scholarly journals A high-coverage artificial chromosome library for the genome-wide screening of drug-resistance genes in malaria parasites

2012 ◽  
Vol 22 (5) ◽  
pp. 985-992 ◽  
Author(s):  
S. Iwanaga ◽  
I. Kaneko ◽  
M. Yuda
Keyword(s):  
Drug Resistance ◽  
Resistance Genes ◽  
Artificial Chromosome ◽  
Malaria Parasites ◽  
High Coverage ◽  
Genome Wide

scholarly journals Genome-wide Mapping of the Coactivator Ada2p Yields Insight into the Functional Roles of SAGA/ADA Complex inCandida albicans

2009 ◽  
Vol 20 (9) ◽  
pp. 2389-2400 ◽  
Author(s):  
Adnane Sellam ◽  
Christopher Askew ◽  
Elias Epp ◽  
Hugo Lavoie ◽  
Malcolm Whiteway ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Genes ◽  
Target Genes ◽  
Transferase Activity ◽  
Histone Acetyl Transferase ◽  
Functional Roles ◽  
Cellular Processes ◽  
Oxidative Resistance ◽  
Genome Wide ◽  
Insight Into

The SAGA/ADA coactivator complex, which regulates numerous cellular processes by coordinating histone acetylation, is widely conserved throughout eukaryotes, and analysis of the Candida albicans genome identifies the components of this complex in the fungal pathogen. We investigated the multiple functions of SAGA/ADA in C. albicans by determining the genome-wide occupancy of Ada2p using chromatin immunoprecipitation (ChIP). Ada2p is recruited to 200 promoters upstream of genes involved in different stress-response functions and metabolic processes. Phenotypic and transcriptomic analysis of ada2 mutant showed that Ada2p is required for the responses to oxidative stress, as well as to treatments with tunicamycin and fluconazole. Ada2p recruitment to the promoters of oxidative resistance genes is mediated by the transcription factor Cap1p, and coactivator function were also established for Gal4p, which recruits Ada2p to the promoters of glycolysis and pyruvate metabolism genes. Cooccupancy of Ada2p and the drug resistance regulator Mrr1p on the promoters of core resistance genes characterizing drug resistance in clinical strains was also demonstrated. Ada2p recruitment to the promoters of these genes were shown to be completely dependent on Mrr1p. Furthermore, ADA2 deletion causes a decrease in H3K9 acetylation levels of target genes, thus illustrating its importance for histone acetyl transferase activity.

scholarly journals Genome wide association with quantitative resistance phenotypes in Mycobacterium tuberculosis reveals novel resistance genes and regulatory regions

2018 ◽  
Author(s):  
Maha R Farhat ◽  
Luca Freschi ◽  
Roger Calderon ◽  
Thomas Ioerger ◽  
Matthew Snyder ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Resistance Genes ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Quantitative Resistance ◽  
Quantitative Measure ◽  
Resistance Phenotype ◽  
Noncoding Regions ◽  
Genome Wide

AbstractDrug resistance is threatening attempts at tuberculosis epidemic control. Molecular diagnostics for drug resistance that rely on the detection of resistance-related mutations could expedite patient care and accelerate progress in TB eradication. We performed minimum inhibitory concentration testing for 12 anti-TB drugs together with Illumina whole genome sequencing on 1452 clinical Mycobacterium tuberculosis (MTB) isolates. We then used a linear mixed model to evaluate genome wide associations between mutations in MTB genes or noncoding regions and drug resistance, followed by validation of our findings in an independent dataset of 792 patient isolates. Novel associations at 13 genomic loci were confirmed in the validation set, with 2 involving noncoding regions. We found promoter mutations to have smaller average effects on resistance levels than gene body mutations in genes where both can contribute to resistance. Enabled by a quantitative measure of resistance, we estimated the heritability of the resistance phenotype to 11 anti-TB drugs and identify a lower than expected contribution from known resistance genes. We also report the proportion of variation in resistance levels explained by the novel loci identified here. This study highlights the complexity of the genomic mechanisms associated with the MTB resistance phenotype, including the relatively large number of potentially causative or compensatory loci, and emphasizes the contribution of the noncoding portion of the genome.

scholarly journals Genetic features of persistently antimicrobial drug-susceptible extraintestinal pathogenic Escherichia coli pandemic sequence type 95

2021 ◽  
Author(s):  
Yuan Hu Allegretti ◽  
Reina Yamaji ◽  
Sheila Adams-Sapper ◽  
Lee W Riley
Keyword(s):  
Escherichia Coli ◽  
Drug Resistance ◽  
Resistance Genes ◽  
Genome Wide Association Study ◽  
Drug Susceptibility ◽  
Sequence Type ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Features

Extraintestinal pathogenic Escherichia coli (ExPEC) belonging to multilocus sequence type 95 (ST95) is one of the most widespread ExPEC lineages associated with bloodstream infections (BSI) and urinary tract infections (UTI). In contrast to other widespread ExPEC sequence types, a large proportion ST95 strains remains susceptible to all antimicrobial agents used to treat BSI or UTI. We aimed to identify genomic features of ST95 associated with persistent drug susceptibility. We conducted a genome-wide association study of 80 ExPEC ST95 isolates from patients with BSI or UTI in Northern California, and 1669 ST95 isolates deposited in the Enterobase database. Of the total of 1749 ST95 isolates, we compared whole-genome sequences of 887 drug-susceptible strains and 862 strains resistant to one or more drugs (defined genotypically as strains harboring drug-resistance genes annotated in the ResFinder database) to identify genetic features associated with strains devoid of drug-resistance genes. By a genome-wide association study of 553 UTI and BSI ST95 isolates, we found 44 accessory genes significantly associated with drug susceptibility, six of which encoded hypothetical proteins. Fifteen of these were not found in any of the WGSs of ST131 ExPEC strains, which are frequently multidrug-resistant, and eight of these genes were annotated to encode transporter or transfer systems. These findings highlight the potential mechanisms by which ST95 strains may resist the acquisition of mobile DNA elements carrying drug-resistance genes.

The gut microbiota resistome provides development of drug resistance in causative agents of human infectious diseases

2017 ◽  
pp. 20-32 ◽  
Author(s):  
Е.Н. Ильина ◽  
Е.И. Олехнович ◽  
А.В. Павленко
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Integrated Approach ◽  
Modern Medicine ◽  
Pathogenic Microorganisms ◽  
Human Pathogens ◽  
Potential Source ◽  
Causative Agents ◽  
Bacterial Genes

С течением времени подходы к изучению резистентности к антибиотикам трансформировались от сосредоточения на выделенных в виде чистой культуры патогенных микроорганизмах к исследованию резистентности на уровне микробных сообществ, составляющих биотопы человека и окружающей среды. По мере того, как продвигается изучение устойчивости к антибиотикам, возникает необходимость использования комплексного подхода для улучшения информирования мирового сообщества о наблюдаемых тенденциях в этой области. Все более очевидным становится то, что, хотя не все гены резистентности могут географически и филогенетически распространяться, угроза, которую они представляют, действительно серьезная и требует комплексных междисциплинарных исследований. В настоящее время резистентность к антибиотикам среди патогенов человека стала основной угрозой в современной медицине, и существует значительный интерес к определению ниши, в которых бактерии могут получить гены антибиотикорезистентности, и механизмов их передачи. В данном обзоре мы рассматриваем проблемы, возникшие на фоне широкого использования человечеством антибактериальных препаратов, в свете формирования микрофлорой кишечника резервуара генов резистентности. Over the time, studies of antibiotic resistance have transformed from focusing on pathogenic microorganisms isolated as a pure culture to analysis of resistance at the level of microbial communities that constitute human and environmental biotopes. Advancing studies of antibiotic resistance require an integrated approach to enhance availability of information about observed tendencies in this field to the global community. It becomes increasingly obvious that, even though not all resistance genes can geographically and phylogenetically spread, the threat they pose is indeed serious and requires complex interdisciplinary research. Currently, the antibiotic resistance of human pathogens has become a challenge to modern medicine, which is now focusing on determining a potential source for bacterial genes of drug resistance and mechanisms for the gene transmission. In this review, we discussed problems generated by the widespread use of antibacterial drugs in the light of forming a reservoir of resistance genes by gut microflora.

Genome-Wide Analysis of NBS-Encoding Disease Resistance Genes in Maize Inbred Line B73

2009 ◽  
Vol 35 (3) ◽  
pp. 566-570 ◽  
Author(s):  
Jie-Ming WANG ◽  
Hai-Yang JIANG ◽  
Yang ZHAO ◽  
Yan XIANG ◽  
Su-Wen ZHU ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Inbred Line ◽  
Resistance Genes ◽  
Disease Resistance Genes ◽  
Maize Inbred Line ◽  
Genome Wide Analysis ◽  
Genome Wide

scholarly journals Genome diversity in Ukraine

GigaScience ◽  
2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Taras K Oleksyk ◽  
Walter W Wolfsberger ◽  
Alexandra M Weber ◽  
Khrystyna Shchubelka ◽  
Olga T Oleksyk ◽  
...  
Keyword(s):  
Sequence Data ◽  
Copy Number Variations ◽  
Genomic Variation ◽  
High Coverage ◽  
Genome Data ◽  
New Information ◽  
Genome Wide ◽  
Public Data ◽  
Genome Wide Data ◽  
Multiple Samples

Abstract Background The main goal of this collaborative effort is to provide genome-wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for public data release. BGISEQ-500 sequence data and genotypes by an Illumina GWAS chip were cross-validated on multiple samples and additionally referenced to 1 sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage. Results The genome data have been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, copy number variations, single-nucletide polymorphisms, and microsatellites. To our knowledge, this study provides the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for medical research in a large understudied population. Conclusions Our results indicate that the genetic diversity of the Ukrainian population is uniquely shaped by evolutionary and demographic forces and cannot be ignored in future genetic and biomedical studies. These data will contribute a wealth of new information bringing forth a wealth of novel, endemic and medically related alleles.

scholarly journals Microevolution within ST11 group Clostridioides difficile isolates through mobile genetic elements based on complete genome sequencing

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuan Wu ◽  
Lin Yang ◽  
Wen-Ge Li ◽  
Wen Zhu Zhang ◽  
Zheng Jie Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Genes ◽  
Point Mutations ◽  
Evolutionary Process ◽  
Mobile Genetic Elements ◽  
Genetic Elements ◽  
Clostridioides Difficile ◽  
Hospitalized Elderly ◽  
Great Heterogeneity ◽  
High Level

Abstract Background Clade 5 Clostridioides difficile diverges significantly from the other clades and is therefore, attracting increasing attention due its great heterogeneity. In this study, we used third-generation sequencing techniques to sequence the complete whole genomes of three ST11 C. difficile isolates, RT078 and another two new ribotypes (RTs), obtained from three independent hospitalized elderly patients undergoing antibiotics treatment. Mobile genetic elements (MGEs), antibiotic-resistance, drug resistance genes, and virulent-related genes were analyzed and compared within these three isolates. Results Isolates 10,010 and 12,038 carried a distinct deletion in tcdA compared with isolate 21,062. Furthermore, all three isolates had identical deletions and point-mutations in tcdC, which was once thought to be a unique characteristic of RT078. Isolate 21,062 (RT078) had a unique plasmid, different numbers of transposons and genetic organization, and harboring special CRISPR spacers. All three isolates retained high-level sensitivity to 11 drugs and isolate 21,062 (RT078) carried distinct drug-resistance genes and loss of numerous flagellum-related genes. Conclusions We concluded that capillary electrophoresis based PCR-ribotyping is important for confirming RT078. Furthermore, RT078 isolates displayed specific MGEs, indicating an independent evolutionary process. In the further study, we could testify these findings with more RT078 isolates of divergent origins.

scholarly journals α-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia: a prodromal Parkinson’s disease model

Brain ◽  
2019 ◽  
Vol 143 (1) ◽  
pp. 249-265 ◽  
Author(s):  
Tomoyuki Taguchi ◽  
Masashi Ikuno ◽  
Mari Hondo ◽  
Laxmi Kumar Parajuli ◽  
Katsutoshi Taguchi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mice ◽  
Rem Sleep ◽  
Genome Wide Association Study ◽  
Artificial Chromosome ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Familial Parkinson’S Disease

Abstract Parkinson’s disease is one of the most common movement disorders and is characterized by dopaminergic cell loss and the accumulation of pathological α-synuclein, but its precise pathogenetic mechanisms remain elusive. To develop disease-modifying therapies for Parkinson’s disease, an animal model that recapitulates the pathology and symptoms of the disease, especially in the prodromal stage, is indispensable. As subjects with α-synuclein gene (SNCA) multiplication as well as point mutations develop familial Parkinson’s disease and a genome-wide association study in Parkinson’s disease has identified SNCA as a risk gene for Parkinson’s disease, the increased expression of α-synuclein is closely associated with the aetiology of Parkinson’s disease. In this study we generated bacterial artificial chromosome transgenic mice harbouring SNCA and its gene expression regulatory regions in order to maintain the native expression pattern of α-synuclein. Furthermore, to enhance the pathological properties of α-synuclein, we inserted into SNCA an A53T mutation, two single-nucleotide polymorphisms identified in a genome-wide association study in Parkinson’s disease and a Rep1 polymorphism, all of which are causal of familial Parkinson’s disease or increase the risk of sporadic Parkinson’s disease. These A53T SNCA bacterial artificial chromosome transgenic mice showed an expression pattern of human α-synuclein very similar to that of endogenous mouse α-synuclein. They expressed truncated, oligomeric and proteinase K-resistant phosphorylated forms of α-synuclein in the regions that are specifically affected in Parkinson’s disease and/or dementia with Lewy bodies, including the olfactory bulb, cerebral cortex, striatum and substantia nigra. Surprisingly, these mice exhibited rapid eye movement (REM) sleep without atonia, which is a key feature of REM sleep behaviour disorder, at as early as 5 months of age. Consistent with this observation, the REM sleep-regulating neuronal populations in the lower brainstem, including the sublaterodorsal tegmental nucleus, nuclei in the ventromedial medullary reticular formation and the pedunculopontine nuclei, expressed phosphorylated α-synuclein. In addition, they also showed hyposmia at 9 months of age, which is consistent with the significant accumulation of phosphorylated α-synuclein in the olfactory bulb. The dopaminergic neurons in the substantia nigra pars compacta degenerated, and their number was decreased in an age-dependent manner by up to 17.1% at 18 months of age compared to wild-type, although the mice did not show any related locomotor dysfunction. In conclusion, we created a novel mouse model of prodromal Parkinson’s disease that showed RBD-like behaviour and hyposmia without motor symptoms.

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