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Infectious Diseases of Poverty May 2017Brucellosis was a common human and livestock disease caused by Brucella strains, the category B priority pathogens by the US Center for Disease Control (CDC). Identified...
BACKGROUND
Brucellosis was a common human and livestock disease caused by Brucella strains, the category B priority pathogens by the US Center for Disease Control (CDC). Identified as a priority disease in human and livestock populations, the increasing incidence in recent years in China needs urgent control measures for this disease but the molecular background important for monitoring the epidemiology of Brucella strains at the national level is still lacking.
METHODS
A total of 600 Brucella isolates collected during 60 years (from 1953 to 2013) in China were genotyped by multiple locus variable-number tandem repeat analysis (MLVA) and the variation degree of MLVA11 loci was calculated by the Hunter Gaston Diversity Index (HGDI) values. The charts and map were processed by Excel 2013, and cluster analysis and epidemiological distribution was performed using BioNumerics (version 5.1).
RESULTS
The 600 representative Brucella isolates fell into 104 genotypes with 58 singleton genotypes by the MLVA11 assay, including B. melitensis biovars 2 and 3 (five main genotypes), B. abortus biovars 1 and 3 (two main genotypes), B. suis biovars 1 and 3 (three main genotypes), and B. canis (two main genotypes) respectively. While most B. suis biovar 1 and biovar 3 were respectively found in northern provinces and southern provinces, B. melitensis and B. abortus strains were dominant in China. Canine Brucellosis was only found in animals without any human cases reported. Eight Brucellosis epidemic peaks emerged during the 60 years between 1953 and 2013: 1955 - 1959, 1962 - 1969, 1971 - 1975, 1977 - 1983, 1985 - 1989, 1992 - 1997, 2000 - 2008 and 2010 - 2013 in China.
CONCLUSIONS
Brucellosis has its unique molecular epidemiological patterns with specific spatial and temporal distribution according to MLVA.
TRIAL REGISTRATION
IDOP-D-16-00101.
Topics: Animals; Brucella; Brucellosis; Cattle; China; Cluster Analysis; DNA, Bacterial; Dogs; Humans; Minisatellite Repeats; Molecular Epidemiology; Multilocus Sequence Typing; Sheep
PubMed: 28460642
DOI: 10.1186/s40249-017-0296-0 -
Nature Communications Sep 2023Markedly expanded tandem repeats (TRs) have been correlated with ~60 diseases. TR diversity has been considered a clue toward understanding missing heritability....
Markedly expanded tandem repeats (TRs) have been correlated with ~60 diseases. TR diversity has been considered a clue toward understanding missing heritability. However, haplotype-resolved long TRs remain mostly hidden or blacked out because their complex structures (TRs composed of various units and minisatellites containing >10-bp units) make them difficult to determine accurately with existing methods. Here, using a high-precision algorithm to determine complex TR structures from long, accurate reads of PacBio HiFi, an investigation of 270 Japanese control samples yields several genome-wide findings. Approximately 322,000 TRs are difficult to impute from the surrounding single-nucleotide variants. Greater genetic divergence of TR loci is significantly correlated with more events of younger replication slippage. Complex TRs are more abundant than single-unit TRs, and a tendency for complex TRs to consist of <10-bp units and single-unit TRs to be minisatellites is statistically significant at loci with ≥500-bp TRs. Of note, 8909 loci with extended TRs (>100b longer than the mode) contain several known disease-associated TRs and are considered candidates for association with disorders. Overall, complex TRs and minisatellites are found to be abundant and diverse, even in genetically small Japanese populations, yielding insights into the landscape of long TRs.
Topics: Humans; Genome, Human; Tandem Repeat Sequences; Minisatellite Repeats; Algorithms; Genetic Drift
PubMed: 37709751
DOI: 10.1038/s41467-023-41262-1 -
Nature Communications Apr 2021Variable number tandem repeats (VNTRs) account for significant genetic variation in many organisms. In humans, VNTRs have been implicated in both Mendelian and complex...
Variable number tandem repeats (VNTRs) account for significant genetic variation in many organisms. In humans, VNTRs have been implicated in both Mendelian and complex disorders, but are largely ignored by genomic pipelines due to the complexity of genotyping and the computational expense. We describe adVNTR-NN, a method that uses shallow neural networks to genotype a VNTR in 18 seconds on 55X whole genome data, while maintaining high accuracy. We use adVNTR-NN to genotype 10,264 VNTRs in 652 GTEx individuals. Associating VNTR length with gene expression in 46 tissues, we identify 163 "eVNTRs". Of the 22 eVNTRs in blood where independent data is available, 21 (95%) are replicated in terms of significance and direction of association. 49% of the eVNTR loci show a strong and likely causal impact on the expression of genes and 80% have maximum effect size at least 0.3. The impacted genes are involved in diseases including Alzheimer's, obesity and familial cancers, highlighting the importance of VNTRs for understanding the genetic basis of complex diseases.
Topics: Alleles; Cerebral Cortex; Cohort Studies; Gene Expression Regulation; Genetic Loci; Genotype; Humans; Minisatellite Repeats; Reproducibility of Results
PubMed: 33824302
DOI: 10.1038/s41467-021-22206-z -
Medicine and Science in Sports and... Apr 2018Most candidate gene studies on the neurobiology of voluntary exercise behavior have focused on the dopaminergic signaling pathway and its role in the mesolimbic reward...
PURPOSE
Most candidate gene studies on the neurobiology of voluntary exercise behavior have focused on the dopaminergic signaling pathway and its role in the mesolimbic reward system. We hypothesized that dopaminergic candidate genes may influence exercise behavior through additional effects on executive functioning and that these effects are only detected when the types of exercise activity are taken into account.
METHODS
Data on voluntary exercise behavior and at least one single-nucleotide polymorphism/variable number of tandem repeat (VNTR) were available for 12,929 participants of the Netherlands Twin Registry. Exercise activity was classified as externally paced if a high level of executive function skill was required. The total volume of voluntary exercise (minutes per week) as well as the volume specifically spent on externally paced activities were tested for association with nine functional dopaminergic polymorphisms (DRD1: rs265981, DRD2/ANKK1: rs1800497, DRD3: rs6280, DRD4: VNTR 48 bp, DRD5: VNTR 130-166 bp, DBH: rs2519152, DAT1: VNTR 40 bp, COMT: rs4680, MAOA: VNTR 30 bp), a polygenic score (PGS) based on nine alleles leading to lower dopamine responsiveness, and a PGS based on three alleles associated with both higher reward sensitivity and better executive functioning (DRD2/ANKK1: "G" allele, COMT: Met allele, DAT1: 440-bp allele).
RESULTS
No association with total exercise volume or externally paced exercise volume was found for individual alleles or the nine-allele PGS. The volume of externally paced exercise behavior was significantly associated with the reward and executive function congruent PGS. This association was driven by the DAT1 440-bp and COMT Met allele, which acted as increaser alleles for externally paced exercise behavior.
CONCLUSIONS
Taking into account the types of exercise activity may increase the success of identifying genetic variants and unraveling the neurobiology of voluntary exercise behavior.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Child; Dopamine; Dopamine Plasma Membrane Transport Proteins; Exercise; Female; Genotype; Humans; Male; Middle Aged; Minisatellite Repeats; Multifactorial Inheritance; Netherlands; Phenotype; Polymorphism, Single Nucleotide; Receptors, Dopamine; Reward; Young Adult
PubMed: 29135816
DOI: 10.1249/MSS.0000000000001479 -
Immunogenetics Mar 2018Rhesus macaque is an important animal model for studies testing interventions like antibody therapeutics; as such knowledge of inter-individual variations in function of...
Rhesus macaque is an important animal model for studies testing interventions like antibody therapeutics; as such knowledge of inter-individual variations in function of genes affecting antibody recycling is important for optimal experimental design. Neonatal Fc receptor (FcRn), a heterodimer composed of FCGRT and β2-m chains, plays critical role in extending catabolic half-life of IgG. We studied genomic polymorphisms in rhesus macaque FcRn and asked if they are functional by assessing correlations with serum IgG or β2-m levels. We tested 75 animals and report the presence of a VNTR polymorphism in promoter of FcRn as well as a single nucleotide polymorphism in the signal peptide of β2-m. A VNTR minor allele was associated with lower levels of serum IgG. This polymorphism may account for inter-animal variation in antibody levels and has relevance for effective design of rhesus macaque studies investigating vaccine-induced antibody responses and passive immunizations.
Topics: Alleles; Animals; Antibodies; Histocompatibility Antigens Class I; Humans; Immunoglobulin G; Macaca mulatta; Minisatellite Repeats; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Receptors, Fc
PubMed: 28785825
DOI: 10.1007/s00251-017-1022-6 -
Veterinary Microbiology Jun 2019Swine brucellosis due to Brucella suis biovar 2 (bv2) is enzootic in wild boar and hare in continental Europe and may cause major economic losses to the pig industry,...
Swine brucellosis due to Brucella suis biovar 2 (bv2) is enzootic in wild boar and hare in continental Europe and may cause major economic losses to the pig industry, mainly in free-ranged pig farms. The high nucleotide identity found among the B. suis biovar 2 isolates has long hindered the full understanding of the epidemiology and the phylogeography of the disease. Here, we used multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) and whole-genome analysis to identify single-nucleotide polymorphisms (SNPs) in order to gain insights from the largest B. suis bv2 dataset analyzed so far composed of domestic pigs and wildlife isolates collected throughout Europe since the 1970s. We found four major clades with a specific phylogeographic pattern. The Iberian clade contains isolates exclusively from the Iberian Peninsula. The Central European clade includes most isolates from France, Northern Italy, Switzerland and an important proportion of those of Northern Spain. The Eastern European clade clustered isolates from Croatia and Hungary mainly but also from areas of France, Germany, Italy and Poland. Finally, a separated Sardinian clade grouped three isolates from this island. At fine scale, MLVA demonstrated an endemic status of the infection in Europe and it allowed tracking a large outbreak formed by different farms from Spain linked to the same infection source. The whole genome SNP analysis showed that the strains form genetically distinct clades, shared between wild boar and pigs, in agreement with the MLVA clades. Interestingly, all hare isolates clustered together within two groups composed exclusively of wildlife isolates. Our results support the hypothesis that maintenance and spread of B. suis bv2 in Europe is a dynamic process linked to the natural expansion of wild boar as the main wild reservoir of the infection, while spread over long distances is found largely dependent on anthropogenic activities.
Topics: Animals; Animals, Wild; Bacterial Typing Techniques; Brucella suis; Brucellosis; Disease Outbreaks; Europe; Genotype; Minisatellite Repeats; Multilocus Sequence Typing; Phylogeny; Phylogeography; Sus scrofa; Swine; Swine Diseases; Whole Genome Sequencing
PubMed: 31176415
DOI: 10.1016/j.vetmic.2019.04.025 -
Psychiatria Danubina Mar 2018the objective of this study was to examine the associations between Cloninger temperament and character dimensions with the DAT1 VNTR and COMT Val158Met polymorphisms.
BACKGROUND
the objective of this study was to examine the associations between Cloninger temperament and character dimensions with the DAT1 VNTR and COMT Val158Met polymorphisms.
SUBJECTS AND METHODS
The study was conducted on 101 subjects, consisting of students of the Police College in Zagreb and staff of the Sestre Milosrdnice University Hospital in Zagreb. The Cloninger Temperament and Character Inventory (TCI) was used to test personality traits.
RESULTS
A main effect of the DAT1 VNTR polymorphism was found on the subscale self-directedness - SD2 (F=5.18, df=1, p<0.05), where a higher result was detected in carriers of the 9/9 genotype (M=7.33, SD=0.51) than those carrying the 10-repeat allele (M=6.02, SD=1.36). Also for the COMT Val158Met polymorphism, main effects were found on the subscales: NS3 (novelty seeking) (F=5.18, df=1, p<0.05), where a higher result was found in carriers of the Val allele (M=5.03, SD=2.22) than in carriers of the Met/Met genotype (MD=4.76, SD=2.37), SD3 (self-directedness) (F=5.18, df=1, p<0.05) where a higher result was found in carriers of the Val/Val genotype (M=4.50, SD=0.78) than in those carrying the Met allele (M=3.80, SD=1.31); C3 (cooperativeness) (F=5.18, df=1, p<0.05), where a high result was found in carriers of the Val allele (M=5.68, SD=1.25) than those carrying the Met/Met genotype (M=5.08, SD=1.11); and ST3 (self-transcendence) (F=5.18, df=1, p<0.05), where a higher result was found in carriers of the Met/Met genotype (M=3.46, SD=2.37) than carriers of the Val allele (M=2.69, SD=1.84). Two significant interactions were detected, on the subscale NS3 (novelty seeking) (F=5.18, df=1, p<0.05), and on the subscale C2 (cooperativeness) (F=5.18, df=1, p<0.05).
CONCLUSIONS
Cloninger's (1987) hypothesis about negative relationship between novelty seeking and dopamine was confirmed on allele level, because higher novelty seeking was found in Val allele carriers comparing to Met/Met genotype carriers.
Topics: Adult; Alleles; Catechol O-Methyltransferase; Character; Croatia; Dopamine; Dopamine Plasma Membrane Transport Proteins; Exploratory Behavior; Female; Genetic Carrier Screening; Genotype; Humans; Male; Methionine; Minisatellite Repeats; Personality Assessment; Polymorphism, Genetic; Psychometrics; Temperament; Valine
PubMed: 29546858
DOI: 10.24869/psyd.2018.47 -
Tuberculosis (Edinburgh, Scotland) Sep 2019The molecular epidemiology of Mycobacterium tuberculosis (M. tuberculosis, Mtb) is poorly documented in Ethiopia. The data that exists has not yet been collected in an... (Meta-Analysis)
Meta-Analysis
The molecular epidemiology of Mycobacterium tuberculosis (M. tuberculosis, Mtb) is poorly documented in Ethiopia. The data that exists has not yet been collected in an overview metadata form. Thus, this review summarizes available literature on the genomic diversity, geospatial distribution and transmission patterns of Mtb lineages (L) and sublineages in Ethiopia. Spoligotyping and Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR) based articles were identified from MEDLINE via PubMed and Scopus. The last date of article search was done on 12th February 2019. Articles were selected following the PRISMA flow diagram. The proportion of (sub)lineages was summarized at national level and further disaggregated by region. Clustering and recent transmission index (RTI) were determined using metan command and random effect meta-analysis model. The meta-analysis was computed using Stata 14 (Stata Corp. College Station, TX, USA). Among 4371 clinical isolates, 99.5% were Mtb and 0.5% were M. bovis. Proportionally, L4, L3, L1 and L7 made up 62.3%, 21.7%, 7.9% and 3.4% of the total isolates, respectively. Among sublineages, L4.2. ETH/SIT149, L4.10/SIT53, L3. ETH1/SIT25 and L4.6/SIT37 were the leading clustered isolates accounting for 14.4%, 9.7%, 7.2% and 5.5%, respectively. Based on MIRU-VNTR, the rate of clustering was 41% and the secondary case rate from a single source case was estimated at 29%. Clustering and recent transmission index was higher in eastern and southwestern Ethiopia compared with the northwestern part of the country. High level of genetic diversity with a high rate of clustering was noted which collectively mirrored the phenomena of micro-epidemics and super-spreading. The largest set of clustered strains deserves special attention and further characterization using whole genome sequencing (WGS) to better understand the evolution, genomic diversity and transmission dynamics of Mtb.
Topics: Bacterial Typing Techniques; Bias; Cluster Analysis; Ethiopia; Genetic Variation; Humans; Minisatellite Repeats; Mycobacterium tuberculosis; Phylogeny; Tuberculosis
PubMed: 31430694
DOI: 10.1016/j.tube.2019.101858 -
Polish Journal of Microbiology Jun 2018Mastitis in goats is mainly caused by coagulase-negative Staphylococcus (CNS). The identification methods for this group are based on evaluating the expression of...
Mastitis in goats is mainly caused by coagulase-negative Staphylococcus (CNS). The identification methods for this group are based on evaluating the expression of phenotypic characteristics such as the ability to metabolize various substrates; however, this is disadvantageous as these methods are dependent on gene expression. In recent years, genotyping methods such as the Multiple Locus Variable-Number Tandem Repeat Analysis (MLVA) and gene identification have been useful for epidemiological study of several bacterial species. To develop a genotyping method, the genome sequence of Staphylococcus chromogenes MU970 was analysed. The analysis showed nine virulence genes described in Staphylococcus aureus. The MLVA was developed using four loci identified in the genome of S. chromogenes MU970. This genotyping method was examined in 23 strains of CNS isolated from goat mastitis. The rate of discrimination for MLVA was 0.8893, and the highest rates of discrimination per the index of Simpson and Hunter-Gaston were 0.926 and 0.968 for the locus 346_06, respectively. The virulence genes were present in all strains of S. chromogenes but not in other CNS. The genotyping method presented in this paper is a viable and easy method for typifying CNS isolates from mastitis cases in different regions and is an ideal mean of tracking this disease.
Topics: Animals; DNA Primers; Female; Genome, Bacterial; Genotyping Techniques; Goat Diseases; Goats; Mastitis; Milk; Minisatellite Repeats; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Virulence Factors
PubMed: 30015455
DOI: 10.21307/pjm-2018-019 -
Annals of Laboratory Medicine Mar 2016To the best of our knowledge, the association between pediatric AML and mitochondrial aberrations has not been studied. We investigated various mitochondrial aberrations...
BACKGROUND
To the best of our knowledge, the association between pediatric AML and mitochondrial aberrations has not been studied. We investigated various mitochondrial aberrations in pediatric AML and evaluated their impact on clinical outcomes.
METHODS
Sequencing, mitochondrial DNA (mtDNA) copy number determination, mtDNA 4,977-bp large deletion assessments, and gene scan analyses were performed on the bone marrow mononuclear cells of 55 pediatric AML patients and on the peripheral blood mononuclear cells of 55 normal controls. Changes in the mitochondrial mass, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) levels were also examined.
RESULTS
mtDNA copy numbers were about two-fold higher in pediatric AML cells than in controls (P<0.0001). Furthermore, a close relationship was found between mtDNA copy number tertiles and the risk of pediatric AML. Intracellular ROS levels, mitochondrial mass, and mitochondrial membrane potentials were all elevated in pediatric AML. The frequency of the mtDNA 4,977-bp large deletion was significantly higher (P<0.01) in pediatric AML cells, and pediatric AML patients harboring high amount of mtDNA 4,977-bp deletions showed shorter overall survival and event-free survival rates, albeit without statistical significance.
CONCLUSIONS
The present findings demonstrate an association between mitochondrial genome alterations and the risk of pediatric AML.
Topics: Bone Marrow Cells; Case-Control Studies; Child; Cohort Studies; DNA, Mitochondrial; Female; Flow Cytometry; Gene Deletion; Gene Dosage; Genome, Mitochondrial; Humans; Leukemia, Myeloid, Acute; Male; Membrane Potential, Mitochondrial; Minisatellite Repeats; Odds Ratio; Reactive Oxygen Species; Sequence Analysis, DNA; Survival Rate
PubMed: 26709256
DOI: 10.3343/alm.2016.36.2.101