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1.
Yi Chuan ; 41(7): 644-652, 2019 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-31307973

RESUMO

Single nucleotide polymorphism (SNP) chips have been widely used in genetic studies and breeding applications in animal and plant species. The quality of SNP genotypes is of paramount importance. More often than not, there are situations in which a number of genotypes may fail, requiring them to be imputed. There are also situations in which ungenotyped loci need to be imputed between different chips, or high-density genotypes need to be imputed based on low-density genotypes. Under these circumstances, the validity and reliability of subsequent data analyses is subject to the accuracy of these imputed genotypes. For justifying a better understanding of factors affecting imputation accuracy, in the present study, the impacts of SNP genotyping call rate and SNP genotyping error rate on the accuracy of genotype imputation were investigated under two scenarios in 20 116 U.S. Holstein cattle, each genotyped with a GGP 50K SNP chip. When the two factors were not correlated in scenario 1, simulated genotyping call rate varied from 50% to 100% and simulated genotyping error rate changed from 0% to 50%, with both factors being independent of each other. In scenario 2, genotyping error rates were correlated with genotyping call rate, and the relationship was set up by fitting a linear regression model between the two variables on a real dataset. That is, the simulated SNP call rate varied from 100% to 50% whereas the SNP genotyping rate changed from 0% to 13.55%. Finally, a 5-fold cross-validation was used to assess the subsequent imputation accuracy. The results showed that when original SNP genotyping call rate were independent of SNP genotyping error rate, the imputation accuracy did not change significantly with the original genotyping call rate (P>0.05), but it decreased significantly as the genotyping error rate increased (P<0.01). However, when original genotyping call rate was negatively correlated with genotyping error rate, the imputation error increased with elevated original genotyping error rate. In both scenarios, genotyping call rate needs to be no less than 0.90 in order to obtain 98% or higher genotype imputation accuracy. The present results can provide guidance for establishing quality assurance criteria for SNP genotyping in practice.


Assuntos
Cruzamento , Bovinos/genética , Genótipo , Técnicas de Genotipagem/veterinária , Polimorfismo de Nucleotídeo Único , Animais , Análise de Sequência com Séries de Oligonucleotídeos , Reprodutibilidade dos Testes
2.
DNA Cell Biol ; 38(8): 887-894, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31295021

RESUMO

Circular RNAs (circRNAs), as with other noncoding RNAs, have emerged as novel molecules of interest in gene regulation and in the development of many diseases. However, the expression and function of circRNAs in inflammation-induced lymphangiogenesis (LG) are still unknown. Microarray profiling in inflamed human lymphatic endothelial cells identified 82 differentially expressed circRNAs, including 6 downregulated and 76 upregulated circRNAs. One of the top 10 upregulated circRNAs, cZNF609, was selected for subsequent quantitative real-time PCR validation, and was found to be significantly upregulated in inflamed corneas from both mouse and human eyes. The expression of miR-184 was significantly lower in inflamed corneas than in control ones, which suggested that cZNF609 might serve as a sponge for miR-184. The expression of heparanase, a potential target gene of miR-184, was significantly increased in inflamed corneas. Therefore, circRNAs may serve as potential regulators of corneal LG. These findings lay a foundation for functional research on circRNAs in corneal LG pathogenesis.


Assuntos
Córnea/fisiologia , Endoftalmite/genética , Linfangiogênese/genética , RNA , Animais , Células Cultivadas , Córnea/patologia , Endoftalmite/etiologia , Células Endoteliais , Humanos , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs , Análise de Sequência com Séries de Oligonucleotídeos
3.
Gene ; 712: 143961, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31279709

RESUMO

Since international federation of gynecology and obstetrics (FIGO) staging is mainly based on clinical assessment, an integrated approach for mining RNA based biomarkers for understanding the molecular deregulation of signaling pathways and RNAs in cervical cancer was proposed in this study. Publicly available data were mined for identifying significant RNAs after patient staging. Significant miRNA families were identified from mRNA-miRNA and lncRNA-miRNA interaction network analyses followed by stage specific mRNA-miRNA-lncRNA association network generation. Integrated bioinformatic analyses of selected mRNAs and lncRNAs were performed. Results suggest that HBA1, HBA2, HBB, SLC2A1, CXCL10 (stage I), PKIA (stage III) and S100A7 (stage IV) were important. miRNA family enrichment of interacting miRNA partners of selected RNAs indicated the enrichment of let-7 family. Assembly of collagen fibrils and other multimeric structures_Homosapiens_R-HSA-2022090 in pathway analysis and progesterone_CTD_00006624 in DSigDB analysis were the most significant and SLC2A1, hsa-miR-188-3p, hsa-miR-378a-3p and hsa-miR-150-5p were selected as survival markers.


Assuntos
Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Mineração de Dados/métodos , RNA Neoplásico/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Colágeno/química , Metilação de DNA , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Papillomaviridae/metabolismo , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia
4.
Gene ; 712: 143962, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31288057

RESUMO

Veratrum nigrum is protected plant of Melanthiaceae family, able to synthetize unique steroidal alkaloids important for pharmacy. Transcriptomes from leaves, stems and rhizomes of in vitro maintained V. nigrum plants were sequenced and annotated for genes and markers discovery. Sequencing of samples derived from the different organs resulted in a total of 108,511 contigs with a mean length of 596 bp. Transcripts derived from leaf and stalk were annotated at 28%, and 38% in Nr nucleotide database, respectively. The sequencing revealed 949 unigenes related with lipid metabolism, including 73 transcripts involved in steroids and genus-specific steroid alkaloids biosynthesis. Additionally, 3203 candidate SSRs markers we identified in unigenes with average density of one SSR locus every 6.2 kb sequence. Unraveling of biochemical machinery of the pathway responsible for steroidal alkaloids will open possibility to design and optimize biotechnological process. The transcriptomic data provide valuable resources for biochemical, molecular genetics, comparative transcriptomics, functional genomics, ecological and evolutionary studies of V. nigrum.


Assuntos
Alcaloides/biossíntese , Regulação da Expressão Gênica de Plantas , Esteroides/biossíntese , Transcriptoma , Veratrum/metabolismo , Mapeamento de Sequências Contíguas , DNA Complementar/metabolismo , Biblioteca Gênica , Ontologia Genética , Marcadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Repetições de Microssatélites , Anotação de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Análise de Sequência de RNA
5.
BMC Plant Biol ; 19(1): 318, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311506

RESUMO

BACKGROUND: Single Nucleotide Polymorphism (SNP) array and re-sequencing technologies have different properties (e.g. calling rate, minor allele frequency profile) and drawbacks (e.g. ascertainment bias). This lead us to study their complementarity and the consequences of using them separately or combined in diversity analyses and Genome-Wide Association Studies (GWAS). We performed GWAS on three traits (grain yield, plant height and male flowering time) measured in 22 environments on a panel of 247 F1 hybrids obtained by crossing 247 diverse dent maize inbred lines with a same flint line. The 247 lines were genotyped using three genotyping technologies (Genotyping-By-Sequencing, Illumina Infinium 50 K and Affymetrix Axiom 600 K arrays). RESULTS: The effects of ascertainment bias of the 50 K and 600 K arrays were negligible for deciphering global genetic trends of diversity and for estimating relatedness in this panel. We developed an original approach based on linkage disequilibrium (LD) extent in order to determine whether SNPs significantly associated with a trait and that are physically linked should be considered as a single Quantitative Trait Locus (QTL) or several independent QTLs. Using this approach, we showed that the combination of the three technologies, which have different SNP distributions and densities, allowed us to detect more QTLs (gain in power) and potentially refine the localization of the causal polymorphisms (gain in resolution). CONCLUSIONS: Conceptually different technologies are complementary for detecting QTLs by tagging different haplotypes in association studies. Considering LD, marker density and the combination of different technologies (SNP-arrays and re-sequencing), the genotypic data available were most likely enough to well represent polymorphisms in the centromeric regions, whereas using more markers would be beneficial for telomeric regions.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Técnicas de Genotipagem , Haplótipos , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Zea mays/genética , Alelos , Biodiversidade , Cromossomos de Plantas , Marcadores Genéticos , Genoma de Planta , Desequilíbrio de Ligação , Zea mays/crescimento & desenvolvimento
6.
Zhonghua Gan Zang Bing Za Zhi ; 27(7): 533-540, 2019 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-31357780

RESUMO

Objective: To analyze non-alcoholic steatohepatitis (NASH)-related differentially expressed genes (DEGs) by bioinformatics methods to find key pathways and potential therapeutic targets for NASH. Methods: GSE61260 chip was downloaded from the public microarray database and liver biopsy samples from 24 NASH cases and 38 healthy controls were included. The Limma software package in R language was used to screen DEGs under the condition of difference multiple > 1.5 and adj. P < 0.05. The clusterProfiler software package was used for GO analysis and KEGG analysis. The STRING online database was used for protein-protein interaction analysis, and the L1000 and DrugBank databases were used for drug prediction. Results: Compared with healthy control group, 857 DEGs were screened out in NASH group including 167 up-regulated genes and 690 down-regulated genes. GO analysis showed that DEGs were mainly involved in inflammation and cholesterol metabolism. KEGG analysis showed that DEGs were mainly enriched in PPAR, non-alcoholic fatty liver disease, oxidative phosphorylation and other signaling pathways. Among them, eight genes of ACSL4, CYP7A1, FABP4, FABP5, lipoprotein lipase, ME1, OLR1 and PLIN1 were enriched in PPAR signaling pathway, and 165 interaction nodes were formed with 47 DEGs-encoded proteins. Lipoprotein lipase interacted with 21 DEGs, and its up-regulated expression had improved lipid metabolism, insulin resistance and anti-inflammatory effects. Four drugs (gemfibrozil, bezafibrate, omega-3 carboxylic acid and glycyrrhizic acid) were screened by L1000 and DrugBank to activate lipoprotein lipase. Presently, these four drugs are clinically used to treat hypertriglyceridemia or to improve inflammation. In this regard, we speculated that the pharmacological effects of these four drugs had improved NASH by activating lipoprotein lipase to promote liver lipid metabolism and alleviate inflammation. Conclusion: PPAR signaling pathway is closely associated to the occurrence and development of NASH, and thereby lipoprotein lipase agonist is a new attempt to treat NASH.


Assuntos
Ativadores de Enzimas/farmacologia , Metabolismo dos Lipídeos , Lipase Lipoproteica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Bezafibrato/farmacologia , Biópsia , Ácidos Carboxílicos/farmacologia , Estudos de Casos e Controles , Biologia Computacional , Genfibrozila/farmacologia , Ácido Glicirrízico/farmacologia , Humanos , Hepatopatia Gordurosa não Alcoólica/enzimologia , Análise de Sequência com Séries de Oligonucleotídeos , Receptores Depuradores Classe E
7.
Vet Microbiol ; 235: 118-126, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31282369

RESUMO

The aim of the present study was to investigate the diversity of methicillin-resistant Staphylococcus aureus (MRSA) that originated from Austrian companion animals during the last five-year period. A total of 90 non-repetitive MRSA isolates were obtained during diagnostic activities from autumn 2013 to autumn 2018. They originated from horses (n = 62), cats (n = 13), dogs (n = 10), rabbits (n = 2), a domestic canary, a zoo-kept hammer-headed bat (Hypsignathus monstrosus) and a semi-captive northern bald ibis (Geronticus eremita). Antimicrobial susceptibility testing was performed. All isolates were mecA-positive and mecC-negative. The isolates were genotyped by SCCmec, spa and dru typing, Multiple-Locus Variable number of tandem repeat Analyses (MLVA), S. aureus DNA microarray, and whole-genome sequencing (WGS). Eight sequence types (STs - ST398, ST5275 (new ST), ST225, ST8, ST22, ST152, ST1, and ST45), three SCCmec types (II, IV, and V), sixteen spa types (t003, t008, t011, t015, t032, t034, t1381, t1928, t1985, t223, t334, t355, t430, t6447, t6867, and t7105), fourteen dru types (dt10a, dt10az, dt10q, dt10r, dt11a, dt5e, dt6j, dt9a, dt9ak, dt9g, and four new types dt8as, dt7ak, dt4j, dt14n), and thirty-five MLVA types were detected. WGS-based core genome MLST (cgMLST) displayed five main clusters. Compared to the time period 2004-2013, the results of the present study show not only a higher diversity among the MRSA isolates within the population of Austrian companion animals, but also the introduction of new clones. Although ST398 isolates remained predominant, mainly due to high presence of this lineage among horses, increasing isolation rates of human-associated MRSA clones were observed in cats and dogs.


Assuntos
Variação Genética , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/genética , Animais de Estimação/microbiologia , Infecções Estafilocócicas/veterinária , Animais , Antibacterianos/farmacologia , Técnicas de Tipagem Bacteriana , Gatos/microbiologia , Cães/microbiologia , Genótipo , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Análise de Sequência com Séries de Oligonucleotídeos , Sequenciamento Completo do Genoma
8.
Nat Commun ; 10(1): 2512, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175307

RESUMO

DNA is a common biomaterial in nature as well as a good building block for producing useful structures, due to its fine feature size and liquid crystalline phase. Here, we demonstrate that a combination of shear-induced flow and microposts can be used to create various kinds of interesting microstructure DNA arrays. Our facile method provides a platform for forming multi-scale hierarchical orientations of soft- and biomaterials, using a process of simple shearing and controlled evaporation on a patterned substrate. This approach enables potential patterning applications using DNA or other anisotropic biomaterials based on their unique structural characteristics.


Assuntos
DNA/ultraestrutura , Microtecnologia , Estresse Mecânico , Materiais Biocompatíveis , Microscopia Confocal , Análise de Sequência com Séries de Oligonucleotídeos
11.
Nat Commun ; 10(1): 2879, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253767

RESUMO

Drug development often relies on high-throughput cell-based screening of large compound libraries. However, the lack of miniaturized and parallelized methodologies in chemistry as well as strict separation and incompatibility of the synthesis of bioactive compounds from their biological screenings makes this process expensive and inefficient. Here, we demonstrate an on-chip platform that combines solution-based synthesis of compound libraries with high-throughput biological screenings (chemBIOS). The chemBIOS platform is compatible with both organic solvents required for the synthesis and aqueous solutions necessary for biological screenings. We use the chemBIOS platform to perform 75 parallel, three-component reactions to synthesize a library of lipidoids, followed by characterization via MALDI-MS, on-chip formation of lipoplexes, and on-chip cell screening. The entire process from the library synthesis to cell screening takes only 3 days and about 1 mL of total solutions, demonstrating the potential of the chemBIOS technology to increase efficiency and accelerate screenings and drug development.


Assuntos
Técnicas de Química Combinatória , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Células HEK293 , Humanos , Dispositivos Lab-On-A-Chip , Lipossomos , Bibliotecas de Moléculas Pequenas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
12.
Gene ; 711: 143941, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31242453

RESUMO

Inorganic arsenic is a well-known carcinogen associated with several types of cancer, but the mechanisms involved in arsenic-induced carcinogenesis are not fully understood. Recent evidence points to epigenetic dysregulation as an important mechanism in this process; however, the effects of epigenetic alterations in gene expression have not been explored in depth. Using microarray data and applying a multivariate clustering analysis in a Gaussian mixture model, we describe the alterations in DNA methylation around the promoter region and the impact on gene expression in HaCaT cells during the transformation process caused by chronic exposure to arsenic. Using this clustering approach, the genes were grouped according to their methylation and expression status in the epigenetic landscape, and the changes that occurred during the cellular transformation were identified adequately. Thus, we present a valuable method for identifying epigenomic dysregulation.


Assuntos
Arsênico/toxicidade , Transformação Celular Neoplásica/patologia , Metilação de DNA/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Neoplasias Cutâneas/patologia , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Epigênese Genética/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Transplante de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Regiões Promotoras Genéticas , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/genética
13.
BMC Plant Biol ; 19(1): 262, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208336

RESUMO

BACKGROUND: Stored potato (Solanum tuberosum L.) tubers are sensitive to wet conditions that can cause rotting in long-term storage. To study the effect of water on the tuber surface during storage, microarray analysis, RNA-Seq profiling, qRT-PCR and phytohormone measurements were performed to study gene expression and hormone content in wet tubers incubated at two temperatures: 4 °C and 15 °C. The growth of the plants was also observed in a greenhouse after the incubation of tubers in wet conditions. RESULTS: Wet conditions induced a low-oxygen response, suggesting reduced oxygen availability in wet tubers at both temperatures when compared to that in the corresponding dry samples. Wet conditions induced genes coding for heat shock proteins, as well as proteins involved in fermentative energy production and defense against reactive oxygen species (ROS), which are transcripts that have been previously associated with low-oxygen stress in hypoxic or anoxic conditions. Wet treatment also induced senescence-related gene expression and genes involved in cell wall loosening, but downregulated genes encoding protease inhibitors and proteins involved in chloroplast functions and in the biosynthesis of secondary metabolites. Many genes involved in the production of phytohormones and signaling were also affected by wet conditions, suggesting altered regulation of growth by wet conditions. Hormone measurements after incubation showed increased salicylic acid (SA), abscisic acid (ABA) and auxin (IAA) concentrations as well as reduced production of jasmonate 12-oxo-phytodienoic acid (OPDA) in wet tubers. After incubation in wet conditions, the tubers produced fewer stems and more roots compared to controls incubated in dry conditions. CONCLUSIONS: In wet conditions, tubers invest in ROS protection and defense against the abiotic stress caused by reduced oxygen due to excessive water. Changes in ABA, SA and IAA that are antagonistic to jasmonates affect growth and defenses, causing induction of root growth and rendering tubers susceptible to necrotrophic pathogens. Water on the tuber surface may function as a signal for growth, similar to germination of seeds.


Assuntos
Armazenamento de Alimentos , Reguladores de Crescimento de Planta/metabolismo , Tubérculos/metabolismo , Solanum tuberosum/metabolismo , Metabolismo dos Carboidratos , Parede Celular/metabolismo , Cloroplastos/metabolismo , Regulação da Expressão Gênica de Plantas , Análise de Sequência com Séries de Oligonucleotídeos , Estresse Oxidativo , Tubérculos/crescimento & desenvolvimento , Metabolismo Secundário , Solanum tuberosum/crescimento & desenvolvimento , Transcriptoma , Água
14.
J Plant Res ; 132(4): 541-568, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31165947

RESUMO

Soybean (Glycine max) roots establish associations with nodule-inducing rhizobia and arbuscular mycorrhizal (AM) fungi. Both rhizobia and AM fungi have been shown to affect the activity of and colonization by the other, and their interactions can be detected within host plants. Here, we report the transcription profiles of genes differentially expressed in soybean roots in the presence of rhizobial, AM, or rhizobial-AM dual symbiosis, compared with those in control (uninoculated) roots. Following inoculation, soybean plants were grown in a glasshouse for 6 weeks; thereafter their root transcriptomes were analyzed using an oligo DNA microarray. Among the four treatments, the root nodule number and host plant growth were highest in plants with dual symbiosis. We observed that the expression of 187, 441, and 548 host genes was up-regulated and 119, 1,439, and 1,298 host genes were down-regulated during rhizobial, AM, and dual symbiosis, respectively. The expression of 34 host genes was up-regulated in each of the three symbioses. These 34 genes encoded several membrane transporters, type 1 metallothionein, and transcription factors in the MYB and bHLH families. We identified 56 host genes that were specifically up-regulated during dual symbiosis. These genes encoded several nodulin proteins, phenylpropanoid metabolism-related proteins, and carbonic anhydrase. The nodulin genes up-regulated by the AM fungal colonization probably led to the observed increases in root nodule number and host plant growth. Some other nodulin genes were down-regulated specifically during AM symbiosis. Based on the results above, we suggest that the contribution of AM fungal colonization is crucial to biological N2-fixation and host growth in soybean with rhizobial-AM dual symbiosis.


Assuntos
Micorrizas/metabolismo , Raízes de Plantas/metabolismo , Rhizobium/metabolismo , Soja/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Análise de Sequência com Séries de Oligonucleotídeos , Raízes de Plantas/microbiologia , Nódulos Radiculares de Plantas/metabolismo , Nódulos Radiculares de Plantas/microbiologia , Soja/genética , Simbiose
15.
J Biol Regul Homeost Agents ; 33(3): 695-706, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184088

RESUMO

Lipids are an alternative energy source for cells and provide structural integrity in cell membrane and their metabolism is regulated with the use of different pathways, such as integrin signalling, oxidative stress, mechanical stress, and pH changes. All of those processes take place in the oral mucosa which is subject to different environmental impacts. In this study, porcine buccal pouch mucosal cells (pBPMCs) were used during long-term primary in vitro culture. The cultured cells were collected at 7, 15 and 30 days of IVC and subsequently transferred to RNA isolation. In the results of the following microarray analysis, we analyzed the genes detected, belonging to ontology groups, such as "cellular lipid metabolic process", "response to lipid" and "response to lipopolysaccharides. All of the genes involved in these ontological groups were expressed at higher levels at 7 days of IVC and substantially decreased in expression at days 15 and 30 of primary culture. We observed new genes, which may be recognized as markers in regulation of lipid metabolism in mucosal cells in vitro. The results suggested that the biochemical mechanism-involved lipids were accompanied by increased enzymatic activation and synthesis of crucial growth factors reaching high activity at day 7 of culture, which is also well documented as a stage of tissue regeneration period within oral mucosa. Therefore, this "biochemical fingerprint" may be an additional checkpoint of the integrity, resistance and easy adaptability of oral tissues, which are important conditions of success in tissue engineering and grafting for tissue reconstruction.


Assuntos
Expressão Gênica , Metabolismo dos Lipídeos , Lipopolissacarídeos , Mucosa Bucal/citologia , Animais , Células Cultivadas , Bochecha , Análise de Sequência com Séries de Oligonucleotídeos , Cultura Primária de Células , Suínos
16.
Genet Sel Evol ; 51(1): 33, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242856

RESUMO

BACKGROUND: In this paper, we evaluate the performance of using family-specific low-density genotype arrays to increase the accuracy of pedigree-based imputation. Genotype imputation is a widely used tool that decreases the costs of genotyping a population by genotyping the majority of individuals on a low-density array and using statistical regularities between the low-density and high-density individuals to fill in the missing genotypes. Previous work on population-based imputation has found that it is possible to increase the accuracy of imputation by maximizing the number of informative markers on an array. In the context of pedigree-based imputation, where the informativeness of a marker depends only on the genotypes of an individual's parents, it may be beneficial to select the markers on each low-density array on a family-by-family basis. RESULTS: In this paper, we examined four family-specific low-density marker selection strategies and evaluated their performance in the context of a real pig breeding dataset. We found that family-specific or sire-specific arrays could increase imputation accuracy by 0.11 at one marker per chromosome, by 0.027 at 25 markers per chromosome and by 0.007 at 100 markers per chromosome. CONCLUSIONS: These results suggest that there may be room to use family-specific genotyping for very-low-density arrays particularly if a given sire or sire-dam pairing have a large number of offspring.


Assuntos
Algoritmos , Marcadores Genéticos , Análise de Sequência com Séries de Oligonucleotídeos/veterinária , Suínos/genética , Animais , Cruzamento , Feminino , Genótipo , Masculino , Linhagem , Reprodutibilidade dos Testes
17.
Gene ; 712: 143911, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31176730

RESUMO

MicroRNA-23b (miR-23b) is associated with inflammation and autoimmune diseases. This study evaluated miR-23b expression and assessed its potential as a biomarker of disease activity for rheumatoid arthritis (RA). Differential expression of microRNAs was determined by miRNA microarray analysis in fibroblast-like synoviocytes (FLSs) from four trauma patients as healthy controls (HCs) and eight RA patients. The microarray results showed elevated expression of miR-23b in FLSs from RA patients and this finding was corroborated by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization using synovial tissues (STs). Furthermore, we found miR-23b levels in plasma of RA patients were significantly higher than in HCs, and plasma miR-23b levels positively correlated with the erythrocyte sedimentation rate (ESR), hypersensitive C-reactive protein (hs-CRP), C-reactive protein (CRP), DAS28, and platelet (PLT) count (P < 0.05). MiR-23b levels in plasma inversely correlated with the levels of hemoglobin (Hb), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (P < 0.05), but not with rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (ACPA) (P > 0.05). Moreover, patients with anorexia showed higher levels of miR-23b in plasma than those without anorexia. Similar results were observed with fatigue. Appropriate treatment for RA not only ameliorated the disease condition but also reversed the elevated plasma miR-23b level remarkably. These results suggest that circulating miR-23b may be a promising biomarker for RA disease activity.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/genética , MicroRNAs/sangue , Adulto , Idoso , Anticorpos Anti-Proteína Citrulinada/metabolismo , Bilirrubina/química , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Colesterol/metabolismo , LDL-Colesterol/metabolismo , Feminino , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hemoglobinas/química , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Contagem de Plaquetas , Fator Reumatoide/metabolismo , Membrana Sinovial/citologia , Membrana Sinovial/metabolismo
18.
Nat Commun ; 10(1): 2209, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101809

RESUMO

Changes in bulk transcriptional profiles of heterogeneous samples often reflect changes in proportions of individual cell types. Several robust techniques have been developed to dissect the composition of such mixed samples given transcriptional signatures of the pure components or their proportions. These approaches are insufficient, however, in situations when no information about individual mixture components is available. This problem is known as the  complete deconvolution problem, where the composition is revealed without any a priori knowledge about cell types and their proportions. Here, we identify a previously unrecognized property of tissue-specific genes - their mutual linearity - and use it to reveal the structure of the topological space of mixed transcriptional profiles and provide a noise-robust approach to the complete deconvolution problem. Furthermore, our analysis reveals systematic bias of all deconvolution techniques due to differences in cell size or RNA-content, and we demonstrate how to address this bias at the experimental design level.


Assuntos
Biologia Computacional/métodos , Modelos Genéticos , Transcriptoma , Algoritmos , Animais , Tamanho Celular , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica/métodos , Células HEK293 , Humanos , Células Jurkat , Modelos Lineares , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise de Sequência de RNA/métodos
19.
Ann Otol Rhinol Laryngol ; 128(6_suppl): 134S-138S, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31092042

RESUMO

OBJECTIVES: Glucocorticoids are given for sensorineural hearing loss, but little is known of their molecular impact on the inner ear. Furthermore, in spite of claims of improved hearing recovery with intratympanic delivery of steroids, no studies have actually documented the inner ear molecular functions that are enhanced with this delivery method. METHODS: To assess steroid-driven processes in the inner ear, gene chip analyses were conducted on mice treated systemically with the glucocorticoids prednisolone or dexamethasone or the mineralocorticoid aldosterone. Other mice were given the same steroids intratympanically. Inner ears were harvested at 6 hours and processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34 000 genes. Results were statistically analyzed for up or down expression of each gene against control (untreated) mice. RESULTS: Analyses showed approximately 17 500 genes are normally expressed in the inner ear and steroids alter expression of 55% to 82% of these. Dexamethasone changed expression of 9424 (53.9%) inner ear genes following systemic injection but 14 899 ear genes (85%) if given intratympanically. A similar pattern was seen with prednisolone, as 7560 genes were impacted by oral delivery and 11 164 genes (63.8%) when given intratympanically. The mineralocorticoid aldosterone changed expression of only 268 inner ear genes if given orally, but this increased to 10 124 genes (57.9%) if injected intratympanically. Furthermore, the glucocorticoids given actually impacted more inner ear genes via the mineralocorticoid receptor than the glucocorticoid receptor. CONCLUSIONS: Thousands of inner ear genes were affected by steroids, and this number increased significantly if steroids were delivered intratympanically. Also, the impact of glucocorticoids on inner ear mineralocorticoid functions is more substantial than previously known. Thus, the application of therapeutic steroids for hearing loss needs to be reassessed in light of their more comprehensive impact on inner ear genes. Furthermore, simply ascribing the efficacy of steroids to immunosuppression no longer appears to be warranted.


Assuntos
Dexametasona/administração & dosagem , Orelha Interna/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Prednisolona/administração & dosagem , Animais , Injeção Intratimpânica , Camundongos , Camundongos Endogâmicos BALB C , Análise de Sequência com Séries de Oligonucleotídeos
20.
Cytogenet Genome Res ; 157(4): 203-212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31108493

RESUMO

Essential hypertension (EH), a major cause of cardiovascular diseases, is an important public health issue. However, the molecular mechanisms involved in EH remain unknown. Circular RNA (circRNA) is a novel promising biomarker for the disease. The purpose of the present study was to determine the expression of circRNAs in the blood of EH patients and to evaluate the performance of circRNA for early diagnosis of EH. A total of 178 subjects were recruited in the case-control study. Initial screening was done by using the Agilent human circRNA microarray followed by qRT-PCR validation. Finally, miRNAs were combined with circRNAs to create a new early prediction model for EH. The expression level of hsa_circ_0126991 in EH patients was significantly higher in comparison with healthy controls (p < 0.0001). Using the interaction of miR-10a-5p in combination with hsa_circ_0126991 led to a sensitivity of 0.708, a specificity of 0.764, and combined area under the curve of 0.774 (95% CI: 0.705-0.843) for early diagnosis of EH. In summary, the present study uncovered a novel perspective that hyperexpression of hsa_circ_0126991 is correlated with the risk of EH and may serve as a stable biomarker for early diagnosis of EH.


Assuntos
Biomarcadores/sangue , Hipertensão Essencial/diagnóstico , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA/genética , Regulação para Cima , Idoso , Estudos de Casos e Controles , Diagnóstico Precoce , Hipertensão Essencial/sangue , Hipertensão Essencial/genética , Feminino , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , RNA/sangue , Estudos Retrospectivos , Sensibilidade e Especificidade
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