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1.
Hum Genomics ; 13(1): 31, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288856

RESUMO

Neurodevelopmental disorders (NDDs) represent a growing medical challenge in modern societies. Ever-increasing sophisticated diagnostic tools have been continuously revealing a remarkably complex architecture that embraces genetic mutations of distinct types (chromosomal rearrangements, copy number variants, small indels, and nucleotide substitutions) with distinct frequencies in the population (common, rare, de novo). Such a network of interacting players creates difficulties in establishing rigorous genotype-phenotype correlations. Furthermore, individual lifestyles may also contribute to the severity of the symptoms fueling a large spectrum of gene-environment interactions that have a key role on the relationships between genotypes and phenotypes.Herein, a review of the genetic discoveries related to NDDs is presented with the aim to provide useful general information for the medical community.

2.
Interdiscip Sci ; 11(3): 367-372, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30911903

RESUMO

Finding DNA sites with high potential for the formation of hairpin/cruciform structures is an important task. Previous works studied the distances between adjacent reversed complement words (symmetric word pairs) and also for non-adjacent words. It was observed that for some words a few distances were favoured (peaks) and that in some distributions there was strong peak regularity. The present work extends previous studies, by improving the detection and characterization of peak regularities in the symmetric word pairs distance distributions of the human genome. This work also analyzes the location of the sequences that originate the observed strong peak periodicity in the distance distribution. The results obtained in this work may indicate genomic sites with potential for the formation of hairpin/cruciform structures.

3.
Artigo em Inglês | MEDLINE | ID: mdl-30348666

RESUMO

Candida glabrata is an emerging fungal pathogen. Its increased prevalence is associated to its ability to rapidly develop antifungal drug resistance, particularly to azoles.In order to unravel new molecular mechanisms behind azole resistance, a transcriptomics analysis of the evolution of a C. glabrata clinical isolate (044) from azole susceptibility to posaconazole resistance (21st day), clotrimazole resistance (31st day) and fluconazole and voriconazole resistance (45th day), induced by longstanding incubation with fluconazole, was carried out. All the evolved strains were found to accumulate lower concentrations of azole drugs, when compared to the parental strain, while the ergosterol concentration remained mostly constant. However, only the population displaying resistance to all azoles was found to have a GOF mutation in the CgPDR1 gene, leading to the up-regulation of genes encoding multidrug resistance transporters. Intermediate strains, exhibiting posacozole/clotrimazole-resistance and increased fluconazole/voriconazole MIC levels, were found to display alternative ways to resist azole drugs. Particularly, posacozole/clotrimazole-resistance after 31 days was correlated with increased expression of adhesin genes. This finding led us to identify the Epa3 adhesin as a new determinant of azole resistance. Besides being required for biofilm formation, Epa3 expression was found to decrease the intracellular accumulation of azole antifungal drugs.Altogether, this work provides a glimps of the transcriptomics evolution of a C. glabrata population towards multi-azole resistance, highlighting the multifactorial nature of acquisition of azole resistance, and pointing out a new player in azole resistance.

4.
Genes (Basel) ; 9(9)2018 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-30200636

RESUMO

The sequencing of ancient DNA samples provides a novel way to find, characterize, and distinguish exogenous genomes of endogenous targets. After sequencing, computational composition analysis enables filtering of undesired sources in the focal organism, with the purpose of improving the quality of assemblies and subsequent data analysis. More importantly, such analysis allows extinct and extant species to be identified without requiring a specific or new sequencing run. However, the identification of exogenous organisms is a complex task, given the nature and degradation of the samples, and the evident necessity of using efficient computational tools, which rely on algorithms that are both fast and highly sensitive. In this work, we relied on a fast and highly sensitive tool, FALCON-meta, which measures similarity against whole-genome reference databases, to analyse the metagenomic composition of an ancient polar bear (Ursus maritimus) jawbone fossil. The fossil was collected in Svalbard, Norway, and has an estimated age of 110,000 to 130,000 years. The FASTQ samples contained 349 GB of nonamplified shotgun sequencing data. We identified and localized, relative to the FASTQ samples, the genomes with significant similarities to reference microbial genomes, including those of viruses, bacteria, and archaea, and to fungal, mitochondrial, and plastidial sequences. Among other striking features, we found significant similarities between modern-human, some bacterial and viral sequences (contamination) and the organelle sequences of wild carrot and tomato relative to the whole samples. For each exogenous candidate, we ran a damage pattern analysis, which in addition to revealing shallow levels of damage in the plant candidates, identified the source as contamination.

5.
Interdiscip Sci ; 10(1): 1-11, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29214497

RESUMO

In this work, we study reverse complementary genomic word pairs in the human DNA, by comparing both the distance distribution and the frequency of a word to those of its reverse complement. Several measures of dissimilarity between distance distributions are considered, and it is found that the peak dissimilarity works best in this setting. We report the existence of reverse complementary word pairs with very dissimilar distance distributions, as well as word pairs with very similar distance distributions even when both distributions are irregular and contain strong peaks. The association between distribution dissimilarity and frequency discrepancy is also explored, and it is speculated that symmetric pairs combining low and high values of each measure may uncover features of interest. Taken together, our results suggest that some asymmetries in the human genome go far beyond Chargaff's rules. This study uses both the complete human genome and its repeat-masked version.


Assuntos
DNA Complementar/genética , Genômica , Genoma Humano , Humanos , Anotação de Sequência Molecular
6.
Sci Rep ; 7(1): 728, 2017 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-28389642

RESUMO

We address the problem of discovering pairs of symmetric genomic words (i.e., words and the corresponding reversed complements) occurring at distances that are overrepresented. For this purpose, we developed new procedures to identify symmetric word pairs with uncommon empirical distance distribution and with clusters of overrepresented short distances. We speculate that patterns of overrepresentation of short distances between symmetric word pairs may allow the occurrence of non-standard DNA conformations, such as hairpin/cruciform structures. We focused on the human genome, and analysed both the complete genome as well as a version with known repetitive sequences masked out. We reported several well-defined features in the distributions of distances, which can be classified into three different profiles, showing enrichment in distinct distance ranges. We analysed in greater detail certain pairs of symmetric words of length seven, found by our procedure, characterised by the surprising fact that they occur at single distances more frequently than expected.


Assuntos
DNA , Genoma Humano , Genômica , Análise de Sequência de DNA , Algoritmos , Cromossomos Humanos , DNA/química , DNA/genética , Bases de Dados Genéticas , Genômica/métodos , Humanos , Cadeias de Markov , Modelos Genéticos , Conformação de Ácido Nucleico , Análise de Sequência de DNA/métodos , Relação Estrutura-Atividade
7.
Interdiscip Sci ; 9(1): 14-23, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27866321

RESUMO

Single-strand DNA symmetry is pointed as a universal law observed in the genomes from all living organisms. It is a somewhat broadly defined concept, which has been refined into some more specific measurable effects. Here we discuss the exceptional symmetry effect. Exceptional symmetry is the symmetry effect beyond that expected in independence contexts, and it can be measured for each word, for each equivalent composition group, or globally, combining the effects of all possible words of a given length. Global exceptional symmetry was found in several species, but there are genomic words with no exceptional symmetry effect, whereas others show a very high exceptional symmetry effect. In this work, we discuss a measure to evaluate the exceptional symmetry effect by symmetric word pair, and compare it with others. We present a detailed study of the exceptional symmetry by symmetric pairs and take the CG content into account. We also introduce and discuss the exceptional symmetry profile for the DNA of each organism, and we perform a multiple comparison for 31 genomes: 7 viruses; 5 archaea; 5 bacteria; 14 eukaryotes.


Assuntos
Genômica/métodos , Modelos Genéticos , Estatística como Assunto/métodos , DNA de Cadeia Simples/genética
8.
Sci Rep ; 6: 38383, 2016 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-27929068

RESUMO

The NET (for NocA, Nlz, Elbow, TLP-1) protein family is a group of conserved zinc finger proteins linked to embryonic development and recently associated with breast cancer. The members of this family act as transcriptional repressors interacting with both class I histone deacetylases and Groucho/TLE co-repressors. In Drosophila, the NET family members Elbow and NocA are vital for the development of tracheae, eyes, wings and legs, whereas in vertebrates ZNF703 and ZNF503 are important for the development of the nervous system, eyes and limbs. Despite the relevance of this protein family in embryogenesis and cancer, many aspects of its origin and evolution remain unknown. Here, we show that NET family members are present and expressed in multiple metazoan lineages, from cnidarians to vertebrates. We identified several protein domains conserved in all metazoan species or in specific taxonomic groups. Our phylogenetic analysis suggests that the NET family emerged in the last common ancestor of cnidarians and bilaterians and that several rounds of independent events of gene duplication occurred throughout evolution. Overall, we provide novel data on the expression and evolutionary history of the NET family that can be relevant to understanding its biological role in both normal conditions and disease.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Drosophila/genética , Evolução Molecular , Família Multigênica/genética , Proteínas Repressoras/genética , Vertebrados/genética , Animais , Proteínas de Ligação a DNA/genética , Drosophila/genética , Duplicação Gênica , Proteínas Nucleares/genética , Filogenia , Fatores de Transcrição/genética
9.
Eur J Hum Genet ; 25(1): 2-7, 2016 01.
Artigo em Inglês | MEDLINE | ID: mdl-27703146

RESUMO

Understanding the functional sequelae of amino-acid replacements is of fundamental importance in medical genetics. Perhaps, the most intuitive way to assess the potential pathogenicity of a given human missense variant is by measuring the degree of evolutionary conservation of the substituted amino-acid residue, a feature that generally serves as a good proxy metric for the functional/structural importance of that residue. However, the presence of putatively compensated variants as the wild-type alleles in orthologous proteins of other mammalian species not only challenges this classical view of amino-acid essentiality but also precludes the accurate evaluation of the functional impact of this type of missense variant using currently available bioinformatic prediction tools. Compensated variants constitute at least 4% of all known missense variants causing human-inherited disease and hence represent an important potential source of error in that they are likely to be disproportionately misclassified as benign variants. The consequent under-reporting of compensated variants is exacerbated in the context of next-generation sequencing where their inappropriate exclusion constitutes an unfortunate natural consequence of the filtering and prioritization of the very large number of variants generated. Here we demonstrate the reduced performance of currently available pathogenicity prediction tools when applied to compensated variants and propose an alternative machine-learning approach to assess likely pathogenicity for this particular type of variant.


Assuntos
Substituição de Aminoácidos/genética , Simulação por Computador , Doenças Genéticas Inatas , Mutação/genética , Alelos , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Máquina de Vetores de Suporte
10.
Artigo em Inglês | MEDLINE | ID: mdl-27589961

RESUMO

Fully automated text mining (TM) systems promote efficient literature searching, retrieval, and review but are not sufficient to produce ready-to-consume curated documents. These systems are not meant to replace biocurators, but instead to assist them in one or more literature curation steps. To do so, the user interface is an important aspect that needs to be considered for tool adoption. The BioCreative Interactive task (IAT) is a track designed for exploring user-system interactions, promoting development of useful TM tools, and providing a communication channel between the biocuration and the TM communities. In BioCreative V, the IAT track followed a format similar to previous interactive tracks, where the utility and usability of TM tools, as well as the generation of use cases, have been the focal points. The proposed curation tasks are user-centric and formally evaluated by biocurators. In BioCreative V IAT, seven TM systems and 43 biocurators participated. Two levels of user participation were offered to broaden curator involvement and obtain more feedback on usability aspects. The full level participation involved training on the system, curation of a set of documents with and without TM assistance, tracking of time-on-task, and completion of a user survey. The partial level participation was designed to focus on usability aspects of the interface and not the performance per se In this case, biocurators navigated the system by performing pre-designed tasks and then were asked whether they were able to achieve the task and the level of difficulty in completing the task. In this manuscript, we describe the development of the interactive task, from planning to execution and discuss major findings for the systems tested.Database URL: http://www.biocreative.org.


Assuntos
Curadoria de Dados/métodos , Mineração de Dados/métodos , Processamento Eletrônico de Dados/métodos
11.
Artigo em Inglês | MEDLINE | ID: mdl-27278817

RESUMO

The veritable deluge of biological data over recent years has led to the establishment of a considerable number of knowledge resources that compile curated information extracted from the literature and store it in structured form, facilitating its use and exploitation. In this article, we focus on the curation of inherited genetic variants and associated clinical attributes, such as zygosity, penetrance or inheritance mode, and describe the use of Egas for this task. Egas is a web-based platform for text-mining assisted literature curation that focuses on usability through modern design solutions and simple user interactions. Egas offers a flexible and customizable tool that allows defining the concept types and relations of interest for a given annotation task, as well as the ontologies used for normalizing each concept type. Further, annotations may be performed on raw documents or on the results of automated concept identification and relation extraction tools. Users can inspect, correct or remove automatic text-mining results, manually add new annotations, and export the results to standard formats. Egas is compatible with the most recent versions of Google Chrome, Mozilla Firefox, Internet Explorer and Safari and is available for use at https://demo.bmd-software.com/egas/Database URL: https://demo.bmd-software.com/egas/.


Assuntos
Curadoria de Dados/métodos , Mineração de Dados/métodos , Internet , Interface Usuário-Computador , Navegador , Animais , Humanos
12.
BMC Bioinformatics ; 17: 59, 2016 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-26842742

RESUMO

BACKGROUND: The second Chargaff's parity rule and its extensions are recognized as universal phenomena in DNA sequences. However, parity of the frequencies of reverse complementary oligonucleotides could be a mere consequence of the single nucleotide parity rule, if nucleotide independence is assumed. Exceptional symmetry (symmetry beyond that expected under an independent nucleotide assumption) was proposed previously as a meaningful measure of the extension of the second parity rule to oligonucleotides. The global exceptional symmetry was detected in long and short genomes. RESULTS: To explore the exceptional genomic word symmetry along the genome sequences, we propose a sliding window method to extract the values of exceptional symmetry (for all words or by word groups). We compare the exceptional symmetry effect size distribution in all human chromosomes against control scenarios (positive and negative controls), testing the differences and performing a residual analysis. We explore local exceptional symmetry in equivalent composition word groups, and find that the behaviour of the local exceptional symmetry depends on the word group. CONCLUSIONS: We conclude that the exceptional symmetry is a local phenomenon in genome sequences, with distinct characteristics along the sequence of each chromosome. The local exceptional symmetry along the genomic sequences shows outlying segments, and those segments have high biological annotation density.


Assuntos
Cromossomos Humanos/genética , DNA/genética , Genoma Humano , Modelos Genéticos , Modelos Estatísticos , Genômica , Humanos , Transcriptoma
13.
Oncotarget ; 7(2): 1973-83, 2016 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-26675378

RESUMO

Nicotinamide adenine dinucleotide (NAD) is a cofactor in redox reactions and a substrate for NAD-consuming enzymes, such as PARPs and sirtuins. As cancer cells have increased NAD requirements, the main NAD salvage enzymes in humans, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT), are involved in the development of novel anti-cancer therapies. Knowledge of the expression patterns of both genes in tissues and tumors is critical for the use of nicotinic acid (NA) as cytoprotective in therapies using NAMPT inhibitors. Herein, we provide a comprehensive study of NAPRT and NAMPT expression across human tissues and tumor cell lines. We show that both genes are widely expressed under normal conditions and describe the occurrence of novel NAPRT transcripts. Also, we explore some of the NAPRT gene expression mechanisms. Our findings underline that the efficiency of NA in treatments with NAMPT inhibitors is dependent on the knowledge of the expression profiles and regulation of both NAMPT and NAPRT.


Assuntos
Processamento Alternativo , Citocinas/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Mutação/genética , Neoplasias/genética , Nicotinamida Fosforribosiltransferase/genética , Pentosiltransferases/genética , Humanos , Neoplasias/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
14.
Antimicrob Agents Chemother ; 59(10): 6629-33, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26248365

RESUMO

Candida parapsilosis is the second most prevalent fungal agent causing bloodstream infections. Nevertheless, there is little information about the molecular mechanisms underlying azole resistance in this species. Mutations (G1747A, A2619C, and A3191C) in the MRR1 transcription factor gene were identified in fluconazole- and voriconazole-resistant strains. Independent expression of MRR1 genes harboring these mutations showed that G1747A (G583R) and A2619C (K873N) are gain-of-function mutations responsible for azole resistance, the first described in C. parapsilosis.


Assuntos
Fluconazol/farmacologia , Proteínas Fúngicas/genética , Fatores de Transcrição/genética , Voriconazol/farmacologia , Candida/efeitos dos fármacos , Candida/genética , Farmacorresistência Fúngica , Proteínas Fúngicas/fisiologia , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica/genética , Dados de Sequência Molecular , Mutação/genética , Fatores de Transcrição/fisiologia
15.
Sci Rep ; 5: 10203, 2015 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-25984837

RESUMO

Species evolution is indirectly registered in their genomic structure. The emergence and advances in sequencing technology provided a way to access genome information, namely to identify and study evolutionary macro-events, as well as chromosome alterations for clinical purposes. This paper describes a completely alignment-free computational method, based on a blind unsupervised approach, to detect large-scale and small-scale genomic rearrangements between pairs of DNA sequences. To illustrate the power and usefulness of the method we give complete chromosomal information maps for the pairs human-chimpanzee and human-orangutan. The tool by means of which these results were obtained has been made publicly available and is described in detail.


Assuntos
Biologia Computacional/métodos , Rearranjo Gênico , Genômica/métodos , Algoritmos , Animais , Humanos , Navegador
16.
Bioinformatics ; 31(15): 2421-5, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25840045

RESUMO

MOTIVATION: Ebola virus causes high mortality hemorrhagic fevers, with more than 25 000 cases and 10 000 deaths in the current outbreak. Only experimental therapies are available, thus, novel diagnosis tools and druggable targets are needed. RESULTS: Analysis of Ebola virus genomes from the current outbreak reveals the presence of short DNA sequences that appear nowhere in the human genome. We identify the shortest such sequences with lengths between 12 and 14. Only three absent sequences of length 12 exist and they consistently appear at the same location on two of the Ebola virus proteins, in all Ebola virus genomes, but nowhere in the human genome. The alignment-free method used is able to identify pathogen-specific signatures for quick and precise action against infectious agents, of which the current Ebola virus outbreak provides a compelling example.


Assuntos
DNA Viral/química , Ebolavirus/genética , Surtos de Doenças , Genoma Humano , Genoma Viral , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Humanos , Análise de Sequência de DNA , Proteínas Virais/genética
17.
Sci Rep ; 4: 6311, 2014 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-25201160

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase domain containing 1 (NAPRT1) are the main human NAD salvage enzymes. NAD regulates energy metabolism and cell signaling, and the enzymes that control NAD availability are linked to pathologies such as cancer and neurodegeneration. Here, we have screened normal and tumor samples from different tissues and populations of origin for mutations in human NAMPT and NAPRT1, and evaluated their potential pathogenicity. We have identified several novel polymorphisms and showed that NAPRT1 has a greater genetic diversity than NAMPT, where any alteration can have a greater functional impact. Some variants presented different frequencies between normal and tumor samples that were most likely related to their population of origin. The novel mutations described that affect protein structure or expression levels can be functionally relevant and should be considered in a disease context. Particularly, mutations that decrease NAPRT1 expression can predict the usefulness of Nicotinic Acid in tumor treatments with NAMPT inhibitors.


Assuntos
Citocinas/genética , Neoplasias/enzimologia , Neoplasias/genética , Nicotinamida Fosforribosiltransferase/genética , Pentosiltransferases/genética , Sequência de Aminoácidos , Sequência de Bases , Frequência do Gene/genética , Humanos , NAD/metabolismo , Pentosiltransferases/biossíntese , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência
18.
FEMS Yeast Res ; 14(7): 1119-23, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25132632

RESUMO

Acquisition of azole resistance by clinically relevant yeasts in nature may result in a significant, yet undetermined, impact in human health. The main goal of this study was to assess the development of cross-resistance between agricultural and clinical azoles by Candida spp. An in vitro induction assay was performed, for a period of 90 days, with prochloraz (PCZ) - an agricultural antifungal. Afterward, the induced molecular resistance mechanisms were unveiled. MIC value of PCZ increased significantly in all Candida spp. isolates. However, only C. glabrata developed cross-resistance to fluconazole and posaconazole. The increased MIC values were stable. Candida glabrata azole resistance acquisition triggered by PCZ exposure involved the upregulation of the ATP binding cassette multidrug transporter genes and the transcription factor, PDR1. Single mutation previously implicated in azole resistance was found in PDR1 while ERG11 showed several synonymous single nucleotide polymorphisms. These results might explain why C. glabrata is so commonly less susceptible to clinical azoles, suggesting that its exposure to agricultural azole antifungals may be associated to the emergence of cross-resistance. Such studies forward potential explanations for the worldwide increasing clinical prevalence of C. glabrata and the associated worse prognosis of an infection by this species.


Assuntos
Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Farmacorresistência Fúngica , Fungicidas Industriais/farmacologia , Imidazóis/farmacologia , Triazóis/farmacologia , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
Antimicrob Agents Chemother ; 58(8): 4604-11, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24867987

RESUMO

Candida krusei is an important agent of opportunistic infections that often displays resistance to several antifungals. We describe here the in vivo acquisition of resistance to voriconazole (VRC) by C. krusei isolates recovered from a leukemia patient during a long period of VRC therapy. In order to mimic the in vivo development of VRC resistance, a susceptible C. krusei isolate was exposed daily to 1 µg/ml of VRC in vitro. Interestingly, after 5 days of exposure to VRC, a MIC of 4 µg/ml was achieved; this value remained constant after 25 additional days of treatment with VRC and also after 30 consecutive days of incubation in VRC-free medium. Our objective was to determine the associated molecular resistance mechanisms, such as expression of efflux pump genes and ERG11 gene mutations, among the resistant strains. Synergistic effects between the efflux blocker tacrolimus (FK506) and VRC were found in all of the resistant strains. Moreover, ABC1 gene expression increased over time in both the in vivo- and in vitro-induced resistant strains, in contrast to the ABC2 and ERG11 genes, whose expression was invariably lower and constant. ERG11 gene sequencing showed two different types of mutations, i.e., heterozygosity at T1389T/C, corresponding to synonymous mutations, in C. krusei strains and a missense mutation at position T418C, resulting in a change from Tyr to His, among resistant C. krusei clinical isolates. This study highlights the relevance of ATP-dependent efflux pump (namely, Abc1p) activity in VRC resistance and describes new mutations in the ERG11 gene among resistant C. krusei clinical isolates.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Candida/efeitos dos fármacos , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genética , Esterol 14-Desmetilase/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Adulto , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Candida/genética , Candida/metabolismo , Candidíase/complicações , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Candidíase/patologia , Farmacorresistência Fúngica/efeitos dos fármacos , Fluconazol/farmacologia , Proteínas Fúngicas/metabolismo , Expressão Gênica , Humanos , Masculino , Mutação , Infecções Oportunistas/complicações , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/microbiologia , Infecções Oportunistas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Esterol 14-Desmetilase/metabolismo , Tacrolimo/farmacologia , Voriconazol/farmacologia
20.
PLoS One ; 8(6): e64884, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23750218

RESUMO

Alus are the most abundant and successful short interspersed nuclear elements found in primate genomes. In humans, they represent about 10% of the genome, although few are retrotransposition-competent and are clustered into subfamilies according to the source gene from which they evolved. Recombination between them can lead to genomic rearrangements of clinical and evolutionary significance. In this study, we have addressed the role of recombination in the origin of chimeric Alu source genes by the analysis of all known consensus sequences of human Alus. From the allelic diversity of Alu consensus sequences, validated in extant elements resulting from whole genome searches, distinct events of recombination were detected in the origin of particular subfamilies of AluS and AluY source genes. These results demonstrate that at least two subfamilies are likely to have emerged from ectopic Alu-Alu recombination, which stimulates further research regarding the potential of chimeric active Alus to punctuate the genome.


Assuntos
Elementos Alu/genética , Evolução Molecular , Recombinação Genética , Sequência de Bases , Sequência Consenso/genética , Genômica , Humanos , Mutação INDEL/genética , Dados de Sequência Molecular , Fenótipo , Polimorfismo Genético/genética
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