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Experimental Biology and Medicine... May 2022SINE-VNTR-Alus (SVAs) are the youngest retrotransposon family in the human genome. Their ongoing mobilization has generated genetic variation within the human... (Review)
Review
SINE-VNTR-Alus (SVAs) are the youngest retrotransposon family in the human genome. Their ongoing mobilization has generated genetic variation within the human population. At least 24 insertions to date, detailed in this review, have been associated with disease. The predominant mechanisms through which this occurs are alterations to normal splicing patterns, exonic insertions causing loss-of-function mutations, and large genomic deletions. Dissecting the functional impact of these SVAs and the mechanism through which they cause disease provides insight into the consequences of their presence in the genome and how these elements could influence phenotypes. Many of these disease-associated SVAs have been difficult to characterize and would not have been identified through routine analyses. However, the number identified has increased in recent years as DNA and RNA sequencing data became more widely available. Therefore, as the search for complex structural variation in disease continues, it is likely to yield further disease-causing SVA insertions.
Topics: Alu Elements; Genome, Human; Humans; Minisatellite Repeats; Retroelements
PubMed: 35387528
DOI: 10.1177/15353702221082612 -
The Brazilian Journal of Infectious... 2022Listeria monocytogenes is responsible for causing listeriosis, a type of food poisoning with high mortality. This bacterium is mainly transmitted to humans through the...
Listeria monocytogenes is responsible for causing listeriosis, a type of food poisoning with high mortality. This bacterium is mainly transmitted to humans through the consumption of contaminated foods. Detection of L. monocytogenes through molecular methods is crucial for food safety and clinical diagnosis. Present techniques are characterized by low discrimination power and high cost, as well as being time-consuming and taking several days to give the final result. In our study, MLVA-HRM (Multiple-Locus Variable-number tandem repeats Analysis ‒ High-Resolution Melting) was investigated as an alternative method for a fast and precise method for the genotyping of L. monocytogenes isolates. Forty-eight isolates of L. monocytogenes obtained from the microbial bank of Department of Microbiology, Iran University of Medical Sciences, were typed by MLVA-HRM analysis using five Variable Numbers of Tandem Repeat (VNTR) loci. A total of 43 different types were obtained. This research demonstrated the usefulness of the MLVA-HRMA method and its ability to discriminate L. monocytogenes isolates. Since this method is easier and more efficient than existing methods, it can be widely used in food processing plants and diagnostic laboratories as a fast and accurate method.
Topics: Food Microbiology; Genotype; Humans; Listeria monocytogenes; Listeriosis; Minisatellite Repeats; Tandem Repeat Sequences
PubMed: 35341738
DOI: 10.1016/j.bjid.2022.102348 -
BMC Genomics Mar 2022PRDM9 is a key regulator of meiotic recombination in most metazoans, responsible for reshuffling parental genomes. During meiosis, the PRDM9 protein recognizes and binds...
BACKGROUND
PRDM9 is a key regulator of meiotic recombination in most metazoans, responsible for reshuffling parental genomes. During meiosis, the PRDM9 protein recognizes and binds specific target motifs via its array of CH zinc-fingers encoded by a rapidly evolving minisatellite. The gene coding for PRDM9 is the only speciation gene identified in vertebrates to date and shows high variation, particularly in the DNA-recognizing positions of the zinc-finger array, within and between species. Across all vertebrate genomes studied for PRDM9 evolution, only one genome lacks variability between repeat types - that of the North Pacific minke whale. This study aims to understand the evolution and diversity of Prdm9 in minke whales, which display the most unusual genome reference allele of Prdm9 so far discovered in mammals.
RESULTS
Minke whales possess all the features characteristic of PRDM9-directed recombination, including complete KRAB, SSXRD and SET domains and a rapidly evolving array of CH-type-Zincfingers (ZnF) with evidence of rapid evolution, particularly at DNA-recognizing positions that evolve under positive diversifying selection. Seventeen novel PRDM9 variants were identified within the Antarctic minke whale species, plus a single distinct PRDM9 variant in Common minke whales - shared across North Atlantic and North Pacific minke whale subspecies boundaries.
CONCLUSION
The PRDM9 ZnF array evolves rapidly, in minke whales, with at least one DNA-recognizing position under positive selection. Extensive PRDM9 diversity is observed, particularly in the Antarctic in minke whales. Common minke whales shared a specific Prdm9 allele across subspecies boundaries, suggesting incomplete speciation by the mechanisms associated with PRDM9 hybrid sterility.
Topics: Alleles; Animals; Histone-Lysine N-Methyltransferase; Meiosis; Minke Whale; Zinc Fingers
PubMed: 35296233
DOI: 10.1186/s12864-022-08305-1 -
International Journal of... 2022Triatomine insects, native to northeastern Brazil, have been found in the urban peridomicile. The city of Sobral has a high number of tuberculosis cases and several...
BACKGROUND
Triatomine insects, native to northeastern Brazil, have been found in the urban peridomicile. The city of Sobral has a high number of tuberculosis cases and several triatomine species. This study investigates the presence of mycobacteria, particularly Mycobacterium tuberculosis complex (MTBC) species, in triatomines captured in the urban perimeter of Sobral.
METHODS
We analyzed 167 triatomines captured in urban households and peridomiciles of Sobral. Mycobacteria were identified by the PRA-hsp65 method followed by partial sequencing of the hsp65 and rpoB genes. The sequences confirmed as MTBC were also typed by mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and spoligotyping.
RESULTS
Triatoma brasiliensis (38.6%), Triatoma pseudomaculata (32.9%), Panstrongylus lutzi (24.3%) were the most frequently identified. In 51.1% (70/167) of them, species of the Mycobacteriaceae family were detected by PRA-hsp65; of these, 31.4% (22/70) were identified as belonging to MTBC species. Nine (12.9%) of the triatomine samples were confirmed by sequencing as belonging to MTBC species. MIRU-VNTR genotyping suggests that the presence of different MTBC sublines in the triatomines should be investigated.
CONCLUSION
This is the first report of MTBC lineages in triatomine insects. These results indicate the migration and adaptation of these insects in an urban setting.
Topics: Brazil; Genotype; Humans; Minisatellite Repeats; Mycobacterium tuberculosis; Polymerase Chain Reaction; Prevalence; Tuberculosis
PubMed: 35295024
DOI: 10.4103/ijmy.ijmy_230_21 -
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 -
PLoS Genetics Mar 2022Congenital idiopathic megaesophagus (CIM) is a gastrointestinal (GI) motility disorder of dogs in which reduced peristaltic activity and dilation of the esophagus...
Congenital idiopathic megaesophagus in the German shepherd dog is a sex-differentiated trait and is associated with an intronic variable number tandem repeat in Melanin-Concentrating Hormone Receptor 2.
Congenital idiopathic megaesophagus (CIM) is a gastrointestinal (GI) motility disorder of dogs in which reduced peristaltic activity and dilation of the esophagus prevent the normal transport of food into the stomach. Affected puppies regurgitate meals and water, fail to thrive, and experience complications such as aspiration pneumonia that may necessitate euthanasia. The German shepherd dog (GSD) has the highest disease incidence, indicative of a genetic predisposition. Here, we discover that male GSDs are twice as likely to be affected as females and show that the sex bias is independent of body size. We propose that female endogenous factors (e.g., estrogen) are protective via their role in promoting relaxation of the sphincter between the esophagus and stomach, facilitating food passage. A genome-wide association study for CIM revealed an association on canine chromosome 12 (P-val = 3.12x10-13), with the lead SNPs located upstream or within Melanin-Concentrating Hormone Receptor 2 (MCHR2), a compelling positional candidate gene having a role in appetite, weight, and GI motility. Within the first intron of MCHR2, we identified a 33 bp variable number tandem repeat (VNTR) containing a consensus binding sequence for the T-box family of transcription factors. Across dogs and wolves, the major allele includes two copies of the repeat, whereas the predominant alleles in GSDs have one or three copies. The single-copy allele is strongly associated with CIM (P-val = 1.32x10-17), with homozygosity for this allele posing the most significant risk. Our findings suggest that the number of T-box protein binding motifs may correlate with MCHR2 expression and that an imbalance of melanin-concentrating hormone plays a role in CIM. We describe herein the first genetic factors identified in CIM: sex and a major locus on chromosome 12, which together predict disease state in the GSD with greater than 75% accuracy.
Topics: Animals; Dogs; Esophageal Achalasia; Female; Genome-Wide Association Study; Introns; Male; Minisatellite Repeats; Receptors, Pituitary Hormone
PubMed: 35271580
DOI: 10.1371/journal.pgen.1010044 -
Folia Morphologica 2023There is a specific polymorphism of the ACAN gene called the variable number of tandem repeats (VNTR), which is particularly interesting in the light of the development...
BACKGROUND
There is a specific polymorphism of the ACAN gene called the variable number of tandem repeats (VNTR), which is particularly interesting in the light of the development of intervertebral disc pathology and associated low back pain.
MATERIALS AND METHODS
The nucleus pulposus specimens were harvested from the L5/S1 intervertebral discs. The aggrecan content was determined using enzyme- linked immunosorbent assay (ELISA). Moreover, the VNTR polymorphism in the ACAN gene was evaluated.
RESULTS
The genotyping of VNTR polymorphism in ACAN gene was successful in 94 tissue samples (48 homozygotes and 46 heterozygotes). The alleles were divided into four groups, in accordance with the number of tandem repeats in the ACAN gene. No difference between groups in the mean aggrecan mass nor in the mean degree of tissue moisture was observed.
CONCLUSIONS
No relationship between the ACAN gene VNTR polymorphism and the aggrecan content was observed in studied Caucasian cadavers. Such a relationship may be a more complex phenomenon and exists in other populations.
Topics: Humans; Aggrecans; Genetic Predisposition to Disease; Intervertebral Disc; Minisatellite Repeats; Polymorphism, Genetic
PubMed: 35239182
DOI: 10.5603/FM.a2022.0019 -
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 -
BMC Infectious Diseases Feb 2022Drug-resistant tuberculosis (TB) continues to be a public health threat. There are few studies on transmission and genotyping of MDR-TB family households in China. This...
BACKGROUND
Drug-resistant tuberculosis (TB) continues to be a public health threat. There are few studies on transmission and genotyping of MDR-TB family households in China. This study aimed to investigate transmission of multidrug-resistant tuberculosis (MDR-TB) within family households by deletion-targeted multiplex polymerase chain reaction (DTM-PCR), mycobacterial interspersed repetitive unit variable number tandem repeats (MIRU-VNTR) genotyping.
METHODS
Among 993 MDR-TB patients registered from Wuhan Institute for Tuberculosis Control, drug resistance and the time interval between the index patients and secondary patients were analyzed in 49 MDR-TB patients from 23 families, in which 22 MDR-TB strains from 11 families who had matched strains were genotyped by DTM-PCR and standard 24-loci MIRU-VNTR genotyping method.
RESULTS
The time interval between the index patients and the secondary patients ranged from half a month to 110 months. Thirteen secondary patients developed active MDR-TB within two years and accounted for 50% (13/26) of all secondary patients. Among eleven pairs of MDR-TB families, six pairs had identical genotypes, the cluster rate was 54.5% (12/22); three pairs had a single MIRU-VNTR locus variation. If a single MIRU-VNTR locus variation was tolerated in the cluster definition, the cluster rate raised to 81.8% (18/22).
CONCLUSIONS
The family households of MDR-TB patients are at risk for infection of MDR-TB. To reduce transmission, MDR-TB patients should be diagnosed earlier and promptly treated in an effective manner, meanwhile, the close family contacts should be screened for TB infection.
Topics: Genotype; Humans; Minisatellite Repeats; Multiplex Polymerase Chain Reaction; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 35219320
DOI: 10.1186/s12879-022-07188-7 -
Microbiology Spectrum Feb 2022Although the number of multidrug-resistant (MDR) tuberculosis (TB) cases is high overall, a major gap exists in our understanding of the molecular characteristics and...
Although the number of multidrug-resistant (MDR) tuberculosis (TB) cases is high overall, a major gap exists in our understanding of the molecular characteristics and transmission dynamics of the MDR Mycobacterium tuberculosis isolates circulating in Bangladesh. The present study aims to characterize the MDR-TB isolates of Bangladesh and to investigate the mode of transmission. A total of 544 MDR-TB isolates were obtained from a nationwide drug-resistant TB surveillance study conducted between October 2011 and March 2017 covering all geographic divisions of Bangladesh. The isolates were characterized using TbD1 deletion analysis, spoligotyping, and mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing. Deletion analysis showed that 440 (80.9%) isolates were the modern type, while the remainder were the ancestral type. The largest circulating lineage was the Beijing type, comprising 208 isolates (38.2%), followed by T, EAI, and LAM with 93 (17.1%), 58 (10.7%), and 52 (9.5%) isolates, respectively. Combined MIRU-VNTR and spoligotyping analysis demonstrated that the majority of the clustered isolates were of the Beijing and T1 lineages. The overall rate of recent transmission was estimated at 33.8%. In conclusion, the MDR M. tuberculosis isolates circulating in Bangladesh are mostly of the modern virulent type. The Beijing and T lineages are the predominant types and most of the transmission of MDR-TB can be attributed to them. The findings also suggest that, along with the remarkable transmission, the emergence of MDR-TB in Bangladesh is largely due to acquired resistance. Rapid and accurate diagnosis and successful treatment will be crucial for controlling MDR-TB in Bangladesh. Multidrug-resistant TB is considered to be the major threat to tuberculosis control activities worldwide, including in Bangladesh. Despite the fact that the number of MDR-TB cases is high, a major gap exists in our understanding of the molecular epidemiology of the MDR-TB isolates in Bangladesh. In our study, we characterized and classified the MDR-TB isolates circulating in Bangladesh and investigated their mode of transmission. Our results demonstrated that the MDR M. tuberculosis isolates circulating in Bangladesh are mostly of the modern virulent type. The Beijing and T lineages are the predominant types and are implicated in the majority of MDR-TB transmission. Our findings reveal that, along with the remarkable transmission, the emergence of MDR-TB in Bangladesh is largely due to acquired resistance, which may be due to nonadherence to treatment or inadequate treatment of TB patients. Rapid diagnosis and adherence to an appropriate treatment regimen are therefore crucial to controlling MDR-TB in Bangladesh.
Topics: Adult; Bangladesh; DNA, Bacterial; Female; Genetic Variation; Genotype; Humans; Male; Middle Aged; Minisatellite Repeats; Molecular Epidemiology; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis, Multidrug-Resistant; Young Adult
PubMed: 35196788
DOI: 10.1128/spectrum.01848-21