compared to other standard tests for drug resistance. MAIN CONCLUSIONS qPCR genotyping proved to be an efficient method to detect genes that confer M. tuberculosis resistance to INH. Thus, qPCR genotyping may be an alternative instead of sequencing.

Humans , Genetic Markers/genetics , Drug Resistance, Bacterial/genetics , Isoniazid/pharmacology , Mutation/genetics , Mycobacterium tuberculosis/genetics , Antitubercular Agents/pharmacology , DNA, Bacterial/genetics , Microbial Sensitivity Tests , Sensitivity and Specificity , Real-Time Polymerase Chain Reaction , Genotype , Mycobacterium tuberculosis/drug effects
Braz. arch. biol. technol ; 63: e20190511, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132257


Abstract Long-chain non-encoded RNAs (lncRNAs) are important in many life activities and can participate in the occurrence of hepatocellular carcinoma (HCC). Moreover, lncRNAs can be used as basis for developing new strategies to hinder liver cancer. To investigate the utility of lncRNAs in HCC as potential biomarkers for early detection and diagnosis, we mined genomic data from the Cancer Genome Atlas (TCGA), and analyzed the gene expressions from 374 tumor patients and 50 normal patients. The abnormal expressions of 387 differentially expressed lncRNAs (DElncRNAs) were identified from a total of 3099 lncRNAs. Moreover, 18 modules were divided based on WGCNA, and 2 of the 18 modules were positively correlated with stage and grade, and negatively correlated with survival time. Finally, 10 lncRNAs were found and their main functions are the enhancement of cellular metabolic capacity and cell proliferation. These 10 lncRNAs may serve as novel prognostic markers and therapeutic targets, and may help guide subsequent studies on HCC.

Humans , Biomarkers, Tumor/genetics , Genetic Markers/genetics , Carcinoma, Hepatocellular/genetics , RNA, Long Noncoding/genetics , Liver Neoplasms/genetics
Biol. Res ; 53: 15, 2020. tab, graf
Article in English | LILACS | ID: biblio-1100921


BACKGROUND: Current South American populations trace their origins mainly to three continental ancestries, i.e. European, Amerindian and African. Individual variation in relative proportions of each of these ancestries may be confounded with socio-economic factors due to population stratification. Therefore, ancestry is a potential confounder variable that should be considered in epidemiologic studies and in public health plans. However, there are few studies that have assessed the ancestry of the current admixed Chilean population. This is partly due to the high cost of genome-scale technologies commonly used to estimate ancestry. In this study we have designed a small panel of SNPs to accurately assess ancestry in the largest sampling to date of the Chilean mestizo population (n = 3349) from eight cities. Our panel is also able to distinguish between the two main Amerindian components of Chileans: Aymara from the north and Mapuche from the south. RESULTS: A panel of 150 ancestry-informative markers (AIMs) of SNP type was selected to maximize ancestry informativeness and genome coverage. Of these, 147 were successfully genotyped by KASPar assays in 2843 samples, with an average missing rate of 0.012, and a 0.95 concordance with microarray data. The ancestries estimated with the panel of AIMs had relative high correlations (0.88 for European, 0.91 for Amerindian, 0.70 for Aymara, and 0.68 for Mapuche components) with those obtained with AXIOM LAT1 array. The country's average ancestry was 0.53 ± 0.14 European, 0.04 ± 0.04 African, and 0.42 ± 0.14 Amerindian, disaggregated into 0.18 ± 0.15 Aymara and 0.25 ± 0.13 Mapuche. However, Mapuche ancestry was highest in the south (40.03%) and Aymara in the north (35.61%) as expected from the historical location of these ethnic groups. We make our results available through an online app and demonstrate how it can be used to adjust for ancestry when testing association between incidence of a disease and nongenetic risk factors. CONCLUSIONS: We have conducted the most extensive sampling, across many different cities, of current Chilean population. Ancestry varied significantly by latitude and human development. The panel of AIMs is available to the community for estimating ancestry at low cost in Chileans and other populations with similar ancestry.

Humans , Male , Female , Ethnic Groups/genetics , Indians, South American/genetics , Polymorphism, Single Nucleotide/genetics , Population Groups/genetics , Genetics, Population/organization & administration , Saliva , Genetic Markers/genetics , Chile , Phylogeography , Genotyping Techniques , Gene Frequency/genetics , Genotype
Braz. j. med. biol. res ; 52(11): e8333, 2019. tab, graf
Article in English | LILACS | ID: biblio-1039264


Not much is known about the roles of long non-coding RNAs (lncRNAs) for chronic kidney disease (CKD). In this study, we included CKD patient cohorts and normal controls as a discovery cohort to identify putative lncRNA biomarkers associated with CKD. We first compared the lncRNA expression profiles of CKD patients with normal controls, and identified differentially expressed lncRNAs and mRNAs. Co-expression network based on the enriched differentially expressed mRNAs and lncRNAs was constructed using WGCNA to identify important modules related to CKD. A lncRNA-miRNA-mRNA pathway network based on the hub lncRNAs and mRNAs, related miRNAs, and overlapping pathways was further constructed to reveal putative biomarkers. A total of 821 significantly differentially expressed mRNAs and lncRNAs were screened between CKD and control samples, which were enriched in nine modules using weighted correlation network analysis (WGCNA), especially brown and yellow modules. Co-expression network based on the enriched differentially expressed mRNAs and lncRNAs in brown and yellow modules uncovered 7 hub lncRNAs and 53 hub mRNAs. A lncRNA-miRNA-mRNA pathway network further revealed that lncRNAs of HCP5 and NOP14-AS1 and genes of CCND2, COL3A1, COL4A1, and RAC2 were significantly correlated with CKD. The lncRNAs of NOP14-AS1 and HCP5 were potential prognostic biomarkers for predicting the risk of CKD.

Humans , RNA, Messenger/genetics , Genetic Markers/genetics , Renal Insufficiency, Chronic/genetics , RNA, Long Noncoding/genetics , Prognosis , Case-Control Studies , Mass Screening , Gene Expression Profiling , Renal Insufficiency, Chronic/diagnosis
Braz. oral res. (Online) ; 33: e058, 2019. tab, graf
Article in English | LILACS | ID: biblio-1019608


Abstract Cementum is the mineralized tissue covering the tooth root that functions in tooth attachment and post-eruptive adjustment of tooth position. It has been reported to be highly similar to bone in several respects but remains poorly understood in terms of development and regeneration. Here, we investigate whether cementocytes, the residing cells in cellular cementum, have the potential to be protagonist in cementum homeostasis, responding to endocrine signals and directing local cementum metabolism. Cells from healthy erupted human teeth were isolated using sequential collagenase/EDTA digestions, and maintained in standard cell culture conditions. A cementocyte-like cell line was cloned (HCY-23, for human cementocyte clone 23), which presented a cementocyte compatible gene expression signature, including the expression of dentin matrix protein 1 ( DMP1 ), sclerostin ( SOST ), and E11/gp38/podoplanin ( E11 ). In contrast, these cells did not express the odontoblast/dentin marker dentin sialoprotein ( DSPP ). HCY-23 cells produced mineral-like nodules in vitro under differentiation conditions, and were highly responsive to inorganic phosphate (Pi). Within the limits of the present study, it can be concluded that cementocytes are phosphate-responsive cells, and have the potential do play a key role in periodontal homeostasis and regeneration.

Humans , Male , Female , Adolescent , Adult , Young Adult , Genetic Markers/genetics , Cell Culture Techniques/methods , Dental Cementum/cytology , Phosphates/pharmacology , Phosphoproteins/analysis , Phosphoproteins/genetics , Sialoglycoproteins/analysis , Sialoglycoproteins/genetics , Time Factors , Membrane Glycoproteins/analysis , Membrane Glycoproteins/genetics , Gene Expression , Cell Line , Analysis of Variance , Extracellular Matrix Proteins/analysis , Extracellular Matrix Proteins/genetics , Fluorescent Antibody Technique , Bone Morphogenetic Proteins/analysis , Bone Morphogenetic Proteins/genetics , Dental Cementum/metabolism , Adaptor Proteins, Signal Transducing , Molar/cytology
An. bras. dermatol ; 93(1): 148-150, Jan.-Feb. 2018. tab, graf
Article in English | LILACS | ID: biblio-1038264


Abstract: Porphyria cutanea tarda has a complex etiology with genetic factors not completely elucidated. The miscegenation of the Brazilian population has important implications in the predisposition to diseases. There are no studies concerning the genetic ancestry of patients with porphyria cutanea tarda from a mixed population. Thirty patients living in Rio de Janeiro with sporadic porphyria cutanea tarda were studied for the genetic ancestry through informative markers - INDELS. There was a significant predominance of European ancestry across the sample of patients with porphyria cutanea tarda (70.2%), and a small contribution of African and Amerindian ancestry, 20.1% and 10.9%, respectively.

Humans , Porphyria Cutanea Tarda/genetics , European Continental Ancestry Group/genetics , Brazil/ethnology , Genetic Markers/genetics , Cross-Sectional Studies , Genotype
Arch. endocrinol. metab. (Online) ; 62(1): 79-86, Jan.-Feb. 2018. tab
Article in English | LILACS | ID: biblio-887629


ABSTRACT Objective Monocyte chemoattractant protein 1 (MCP-1) has been suggested to be involved in the pathophysiology of insulin resistance (IR); therefore, variants in the MCP-1 gene may contribute to the development of this disease. The aim of this study was to analyze the relationship of the -2518 A>G MCP-1 (rs1024611) gene polymorphism with insulin resistance in Mexican children. Subjects and methods A cross-sectional study was performed in 174 children, including 117 children without insulin resistance and 57 children with IR, with an age range of 6-11 years. Levels for serum insulin and high-sensitivity C-reactive protein were determined. The -2518 A>G MCP-1 polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Insulin resistance was defined as a HOMA-IR in the upper 75th percentile, which was ≥ 2.4 for all children. Results Genotype frequencies of the rs1024611 polymorphism for the insulin-sensitive group were 17% AA, 48% AG and 35% GG, and the frequency of G allele was 59%, whereas frequencies for the insulin-resistant group were 12% AA, 37% AG and 51% GG, and the frequency of G allele was 69%. The genotype and allele frequencies between groups did not show significant differences. However, the GG genotype was the most frequent in children with IR. The GG genotype was associated with insulin resistance (OR = 2.2, P = 0.03) in a genetic model. Conclusion The -2518 A>G MCP-1 gene polymorphism may be related to the development of insulin resistance in Mexican children.

Humans , Male , Female , Child , Insulin Resistance/genetics , Chemokine CCL2/genetics , Polymorphism, Single Nucleotide/genetics , Genetic Markers/genetics , Case-Control Studies , Cross-Sectional Studies , Genetic Predisposition to Disease , Gene Frequency , Genotype
Einstein (Säo Paulo) ; 15(3): 269-272, July-Sept. 2017. tab
Article in English | LILACS | ID: biblio-891406


ABSTRACT Objective To verify the incidence of the G679A mutation in exon 2 of the gene inhibin alpha (INHA), in women with secondary amenorrhea and diagnosis of premature ovarian insufficiency, and in controls. Methods A 5mL sample of peripheral blood was collected from all study participants in an EDTA tube and was used for DNA extraction. For the patient group, 5mL of blood were also collected in a tube containing heparin for karyotype, and 5mL were collected in a dry tube for follicle stimulant hormone dosage. All patient and control samples were initially submitted to analysis of the G679A variant in exon 2 of the INHA gene by PCR-RFLP technique. Samples from patients with premature ovarian insufficiency after PCR-RFLP were submitted to Sanger sequencing of the encoding exons 2 and 3. Sequencing was performed on ABI 3500 GeneticAnalyzer equipment and the results were evaluated by SeqA and Variant Reporter software. Results Samples of 70 women with premature ovarian insufficiency and 97 fertile controls were evaluated. The G769A variant was found in only one patient in the Premature Ovarian Insufficiency Group and in no control, and it appears to be rare in Brazilian patients with premature ovarian insufficiency. This polymorphism was previously associated to premature ovarian insufficiency in several populations worldwide. Conclusion There is genetic heterogeneity regarding the INHA gene in different populations, and among the causes of premature ovarian insufficiency.

RESUMO Objetivo Verificar a incidência da mutação G679A no éxon 2 do gene da inibina alfa (INHA) em mulheres com amenorreia secundária e diagnóstico de insuficiência ovariana prematura e em controles. Métodos Uma amostra de 5mL de sangue periférico foi coletada de todos os participantes do estudo em tubo de EDTA e utilizada para a extração de DNA. Para o grupo de pacientes, foram coletados também 5mL de sangue em tubo contendo heparina para realização de cariótipo, e 5mL um tubo seco para dosagem de hormônio folículo-estimulante. As amostras de pacientes e controles foram inicialmente submetidas à análise da variante G679A no éxon 2 do gene INHA pela técnica de PCR-RFLP. As amostras de pacientes com insuficiência ovariana prematura após PCR-RFLP foram submetidas ao sequenciamento de Sanger dos éxons codantes 2 e 3. O sequenciamento foi realizado em equipamento ABI 3500 GeneticAnalyzer, e os resultados foram avaliados pelos programas SeqA and Variant Reporter. Resultados Foram avaliadas amostras de 70 mulheres com insuficiência ovariana prematura e de 97 controles férteis. A variante G769A foi encontrada em apenas uma paciente do Grupo Insuficiência Ovariana Prematura e em nenhum controle, e parece ser rara nas pacientes brasileiras com insuficiência ovariana prematura. Este polimorfismo foi previamente associado à insuficiência ovariana prematura em diversas populações no mundo. Conclusão O estudo evidenciou que há heterogeneidade genética quanto ao INHA em diferentes populações e entre as causas de insuficiência ovariana prematura.

Humans , Female , Adult , Polymorphism, Genetic/genetics , Exons/genetics , Primary Ovarian Insufficiency/genetics , Inhibins/economics , Mutation/genetics , Polymorphism, Restriction Fragment Length , Genetic Markers/genetics , Case-Control Studies , Polymerase Chain Reaction
Neotrop. ichthyol ; 14(2)2016. tab
Article in English | LILACS | ID: lil-796526


Monitoring of the interspecific hybrid production and trade is essential for the appropriate management of these animals in fish farms. The identification of catfish hybrids by morphological analysis is unreliable, particularly of juveniles and post-F1 individuals. Therefore, in the present study, we used five molecular markers (four nuclear genes and one mitochondrial gene) to detect hybrids in the trade of pimelodid juvenile fish from different stocks purchased of five seed producers in Brazil. Samples commercialized as pintado (pure species Pseudoplatystoma corruscans ) from three fish farms were genetically identified as hybrid cachapinta ( P. reticulatum x P. corruscans ). In the stocks purchased as cachandiá (hybrid between P. reticulatum x Leiarius marmoratus ) and cachapira (hybrid between P. reticulatum x Phractocephalus hemioliopterus ), we suggested the occurrence of intergenus crosses involving the hybrid cachapinta, which was used instead of the pure species P. reticulatum . The problems involving the hybrid cachapinta production were discussed in the present study, especially because these animals have caused genetic contamination and threatened the genetic integrity of natural and cultivated populations. In order to improve the surveillance of the production and provide criteria for the correct management of catfish hybrids, genetic markers has become an excellent alternative to the morphological identification, including juveniles or post-F1 generations.

O monitoramento da produção e comércio de híbridos interespecíficos é essencial para o manejo adequado desses animais em pisciculturas. A identificação de híbridos de bagres por análise morfológica não é confiável, especialmente de juvenis e indivíduos pós-F1. Portanto, no presente estudo, cinco marcadores moleculares (quatro genes nucleares e um gene mitocondrial) foram utilizados para detectar híbridos no comércio de juvenis pimelodídeos de diferentes estoques, comprados de cinco produtores de alevinos no Brasil. As amostras comercializadas como pintado (espécie pura Pseudoplatystoma corruscans ) foram geneticamente identificadas como híbrido cachapinta ( P. reticulatum x P. corruscans ). Nos estoques comprados como cachandiá (híbrido entre P. reticulatum x Leiarius marmoratus ) e cachapira (híbrido entre P. reticulatum x Phractocephalus hemioliopterus ), sugere-se a ocorrência de cruzamentos intergêneros envolvendo o híbrido cachapinta, que foi usado ao invés da espécie pura P. reticulatum . Os problemas envolvendo a produção de cachapinta foram discutidos no presente estudo, especialmente porque estes animais têm causado contaminação genética e ameaçado a integridade genética das populações naturais e cultivadas. Com o intuito de melhorar a fiscalização da produção e fornecer critérios para o manejo correto dos híbridos de bagre, marcadores genéticos têm se tornado uma excelente alternativa para a identificação morfológica, incluindo juvenis ou gerações pós-F1.

Animals , Catfishes/growth & development , Catfishes/genetics , Fisheries/analysis , Genetic Markers/genetics
Rev. méd. Chile ; 143(4): 439-443, abr. 2015. tab
Article in Spanish | LILACS | ID: lil-747549


Background: Amerindian admixture is an important parameter to consider in epidemiological studies in American countries, to make a proper selection of cases and controls. Aim: To compare Amerindian admixture estimates obtained using ABO*A and ABO*O blood group alleles and ancestral identity markers (AIMs) in the mixed Chilean population. Subjects and Methods: Amerindian admixture rates were determined in 720 Chilean volunteers residing in Arica and born in the 15 regions of the country, using ABO*O and ABO*A alleles and 40 AIMs selected from more than 500,000 single nucleotide polymorphisms (SNP´s). Results: Mean admixture estimates obtained using ABO*O and ABO*A alleles and AIM s were 35, 47% and 48% respectively. There was concordance in estimates, with the exception of the admixture based on ABO*O allele and AIMs. Conclusions: In Chile, Amerindian admixture estimates obtained using ABO*A could be used as an alternative to AIMs in justified cases provided the sample size is reasonably large.

Female , Humans , Male , ABO Blood-Group System/genetics , European Continental Ancestry Group/genetics , Indians, South American/genetics , Chile/ethnology , Genetics, Population , Gene Frequency/genetics , Genetic Markers/genetics , Phenotype , Polymorphism, Single Nucleotide/genetics , Reproducibility of Results
Femina ; 43(1)jan.-fev. 2015.
Article in Portuguese | LILACS | ID: lil-754438


Este artigo objetivou oferecer uma visão atual do papel dos marcadores gênicos no carcinoma de endométrio. Os principais genes descritos são o TP53, o Bcl-2, o c-erbB2 e o p16. Nos últimos anos, com a ampliação do conhecimento na área de biologia molecular, tem sido sugerido que os marcadores biológicos possam ser tão ou mais importantes do que os fatores prognósticos convencionais.

The main of this study is offer the present situation of genic markers in endometrial carcinoma. The principal genes have been described are TP53, Bcl-2, c-erbB2 and p16. In the last few years, thanks to improvements in molecular biology, some biological markers have been suggested to be as important as or more important than conventional prognostic factors.

Humans , Female , Adult , Endometrial Neoplasms , Biomarkers/analysis , /physiology , /physiology , Hysterectomy , Genetic Markers/genetics
Article in Korean | WPRIM | ID: wpr-186433


The aim of this study was to analyze the use of 12 single-nucleotide polymorphisms in genes ELAC2, RNASEL and MSR1 as biomarkers for prostate cancer (PCa) detection and progression, as well as perform a genetic classification of high-risk patients. A cohort of 451 men (235 patients and 216 controls) was studied. We calculated means of regression analysis using clinical values (stage, prostate-specific antigen, Gleason score and progression) in patients and controls at the basal stage and after a follow-up of 72 months. Significantly different allele frequencies between patients and controls were observed for rs1904577 and rs918 (MSR1 gene) and for rs17552022 and rs5030739 (ELAC2). We found evidence of increased risk for PCa in rs486907 and rs2127565 in variants AA and CC, respectively. In addition, rs627928 (TT-GT), rs486907 (AG) and rs3747531 (CG-CC) were associated with low tumor aggressiveness. Some had a weak linkage, such as rs1904577 and rs2127565, rs4792311 and rs17552022, and rs1904577 and rs918. Our study provides the proof-of-principle that some of the genetic variants (such as rs486907, rs627928 and rs2127565) in genes RNASEL, MSR1 and ELAC2 can be used as predictors of aggressiveness and progression of PCa. In the future, clinical use of these biomarkers, in combination with current ones, could potentially reduce the rate of unnecessary biopsies and specific treatments.

Aged , Aged, 80 and over , Cohort Studies , Disease Progression , Endoribonucleases/genetics , Gene Frequency , Genetic Markers/genetics , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Neoplasm Proteins/genetics , Polymorphism, Single Nucleotide , Prognosis , Prostate/metabolism , Prostatic Neoplasms/diagnosis , Scavenger Receptors, Class A/genetics
Article in English | WPRIM | ID: wpr-23737


Gastric cancer is one of the most common cancers in the world. The aims of this study were to evaluate the association between polymorphisms in TFF gene family, TFF1, TFF2, and TFF3 and the risk of gastric cancer (GC) and GC subgroups in a Korean population via a case-control study. The eight polymorphisms in TFF gene family were identified by sequencing and genotyped with 377 GC patients and 396 controls by using TaqMan genotyping assay. The rs184432 TT genotype of TFF1 was significantly associated with a reduced risk of GC (odds ratio, [OR) = 0.45; 95% confidence interval, [CI] = 0.25-0.82; P = 0.009), more protective against diffuse-type GC (OR = 0.20; 95% CI = 0.05-0.89; P = 0.035) than GC (OR = 0.34; 95% CI = 0.14-0.82; P = 0.017) in subjects aged < 60 yr, and correlated with lymph node metastasis negative GC and diffuse-type GC (OR = 0.44; 95% CI = 0.23-0.86; P = 0.016 and OR = 0.20; 95% CI = 0.05-0.87; P = 0.031, respectively). In addition, a decreased risk of lymph node metastasis negative GC and diffuse-type GC was observed for rs225359 TT genotype of TFF1 (OR = 0.46, 95% CI = 0.24-0.88; P = 0.020 and OR = 0.21, 95% CI = 0.05-0.88; P = 0.033, respectively). These findings suggest that the rs184432 and rs225359 polymorphisms in TFF1 have protective effects for GC and contribute to the development of GC in Korean individuals.

Adult , Aged , Biomarkers, Tumor/genetics , Female , Genetic Markers/genetics , Genetic Predisposition to Disease/epidemiology , Humans , Incidence , Male , Middle Aged , Peptides/genetics , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic/genetics , Reproducibility of Results , Republic of Korea/epidemiology , Risk Assessment/methods , Sensitivity and Specificity , Stomach Neoplasms/epidemiology , Tumor Suppressor Proteins/genetics
Rev. biol. trop ; 62(4): 1659-1671, oct.-dic. 2014. ilus, graf, mapas, tab
Article in English | LILACS | ID: lil-753718


CYP2D6 differences have already been demonstrated within Latin American populations by the CEIBA.FP Consortium of the Ibero-American Network of Pharmacogenetics (RIBEF, as per the acronym in Spanish). However, within the population of Costa Rica, no research has been conducted until now, even though this population has a trihybrid component ancestry that represents an interesting condition. Thus, the present study was aimed to determine the frequency of Ultra-rapid Metabolizers (UMs) and Poor Metabolizers (PMs) in a Costa Rican population, as well as to determine whether there are differences in the CYP2D6-predicted phenotype frequencies among three Costa Rican groups with different ethnic backgrounds. Additionally, these frequencies of PMs and UMs obtained were compared with Ibero-American populations published data. Finally, we also aimed to describe allele frequencies among different Costa Rican ethnic groups. This research has been undertaken within the framework of the RIBEF CEIBA Consortium studies on Latin American populations. A total of 385 individuals were included in the study: 139 mestizos, 197 Amerindians, and 49 Afro-Caribbeans. CYP2D6 genotypes were determined by XL-PCR and Real-Time PCR. The CYP2D6 variant alleles *2, *3, *4, *5, *6, *10, *17, *29, *35 and *41 were also determined. For the entire Costa Rican population, the frequency of PMs and UMs was 6% and 6.5%, respectively. The percentage of UMs in the mestizo population was higher than in the Amerindian population. CYP2D6 UMs vary from 3.6% to 10.1% and PMs from 1.4% to 10.2% among three Costa Rican groups. The highest frequencies of UMs (10.1%) and PMs (10.2%) were found in the mestizo and Amerindian populations, respectively. In conclusion, the frequencies of UMs and PMs for CYP2D6 varied widely across the mestizo, Amerindian and Afro-Caribbean Costa Rican populations. Future research in this population should be oriented to identify new CYP2D6 variants through sequencing methods, as well as to determine CYP2D6 phenotype, in order to establish the phenotype-genotype relation. Finally, further studies involving genetic markers of ancestry are needed in the Costa Rican population.

El Consorcio de la Red Iberoamericana de Farmacogenética CEIBA.FP ha demostrado que existen diferencias en cuanto a CYP2D6 en las poblaciones latinoamericanas. Sin embargo, hasta ahora, se sabe poco de este gen de importancia farmacogenética en la población de Costa Rica, la cual tiene una ancestría trihíbrida. El presente estudio tiene como objetivos: determinar la frecuencia de los fenotipos extrapolados de CYP2D6 en una población costarricense y determinar si existen diferencias en cuanto a las frecuencias de metabolizadores lentos (PMs) y ultra-rápidos (UMs) entre tres grupos con distinto origen étnico. Adicionalmente, las frecuencias de PMs y UMs obtenidas en este estudio fueron comparadas con datos de poblaciones iberoamericanas. Por último, se pretende describir las frecuencias alélicas en los distintos grupos. En el estudio se incluyeron 385 muestras de individuos: 139 mestizos, 197 amerindios y 49 afro-caribeños. Los genotipos CYP2D6 fueron determinados por XL-PCR y PCR tiempo real. Se determinaron las variantes alélicas *2, *3, *4, *5, *6, *10, *17, *29, *35 y *41. Para la población total estudiada las frecuencia de PMs y UMs fueron respectivamente 6% y 6.5%. El porcentaje de individuos UMs fue mayor en la población mestiza que en la amerindia. La frecuencia de UMs varió de 3.6 a 10.1% y la de PMs de 1.4 a 10.1% en los grupos costarricenses. Las frecuencias más altas de UMs (10.1%) y de PMs (10.2%) se encontraron respectivamente en las poblaciones mestiza y amerindia. En conclusión, las frecuencias de UMs y PMs de CYP2D6 varían ampliamente en las poblaciones mestiza, amerindia y afro-caribeña de Costa Rica. Investigaciones futuras en la población de Costa Rica deberían orientarse a identificar nuevas variantes del CYP2D6 mediante métodos de secuenciación, así como a determi- nar el fenotipo de CYP2D6 con el objetivo de establecer la relación fenotipo-genotipo. Finalmente, es necesario realizar estudios adicionales que involucren marcadores genéticos de ancestría en la población costarricense.

Humans , /genetics , Polymorphism, Genetic/genetics , African Continental Ancestry Group/genetics , Costa Rica , Genotype , Gene Frequency/genetics , Genetic Markers/genetics , Indians, South American/genetics , Phenotype , Polymerase Chain Reaction
Neotrop. ichthyol ; 12(4): 871-878, Oct-Dec/2014. tab, graf
Article in English | LILACS | ID: lil-732613


Species of the family Scorpaenidae are responsible for accidents and sporadic casualties by the shore they inhabit. The species Scorpaena plumieri from this family populate the Northeastern and Eastern coast of Brazil causing human envenomation characterized by local and systemic symptoms. In experimental animals the venom induces cardiotoxic, hypotensive, and airway respiratory effects. As first step to identify the venom components we isolated gland mRNA to produce a cDNA library from the fish gland. This report describes the partial sequencing of 356 gland transcripts from S. plumieri. BLAST analysis of transcripts showed that 30% were unknown sequences, 17% hypothetical proteins, 17% related to metabolic enzymes, 14% belonged to signal transducing functions and the remaining groups (7-8%) composed by gene related with expressing proteins, regulatory proteins and structural proteins. A considerable number of these EST were not found in available databases suggesting the existence of new proteins and/or functions yet to be discovered. By screening the library with antibodies against a lectin fraction from S. plumieri venom we identified several clones whose DNA sequence showed similarities with lectins found in fish. In silico analysis of these clones confirm the identity of these molecules in the venom gland of S. plumieri. .

Espécies da família Scorpaenidae são responsáveis por acidentes e mortes esporádicas ao longo da costa que habitam. A espécie Scorpaena plumieri desta família povoam a costa Leste e Nordeste do Brasil, causando envenenamento humano caracterizado por sintomas locais e sistêmicos. Em modelos experimentais animais a peçonha induz cardiotoxicidade, efeitos hipotensivos e alterações nas vias aéreas respiratórias. Como primeiro passo para identificar os componentes da peçonha foram isolados os mRNA das glândulas do peixe para produzir uma biblioteca de cDNAs. Esse artigo descreve o sequenciamento parcial de 356 transcritos das glândulas de S. plumieri. Análises em bancos de dados (BLAST) dos transcritos demonstraram que 30% eram sequências desconhecidas, 17% proteínas hipotéticas, 17% relacionadas às enzimas do metabolismo, 14% pertenciam a funções de transdução de sinais e os demais grupos (7-8%) formados por genes relacionados com a expressão de proteínas, proteínas regulatórias e estruturais. Um número considerável destes EST não foi encontrado em bases de dados disponíveis, sugerindo a existência de novas proteínas e/ou funções ainda a serem descobertas. Ao fazer um barrido da biblioteca com anticorpos produzidos contra uma fração das lectinas do veneno de S. plumieri, identificamos vários clones, cuja sequência de DNA mostram semelhanças com lectinas encontradas em peixes. A análise in silico destes clones confirmam a identidade destas moléculas na glândula de peçonha de S. plumieri.

Animals , Lecithins/genetics , Genetic Markers/genetics , Fishes, Poisonous/genetics , DNA, Complementary/analysis
Einstein (Säo Paulo) ; 12(3): 366-373, Jul-Sep/2014.
Article in English | LILACS | ID: lil-723923


Personalized medicine is the use of biomarkers, most of them molecular markers, for detection of specific genetic traits to guide various approaches for preventing and treating different conditions. The identification of several genes related to heredity, oncology and infectious diseases lead to the detection of genetic polymorphisms that are involved not only in different clinical progression of these diseases but also in variations in treatment response. Currently, it is possible to detect these polymorphisms using several methodologies: detection of single nucleotide polymorphisms using polymerase chain reaction methods; nucleic acid microarray detection; and nucleic acid sequencing with automatized DNA sequencers using Sanger-derived methods and new generation sequencing. Personalized medicine assays are directed towards detecting genetic variations that alter interactions of drugs with targets or the metabolic pathways of drugs (upstream and downstream) and can be utilized for the selection of drug formulations and detect different immunogenicities of the drug. Personalized medicine applications have already been described in different areas of Medicine and allow specific treatment approaches to be applied to each patient and pathology according to the results of these assays. The application of such a protocol demands an increasing interaction between the clinical laboratory and the clinical staff. For its implementation, a coordinated team composed of basic researchers and physicians highly specialized in their areas supported by a highly specialized team of clinical analysts particularly trained in molecular biology assays is necessary.

Medicina personalizada é o uso de biomarcadores, em sua maioria marcadores moleculares, para a detecção de traços genéticos específicos, a fim de orientar diversas abordagens para a prevenção e o tratamento de diferentes doenças. A identificação de vários genes relacionados a doenças hereditárias, oncológicas e infecciosas permite a detecção de polimorfismos genéticos que estão envolvidos em diferentes evoluções clínicas dessas doenças, bem como com variações na resposta ao tratamento. Atualmente, já é possível detectar esses polimorfismos utilizando diversas metodologias: a detecção de polimorfismos de nucleotídeo único pela reação de polimerização em cadeia; a detecção de microarranjos de ácidos nucleicos; e o sequenciamento de ácidos nucleicos com sequenciadores de DNA automatizados usando métodos derivados de sequenciamento Sanger ou de nova geração. Os ensaios de medicina personalizada são dirigidos para detectar variações genéticas que alteram interações de fármacos com alvos ou vias metabólicas de fármacos (anabólicas e catabólicas), podendo ser utilizados para a seleção de formulações farmacêuticas e para detectar diferentes imunogenicidades da droga. As aplicações de medicina personalizada já foram descritas em várias áreas da Medicina e permitem que abordagens de tratamento específicas sejam aplicadas para cada paciente e para cada doença, de acordo com os resultados dos ensaios utilizados. A aplicação de um protocolo desse tipo exige uma relação intensa entre o laboratório e o corpo clínico. Para sua execução, é necessária uma equipe coordenada, composta por investigadores de pesquisa básica e médicos altamente especializados em suas áreas, apoiada por um time bastante especializado de analistas clínicos treinados em testes de biologia molecular.

Humans , Genetic Markers/genetics , Precision Medicine/methods , Neoplasms/drug therapy , Neoplasms/genetics , Anticoagulants/pharmacology , Hepatitis C/drug therapy , Hepatitis C/genetics , Pharmacogenetics , Platelet Aggregation Inhibitors/pharmacology , Biomarkers, Tumor/genetics