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Molecular Neurobiology Jun 2019A promoter can be regulated by various cis-acting elements so that delineation of the regulatory modes among them may help understand developmental, environmental and...
A promoter can be regulated by various cis-acting elements so that delineation of the regulatory modes among them may help understand developmental, environmental and genetic mechanisms in gene activity. Here we report that the human dopamine transporter gene SLC6A3 carries a 5' distal 5-kb super enhancer (5KSE) which upregulated the promoter by 5-fold. Interestingly, 5KSE is able to prevent 3' downstream variable number tandem repeats (3'VNTRs) from silencing the promoter. This new enhancer consists of a 5'VNTR and three repetitive sub-elements that are conserved in primates. Two of 5KSE's sub-elements, E-9.7 and E-8.7, upregulate the promoter, but only the later could continue doing so in the presence of 3'VNTRs. Finally, E-8.7 is activated by novel dopaminergic transcription factors including SRP54 and Nfe2l1. Together, these results reveal a multimodal regulatory mechanism in SLC6A3.
Topics: Adult; Animals; Cell Line, Tumor; Dopamine Plasma Membrane Transport Proteins; Enhancer Elements, Genetic; Haplotypes; Humans; Male; Mice, Inbred C57BL; Minisatellite Repeats; Models, Biological; Promoter Regions, Genetic; Transcription Factors; Transcription, Genetic
PubMed: 30259411
DOI: 10.1007/s12035-018-1357-5 -
Scientific Reports Jan 2022Schizophrenia is a severe, disabling psychiatric disorder with unclear etiology. Family-based, twins, and adoption studies have shown that genetic factors have major...
Schizophrenia is a severe, disabling psychiatric disorder with unclear etiology. Family-based, twins, and adoption studies have shown that genetic factors have major contributions in schizophrenia occurrence. Until now, many studies have discovered the association of schizophrenia and its comorbid symptoms with functional polymorphisms that lie within serotonin reuptake pathway genes. Here, we aimed to investigate the association of three variable number tandem repeats (VNTR) functional polymorphisms in MAOA and SLC6A4 with schizophrenia in the Iranian population. Two hundred and forty-one subjects with schizophrenia and three hundred and seventy age and sex-matched healthy controls were genotyped for MAOA promoter uVNTR, 5-HTTLPR, and STin2 polymorphisms. Genotyping was performed by polymerase chain reaction (PCR) with locus-specific primers and running the PCR product on agarose 2.5% gel electrophoresis. Finally, the statistical inference was performed using R programming language and Haploview software. MAOA promoter uVNTR analysis of allele frequency showed no differences between schizophrenia subjects and healthy controls in both males and females and no significant differences were observed between female cases and female controls in MAOA promoter uVNTR 4 repeat frequency. Also, there were no differences between Schizophrenia and healthy control groups in 5-HTTLPR allele and genotype frequency but, 5-HTTLPR S allele carriers are significantly more frequent among cases. In addition, STin2.12 repeats were significantly more frequent among schizophrenia patients. Genotype comparison suggested that 5-HTTLPR S allele and STin2.12 repeat carriers were significantly more frequent among schizophrenia cases and being STin2.12 repeat carrier significantly increase the risk of schizophrenia occurrence. Besides, analysis of haplotype showed stronger linkage disequilibrium between 5-HTTLPR and STin2 haplotype block in cases than controls. These results suggest that SLC6A4 functional polymorphisms potentially could play a possible role as risk factors for the incidence of schizophrenia.
Topics: Adult; Case-Control Studies; Female; Haplotypes; Humans; Male; Middle Aged; Minisatellite Repeats; Monoamine Oxidase; Polymorphism, Single Nucleotide; Schizophrenia; Serotonin Plasma Membrane Transport Proteins
PubMed: 35079035
DOI: 10.1038/s41598-022-05206-x -
Neuropeptides Aug 2017Many facets of human behaviour are likely to have developed in part due to evolutionary changes in the regulation of neuropeptide and other brain-related genes. This has... (Review)
Review
Many facets of human behaviour are likely to have developed in part due to evolutionary changes in the regulation of neuropeptide and other brain-related genes. This has allowed species-specific expression patterns and unique epigenetic modulation in response to our environment, regulating response not only at the molecular level, but also contributing to differences in behaviour between individuals. As such, genetic variants or epigenetic changes that may alter neuropeptide gene expression are predicted to play a role in behavioural conditions and psychiatric illness. It is therefore of interest to identify regulatory elements that have the potential to drive differential gene expression. Retrotransposons are mobile genetic elements that are known to be drivers of genomic diversity, with the ability to alter expression of nearby genes. In particular, the SINE-VNTR-Alu (SVA) class of retrotransposons is specific to hominids, and its appearance and expansion across the genome has been associated with the evolution of numerous behavioural traits, presumably through their ability to confer unique regulatory properties at the site of their insertion. We review the evidence for SVAs as regulatory elements, exploring how polymorphic variation within these repetitive sequences can drive allele specific gene expression, which would be associated with changes in behaviour and disease risk through the alteration of molecular pathways that are central to healthy brain function.
Topics: Animals; Brain; Gene Expression; Genetic Variation; Humans; Minisatellite Repeats; Neuropeptides; Retroelements
PubMed: 27743609
DOI: 10.1016/j.npep.2016.09.006 -
BMC Genomics Jul 2023Drug resistant Mycobacterium tuberculosis prevention and care is a major challenge in Ethiopia. The World health organization has designated Ethiopia as one of the 30...
BACKGROUND
Drug resistant Mycobacterium tuberculosis prevention and care is a major challenge in Ethiopia. The World health organization has designated Ethiopia as one of the 30 high burden multi-drug resistant tuberculosis (MDR-TB) countries. There is limited information regarding genetic diversity and transmission dynamics of MDR-TB in Ethiopia.
OBJECTIVE
To investigate the molecular epidemiology and transmission dynamics of MDR-TB strains using whole genome sequence (WGS) in the Amhara region.
METHODS
Forty-five MDR-TB clinical isolates from Amhara region were collected between 2016 and 2018, and characterized using WGS and 24-loci Mycobacterium Interspersed Repetitive Units Variable Number of Tandem Repeats (MIRU-VNTR) typing. Clusters were defined based on the maximum distance of 12 single nucleotide polymorphisms (SNPs) or alleles as the upper threshold of genomic relatedness. Five or less SNPs or alleles distance or identical 24-loci VNTR typing is denoted as surrogate marker for recent transmission.
RESULTS
Forty-one of the 45 isolates were analyzed by WGS and 44% (18/41) of the isolates were distributed into 4 clusters. Of the 41 MDR-TB isolates, 58.5% were classified as lineage 4, 36.5% lineage 3 and 5% lineage 1. Overall, TUR genotype (54%) was the predominant in MDR-TB strains. 41% (17/41) of the isolates were clustered into four WGS groups and the remaining isolates were unique strains. The predominant cluster (Cluster 1) was composed of nine isolates belonging to lineage 4 and of these, four isolates were in the recent transmission links.
CONCLUSIONS
Majority of MDR-TB strain cluster and predominance of TUR lineage in the Amhara region give rise to concerns for possible ongoing transmission. Efforts to strengthen TB laboratory to advance diagnosis, intensified active case finding, and expanded contact tracing activities are needed in order to improve rapid diagnosis and initiate early treatment. This would lead to the interruption of the transmission chain and stop the spread of MDR-TB in the Amhara region.
Topics: Humans; Antitubercular Agents; Tuberculosis; Mycobacterium tuberculosis; Ethiopia; Molecular Epidemiology; Tuberculosis, Multidrug-Resistant; Genotype; Whole Genome Sequencing; Minisatellite Repeats
PubMed: 37460951
DOI: 10.1186/s12864-023-09502-2 -
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 -
Cells Oct 2022Major Depressive Disorder (MDD) is a highly prevalent multifactorial psychopathology affected by neurotransmitter levels. Monoamine Oxidase A (MAOA) influences several...
Major Depressive Disorder (MDD) is a highly prevalent multifactorial psychopathology affected by neurotransmitter levels. Monoamine Oxidase A (MAOA) influences several neural pathways by modulating these levels. This systematic review (per PRISMA protocol and PECOS strategy) endeavors to understand the polymorphism influence on MDD and evaluate its 3R/3R and 3R* genotypic frequencies fluctuation in MDD patients from different populations. We searched the Web of Science, PubMed, Virtual Health Library, and EMBASE databases for eligible original articles that brought data on genotypic frequencies related to the variant in patients with MDD. We excluded studies with incomplete data (including statistical data), reviews, meta-analyses, and abstracts. Initially, we found 43 articles. After removing duplicates and applying the inclusion/exclusion criteria, seven articles remained. The population samples studied were predominantly Asians, with high 3R and 4R allele frequencies. Notably, we observed higher 3R/3R (female) and 3R* (male) genotype frequencies in the healthy control groups and higher 4R/4R (female) and 4R* (male) genotype frequencies in the MDD groups in the majority of different populations. Despite some similarities in the articles analyzed, there is still no consensus on the variant's role in MDD pathogenesis.
Topics: Female; Humans; Male; Depressive Disorder, Major; Gene Frequency; Minisatellite Repeats; Monoamine Oxidase; Polymorphism, Genetic
PubMed: 36291132
DOI: 10.3390/cells11203267 -
Archives of Razi Institute Dec 2023In the present research, we aimed to determine the characteristics of E. faecalis strains collected from an Iranian Children's Hospital for four years. Sixty-seven E....
In the present research, we aimed to determine the characteristics of E. faecalis strains collected from an Iranian Children's Hospital for four years. Sixty-seven E. faecalis isolates with virulence genes detection, variable-number tandem repeat (VNTR), and multiple-locus variable-number tandem repeat analysis (MLVA) typing were investigated. A high frequency of virulence genes belonged to gelatinase (73%) and Enterococcus faecalis (62%). The MLVA of 67 E. faecalis isolates revealed 52 VNTR patterns and 38 MLVA types (MTs). Furthermore, genetic diversities with the majority of the MT1 as a major MT in different Wards of the Children's Hospital were found.
Topics: Enterococcus faecalis; Iran; Humans; Gram-Positive Bacterial Infections; Minisatellite Repeats; Child; Hospitals, Pediatric; Genetic Variation; Virulence Factors
PubMed: 38828180
DOI: 10.32592/ARI.2023.78.6.1873 -
Graph construction method impacts variation representation and analyses in a bovine super-pangenome.Genome Biology May 2023Several models and algorithms have been proposed to build pangenomes from multiple input assemblies, but their impact on variant representation, and consequently...
BACKGROUND
Several models and algorithms have been proposed to build pangenomes from multiple input assemblies, but their impact on variant representation, and consequently downstream analyses, is largely unknown.
RESULTS
We create multi-species super-pangenomes using pggb, cactus, and minigraph with the Bos taurus taurus reference sequence and eleven haplotype-resolved assemblies from taurine and indicine cattle, bison, yak, and gaur. We recover 221 k nonredundant structural variations (SVs) from the pangenomes, of which 135 k (61%) are common to all three. SVs derived from assembly-based calling show high agreement with the consensus calls from the pangenomes (96%), but validate only a small proportion of variations private to each graph. Pggb and cactus, which also incorporate base-level variation, have approximately 95% exact matches with assembly-derived small variant calls, which significantly improves the edit rate when realigning assemblies compared to minigraph. We use the three pangenomes to investigate 9566 variable number tandem repeats (VNTRs), finding 63% have identical predicted repeat counts in the three graphs, while minigraph can over or underestimate the count given its approximate coordinate system. We examine a highly variable VNTR locus and show that repeat unit copy number impacts the expression of proximal genes and non-coding RNA.
CONCLUSIONS
Our findings indicate good consensus between the three pangenome methods but also show their individual strengths and weaknesses that need to be considered when analysing different types of variants from multiple input assemblies.
Topics: Animals; Cattle; Genome; Minisatellite Repeats; Sequence Analysis, DNA
PubMed: 37217946
DOI: 10.1186/s13059-023-02969-y -
PloS One 2022Mycobacterial Interspersed Repetitive Units-Variable Tandem Repeats (MIRU-VNTR) typing has been widely used for molecular epidemiological studies of tuberculosis (TB)....
INTRODUCTION
Mycobacterial Interspersed Repetitive Units-Variable Tandem Repeats (MIRU-VNTR) typing has been widely used for molecular epidemiological studies of tuberculosis (TB). However, genotyping tools for Mycobacterium tuberculosis (Mtb) may be limiting in some settings due to high cost and workload. In this study developed a customized stepwise MIRU-VNTR typing that prioritizes high discriminatory loci and validated this method using penitentiary system cohort in the country of Georgia.
METHODS
We used a previously generated MIRU-VNTR dataset from recurrent TB cases (32 cases) in Georgia and a new dataset of TB cases from the penitentiary system (102 cases) recruited from 2014 to 2015. A Hunter-Gaston Discriminatory Index (HGDI) was calculated utilizing a 24 standard loci panel, to select high discriminatory power loci, subsequently defined as the customized Georgia-specific set of loci for initial typing. The remaining loci were scored and hierarchically grouped for second and third step typing of the cohort. We then compared the processing time and costs of the customized stepwise method to the standard 24-loci method.
RESULTS
For the customized Georgia-specific set that was used for initial typing, 10 loci were selected with a minimum value of 0.32 to the highest HGDI score locus. Customized 10 loci (step 1) typing of 102 Mtb patient isolates revealed 35.7% clustered cases. This proportion was reduced to 19.5% after hierarchical application of 2nd and 3rd step typing with the corresponding groups of loci. Our customized stepwise MIRU-VNTR genotyping approach reduced the quantity of samples to be typed and therefore overall processing time and costs by 42.6% each.
CONCLUSION
Our study shows that our customized stepwise MIRU-VNTR typing approach is a valid alternative of standard MIRI-VNTR typing panels for molecular epidemiological investigation in Georgia that saves time, workload and costs. Similar approaches could be developed for other settings.
Topics: Bacterial Typing Techniques; DNA, Bacterial; Genotype; Georgia; Humans; Minisatellite Repeats; Molecular Epidemiology; Mycobacterium tuberculosis; Tuberculosis
PubMed: 35231041
DOI: 10.1371/journal.pone.0264472 -
International Journal of... 2022Tuberculosis (TB) remains a serious public health burden in Korea. Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) is preferred for...
Validation and comparative analysis of kogene mycobacterial interspersed repetitive unit-variable number of tandem repeat typing kit and its application on clinically isolated samples from national tuberculosis hospital, Republic of Korea.
BACKGROUND
Tuberculosis (TB) remains a serious public health burden in Korea. Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) is preferred for epidemiological TB investigation. Until recently, the difficulty lies in epidemiological TB investigation due to the absence of commercialized MIRU-VNTR in Korea. Here, we have evaluated the newly designed MIRU-VNTR kit by Kogenebiotech, Korea.
MATERIALS AND METHODS
A total of 200 samples, where 100 are Mycobacrerium tuberculosis (M. tuberculosis), and the other 100 are non-M. tuberculosis, were used. Initially, the Kogenebiotech MIRU-VNTR typing kit (KoMIRU) was compared with Multilocus Variable Number Tandem Repeat Genotyping of M. tuberculosis typing kit (MVNTR) by Philip Supply for validation purpose. Then, Limit of Detection for DNA copies was optimized. Finally, KoMIRU and Genoscreen MIRU-VNTR typing kit (GeMIRU) were tested and comparatively analyzed for its specificity and sensitivity.
RESULTS
The study showed that the KoMIRU has slightly higher discriminatory power over MVNTR, 100% versus 97.5%. In comparative analysis, the KoMIRU has shown comparable capability as GeMIRU, showing 100% for sensitivity and specificity with a 95% CI value of 96.38 to 100.00%. Also, no discrepancies were observed on discriminated lineage strains between KoMIRU and GeMIRU. Out of 100, 84 were identified as Beijing strains, and remains were identified as NEW-1 (n = 8), Uganda (n = 6), East African Indian (EAI) (n = 6), Turkey (n = 2), and Haarlem (n = 1).
CONCLUSION
In this study, KoMIRU has shown a comparable capability to GeMIRU. Furthermore, previous researches had suggested an association between lineage strains and drug resistance; hence, the implementation of KoMIRU can help in TB control and prevention.
Topics: Bacterial Typing Techniques; DNA, Bacterial; Genotype; Hospitals, Chronic Disease; Humans; Interspersed Repetitive Sequences; Minisatellite Repeats; Mycobacterium tuberculosis; Tuberculosis, Lymph Node
PubMed: 35295020
DOI: 10.4103/ijmy.ijmy_8_22