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Revista Portuguesa de Cardiologia Sep 2018We examined the potential role of polymorphisms of the platelet genes GP1BA (rs2243093, rs6065 and VNTR), ITGB3 (rs5918), ITGA2 (rs938043469) and P2RY12 (rs2046934,...
INTRODUCTION
We examined the potential role of polymorphisms of the platelet genes GP1BA (rs2243093, rs6065 and VNTR), ITGB3 (rs5918), ITGA2 (rs938043469) and P2RY12 (rs2046934, rs6801273 and rs6798347) as risk factors for myocardial infarction (MI).
METHODS
The study population was divided into three groups: controls (n=235), MI at age ≤45 years (MI ≤45, n=44), and MI at age >45 years (MI >45, n=78). The control group was further divided into two subgroups (control ≤45 and >45), and subgroups including only men were also considered for statistical analysis. Polymorphisms were detected by polymerase chain reaction and restriction fragment length polymorphism analysis.
RESULTS
Regarding non-genetic risk factors, the control group differed statistically from the MI ≤45 group (p<00.5) in terms of smoking, hypertension, diabetes and obesity, and from the MI >45 group (p<0.05) in terms of hypertension, diabetes, obesity, family history of thrombosis and high cholesterol. For the studied ITGA2 polymorphism, a statistical difference was found when MI >45 was compared with the control group, with a higher risk of MI in the TT genotype (OR 2.852; 95% CI: 1.092-7.451; p=0.032). In the GP1BA rs6065 polymorphism, a statistically significant difference was found between control ≤45 only men and MI ≤45 only men, with a higher risk in the CT genotype (OR 5.568; 95% CI: 1.421-21.822; p=0.016), despite the low numbers included. The other polymorphisms studied did not show any statistically significant correlations.
CONCLUSION
There is a statistically significant association between the TT genotype of the ITGA2 rs938043469 polymorphism and increased risk for MI >45.
Topics: Adolescent; Adult; Aged; Case-Control Studies; Female; Genetic Association Studies; Humans; Integrin beta3; Male; Middle Aged; Minisatellite Repeats; Myocardial Infarction; Platelet Glycoprotein GPIb-IX Complex; Polymorphism, Single Nucleotide; Receptors, Purinergic P2Y12; Risk Factors; Young Adult
PubMed: 30143348
DOI: 10.1016/j.repc.2018.03.015 -
Tuberculosis (Edinburgh, Scotland) Jan 2023To infer the origin and spread of the Mycobacterium tuberculosis Latin American and Mediterranean (L4.3/LAM) sublineage in a Mediterranean country, Tunisia, where it...
BACKGROUND
To infer the origin and spread of the Mycobacterium tuberculosis Latin American and Mediterranean (L4.3/LAM) sublineage in a Mediterranean country, Tunisia, where it predominates.
METHODS
We combined Bayesian (STRUCTURE) and maximum likelihood (MIGRAINE) estimation approaches based on a global 24-loci mycobacterial interspersed repetitive units-variable numbers of tandem repeats (MIRU-VNTR24) genotyping dataset consisting of 1573 L4.3/LAM clinical strains from four continents, including 252 isolates originating from Tunisia.
RESULTS
Phylogenetic analyses coupled with Bayesian estimations suggested that the most predominant L4.3/LAM subpopulation in Tunisia (65.07%), which is dominated by a single clonal complex, TUN4.3_CC1 (94.51%), has evolved from an ancestral pool that is restricted to Europe and Africa, contrasting with the remaining L4.3/LAM subpopulations whose ancestry was traced all over the word. Maximum likelihood analysis revealed that TUN4.3_CC1 has been undergoing a demographic expansion since 131 years ago (CI95%: 90.7-205), thus explaining its preponderance relative to the second most predominant CC, TUN4.3_CC2, whose population was found under contraction.
CONCLUSIONS
The preponderance of L4.3/LAM in Tunisia stems from a 130-year expansion process of a locally evolved clone.
Topics: Mycobacterium tuberculosis; Phylogeny; Latin America; Tunisia; Bayes Theorem; Genotype; Minisatellite Repeats
PubMed: 36584485
DOI: 10.1016/j.tube.2022.102297 -
Hereditas 2019Identification of high resolving DNA-based markers is of paramount importance to unlock the potential of genetic diversity and selection of unique accessions of L.,...
BACKGROUND
Identification of high resolving DNA-based markers is of paramount importance to unlock the potential of genetic diversity and selection of unique accessions of L., within Cross River and Ebonyi States of Nigeria, for breeding and conservation. Therefore, we comparatively explored the effectiveness of start codon targeted (SCoT) and directed amplified minisatellite DNA (DAMD) markers for diversity analysis of the accessions. Fifteen accessions were collected for DNA extraction and amplifications with the markers.
RESULTS
Dendrograms from SCoT and DAMD categorized the accessions into five and three genetic groups, respectively, while the principal component analysis identified five genetic clusters, each from the markers. The average values of allele, gene diversity and polymorphic information content detected with SCoT and DAMD demonstrate that the two markers were effective and efficient, especially, SCoT in genetic diversity study of the accessions of pepper. Number of polymorphic loci (NPL) and percentage polymorphic loci (PPL) from SCoT (NPL = 64, PPL = 80.00-95.73%) and DAMD (NPL = 56, PPL = 53.33-86.67%) were high, but higher in SCoT markers. Other effective genetic parameters (effective number of alleles, Nei's genetic diversity and Shannon's information indices) identified with the two marker systems elucidated the allelic richness, rich genetic diversity within the populations and informative nature of the markers, especially SCoT. The intraspecific genetic diversity, interspecific genetic diversity, and coefficient of differentiation obtained with SCoT and DAMD further exposed the genetic structure with more genetic divergence within than among the populations of the accessions. Estimate of gene flow from the SCoT markers was 3.8375 and 0.6.2042 for the DAMD markers. The estimate of gene flow values from the markers indicated extensiveness with SCoT (Nm = 3.8375) and extremely extensive with DAMD (Nm = 6.2042) among the populations.
CONCLUSION
This study shows that SCoT markers may be more useful and informative than DAMD in measuring genetic diversity and differentiation of the accessions of the genus . Genetic parameters obtained with SCoT showed that the accessions from Cross River were more genetically diverse than the ones from Ebonyi State. Therefore, SCoT may be a preferred marker in evaluating genetic diversity for improvement and conservation of this spicy crop, .
Topics: Alleles; Capsicum; Codon, Initiator; Gene Flow; Genetic Markers; Genetic Variation; Genetics, Population; Minisatellite Repeats; Nigeria
PubMed: 31641342
DOI: 10.1186/s41065-019-0108-6 -
Human Brain Mapping Dec 2019Previous studies have linked the low expression variant of a variable number of tandem repeat polymorphism in the monoamine oxidase A gene (MAOA-L) to the risk for...
Previous studies have linked the low expression variant of a variable number of tandem repeat polymorphism in the monoamine oxidase A gene (MAOA-L) to the risk for impulsivity and aggression, brain developmental abnormalities, altered cortico-limbic circuit function, and an exaggerated neural serotonergic tone. However, the neurobiological effects of this variant on human brain network architecture are incompletely understood. We studied healthy individuals and used multimodal neuroimaging (sample size range: 219-284 across modalities) and network-based statistics (NBS) to probe the specificity of MAOA-L-related connectomic alterations to cortical-limbic circuits and the emotion processing domain. We assessed the spatial distribution of affected links across several neuroimaging tasks and data modalities to identify potential alterations in network architecture. Our results revealed a distributed network of node links with a significantly increased connectivity in MAOA-L carriers compared to the carriers of the high expression (H) variant. The hyperconnectivity phenotype primarily consisted of between-lobe ("anisocoupled") network links and showed a pronounced involvement of frontal-temporal connections. Hyperconnectivity was observed across functional magnetic resonance imaging (fMRI) of implicit emotion processing (p = .037), resting-state fMRI (p = .022), and diffusion tensor imaging (p = .044) data, while no effects were seen in fMRI data of another cognitive domain, that is, spatial working memory (p = .540). These observations are in line with prior research on the MAOA-L variant and complement these existing data by novel insights into the specificity and spatial distribution of the neurogenetic effects. Our work highlights the value of multimodal network connectomic approaches for imaging genetics.
Topics: Adult; Brain; Female; Frontal Lobe; Genotype; Humans; Magnetic Resonance Imaging; Male; Minisatellite Repeats; Monoamine Oxidase; Nerve Net; Temporal Lobe; Young Adult
PubMed: 31441562
DOI: 10.1002/hbm.24766 -
Frontiers in Cellular and Infection... 2023The epidemiological situation of tuberculosis (TB) in Poland urges for its continuous and scrupulous monitoring. The objective of this study was to explore the genetic...
INTRODUCTION
The epidemiological situation of tuberculosis (TB) in Poland urges for its continuous and scrupulous monitoring. The objective of this study was to explore the genetic diversity of multidrug-resistant (MDR) and drug-susceptible (DS) isolates from Poland with a combination of spoligotyping and high-resolution mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) analysis. The results were placed in the Northern and Eastern Europe context.
METHODS
The study included 89 (39 MDR and 50 DS) isolates collected from as many patients between 2018 and 2021 in Poland. The analysis was done using spoligotyping, and MIRU-VNTR typing at 24 standard loci. The data were compared to those available on Poland and neighbors and global datasets.
RESULTS
The main identified families were Beijing (28.1%) and Haarlem (16.8%) while 34.8% of isolates were in the heterogeneous L4-unclassified group. Although the Beijing family was the most prevalent (61.5%) among MDR-TB cases, it accounted for only 2% of DS isolates. Among foreign-born patients, a higher ratio of MDR isolates were observed when compared with those who Poland-born (64.3% vs. 40%). Furthermore, all patients from the Former Soviet Union (FSU) countries were infected with MDR-TB.
DISCUSSION
Whereas DS population in Poland is dominated by L4 isolates, MDR isolates are mostly of the Beijing genotype. The rise in the prevalence of the Beijing isolates in Poland, coupled with high proportion of the Beijing genotype among foreign-born TB patients may reflect an ongoing transmission of this family, imported to Poland mainly from FSU countries.
Topics: Humans; Mycobacterium tuberculosis; Phylogeny; Beijing; Poland; Tuberculosis; Tuberculosis, Multidrug-Resistant; Genotype; Minisatellite Repeats
PubMed: 37009494
DOI: 10.3389/fcimb.2023.1161905 -
International Journal of Infectious... Jul 2020Clostridioides difficile is the major cause of infectious nosocomial diarrhoea in industrialized nations. Data on the occurrence of C. difficile in Africa, ribotype (RT)...
BACKGROUND
Clostridioides difficile is the major cause of infectious nosocomial diarrhoea in industrialized nations. Data on the occurrence of C. difficile in Africa, ribotype (RT) distribution, antimicrobial susceptibility patterns and potential zoonotic transmission are scarce.
METHODS
80 Zimbabwean C. difficile isolates from different sources (chicken [n=30], soil [n=21] and humans [n=29]) were investigated using ribotyping, toxin gene detection, resistance testing, multiple-locus variable-number tandem repeat analysis (MLVA), and whole genome sequencing (WGS).
RESULTS
Among chicken isolates, the most common RTs were RT103 (6/30), RT025 (5/30) and RT070 (4/30). Within soil samples, RT025 and RT056 were most common (3/21 each). In contrast, the non-toxigenic RT084 was most frequently found in human isolates (4/29). Toxin genes were detected in only 19/29 human isolates. Susceptibility testing showed no resistance against metronidazole and vancomycin, and resistance against macrolides and rifampicin was scarce (3/80 and 2/80, respectively); however, 26/80 isolates showed moxifloxacin resistance. MLVA and WGS of strains with identical RTs stemming from different sources revealed clustering of RT025 and RT084 isolates from human und non-human samples.
CONCLUSION
No "hypervirulent" strains were found. The detected clusters between human, chicken and soil isolates indicate ongoing transmission between humans and environmental sources and might point towards a zoonotic potential.
Topics: Animals; Chickens; Clostridioides difficile; Drug Resistance, Bacterial; Humans; Minisatellite Repeats; Ribotyping; Soil Microbiology; Zimbabwe
PubMed: 32311450
DOI: 10.1016/j.ijid.2020.04.026 -
BMC Medical Genetics Dec 2014Point mutations or genomic deletions of FOXF1 result in a lethal developmental lung disease Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins. However,...
BACKGROUND
Point mutations or genomic deletions of FOXF1 result in a lethal developmental lung disease Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins. However, the clinical consequences of the constitutively increased dosage of FOXF1 are unknown.
METHODS
Copy-number variations and their parental origin were identified using a combination of array CGH, long-range PCR, DNA sequencing, and microsatellite analyses. Minisatellite sequences across different species were compared using a gready clustering algorithm and genome-wide analysis of the distribution of minisatellite sequences was performed using R statistical software.
RESULTS
We report four unrelated families with 16q24.1 duplications encompassing entire FOXF1. In a 4-year-old boy with speech delay and a café-au-lait macule, we identified an ~15 kb 16q24.1 duplication inherited from the reportedly healthy father, in addition to a de novo ~1.09 Mb mosaic 17q11.2 NF1 deletion. In a 13-year-old patient with autism and mood disorder, we found an ~0.3 Mb duplication harboring FOXF1 and an ~0.5 Mb 16q23.3 duplication, both inherited from the father with bipolar disorder. In a 47-year old patient with pyloric stenosis, mesenterium commune, and aplasia of the appendix, we identified an ~0.4 Mb duplication in 16q24.1 encompassing 16 genes including FOXF1. The patient transmitted the duplication to her daughter, who presented with similar symptoms. In a fourth patient with speech and motor delay, and borderline intellectual disability, we identified an ~1.7 Mb FOXF1 duplication adjacent to a large minisatellite. This duplication has a complex structure and arose de novo on the maternal chromosome, likely as a result of a DNA replication error initiated by the adjacent large tandem repeat. Using bioinformatic and array CGH analyses of the minisatellite, we found a large variation of its size in several different species and individuals, demonstrating both its evolutionarily instability and population polymorphism.
CONCLUSIONS
Our data indicate that constitutional duplication of FOXF1 in humans is not associated with any pediatric lung abnormalities. We propose that patients with gut malrotation, pyloric or duodenal stenosis, and gall bladder agenesis should be tested for FOXF1 alterations. We suggest that instability of minisatellites greater than 1 kb can lead to structural variation due to DNA replication errors.
Topics: Abnormalities, Multiple; Adolescent; Animals; Child, Preschool; Chromosomes, Human, Pair 16; Evolution, Molecular; Female; Forkhead Transcription Factors; Gene Dosage; Gene Duplication; Humans; Male; Middle Aged; Minisatellite Repeats; Pedigree
PubMed: 25472632
DOI: 10.1186/s12881-014-0128-z -
Genome Biology Nov 2019Technological limitations have hindered the large-scale genetic investigation of tandem repeats in disease. We show that long-read sequencing with a single Oxford...
Technological limitations have hindered the large-scale genetic investigation of tandem repeats in disease. We show that long-read sequencing with a single Oxford Nanopore Technologies PromethION flow cell per individual achieves 30× human genome coverage and enables accurate assessment of tandem repeats including the 10,000-bp Alzheimer's disease-associated ABCA7 VNTR. The Guppy "flip-flop" base caller and tandem-genotypes tandem repeat caller are efficient for large-scale tandem repeat assessment, but base calling and alignment challenges persist. We present NanoSatellite, which analyzes tandem repeats directly on electric current data and improves calling of GC-rich tandem repeats, expanded alleles, and motif interruptions.
Topics: ATP-Binding Cassette Transporters; Algorithms; Feasibility Studies; Genome, Human; Genomics; High-Throughput Nucleotide Sequencing; Humans; Minisatellite Repeats; Tandem Repeat Sequences
PubMed: 31727106
DOI: 10.1186/s13059-019-1856-3 -
International Journal of Infectious... Jan 2022Zambia is among the 30 high tuberculosis burden countries in the world. Despite increasing reports of multidrug-resistant tuberculosis (MDR-TB) in routine surveillance,...
OBJECTIVE
Zambia is among the 30 high tuberculosis burden countries in the world. Despite increasing reports of multidrug-resistant tuberculosis (MDR-TB) in routine surveillance, information on the transmission of MDR Mycobacterium tuberculosis strains is largely unknown. This study elucidated the genetic diversity and transmission of MDR M. tuberculosis strains in Lusaka, Zambia.
METHODS
Eighty-five MDR M. tuberculosis samples collected from 2013 to 2017 at the University Teaching Hospital were used. Drug-resistance associated gene sequencing, spoligotyping, 24-loci mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR), and multiplex PCR for RD-Rio sub-lineage identification were applied.
RESULTS
The identified clades were LAM (48%), CAS (29%), T (14%), X (6%) and Harlem (2%). Strains belonging to SITs 21/CAS1-Kili and 20/LAM1 formed the largest clonal complexes. Combined spoligotyping and 24 loci-MIRU-VNTR revealed 47 genotypic patterns with a clustering rate of 63%. Ninety-five percent of LAM strains belonged to the RD-Rio sub-lineage.
CONCLUSION
The high clustering rate suggested that a large proportion of MDR-TB was due to recent transmission rather than the independent acquisition of MDR. This spread was attributed to clonal expansion of SIT21/CAS1-Kili and SIT20/LAM1 strains. Therefore, TB control programs recommending genotyping coupled with conventional epidemiological methods can guide measures for stopping the spread of MDR-TB.
Topics: Genetic Variation; Genotype; Humans; Minisatellite Repeats; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant; Zambia
PubMed: 34718155
DOI: 10.1016/j.ijid.2021.10.044 -
PloS One 2018Anthrax is an endemic disease in China. Cases are reported every year, especially in the northwestern areas. In August 2016, an outbreak of 21 cutaneous anthrax cases...
Anthrax is an endemic disease in China. Cases are reported every year, especially in the northwestern areas. In August 2016, an outbreak of 21 cutaneous anthrax cases was reported in Min County, Gansu Province, China. In this study, the general characteristics of the anthrax outbreak are described. Two molecular typing methods, canonical single-nucleotide polymorphism (canSNP) and multiple-locus variable-number tandem repeat analysis with 15 markers (MLVA15), were used to investigate the possible source of transmission and to identify the genetic relationship among the strains/samples isolated in this outbreak as well as previous isolates. In this outbreak, all patients were infected through contact with diseased livestock or contaminated animal products. Livestock had been introduced into the local area shortly before the outbreak from Gannan Prefecture (in Gansu Province), Sichuan and Qinghai Provinces. In the molecular typing analysis, there were two canSNP subgroups found in Gansu, A.Br.001/002 and A.Br.Ames, and five MLVA15 genotypes were observed. The strains collected from the anthrax outbreak in Min County in 2016 belonged to the A.Br.001/002 canSNP subgroup and the MLVA15-28 and MLVA15-30 genotype. Strains previously isolated from Sichuan, Inner Mongolia and Maqu County (in Gannan Prefecture, Gansu Province) were clustered with these outbreak-related strains/samples according to the MLVA15-30 genotype. The MLVA15-28 genotype was found in strains isolated from Gansu and Xinjiang in previous studies. Combining the epidemiological investigation and molecular typing results, we conclude that the patients in this outbreak were infected by a local pathogen present in the adjoining area of Gansu, Sichuan and Qinghai Provinces.
Topics: Adolescent; Adult; Aged; Animals; Anthrax; Bacillus anthracis; Child; China; Disease Outbreaks; Female; Humans; Livestock; Male; Middle Aged; Minisatellite Repeats; Molecular Epidemiology; Molecular Typing; Polymorphism, Single Nucleotide; Young Adult
PubMed: 30161194
DOI: 10.1371/journal.pone.0203267