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European Journal of Clinical... Aug 2022The multilocus variable-number tandem-repeat analysis (MLVA) typing method is commonly used in Mycoplasma pneumoniae (M. pneumoniae) epidemiology. It remains unknown if...
Mycoplasma pneumoniae multilocus variable-number tandem-repeat analysis genotypes are associated with inflammatory biomarker levels in children with lower respiratory tract infections.
The multilocus variable-number tandem-repeat analysis (MLVA) typing method is commonly used in Mycoplasma pneumoniae (M. pneumoniae) epidemiology. It remains unknown if clinical manifestations of lower respiratory tract infections (LRTI) in children differ between different MLVA genotypes. We aimed to determine if specific M. pneumoniae MLVA genotypes indicate the severity of LRTI in children. We performed a retrospective study of children younger than 18 years with signs of acute M. pneumoniae LRTI from January 1, 2009, to December 31, 2014. All patients who were PCR-positive for M. pneumoniae from pharyngeal swabs and had MLVA genotype successfully defined were included in the study. We compared the epidemiological and clinical data of children infected with different MLVA genotypes. In total, 429 patients (mean age 7.4 years, SD 3.4 years; 54% boys) met the study inclusion criteria. We compared the data of patients infected with the three most common MLVA types: MLVA-3,5,6,2 (86/429), MLVA-3,6,6,2 (71/429) and MLVA-4,5,7,2 (256/429). MLVA-3,5,6,2-infected patients over 5 years of age presented with a significantly higher median C-reactive protein level (34 vs 23 vs 19 mg/L, p = .008) and a higher median white blood cell count (9.4 vs 7.9 vs 8.5 × 10/L, p = .040) compared to MLVA-3,6,6,2- and MLVA-4,5,7,2-infected patients. No such difference was observed in the group of younger than 5 years. The results from our large cohort indicate that different MLVA genotypes may have different pathogenic potential and that children with MLVA-3,5,6,2 LRTI may present with higher inflammatory marker levels in comparison with other MLVA types.
Topics: Biomarkers; Child; Female; Genotype; Humans; Male; Minisatellite Repeats; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Respiratory Tract Infections; Retrospective Studies
PubMed: 35767121
DOI: 10.1007/s10096-022-04467-8 -
Genes May 2022complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global...
complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates.
Topics: Genotype; Microbial Sensitivity Tests; Minisatellite Repeats; Mycobacterium tuberculosis; Phylogeny
PubMed: 35741753
DOI: 10.3390/genes13060990 -
Pathogens and Global Health Feb 2023Tuberculosis (TB) remains the leading cause of deaths from infectious disease worldwide. Nowadays, the tendency of complex (MTBC) to spread between continents due to...
Tuberculosis (TB) remains the leading cause of deaths from infectious disease worldwide. Nowadays, the tendency of complex (MTBC) to spread between continents due to uncontrolled migration movements shows that TB is a global health problem. The number of studies for the detection of MTBC strains' epidemiological features in areas with TB spread risk using molecular-based methods such as spoligotyping and Mycobacterial Interspersed Repetitive Unit (MIRU) Variable Number Tandem Repeats (VNTR) at the clonal level is insufficient. In this study, it was aimed to determine the phylogenetic relationships of MTBC strains at the species level by spoligotyping and 15 locus MIRU-VNTR (MIRU-VNTR) molecular methods of 96 multidrug-resistant (MDR) MTBC strains isolated from sputum samples of patients with a preliminary diagnosis of pulmonary TB or suspected contact history those sent to National Tuberculosis Reference Laboratory from the centers that are members of the Tuberculosis Laboratory Surveillance Network. The phylogenetic relationship between 96 MDR-TB strains was investigated with the combination of bead-based spoligotyping and MIRU-VNTR methods on the MAGPIX® Milliplex Map device. In this study, it was determined that the T1 family is more common in our country and LAM7-TUR family is less common than the Beijing family unlike other studies. It was determined that the strains in the same cluster had different locus profiles, and there was no transmission from the same clone in the clonal typing we performed with spoligotyping and MIRU-VNTR.
Topics: Humans; Mycobacterium tuberculosis; Phylogeny; Minisatellite Repeats; Turkey; Genetic Variation; Tuberculosis; Tuberculosis, Multidrug-Resistant; Genotype; Bacterial Typing Techniques
PubMed: 35642888
DOI: 10.1080/20477724.2022.2084807 -
American Journal of Human Genetics Jun 2022The human genome contains tens of thousands of large tandem repeats and hundreds of genes that show common and highly variable copy-number changes. Due to their large...
The human genome contains tens of thousands of large tandem repeats and hundreds of genes that show common and highly variable copy-number changes. Due to their large size and repetitive nature, these variable number tandem repeats (VNTRs) and multicopy genes are generally recalcitrant to standard genotyping approaches and, as a result, this class of variation is poorly characterized. However, several recent studies have demonstrated that copy-number variation of VNTRs can modify local gene expression, epigenetics, and human traits, indicating that many have a functional role. Here, using read depth from whole-genome sequencing to profile copy number, we report results of a phenome-wide association study (PheWAS) of VNTRs and multicopy genes in a discovery cohort of ∼35,000 samples, identifying 32 traits associated with copy number of 38 VNTRs and multicopy genes at 1% FDR. We replicated many of these signals in an independent cohort and observed that VNTRs showing trait associations were significantly enriched for expression QTLs with nearby genes, providing strong support for our results. Fine-mapping studies indicated that in the majority (∼90%) of cases, the VNTRs and multicopy genes we identified represent the causal variants underlying the observed associations. Furthermore, several lie in regions where prior SNV-based GWASs have failed to identify any significant associations with these traits. Our study indicates that copy number of VNTRs and multicopy genes contributes to diverse human traits and suggests that complex structural variants potentially explain some of the so-called "missing heritability" of SNV-based GWASs.
Topics: DNA Copy Number Variations; Genome, Human; Genome-Wide Association Study; Humans; Minisatellite Repeats; Phenotype
PubMed: 35609568
DOI: 10.1016/j.ajhg.2022.04.016 -
PloS One 2022Nigeria ranks 1st in Africa and 6th globally with the highest burden of tuberculosis (TB). However, only a relatively few studies have addressed the molecular...
Nigeria ranks 1st in Africa and 6th globally with the highest burden of tuberculosis (TB). However, only a relatively few studies have addressed the molecular epidemiology of Mycobacterium tuberculosis in this country. The aim of this work was to analyze the genetic structure of drug-resistant (DR) M. tuberculosis population in the Plateau State (central Nigeria), with the results placed in the broader context of West Africa. The study sample included 67 DR M. tuberculosis isolates, recovered from as many TB patients between November 2015 and January 2016, in the Plateau State. The isolates were subjected to spoligotyping and MIRU-VNTR typing. A total of 20 distinct spoligotypes were obtained, split into 3 clusters (n = 50, 74.6%, 2-33 isolates per cluster) and 17 (25.4%) unique patterns. The Cameroon clade was the largest lineage (62.7%) followed by T (28.3%), LAM (3%), and Haarlem (3%) clades. Upon MIRU-VNTR typing, the isolates produced 31 profiles, i.e. 7 clusters (n = 43, 64.2%, 2-17 isolates per cluster) and 24 singletons. A combined spoligotyping and MIRU-VNTR typing analysis showed 20.9% of the cases clustered and estimated the recent transmission rate at 11.9%. In conclusion, two lineages, namely Cameroon, and T accounted for the majority (91%) of cases. No association was observed between the most prevalent Cameroon lineage and drug resistance, including multidrug resistant (MDR) phenotype, or any of the patient demographic characteristics.
Topics: Genotype; Humans; Minisatellite Repeats; Mycobacterium tuberculosis; Nigeria; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 35609028
DOI: 10.1371/journal.pone.0266837 -
Infection, Genetics and Evolution :... Aug 2022Phylogenetic diversity and distinct phylogeographic distribution of Mycobacterium tuberculosis (MTB) contribute to regional differences in drug resistance. The emergence...
Phylogenetic diversity and distinct phylogeographic distribution of Mycobacterium tuberculosis (MTB) contribute to regional differences in drug resistance. The emergence of pre-extensively drug resistant tuberculosis (Pre-XDR-TB) becomes obstacles to achieve End TB strategy in Bangladesh. This cross-sectional study was conducted to identify the strains of different lineages of MTB, their variations of distribution among Pre-XDR-TB cases and to observe the linkage of particular strains of MTB with drug resistance. A total of 33 Pre-XDR-TB isolates were enrolled in this study. All isolates were confirmed as MTB by MPT 64 antigen detection and genotyped by 24 loci Mycobacterial Interspersed Repetitive Unit-Variable Number of Tandem Repeats (MIRU-VNTR) analysis. Drug resistance was detected by second line Line probe assay (LPA). Beijing was the predominant strain 16 (48.48%), followed by Delhi/CAS 5(15.15%), LAM 4 (12.12%) and Harlem 3(9.10%), EAI 2(6.06%), Cameroon 2(6.06%) and NEW-1 1(3.03%). There were 31 different genotypes consisting of 2 clusters and 29 singletons. All the clustered strains were belonged to Beijing lineage. Recent transmission occurred manly by Beijing strains, showed low transmission rate (12.1%). Of 33 isolates 30(90.90%) were Fluoroquinolones resistant, the mutations involved was Asp94Gly in gyr A MUT 3C gene 13(39.39%) in quinolone resistance determining region (QRDR) followed by 11 (33.33%) in gyr A MUT 1. Three (9.10%) isolates showed resistant to injectable 2nd line drugs and all mutation occurs in G1484T of rrs MUT 2. Beijing lineage was predominant in treatment failure and relapse cases. Levofloxacin was resistant to all Pre-XDR-TB cases, but moxifloxacin showed low level resistance. QUB 26 was the most discriminatory locus (0.85) among 24 loci whereas MIRU 2 was the least (0.03). 24 loci MIRU-VNTR analysis shows high discriminatory index (0.71), found to be powerful tool for genotyping of Pre-XDR-TB, which is the first study in Bangladesh that enhanced the current TB control policy.
Topics: Bangladesh; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Extensively Drug-Resistant Tuberculosis; Genotype; Humans; Minisatellite Repeats; Mycobacterium tuberculosis; Phylogeny; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 35595025
DOI: 10.1016/j.meegid.2022.105304 -
Journal of Gastrointestinal and Liver... Jun 2022Considering the lack of knowledge regarding the influence of the variable number of repeats of 27 pb in intron 4 (4b/4a VNTR - rs61722009) of the endothelial nitric...
BACKGROUND AND AIMS
Considering the lack of knowledge regarding the influence of the variable number of repeats of 27 pb in intron 4 (4b/4a VNTR - rs61722009) of the endothelial nitric oxide synthase (eNOS) on the drug response, we assessed the influence of this polymorphism for the risk of upper gastrointestinal bleeding (UGIB).
METHODS
A case-control study, including 200 cases and 706 controls, was conducted in a Brazilian hospital complex. Cases were participants with UGIB diagnosis. Controls were participants admitted to surgical procedures not related to gastrointestinal problems. The 4b/4a VNTR was determined through polymerase chain reaction followed by fragment analysis. Conditional logistic regression models were designed. The additive interaction between the presence of the 4b/4a VNTR variant and the use of low-dose aspirin (LDA) and nonsteroidal anti-inflammatory drugs (NSAIDs) was calculated by fitting the Cox regression model through the parameters of Synergism index (S) and Relative Excess Risk Due To Interaction (RERI).
RESULTS
The presence of the 4b/4a VNTR variant did not increase the risk of UGIB: carriers of the 4a/4a genotype (OR=0.37, 95%CI: 0.09-1.45) and of the variant allele "4a" (OR=0.91, 95%CI: 0.55-1.51). The risk of UGIB in LDA users carriers of the wild genotype (OR=4.96, 95%CI: 2.04- 2.06) and the variant allele "4a" (OR=3.49, 95%CI: 1.18-10.38) is similar, as well as for NSAID users carriers of the wild genotype (OR=5.73, 95%CI: 2.61-12.60) and variant allele "4a" (OR=5.51, 95%CI: 1.42-15.82). No additive interaction was identified between the presence of the genetic variant and the use of LDA [RERI: -1.44 (95%CI: -6.02-3.14; S: 0.63 (95%CI: -1.97-1.15)] and NSAIDs [RERI: -0.13 (95%CI: -6.79-6.53; S: 0.97 (95%CI: -0.23-4.19)] on the UGIB risk.
CONCLUSION
Our data suggests that there is no increase in the magnitude of UGIB risk in LDA and NSAIDs users' carrying the variant allele "4a".
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Case-Control Studies; Gastrointestinal Hemorrhage; Genetic Predisposition to Disease; Genotype; Humans; Introns; Minisatellite Repeats; Nitric Oxide Synthase Type III; Nucleotide Transport Proteins; Polymorphism, Genetic
PubMed: 35574622
DOI: 10.15403/jgld-4226 -
Biomedica : Revista Del Instituto... Mar 2022Fusarium is a very heterogeneous group of fungi, difficult to classify, with a wide range of living styles, acting as saprophytes, parasites of plants, or pathogens for...
INTRODUCTION
Fusarium is a very heterogeneous group of fungi, difficult to classify, with a wide range of living styles, acting as saprophytes, parasites of plants, or pathogens for humans and animals. Prevalence of clinical fusariosis and lack of effective treatments have increased the interest in the precise diagnosis, which implies a molecular characterization of Fusarium populations.
OBJECTIVE
We compared different genotyping markers in their assessment of the genetic variability and molecular identification of clinical isolates of Fusarium.
MATERIALS AND METHODS
We evaluated the performance of the fingerprinting produced by two random primers: M13, which amplifies a minisatellite sequence, and (GACA)4, which corresponds to a simple repetitive DNA sequence. Using the Hunter Gaston Discriminatory Index (HGDI), an analysis of molecular variance (AMOVA), and a Mantel test, the resolution of these markers was compared to the reference sequencing-based and PCR genotyping methods.
RESULTS
The highest HGDI value was associated with the M13 marker followed by (GACA)4. AMOVA and the Mantel tests supported a strong correlation between the M13 classification and the reference method given by the partial sequencing of the transcription elongation factor 1-alpha (TEF1-α) and rDNA 28S.
CONCLUSION
The strong correlation between the M13 classification and the sequencingbased reference together with its higher resolution demonstrates its adequacy for the characterization of Fusarium populations.
Topics: Animals; Biomarkers; Colombia; DNA Primers; Fusarium; Genotype; Microsatellite Repeats
PubMed: 35471167
DOI: 10.7705/biomedica.5869 -
Veterinary Microbiology May 2022We describe application of whole genome sequencing (WGS) to a collection of 197 Mycobacterium avium subsp paratuberculosis (MAP) isolates gathered from 122 cattle herds...
We describe application of whole genome sequencing (WGS) to a collection of 197 Mycobacterium avium subsp paratuberculosis (MAP) isolates gathered from 122 cattle herds across 27 counties of the island of Ireland. We compare WGS to MAP diversity quantified using mycobacterial interspersed random unit - variable number tandem repeats (MIRU-VNTR). While MIRU-VNTR showed only two major types, WGS could split the 197 isolates into eight major groups. We also found six isolates corresponding to INMV 13, a novel MIRU-VNTR type for Ireland. Evidence for dispersal of MAP across Ireland via cattle movement could be discerned from the data, with mixed infections present in several herds. Furthermore, comparisons of MAP WGS data from Ireland to data from Great Britain and continental Europe revealed many instances of close genetic similarity and hence evidence for international transmission of infection. BEAST MASCOT structured coalescent analyses, with relaxed and strict molecular clocks, estimated the substitution rate to be 0.10-0.13 SNPs/site/year and disclosed greater transitions per lineage per year from Europe to Ireland, indicating transmission into Ireland. Our work therefore reveals new insight into the seeding of MAP infection across Ireland, highlighting how WGS can inform policy formulation to ultimately control MAP transmission at local, national and international scales.
Topics: Animals; Cattle; Genotype; Ireland; Minisatellite Repeats; Mycobacterium avium subsp. paratuberculosis; Paratuberculosis; Whole Genome Sequencing
PubMed: 35405477
DOI: 10.1016/j.vetmic.2022.109416 -
Communications Biology Apr 2022Both the serotonin transporter polymorphism (5-HTTLPR) and the monoamine oxidase A gene (MAOA-uVNTR) are considered genetic contributors for anxiety-related...
Both the serotonin transporter polymorphism (5-HTTLPR) and the monoamine oxidase A gene (MAOA-uVNTR) are considered genetic contributors for anxiety-related symptomatology and aggressive behavior. Nevertheless, an interaction between these genes and the pre-attentive processing of threatening voices -a biological marker for anxiety-related conditions- has not been assessed yet. Among the entire sample of participants in the study with valid genotyping and electroencephalographic (EEG) data (N = 140), here we show that men with low-activity MAOA-uVNTR, and who were not homozygous for the 5-HTTLPR short allele (s) (n = 11), had significantly larger fearful MMN amplitudes -as driven by significant larger ERPs to fearful stimuli- than men with high-activity MAOA-uVNTR variants (n = 20). This is in contrast with previous studies, where significantly reduced fearful MMN amplitudes, driven by increased ERPs to neutral stimuli, were observed in those homozygous for the 5-HTT s-allele. In conclusion, using genetic, neurophysiological, and behavioral measurements, this study illustrates how the intricate interaction between the 5-HTT and the MAOA-uVNTR variants have an impact on threat processing, and social cognition, in male individuals (n = 62).
Topics: Electroencephalography; Genotype; Humans; Male; Minisatellite Repeats; Monoamine Oxidase; Serotonin Plasma Membrane Transport Proteins
PubMed: 35396540
DOI: 10.1038/s42003-022-03297-w