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1.
Microbes Environ ; 35(1)2020.
Artículo en Inglés | MEDLINE | ID: mdl-31932539

RESUMEN

Diverse members of Bradyrhizobium diazoefficiens, B. japonicum, and B. ottawaense were isolated from the roots of field-grown sorghum plants in Fukushima, and classified into "Rhizobia" with nodulated soybeans, "Free-living diazotrophs", and "Non-diazotrophs" by nitrogen fixation and nodulation assays. Genome analyses revealed that B. ottawaense members possessed genes for N2O reduction, but lacked those for the Type VI secretion system (T6SS). T6SS is a new bacterial weapon against microbial competitors. Since T6SS-possessing B. diazoefficiens and B. japonicum have mainly been isolated from soybean nodules in Japan, T6SS-lacking B. ottawaense members may be a cryptic lineage of soybean bradyrhizobia in Japan.


Asunto(s)
Biodiversidad , Bradyrhizobium/genética , Oxidorreductasas/genética , Sorghum/microbiología , Sistemas de Secreción Tipo VI/deficiencia , Bradyrhizobium/clasificación , Bradyrhizobium/aislamiento & purificación , Variación Genética , Fijación del Nitrógeno/genética , Filogenia , Nodulación de la Raíz de la Planta/genética , Raíces de Plantas/microbiología , Rhizobium/clasificación , Rhizobium/genética , Rhizobium/aislamiento & purificación , Sistemas de Secreción Tipo VI/genética
2.
Top Curr Chem (Cham) ; 378(1): 10, 2020 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-31894426

RESUMEN

Single-nucleotide variants (SNVs) that are strongly associated with many genetic diseases and tumors are important both biologically and clinically. Detection of SNVs holds great potential for disease diagnosis and prognosis. Recent advances in DNA nanotechnology have offered numerous principles and strategies amenable to the detection and quantification of SNVs with high sensitivity, specificity, and programmability. In this review, we will focus our discussion on emerging techniques making use of DNA strand displacement, a basic building block in dynamic DNA nanotechnology. Based on their operation principles, we classify current SNV detection methods into three main categories, including strategies using toehold-mediated strand displacement reactions, toehold-exchange reactions, and enzyme-mediated strand displacement reactions. These detection methods discriminate SNVs from their wild-type counterparts through subtle differences in thermodynamics, kinetics, or response to enzymatic manipulation. The remarkable programmability of dynamic DNA nanotechnology also allows the predictable design and flexible operation of diverse strand displacement probes and/or primers. Here, we offer a systematic survey of current strategies, with an emphasis on the molecular mechanisms and their applicability to in vitro diagnostics.


Asunto(s)
ADN/química , ADN/genética , Variación Genética , Nucleótidos/genética , Humanos , Nanotecnología , Hibridación de Ácido Nucleico , Sondas de Ácido Nucleico/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 1-4, 2020 Jan 10.
Artículo en Chino | MEDLINE | ID: mdl-31922584

RESUMEN

OBJECTIVE: To explore susceptibility genes for autism spectrum disorders (ASD). METHODS: Whole-exome sequencing was carried out for 60 family trios affected with sporadic ASD. Genetic variants discovered in over 10% of the patients were selected for genotype-phenotype correlation and pathway enrichment analysis using Phenolyzer software and metascape database. Combining gene-phenotypic scores, pathway-related genes associated with neural and neurite triggering were screened for the candidates. RESULTS: A total of 170 common variants were found to be associated with the ASD phenotype. Among these, there was only one high-confidence gene [SHANK2(0.8146)] and four medium-confidence genes [ERBB2(0.1322), LAMC3(0.1117), PPFIA4(0.1059), DISC1(0.1002)]. Twenty-pathways and four biological processes were found to be statistically significant by pathway enrichment analysis, which included neuron projection morphogenesis (GO: 0048812), regulation of neuroblast proliferation (GO: 1902692), modulation of excitatory postsynaptic potential (GO: 0098815), and dendrite morphogenesis (GO: 0048813). Twenty-one genes were found to be closely associated with neurological and neurite triggering, among which only SHANK2, ERBB2, and DISC1 had above-medium confidence correlation scores with the ASD phenotypes. CONCLUSION: Abnormal neuron projection morphogenesis (GO: 0048812) may be closely related to the occurrence of ASD. SHANK2, ERBB2, and DISC1 are susceptibility genes for ASD.


Asunto(s)
Trastorno del Espectro Autista , Variación Genética , Trastorno del Espectro Autista/genética , Predisposición Genética a la Enfermedad , Humanos , Fenotipo , Sinapsis/genética , Secuenciación del Exoma Completo
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 17-20, 2020 Jan 10.
Artículo en Chino | MEDLINE | ID: mdl-31922588

RESUMEN

OBJECTIVE: To explore the genetic basis of a pedigree affected with hereditary spherocytosis. METHODS: Peripheral blood samples were collected from 17 members of the pedigree. Genomic DNA of the proband was subjected to next generation sequencing. Candidate variant was validated by co-segregation analysis. pCAS2(c.5798+1G) and pCAS2(c.5798+1A) plasmids were constructed by homologous recombination and transfected into 293T cells. Reverse transcription PCR, TA cloning and Sanger sequencing were used to analyze the effect of candidate variant on splicing. Meanwhile, peripheral blood RNAs were extracted to analyze the effect of candidate variant on splicing in vivo. RESULTS: The proband was found to carry a c.5798+1G>A variant of the SPTB gene. The variant has co-segregated with the phenotype in the pedigree. In vitro and in vivo splicing experiments confirmed that the mutation has significantly affected the splicing, resulting in shift of reading frame and produced a premature termination codon. CONCLUSION: The novel c.5798+1G>A variant of the SPTB gene probably underlies the pathogenesis of hereditary spherocytosis in this pedigree.


Asunto(s)
Espectrina , Esferocitosis Hereditaria , Codón sin Sentido/genética , Variación Genética , Células HEK293 , Humanos , Mutación/genética , Linaje , Plásmidos , Empalme del ARN , Espectrina/genética , Esferocitosis Hereditaria/genética , Transfección
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 71-74, 2020 Jan 10.
Artículo en Chino | MEDLINE | ID: mdl-31922602

RESUMEN

OBJECTIVE: To explore the molecular basis for an individual with ABO subtype. METHODS: The ABO phenotype of the proband was determined by convention serological testing. Exons 6 and 7 of the ABO gene were subjected to PCR amplification and bi-directional Sanger sequencing. Haplotypes for exons 6 and 7 of the proband was determined using an ABO haplotype-specific amplification and sequencing technique. RESULTS: Red blood cells of the proband showed a 4+ agglutination strength with anti-A or anti-H, no agglutination reaction with anti-A1, and a 3+ agglutination strength with anti-B. His serum had no reaction with standard A cells, O cells or self cells, but was weakly reactive with B cells at 4℃. The proband was assigned as an ABO subtype based on his serological features. Bi-directional sequencing of the ABO gene revealed heterozygosity of 261 G/del, 297AG, 526CG, 657CT, 703GA, 803GC and 930GA, and homozygosity of 796CC in the proband. Haplotype-specific amplification and sequencing showed that one of his alleles was ABO*O.01.01, and another contained a c.796A>C variation compared with the ABO*B.01 allele, which led to replacement of methionine by leucine at position 266. Searching the ABO allele database of International Society of Blood Transfusion suggested the variation to be a novel one. CONCLUSION: The c.796A>C variation in the ABO*B.01 allele probably underlies the CisAB subtype. Accurate identification of the ABO subtype requires combined use of serological method and genetic testing.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Variación Genética , Sistema del Grupo Sanguíneo ABO/genética , Alelos , Exones , Genotipo , Humanos , Masculino , Fenotipo , Análisis de Secuencia de ADN
6.
Microbes Environ ; 35(1)2020.
Artículo en Inglés | MEDLINE | ID: mdl-31969531

RESUMEN

The Vietnamese Mekong delta is one of the largest rice-producing areas globally. Methylobacterium spp. are persistent colonizers of the rice plant and exert beneficial effects on plant growth and health. Sixty-one Methylobacterium strains belonging to seven species were predominantly isolated from the phyllosphere of rice cultivated in six Mekong delta provinces. Inoculation tests revealed that some strains exhibited plant growth-promoting activity. Moreover, three strains possessed the novel characteristics of inducing leaf bleaching and killing rice seedlings. These results revealed the complex diversity of Methylobacterium in Mekong delta rice and that healthy and productive rice cultivation requires a proper balance of Methylobacterium.


Asunto(s)
Variación Genética , Methylobacterium/genética , Oryza/microbiología , Lechuga/crecimiento & desarrollo , Lechuga/microbiología , Methylobacterium/clasificación , Methylobacterium/fisiología , Oryza/crecimiento & desarrollo , Componentes Aéreos de las Plantas/microbiología , Reguladores del Crecimiento de las Plantas/fisiología , Vietnam
7.
Ecol Lett ; 23(3): 495-505, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31919988

RESUMEN

Many generalist species consist of specialised individuals that use different resources. This within-population niche variation can stabilise population and community dynamics. Consequently, ecologists wish to identify environmental settings that promote such variation. Theory predicts that environments with greater resource diversity favour ecological diversity among consumers (via disruptive selection or plasticity). Alternatively, niche variation might be a side-effect of neutral genomic diversity in larger populations. We tested these alternatives in a metapopulation of threespine stickleback. Stickleback consume benthic and limnetic invertebrates, focusing on the former in small lakes, the latter in large lakes. Intermediate-sized lakes support generalist stickleback populations using an even mixture of the two prey types, and exhibit greater among-individual variation in diet and morphology. In contrast, genomic diversity increases with lake size. Thus, phenotypic diversity and neutral genetic polymorphism are decoupled: trophic diversity being greatest in intermediate-sized lakes with high resource diversity, whereas neutral genetic diversity is greatest in the largest lakes.


Asunto(s)
Smegmamorpha , Animales , Dieta , Variación Genética , Genómica , Invertebrados , Lagos
8.
Nat Commun ; 11(1): 527, 2020 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-31988292

RESUMEN

G-quadruplex (G4) sequences are abundant in untranslated regions (UTRs) of human messenger RNAs, but their functional importance remains unclear. By integrating multiple sources of genetic and genomic data, we show that putative G-quadruplex forming sequences (pG4) in 5' and 3' UTRs are selectively constrained, and enriched for cis-eQTLs and RNA-binding protein (RBP) interactions. Using over 15,000 whole-genome sequences, we find that negative selection acting on central guanines of UTR pG4s is comparable to that of missense variation in protein-coding sequences. At multiple GWAS-implicated SNPs within pG4 UTR sequences, we find robust allelic imbalance in gene expression across diverse tissue contexts in GTEx, suggesting that variants affecting G-quadruplex formation within UTRs may also contribute to phenotypic variation. Our results establish UTR G4s as important cis-regulatory elements and point to a link between disruption of UTR pG4 and disease.


Asunto(s)
G-Cuádruplex , Proteínas de Unión al ARN/metabolismo , Regiones no Traducidas , Estudios de Asociación Genética , Variación Genética , Humanos , Motivos de Nucleótidos , Pliegue del ARN , Proteínas de Unión al ARN/fisiología
9.
Bull Entomol Res ; 110(1): 123-135, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31190661

RESUMEN

Decreased reliance on pesticides can be achieved through a clever use of eco-evolutionary knowledge via intercropping economically valuable crops with companion plants that can hamper pest outbreaks. We created a greenhouse multi-layered microcosm system to test two potato peach aphid clones, performing alone or in competition, on mixes of genetically variable cultivars of cabbage, with and without onion. The onion acted as a nuisance/disturbance for the pest, which was generally for the benefit of the cabbage albeit both plants sharing space and nutrients. The onion effect was context-specific and differed by aphid genotype. Onion variable nuisance negatively affected the numbers of one aphid genotype (green) across all contexts, while the other genotype (pink) numbers were decreased in two contexts only. However, the green performed better than the pink on all cases of cabbage di-mixes despite its numbers being capped when the onion was present. Further, there was also a general aphid propensity to wander off the plant along with a differential production of winged morphs to escape the onion-affected environments. Moreover, through a comparative increase in dry mass, which was subject to onion and aphid effects, a diversity effect was found where the cabbages of fully genetically variable microcosms sustained similar final dry mass compared with non-infested microcosms. Our findings provide fresh insights into the use of multi-layered contextual designs that not only allow disentangling the relative effects of genetic variation and modes of interaction, but also help integrate their benefits into pest management in view of companion planting.


Asunto(s)
Áfidos , Brassica/crecimiento & desarrollo , Cebollas , Agricultura Orgánica/métodos , Animales , Brassica/genética , Variación Genética
10.
Ecol Lett ; 23(2): 265-273, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31769928

RESUMEN

The relative contributions of environmental, maternal and additive genetic factors to the Lifetime reproductive success (LRS) determine whether species can adapt to rapid environmental change. Yet to date, studies quantifying LRS across multiple generations in marine species in the wild are non-existent. Here we used 10-year pedigrees resolved for a wild orange clownfish population from Kimbe Island (PNG) and a quantitative genetic linear mixed model approach to quantify the additive genetic, maternal and environmental contributions to variation in LRS for the self-recruiting portion of the population. We found that the habitat of the breeder, including the anemone species and geographic location, made the greatest contribution to LRS. There were low to negligible contributions of genetic and maternal factors equating with low heritability and evolvability. Our findings imply that our population will be susceptible to short-term, small-scale changes in habitat structure and may have limited capacity to adapt to these changes.


Asunto(s)
Ecosistema , Reproducción , Variación Genética , Linaje
11.
Gene ; 726: 144172, 2020 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-31759981

RESUMEN

Multiple sclerosis is a chronic disease that usually occurs with exacerbations and remissions in young adults, affects the central nervous system white matter in multiple localization, and is thought to be the result of complex interactions of genetic and environmental factors, the most common form is relapsing-remitting MS. Forkhead transcription factors O class (FOXO) are responsible for the regulation of various cellular processes including cell cycle, apoptosis, DNA repair, cellular resistance and metabolism. DNA methylation is such an epigenetic change and has been shown to be associated with almost any biological process. The aim of our study to show the relation between the genetic variants of FOXO3a (rs2253310 rs4966936) and FOXO1 (rs3900833, rs4581585) and global DNA methylation in RRMS. We analyzed DNA obtained from 79 RRMS patients and 104 healthy individuals by PCR-RFLP method for the detection of genetic variants. For the determination of global DNA methylation, results were obtained using ELISA method. The data were evaluated statistically. As a result of our analysis; global DNA methylation is higher in RRMS patients compared to control individuals and it can be effective on the disease. In addition, it has been determined that variants of FOXO3a (rs2253310, rs4966936) and FOXO1 (rs3900833), which have been genotyped, may be effective in disease pathogenesis. These results suggest that DNAmethylation and FOXO gene variants may be effective in neuronal loss in RRMS.


Asunto(s)
Metilación de ADN/genética , ADN/genética , Factores de Transcripción Forkhead/genética , Variación Genética/genética , Esclerosis Múltiple Recurrente-Remitente/genética , Adulto , Epigénesis Genética/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
Hum Genet ; 139(1): 45-59, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31630246

RESUMEN

Due to its long genetic evolutionary history, Africans exhibit more genetic variation than any other population in the world. Their genetic diversity further lends itself to subdivisions of Africans into groups of individuals with a genetic similarity of varying degrees of granularity. It remains challenging to detect fine-scale structure in a computationally efficient and meaningful way. In this paper, we present a proof-of-concept of a novel fine-scale population structure detection tool with Western African samples. These samples consist of 1396 individuals from 25 ethnic groups (two groups are African American descendants). The strategy is based on a recently developed tool called IPCAPS. IPCAPS, or Iterative Pruning to CApture Population Structure, is a genetic divisive clustering strategy that enhances iterative pruning PCA, is robust to outliers and does not require a priori computation of haplotypes. Our strategy identified in total 12 groups and 6 groups were revealed as fine-scale structure detected in the samples from Cameroon, Gambia, Mali, Southwest USA, and Barbados. Our finding helped to explain evolutionary processes in the analyzed West African samples and raise awareness for fine-scale structure resolution when conducting genome-wide association and interaction studies.


Asunto(s)
Grupo de Ascendencia Continental Africana/genética , Grupos Étnicos/genética , Variación Genética , Genética de Población , Estudio de Asociación del Genoma Completo , Haplotipos , Programas Informáticos , África Occidental/etnología , Humanos
13.
Arch Virol ; 165(1): 193-199, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31701223

RESUMEN

BACKGROUD: The presence of PCV3 genome has been detected in pigs affected by different clinical and pathological conditions as well as in healthy animals. Its presence has been reported in many countries of North and South America, Asia and Europe. However, there is no evidence of the presence and genetic characteristics of PCV3 in many European countries and especially the countries of the Balkan Peninsula. PURPOSE: The major objective of this study was to investigate the presence and obtain further genetic characterization of PCV-3 in the pig populations in Serbia. METHODS: To demonstrate the presence of PCV-3 DNA a conventional PCR assay was performed. The samples where no PCR product was observed (n=32), were further tested with a real-time PCR assay. The six PCR samples that were strongly positive for PCV-3 were subjected to amplification and sequencing of their entire cap genes and complete viral genome. RESULTS: We report on the first identification, genetic diversity and potential association in pathogenesis of some systemic and respiratory swine diseases of PCV-3 in Serbia. CONCLUSION: The results imply that PCV-3 circulates widely in the pig population and has a high similarity with previously reported isolates. Detected PCV-3 can be associated with some swine systemic and respiratory diseases but these associations are strongly influenced by the clinical or pathological condition of the animals. Our findings demonstrate that there are certain PCV-3 loads in pigs suffering from active PRRSV infection, Glässer's disease, APP pleuropneumonia, pneumonic pasteurellosis and PRDC; however, the significance of this viral load, as well as the mechanism by which PCV-3 may act as a secondary agent in aggravating the severity during co-infections of these pathogens, requires further research.


Asunto(s)
Circovirus/clasificación , Enfermedades Pulmonares/veterinaria , Enfermedades de los Porcinos/virología , Secuenciación Completa del Genoma/métodos , Animales , Circovirus/aislamiento & purificación , Circovirus/patogenicidad , Granjas , Variación Genética , Enfermedades Pulmonares/virología , Filogenia , Serbia , Porcinos , Carga Viral
14.
Plant Dis ; 104(1): 94-104, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31738690

RESUMEN

In this study, 3,426 grafted grapevines ready to be planted from 15 grapevine nursery fields in Northern Spain were inspected from 2016 to 2018 for black-foot causing pathogens. In all, 1,427 isolates of black-foot pathogens were collected from the asymptomatic inner tissues of surface sterilized secondary roots and characterized based on morphological features and DNA sequence data of the nuclear ribosomal DNA-internal transcribed spacer region, histone H3, translation elongation factor 1-alpha and ß-tubulin genes. Eleven species belonging to the genera Dactylonectria, Ilyonectria, Neonectria, and Thelonectria were identified, including Dactylonectria alcacerensis, D. macrodidyma, D. novozelandica, D. pauciseptata, D. torresensis, Ilyonectria liriodendri, I. pseudodestructans, I. robusta, Neonectria quercicola, Neonectria sp. 1, and Thelonectria olida. In addition, two species are newly described, namely D. riojana and I. vivaria. Twenty-four isolates representing 13 black-foot species were inoculated onto grapevine seedlings cultivar 'Tempranillo'. The pathogenicity tests detected diversity in virulence among fungal species and between isolates within each species. The most virulent species was D. novozelandica isolate BV-0760, followed by D. alcacerensis isolate BV-1240 and I. vivaria sp. nov. isolate BV-2305. This study improves our knowledge on the etiology and virulence of black-foot disease pathogens, and opens up new perspectives in the study of the endophytic phase of these pathogens in grapevines.


Asunto(s)
Variación Genética , Hypocreales , Enfermedades de las Plantas , Vitis , Genes Fúngicos/genética , Hypocreales/clasificación , Hypocreales/citología , Hypocreales/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/estadística & datos numéricos , España , Especificidad de la Especie , Virulencia , Vitis/microbiología
15.
Mol Genet Genomics ; 295(1): 135-142, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31520189

RESUMEN

High-throughput techniques such as whole-exome sequencing (WES) show promise for the identification of candidate genes that underlie Mendelian diseases such as nephrotic syndrome (NS). These techniques have enabled the identification of a proportion of the approximately 54 genes associated with NS. However, the main pitfall of using WES in clinical and research practice is the identification of multiple variants, which hampers interpretation during downstream analysis. One useful strategy is to evaluate the co-inheritance of rare variants in affected family members. Here, we performed WES of a patient with steroid-resistant NS (SRNS) and intermittent microhematuria. Currently, 15 years after kidney transplantation, this patient presents normal kidney function. The patient was found to be homozygous for a rare MYO1E stop-gain variant, and was heterozygous for rare variants in NS-associated genes, COL4A4, KANK1, LAMB2, ANLN, E2F3, and APOL1. We evaluated the presence or absence of these variants in both parents and 11 siblings, three of whom exhibited a milder phenotype of the kidney disease. Analysis of variant segregation in the family, indicated the MYO1E stop-gain variant as the putative causal variant underlying the kidney disease in the patient and two of her affected sisters. Two secondary variants in COL4A4-identified in some other affected family members-require further functional studies to determine whether they play a role in the development of microhematuria in affected family members. Our data illustrate the difficulties in distinguishing the causal pathogenic variants from incidental findings after WES-based variant analysis, especially in heterogenous genetic conditions, such as NS.


Asunto(s)
Exoma/genética , Síndrome Nefrótico/genética , Adulto , Femenino , Variación Genética/genética , Heterocigoto , Homocigoto , Humanos , Riñón/patología , Masculino , Linaje , Fenotipo , Secuenciación del Exoma Completo/métodos , Adulto Joven
16.
Phytopathology ; 110(1): 49-57, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31524081

RESUMEN

Mixed viral infections are common in plants, and the evolutionary dynamics of viral populations may differ depending on whether the infection is caused by single or multiple viral strains. However, comparative studies of single and mixed infections using viral populations in comparable agricultural and geographical locations are lacking. Here, we monitored the occurrence of pepino mosaic virus (PepMV) in tomato crops in two major tomato-producing areas in Murcia (southeastern Spain), supporting evidence showing that PepMV disease-affected plants had single infections of the Chilean 2 (CH2) strain in one area and the other area exhibited long-term (13 years) coexistence of the CH2 and European (EU) strains. We hypothesized that circulating strains of PepMV might be modulating the differentiation between them and shaping the evolutionary dynamics of PepMV populations. Our phylogenetic analysis of 106 CH2 isolates randomly selected from both areas showed a remarkable divergence between the CH2 isolates, with increased nucleotide variability in the geographical area where both strains cocirculate. Furthermore, the potential virus-virus interaction was studied further by constructing six full-length infectious CH2 clones from both areas, and assessing their viral fitness in the presence and absence of an EU-type isolate. All CH2 clones showed decreased fitness in mixed infections and although complete genome sequencing indicated a nucleotide divergence of those CH2 clones by area, the magnitude of the fitness response was irrespective of the CH2 origin. Overall, these results suggest that although agroecological cropping practices may be particularly important for explaining the evolutionary dynamics of PepMV in tomato crops, the cocirculation of both strains may have implications on the genetic variability of PepMV populations.


Asunto(s)
Variación Genética , Lycopersicon esculentum , Potexvirus , Genética de Población , Lycopersicon esculentum/virología , Filogenia , Enfermedades de las Plantas/virología , Potexvirus/genética , España/epidemiología
17.
Arch Virol ; 165(1): 21-31, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31624917

RESUMEN

To obtain insight into the sequence diversity of strawberry latent ringspot virus (SLRSV), isolates from collections and diagnostic samples were sequenced by high-throughput sequencing. For five SLRSV isolates, the complete genome sequences were determined, and for 18 other isolates nearly complete genome sequences were determined. The sequence data were analysed in relation to sequences of SLRSV and related virus isolates available in the NCBI GenBank database. The genome sequences were annotated, and sequences of the protease-polymerase (Pro-Pol) region and coat proteins (CPs) (large and small CP together) were used for phylogenetic analysis. The amino acid sequences of the Pro-Pol region were very similar, whereas the nucleotide sequences of this region were more variable. The amino acid sequences of the CPs were less similar, which was corroborated by the results of a serological comparison performed using antisera raised against different isolates of SLRSV. Based on these results, we propose that SLRSV and related unassigned viruses be assigned to a new genus within the family Secoviridae, named "Stralarivirus". Based on the phylogenetic analysis, this genus should include at least three viruses, i.e., SLRSV-A, SLRSV-B and lychnis mottle virus. The newly generated sequence data provide a basis for designing molecular tests to screen for SLRSV.


Asunto(s)
Fragaria/virología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Secoviridae/clasificación , Análisis de Secuencia de ARN/métodos , Proteínas de la Cápside/genética , ARN Polimerasas Dirigidas por ADN/genética , Variación Genética , Anotación de Secuencia Molecular , Péptido Hidrolasas/genética , Filogenia , Virus de Plantas/clasificación , Virus de Plantas/genética , Virus de Plantas/aislamiento & purificación , ARN Viral/genética , Secoviridae/genética , Secoviridae/aislamiento & purificación
18.
Cell Mol Life Sci ; 77(2): 365-378, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31254042

RESUMEN

The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics; thus the relatively frequent polymorphic and mutant ABCG2 variants in the population may significantly alter disease conditions and pharmacological effects. Low-level or non-functional ABCG2 expression may increase individual drug toxicity, reduce cancer drug resistance, and result in hyperuricemia and gout. In the present work we have studied the cellular expression, trafficking, and function of nine naturally occurring polymorphic and mutant variants of ABCG2. A comprehensive analysis of the membrane localization, transport, and ATPase activity, as well as retention and degradation in intracellular compartments was performed. Among the examined variants, R147W and R383C showed expression and/or protein folding defects, indicating that they could indeed contribute to ABCG2 functional deficiency. These studies and the applied methods should significantly promote the exploration of the medical effects of these personal variants, promote potential therapies, and help to elucidate the specific role of the affected regions in the folding and function of the ABCG2 protein.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Resistencia a Antineoplásicos/genética , Variación Genética/genética , Proteínas de Neoplasias/genética , Adenosina Trifosfatasas/genética , Línea Celular , Línea Celular Tumoral , Células HEK293 , Células HeLa , Humanos , Transporte de Proteínas/genética
19.
Gut ; 69(2): 264-273, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31097538

RESUMEN

OBJECTIVE: The interleukin (IL)23 pathway contributes to IBD pathogenesis and is being actively studied as a therapeutic target in patients with IBD. Unexpected outcomes in these therapeutic trials have highlighted the importance of understanding the cell types and mechanisms through which IL23 regulates immune outcomes. How IL23 regulates macrophage outcomes and the consequences of the IL23R R381Q IBD-protective variant on macrophages are not well defined; macrophages are key players in IBD pathogenesis and inflammation. DESIGN: We analysed protein and RNA expression, signalling and localisation in human monocyte-derived macrophages (MDMs) through western blot, ELISA, real-time PCR, flow cytometry, immunoprecipitation and microscopy. RESULTS: IL23R was critical for optimal levels of pattern-recognition receptor (PRR)-induced signalling and cytokines in human MDMs. In contrast to the coreceptor IL12Rß1, IL23 induced dynamic IL23R cell surface regulation and this required clathrin and dynamin-mediated endocytosis and endocytic recycling-dependent pathways; these pathways were essential for IL23R-mediated outcomes. The IBD-protective IL23R R381Q variant showed distinct outcomes. Relative to IL23R R381, HeLa cells expressing IL23R Q381 showed decreased IL23R recycling and reduced assembly of IL23R Q381 with Janus kinase/signal transducer and activator of transcription pathway members. In MDMs from IL23R Q381 carriers, IL23R accumulated in late endosomes and lysosomes on IL23 treatment and cells demonstrated decreased IL23R- and PRR-induced signalling and cytokines relative to IL23R R381 MDMs. CONCLUSION: Macrophage-mediated inflammatory pathways are key contributors to IBD pathogenesis, and we identify an autocrine/paracrine IL23 requirement in PRR-initiated human macrophage outcomes and in human intestinal myeloid cells, establish that IL23R undergoes ligand-induced recycling, define mechanisms regulating IL23R-induced signalling and determine how the IBD-protective IL23R R381Q variant modulates these processes.


Asunto(s)
Citocinas/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Macrófagos/inmunología , Receptores de Interleucina/inmunología , Comunicación Autocrina/inmunología , Endocitosis/inmunología , Endosomas/inmunología , Variación Genética , Humanos , Inmunidad Innata/genética , Inmunidad Innata/inmunología , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/prevención & control , Interleucina-23/inmunología , Janus Quinasa 2/metabolismo , Comunicación Paracrina/inmunología , Receptores de Interleucina/genética , Receptores de Reconocimiento de Patrones/inmunología , Transducción de Señal/inmunología
20.
Hum Genet ; 139(1): 121-136, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31134333

RESUMEN

In the current era, with increasing availability of results from genetic association studies, finding genetic instruments for inferring causality in observational epidemiology has become apparently simple. Mendelian randomisation (MR) analyses are hence growing in popularity and, in particular, methods that can incorporate multiple instruments are being rapidly developed for these applications. Such analyses have enormous potential, but they all rely on strong, different, and inherently untestable assumptions. These have to be clearly stated and carefully justified for every application in order to avoid conclusions that cannot be replicated. In this article, we review the instrumental variable assumptions and discuss the popular linear additive structural model. We advocate the use of tests for the null hypothesis of 'no causal effect' and calculation of the bounds for a causal effect, whenever possible, as these do not rely on parametric modelling assumptions. We clarify the difference between a randomised trial and an MR study and we comment on the importance of validating instruments, especially when considering them for joint use in an analysis. We urge researchers to stand by their convictions, if satisfied that the relevant assumptions hold, and to interpret their results causally since that is the only reason for performing an MR analysis in the first place.


Asunto(s)
Variación Genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana/métodos , Epidemiología Molecular/métodos , Humanos
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