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1.
Proc Natl Acad Sci U S A ; 121(10): e2319366121, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38422020

RESUMEN

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.


Asunto(s)
Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Anciano , Humanos , Masculino , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Envejecimiento/genética , Mutación , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Pronóstico
2.
Sci Bull (Beijing) ; 68(21): 2607-2619, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37798178

RESUMEN

Epstein-Barr virus (EBV) is the oncogenic driver of multiple cancers. However, the underlying mechanism of virus-cancer immunological interaction during disease pathogenesis remains largely elusive. Here we reported the first comprehensive proteogenomic characterization of natural killer/T-cell lymphoma (NKTCL), a representative disease model to study EBV-induced lymphomagenesis, incorporating genomic, transcriptomic, and in-depth proteomic data. Our multi-omics analysis of NKTCL revealed that EBV gene pattern correlated with immune-related oncogenic signaling. Single-cell transcriptome further delineated the tumor microenvironment as immune-inflamed, -deficient, and -desert phenotypes, in association with different setpoints of cancer-immunity cycle. EBV interacted with transcriptional factors to provoke GPCR interactome (GPCRome) reprogramming. Enhanced expression of chemokine receptor-1 (CCR1) on malignant and immunosuppressive cells modulated virus-cancer interaction on microenvironment. Therapeutic targeting CCR1 showed promising efficacy with EBV eradication, T-cell activation, and lymphoma cell killing in NKTCL organoid. Collectively, our study identified a previously unknown GPCR-mediated malignant progression and translated sensors of viral molecules into EBV-specific anti-cancer therapeutics.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfoma , Células T Asesinas Naturales , Humanos , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Proteómica , Linfoma/complicaciones , Células T Asesinas Naturales/patología , Microambiente Tumoral/genética
3.
Proc Natl Acad Sci U S A ; 119(49): e2211429119, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36442087

RESUMEN

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. Robust identification of clinically and biologically relevant molecular subtypes from nongenomic high-throughput sequencing data remains challenging. We established the largest multicenter AML cohort (n = 655) in China, with all patients subjected to RNA sequencing (RNA-Seq) and 619 (94.5%) to targeted or whole-exome sequencing (TES/WES). Based on an enhanced consensus clustering, eight stable gene expression subgroups (G1-G8) with unique clinical and biological significance were identified, including two unreported (G5 and G8) and three redefined ones (G4, G6, and G7). Apart from four well-known low-risk subgroups including PML::RARA (G1), CBFB::MYH11 (G2), RUNX1::RUNX1T1 (G3), biallelic CEBPA mutations or -like (G4), four meta-subgroups with poor outcomes were recognized. The G5 (myelodysplasia-related/-like) subgroup enriched clinical, cytogenetic and genetic features mimicking secondary AML, and hotspot mutations of IKZF1 (p.N159S) (n = 7). In contrast, most NPM1 mutations and KMT2A and NUP98 fusions clustered into G6-G8, showing high expression of HOXA/B genes and diverse differentiation stages, from hematopoietic stem/progenitor cell down to monocyte, namely HOX-primitive (G7), HOX-mixed (G8), and HOX-committed (G6). Through constructing prediction models, the eight gene expression subgroups could be reproduced in the Cancer Genome Atlas (TCGA) and Beat AML cohorts. Each subgroup was associated with distinct prognosis and drug sensitivities, supporting the clinical applicability of this transcriptome-based classification of AML. These molecular subgroups illuminate the complex molecular network of AML, which may promote systematic studies of disease pathogenesis and foster the screening of targeted agents based on omics.


Asunto(s)
Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Transcriptoma , Leucemia Mieloide Aguda/genética , Diferenciación Celular/genética , Células Madre Hematopoyéticas
4.
Proc Natl Acad Sci U S A ; 119(15): e2120787119, 2022 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-35385357

RESUMEN

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1­G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1­G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7­G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9­G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Transcriptoma , Niño , Humanos , Mutación , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética
5.
EBioMedicine ; 8: 173-183, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27428428

RESUMEN

Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4-IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.


Asunto(s)
Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica , Genómica , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Transcriptoma , Adolescente , Adulto , Anciano , Médula Ósea/patología , Niño , Preescolar , Análisis por Conglomerados , Variaciones en el Número de Copia de ADN , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Persona de Mediana Edad , Mutación , Tasa de Mutación , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Pronóstico , Adulto Joven
6.
Sci Rep ; 5: 14139, 2015 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-26420475

RESUMEN

Of the two cultivated species of allopolyploid cotton, Gossypium barbadense produces extra-long fibers for the production of superior textiles. We sequenced its genome (AD)2 and performed a comparative analysis. We identified three bursts of retrotransposons from 20 million years ago (Mya) and a genome-wide uneven pseudogenization peak at 11-20 Mya, which likely contributed to genomic divergences. Among the 2,483 genes preferentially expressed in fiber, a cell elongation regulator, PRE1, is strikingly At biased and fiber specific, echoing the A-genome origin of spinnable fiber. The expansion of the PRE members implies a genetic factor that underlies fiber elongation. Mature cotton fiber consists of nearly pure cellulose. G. barbadense and G. hirsutum contain 29 and 30 cellulose synthase (CesA) genes, respectively; whereas most of these genes (>25) are expressed in fiber, genes for secondary cell wall biosynthesis exhibited a delayed and higher degree of up-regulation in G. barbadense compared with G. hirsutum, conferring an extended elongation stage and highly active secondary wall deposition during extra-long fiber development. The rapid diversification of sesquiterpene synthase genes in the gossypol pathway exemplifies the chemical diversity of lineage-specific secondary metabolites. The G. barbadense genome advances our understanding of allopolyploidy, which will help improve cotton fiber quality.


Asunto(s)
Evolución Biológica , Fibra de Algodón , Genoma de Planta , Genómica , Gossypium/genética , Gossypium/metabolismo , Metabolómica , Transferasas Alquil y Aril/genética , Transferasas Alquil y Aril/metabolismo , Cromosomas de las Plantas , Análisis por Conglomerados , Biología Computacional/métodos , Perfilación de la Expresión Génica , Estudios de Asociación Genética , Genómica/métodos , Metabolómica/métodos , Anotación de Secuencia Molecular , Fenotipo , Filogenia , Poliploidía , Carácter Cuantitativo Heredable , Sesquiterpenos/metabolismo , Translocación Genética , Fitoalexinas
7.
EBioMedicine ; 2(6): 583-90, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26288819

RESUMEN

Air pollution has been classified as Group 1 carcinogenic to humans, but the underlying tumorigenesis remains unclear. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China attributed to severe air pollution generated by combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis of air pollution. Here we analyzed the somatic mutations of 164 non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used. Whole genome sequencing revealed a mean of 289 somatic exonic mutations per tumor and the frequent C:G â†’ A:T nucleotide substitutions in Xuanwei NSCLCs. Exome sequencing of 2010 genes showed that Xuanwei and CR NSCLCs had a mean of 68 and 22 mutated genes per tumor, respectively (p < 0.0001). We found 167 genes (including TP53, RYR2, KRAS, CACNA1E) which had significantly higher mutation frequencies in Xuanwei than CR patients, and mutations in most genes in Xuanwei NSCLCs differed from those in CR cases. The mutation rates of 70 genes (e.g., RYR2, MYH3, GPR144, CACNA1E) were associated with patients' lifetime benzo(a)pyrene exposure. This study uncovers the mutation spectrum of air pollution-related lung cancers, and provides evidence for pollution exposure-genomic mutation relationship at a large scale.


Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Benzo(a)pireno/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Anciano , Secuencia de Bases , Carcinoma de Pulmón de Células no Pequeñas/inducido químicamente , Transformación Celular Neoplásica , Carbón Mineral/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Frecuencia de los Genes/genética , Genoma/genética , Humanos , Neoplasias Pulmonares/inducido químicamente , Masculino , Persona de Mediana Edad , Mutación/genética , Tasa de Mutación , Análisis de Secuencia de ADN , Humo/efectos adversos
8.
PLoS One ; 9(6): e100794, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24967843

RESUMEN

In this study, we present the complete genome of Fimbriimonas ginsengisoli Gsoil 348T belonging to the class Fimbriimonadia of the phylum Armatimonadetes, formerly called as candidate phylum OP10. The complete genome contains a single circular chromosome of 5.23 Mb including a 45.5 kb prophage. Of the 4820 open reading frames (ORFs), 3,000 (62.2%) genes could be classified into Clusters of Orthologous Groups (COG) families. With the split of rRNA genes, strain Gsoil 348T had no typical 16S-23S-5S ribosomal RNA operon. In this genome, the GC skew inversion which was usually observed in archaea was found. The predicted gene functions suggest that the organism lacks the ability to synthesize histidine, and the TCA cycle is incomplete. Phylogenetic analyses based on ribosomal proteins indicated that strain Gsoil 348T represents a deeply branching lineage of sufficient divergence with other phyla, but also strongly involved in superphylum Terrabacteria.


Asunto(s)
Bacterias/genética , Genómica , Transportadoras de Casetes de Unión a ATP/genética , Bacterias/citología , Bacterias/metabolismo , Bacterias/virología , Sistemas de Secreción Bacterianos/genética , Proliferación Celular , Replicación del ADN/genética , Elementos Transponibles de ADN/genética , Metabolismo Energético/genética , Evolución Molecular , Genoma Bacteriano/genética , Familia de Multigenes/genética , Operón/genética , Oxígeno/metabolismo , Filogenia , Profagos/genética , Vitaminas/metabolismo
9.
Proc Natl Acad Sci U S A ; 111(23): 8589-94, 2014 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-24850867

RESUMEN

Myelodysplastic syndrome (MDS) includes a group of diseases characterized by dysplasia of bone marrow myeloid lineages with ineffective hematopoiesis and frequent evolution to acute myeloid leukemia (AML). Whole-genome sequencing was performed in CD34(+) hematopoietic stem/progenitor cells (HSPCs) from eight cases of refractory anemia with excess blasts (RAEB), the high-risk subtype of MDS. The nucleotide substitution patterns were found similar to those reported in AML, and mutations of 96 protein-coding genes were identified. Clonal architecture analysis revealed the presence of subclones in six of eight cases, whereas mutation detection of CD34(+) versus CD34(-) cells revealed heterogeneity of HSPC expansion status. With 39 marker genes belonging to eight functional categories, mutations were analyzed in 196 MDS cases including mostly RAEB (n = 89) and refractory cytopenia with multilineage dysplasia (RCMD) (n = 95). At least one gene mutation was detected in 91.0% of RAEB, contrary to that in RCMD (55.8%), suggesting a higher mutational burden in the former group. Gene abnormality patterns differed between MDS and AML, with mutations of activated signaling molecules and NPM1 being rare, whereas those of spliceosome more common, in MDS. Finally, gene mutation profiles also bore prognostic value in terms of overall survival and progression free survival.


Asunto(s)
Genoma Humano/genética , Genómica/métodos , Células Madre Hematopoyéticas/metabolismo , Mutación , Síndromes Mielodisplásicos/genética , Antígenos CD34/metabolismo , Biomarcadores de Tumor/genética , Diferenciación Celular/genética , Proliferación Celular , Evolución Clonal , Femenino , Humanos , Estimación de Kaplan-Meier , Cariotipificación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Síndromes Mielodisplásicos/diagnóstico , Nucleofosmina , Pronóstico , Análisis de Secuencia de ADN/métodos
10.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 24(2): 137-41, 149, 2012 Apr.
Artículo en Chino | MEDLINE | ID: mdl-22799154

RESUMEN

OBJECTIVE: To clone and express heat-shock protein 40 gene of Schistosoma japonicum (SjHSP40) and analyze its effect on macrophage activation. METHODS: The fragment of gene encoding SjHSP40 was amplified by PCR. The gene was sub-cloned into the prokaryotic expression vector pGEX-6P-1. The recombinant plasmid pGEX-6P-1-SjHSP40 was transformed into E. coli BL21 (DE3) and induced with IPTG. The recombinant protein was purified with Glutathione-Sepharose 4B resin and analyzed by SDS-PAGE and Western-blot. The fusion protein of GST-SjHSP40 was loaded to the macrophage cell-line RAW264.7 for 48 h. Following that, the surface molecules of the macrophages were analyzed by flow cytometry. RESULTS: DNA sequencing showed that the recombinant plasmid, pGEX-6P-1-SjHSP40, was successfully constructed. The fusion protein of GST-SjHSP40 was induced, purified and specifically recognized by anti-GST antibody. Compared to GST and medium control groups, this fusion protein significantly induced the expression of co-stimulatory molecules (CD40, CD80, and CD86) and MHC-II on the surface of the macrophages. CONCLUSIONS: SjHSP40 significantly up-regulates the expression of co-stimulatory molecules and MHC-II on the surface of the macrophages. These data indicate that SjHSP40 may initiate macrophage activation.


Asunto(s)
Proteínas del Choque Térmico HSP40/metabolismo , Activación de Macrófagos/inmunología , Macrófagos/inmunología , Schistosoma japonicum/inmunología , Schistosoma japonicum/metabolismo , Esquistosomiasis Japónica/inmunología , Animales , Línea Celular , Clonación Molecular , Proteínas del Choque Térmico HSP40/genética , Proteínas del Choque Térmico HSP40/aislamiento & purificación , Ratones , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/metabolismo , Schistosoma japonicum/genética , Esquistosomiasis Japónica/metabolismo
11.
PLoS Negl Trop Dis ; 6(3): e1579, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22479661

RESUMEN

BACKGROUND: Schistosomiasis japonica is a serious debilitating and sometimes fatal disease. Accurate diagnostic tests play a key role in patient management and control of the disease. However, currently available diagnostic methods are not ideal, and the detection of the parasite DNA in blood samples has turned out to be one of the most promising tools for the diagnosis of schistosomiasis. In our previous investigations, a 230-bp sequence from the highly repetitive retrotransposon SjR2 was identified and it showed high sensitivity and specificity for detecting Schistosoma japonicum DNA in the sera of rabbit model and patients. Recently, 29 retrotransposons were found in S. japonicum genome by our group. The present study highlighted the key factors for selecting a new perspective sensitive target DNA sequence for the diagnosis of schistosomiasis, which can serve as example for other parasitic pathogens. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we demonstrated that the key factors based on the bioinformatic analysis for selecting target sequence are the higher genome proportion, repetitive complete copies and partial copies, and active ESTs than the others in the chromosome genome. New primers based on 25 novel retrotransposons and SjR2 were designed and their sensitivity and specificity for detecting S. japonicum DNA were compared. The results showed that a new 303-bp sequence from non-long terminal repeat (LTR) retrotransposon (SjCHGCS19) had high sensitivity and specificity. The 303-bp target sequence was amplified from the sera of rabbit model at 3 d post-infection by nested-PCR and it became negative at 17 weeks post-treatment. Furthermore, the percentage sensitivity of the nested-PCR was 97.67% in 43 serum samples of S. japonicum-infected patients. CONCLUSIONS/SIGNIFICANCE: Our findings highlighted the key factors based on the bioinformatic analysis for selecting target sequence from S. japonicum genome, which provide basis for establishing powerful molecular diagnostic techniques that can be used for monitoring early infection and therapy efficacy to support schistosomiasis control programs.


Asunto(s)
Técnicas de Diagnóstico Molecular/métodos , Parasitología/métodos , Retroelementos , Schistosoma japonicum/aislamiento & purificación , Esquistosomiasis/diagnóstico , Animales , Biología Computacional , Cartilla de ADN/genética , Femenino , Humanos , Reacción en Cadena de la Polimerasa/métodos , Conejos , Schistosoma japonicum/genética , Sensibilidad y Especificidad , Suero/parasitología
12.
Biomed Environ Sci ; 25(1): 82-90, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22424631

RESUMEN

OBJECTIVE: To evaluate four candidate variable number tandem repeat (VNTR) loci for genotyping Mycobacterium tuberculosis complex strains. METHODS: Genomic sequences for two M. tuberculosis strains (CCDC5079 and CCDC5180) were generated, and using published sequence data, four candidate VNTR loci were identified. The VNTRs were used to genotype 225 Chinese clinical M. tuberculosis complex strains. The discriminatory power of the VNTRs was evaluated using BioNumerics 5.0 software. RESULTS: The Hunter-Gaston Index (HGI) for BJ1, BJ2, BJ3, and BJ4 loci was 0.634, 0.917, 0.697, and 0.910, respectively. Combining all four loci gave an HGI value of 0.995, thus confirming that the genotyping had good discriminatory power. The HGI values for BJ1, BJ2, BJ3, and BJ4, obtained from Beijing family strain genotyping, were 0.447, 0.878, 0.315, and 0.850, respectively. Combining all four loci produced an HGI value of 0.988 for genotyping the Beijing family strains. We observed unique patterns for M. bovis and M. africanum strains from the four loci. CONCLUSION: We have shown that the four VNTR loci can be successfully used for genotyping M. tuberculosis complex strains. Notably, these new loci may provide additional information about Chinese M. tuberculosis isolates than that currently afforded by established VNTR loci typing.


Asunto(s)
Técnicas de Genotipaje , Repeticiones de Minisatélite , Mycobacterium tuberculosis/genética , Análisis por Conglomerados , Humanos , Mycobacterium bovis/genética
13.
Genomics ; 99(1): 59-65, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22100282

RESUMEN

Hox genes are characterized by a highly conserved peptide domain and contribute to antero-posterior axis patterning during embryogenesis. These genes have been widely studied in a variety of animal species due to their central role in evolutionary developmental biology. Based on the published genome assembly and unpublished re-sequencing project data, we present the first genome-wide characterization and comparative genomic analysis of the Hox gene family within Schistosoma japonicum. Eight Hox genes were identified and validated in our investigation. Phylogenetic analysis revealed that these genes are distributed among seven orthology groups of the Hox gene family. Our study further suggested that differences in the Lox5 gene copy number existed between the two closely related species, S. japonicum and Schistosoma mansoni. Semi-quantitative real-time polymerase chain reaction experiments revealed that Lox5 and Hox4 gene expression was high in the schistosomulum stage, and all four genes investigated showed highest expression within the eggs.


Asunto(s)
Genes Homeobox , Schistosoma japonicum/genética , Secuencia de Aminoácidos , Animales , Dosificación de Gen , Expresión Génica , Genoma , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena en Tiempo Real de la Polimerasa
14.
J Genet Genomics ; 38(6): 243-52, 2011 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-21703548

RESUMEN

Acidithiobacillus caldus is one of the dominant sulfur-oxidizing bacteria in bioleaching reactors. It plays the essential role in maintaining the high acidity and oxidation of reduced inorganic sulfur compounds during bioleaching process. In this report, the complete genome sequence of A. caldus SM-1 is presented. The genome is composed of one chromosome (2,932,225 bp) and four plasmids (pLAtc1, pLAtc2, pLAtc3, pLAtcm) and it is rich in repetitive sequences (accounting for 11% of the total genome), which are often associated with transposable genetic elements. In particular, twelve copies of ISAtfe and thirty-seven copies of ISAtc1 have been identified, suggesting that they are active transposons in the genome. A. caldus SM-1 encodes all enzymes for the central metabolism and the assimilation of carbon compounds, among which 29 proteins/enzymes were identifiable with proteomic tools. The SM-1 fixes CO(2)via the classical Calvin-Bassham-Benson (CBB) cycle, and can operate complete Embden-Meyerhof pathway (EMP), pentose phosphate pathway (PPP), and gluconeogenesis. It has an incomplete tricarboxylic acid cycle (TCA). Four putative transporters involved in carbohydrate uptake were identified. Taken together, the results suggested that SM-1 was able to assimilate carbohydrates and this was subsequently confirmed experimentally because addition of 1% glucose or sucrose in basic salt medium significantly increased the growth of SM-1. It was concluded that the complete genome of SM-1 provided fundamental data for further investigation of its physiology and genetics, in addition to the carbon metabolism revealed in this study.


Asunto(s)
Acidithiobacillus/genética , Carbono/metabolismo , Genoma Bacteriano , Metabolismo de los Hidratos de Carbono/genética , Dióxido de Carbono/metabolismo , Cromosomas/genética , Elementos Transponibles de ADN/genética , Gluconeogénesis/genética , Glucólisis/genética , Vía de Pentosa Fosfato/genética , Fotosíntesis/genética , Plásmidos/genética
15.
Extremophiles ; 15(4): 487-97, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21607549

RESUMEN

The Acidianus hospitalis W1 genome consists of a minimally sized chromosome of about 2.13 Mb and a conjugative plasmid pAH1 and it is a host for the model filamentous lipothrixvirus AFV1. The chromosome carries three putative replication origins in conserved genomic regions and two large regions where non-essential genes are clustered. Within these variable regions, a few orphan orfB and other elements of the IS200/607/605 family are concentrated with a novel class of MITE-like repeat elements. There are also 26 highly diverse vapBC antitoxin-toxin gene pairs proposed to facilitate maintenance of local chromosomal regions and to minimise the impact of environmental stress. Complex and partially defective CRISPR/Cas/Cmr immune systems are present and interspersed with five vapBC gene pairs. Remnants of integrated viral genomes and plasmids are located at five intron-less tRNA genes and several non-coding RNA genes are predicted that are conserved in other Sulfolobus genomes. The putative metabolic pathways for sulphur metabolism show some significant differences from those proposed for other Acidianus and Sulfolobus species. The small and relatively stable genome of A. hospitalis W1 renders it a promising candidate for developing the first Acidianus genetic systems.


Asunto(s)
Acidianus/genética , Acidianus/virología , Virus de Archaea/genética , Genoma Arqueal/fisiología , Genoma Viral/fisiología , Plásmidos/genética , Acidianus/metabolismo , Proteínas Arqueales/genética , Proteínas Arqueales/metabolismo , Virus de Archaea/metabolismo , Plásmidos/metabolismo
16.
J Integr Plant Biol ; 52(11): 1008-15, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20977658

RESUMEN

Bamboo occupies an important phylogenetic node in the grass family and plays a significant role in the forest industry. We produced 1.2 Mb of tetraploid moso bamboo (Phyllostachys pubescens E. Mazel ex H. de Leh.) sequences from 13 bacterial artificial chromosome (BAC) clones, and these are the largest genomic sequences available so far from the subfamily Bambusoideae. The content of repetitive elements (36.2%) in bamboo is similar to that in rice. Both rice and sorghum exhibit high genomic synteny with bamboo, which suggests that rice and sorghum may be useful as models for decoding Bambusoideae genomes.


Asunto(s)
Bambusa/genética , Genoma de Planta/genética , Oryza/genética , Sorghum/genética , Sintenía/genética , Secuencia de Bases , Cromosomas Artificiales Bacterianos/genética , Clonación Molecular , Genes de Plantas/genética , Anotación de Secuencia Molecular , Datos de Secuencia Molecular , Secuencias Repetitivas de Ácidos Nucleicos/genética , Análisis de Secuencia de ADN , Zea mays/genética
17.
BMC Microbiol ; 10: 67, 2010 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-20196873

RESUMEN

BACKGROUND: Leptospira is the causative agent of leptospirosis. The O-antigen is the distal part of the lipopolysaccharide, which is a key component of outer membrane of Gram-negative bacteria and confers serological specificity. The epidemiology and clinical characteristics of leptospirosis are relative to the serology based taxonomic unit. Identification of Leptospira strains by serotyping is laborious and has several drawbacks. RESULTS: In this study, the O-antigen gene clusters of four epidemic Leptospira serogroups (serogroup Canicola, Autumnalis, Grippotyphosa and Hebdomadis) in China were sequenced and all genes were predicted in silico. Adding published sequences of two serogroups, Icterohaemorrhagiae (strain Lai and Fiocruz L1-130) and Sejroe (strain JB197 and L550), we identified six O-antigen-specific genes for six epidemic serogroups in China. PCR assays using these genes were developed and tested on 75 reference strains and 40 clinical isolates. CONCLUSION: The results show that the PCR-based assays can be reliable and alternative means for rapid typing of these six serogroups of Leptospira.


Asunto(s)
Leptospira/genética , Leptospirosis/microbiología , Familia de Multigenes , Antígenos O/genética , Reacción en Cadena de la Polimerasa/métodos , Serotipificación/métodos , Pruebas de Aglutinación , China/epidemiología , Simulación por Computador , Brotes de Enfermedades , Electroforesis en Gel de Agar , Humanos , Leptospirosis/epidemiología , Sensibilidad y Especificidad
18.
Appl Environ Microbiol ; 75(21): 6812-9, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19734336

RESUMEN

Members of the gram-negative, strictly aerobic genus Comamonas occur in various environments. Here we report the complete genome of Comamonas testosteroni strain CNB-2. Strain CNB-2 has a circular chromosome that is 5,373,643 bp long and has a G+C content of 61.4%. A total of 4,803 open reading frames (ORFs) were identified; 3,514 of these ORFs are functionally assigned to energy production, cell growth, signal transduction, or transportation, while 866 ORFs encode hypothetical proteins and 423 ORFs encode purely hypothetical proteins. The CNB-2 genome has many genes for transportation (22%) and signal transduction (6%), which allows the cells to respond and adapt to changing environments. Strain CNB-2 does not assimilate carbohydrates due to the lack of genes encoding proteins involved in glycolysis and pentose phosphate pathways, and it contains many genes encoding proteins involved in degradation of aromatic compounds. We identified 66 Tct and nine TRAP-T systems and a complete tricarboxylic acid cycle, which may allow CNB-2 to take up and metabolize a range of carboxylic acids. This nutritional bias for carboxylic acids and aromatic compounds enables strain CNB-2 to occupy unique niches in environments. Four different sets of terminal oxidases for the respiratory system were identified, and they putatively functioned at different oxygen concentrations. This study conclusively revealed at the genomic level that the genetic versatility of C. testosteroni is vital for competition with other bacteria in its special niches.


Asunto(s)
Adaptación Biológica , Comamonas testosteroni/genética , ADN Bacteriano/genética , Evolución Molecular , Genoma Bacteriano , Análisis de Secuencia de ADN , Composición de Base , Cromosomas Bacterianos , ADN Bacteriano/química , ADN Circular/genética , Metabolismo Energético/genética , Orden Génico , Redes y Vías Metabólicas/genética , Datos de Secuencia Molecular , Familia de Multigenes , Sistemas de Lectura Abierta
19.
Annu Rev Genomics Hum Genet ; 10: 211-40, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19630560

RESUMEN

Schistosomiasis, caused mainly by Schistosoma japonicum, S. mansoni, and S. hematobium, remains one of the most prevalent and serious parasitic diseases worldwide. The blood flukes have a complex life cycle requiring adaptation for survival in fresh water as free-living forms and as parasites in snail intermediate and vertebrate definitive hosts. Functional genomics analyses, including transcriptomic and proteomic approaches, have been performed on schistosomes, in particular S. mansoni and S. japonicum, using powerful high-throughput methodologies. These investigations have not only chartered gene expression profiles across genders and developmental stages within mammalian and snail hosts, but have also characterized the features of the surface tegument, the eggshell and excretory-secretory proteomes of schistosomes. The integration of the genomic, transcriptomic, and proteomic information, together with genetic manipulation on individual genes, will provide a global insight into the molecular architecture of the biology, pathogenesis, and host-parasite interactions of the human blood flukes. Importantly, these functional genomics analyses lay a foundation on which to develop new antischistosome vaccines as well as drug targets and diagnostic markers for treatment and control of schistosomiasis.


Asunto(s)
Genoma de los Helmintos , Genómica , Interacciones Huésped-Parásitos , Schistosoma/genética , Esquistosomiasis/parasitología , Animales , Humanos , Polimorfismo Genético , Schistosoma/clasificación , Schistosoma/fisiología , Esquistosomiasis/diagnóstico , Esquistosomiasis/terapia
20.
J Bacteriol ; 191(15): 5020-1, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19465650

RESUMEN

Lactobacillus plantarum is a lactic acid bacterium (LAB) species commonly used as a probiotic. We have sequenced the genome of Lactobacillus plantarum JDM1, which is a Chinese commercial LAB with several probiotic functions, using a GS 20 system. We recommend that each commercial probiotic strain should undergo complete genome sequencing to ensure safety and stability.


Asunto(s)
Genoma Bacteriano/genética , Lactobacillus plantarum/genética , Cromosomas Bacterianos/genética , Datos de Secuencia Molecular , Análisis de Secuencia de ADN
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