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Journal of Endocrinological... Mar 2024A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may...
Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.
PURPOSE
A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population.
METHODS
We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies.
RESULTS
TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls.
CONCLUSION
Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.
Topics: Female; Male; Humans; Tyrosine 3-Monooxygenase; Insulin Secretion; Diabetes Mellitus, Type 2; Minisatellite Repeats; Case-Control Studies; Cross-Sectional Studies; Fasting; Insulin; Microsatellite Repeats
PubMed: 37624484
DOI: 10.1007/s40618-023-02175-4 -
Journal of Food Protection Oct 2023Listeria monocytogenes is a serious human pathogen and an enduring challenge to control for the ready-to-eat food processing industry. Cost-effective tools that can be...
Validating the Utility of Multilocus Variable Number Tandem-repeat Analysis (MLVA) as a Subtyping Strategy to Monitor Listeria monocytogenes In-built Food Processing Environments.
Listeria monocytogenes is a serious human pathogen and an enduring challenge to control for the ready-to-eat food processing industry. Cost-effective tools that can be deployed by commercial or in-house laboratories to rapidly investigate and resolve contamination events in the built food processing environment are of value to the food industry. Multilocus variable number tandem-repeat analysis (MLVA) is a molecular subtyping method, which along with other same-generation methods such as pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) is being superseded in disease tracking and outbreak investigations by whole-genome sequencing (WGS). In this paper, it is demonstrated that MLVA can continue to play a valuable role as a valid, fast, simple, and cost-effective method to identify and track Listeria monocytogenes subtypes in factory environments, with the method being highly congruent with MLST. Although MLVA does not have the discriminatory power of WGS to identify truly persistent clones, with careful interpretation of results alongside isolate metadata, it remains a powerful tool in situations and locations where WGS may not be readily available to food business operators.
Topics: Humans; Listeria monocytogenes; Multilocus Sequence Typing; Minisatellite Repeats; Food Handling; Food-Processing Industry; Electrophoresis, Gel, Pulsed-Field; Food Microbiology
PubMed: 37619693
DOI: 10.1016/j.jfp.2023.100147 -
Nucleosides, Nucleotides & Nucleic Acids 2024Circadian rhythmicity has been shown to contribute to the regulation of key physiological and cognitive processes related to performance. The period homolog 3 () is...
OBJECTIVE
Circadian rhythmicity has been shown to contribute to the regulation of key physiological and cognitive processes related to performance. The period homolog 3 () is expressed in a circadian pattern in the suprachiasmatic nucleus. Therefore, in this study, we aimed to evaluate the role of the variable tandem repeat (VNTR) variant of the gene in athletic performance in the Turkish population.
METHODS
This study included 223 subjects, which consisted of 123 athletes and 100 sedentary controls. Blood samples were drawn from all subjects. DNA was extracted from whole-blood samples. The VNTR variant was genotyped using the polymerase chain reaction-restriction method (PCR). The results of the analyses were evaluated for statistical significance.
RESULTS
The mean ages of athletes and controls were 22 ± 2.814 and 23 ± 3.561, respectively. Endurance athletes in the group were 21.1%, and sprint athletes were 78.9%. There was no statistical significance in terms of VNTR genotype distribution or allele frequency. In the recessive model, a statistically significant association was observed when the athletes were compared with the controls according to 4/4 + 4/5 versus 5/5 genotype ( = 0.020).
CONCLUSION
In this case-control study, for the first time in our country, we obtained findings suggesting that the VNTR variant may affect sports performance in the Turkish population. Results need to be replicated in different ethnic and larger samples.
Topics: Humans; Polymorphism, Genetic; Minisatellite Repeats; Case-Control Studies; Period Circadian Proteins; Circadian Rhythm; Gene Frequency; Genotype; Athletes
PubMed: 37610137
DOI: 10.1080/15257770.2023.2248198 -
Cell Aug 2023Many regions in the human genome vary in length among individuals due to variable numbers of tandem repeats (VNTRs). To assess the phenotypic impact of VNTRs...
Many regions in the human genome vary in length among individuals due to variable numbers of tandem repeats (VNTRs). To assess the phenotypic impact of VNTRs genome-wide, we applied a statistical imputation approach to estimate the lengths of 9,561 autosomal VNTR loci in 418,136 unrelated UK Biobank participants and 838 GTEx participants. Association and statistical fine-mapping analyses identified 58 VNTRs that appeared to influence a complex trait in UK Biobank, 18 of which also appeared to modulate expression or splicing of a nearby gene. Non-coding VNTRs at TMCO1 and EIF3H appeared to generate the largest known contributions of common human genetic variation to risk of glaucoma and colorectal cancer, respectively. Each of these two VNTRs associated with a >2-fold range of risk across individuals. These results reveal a substantial and previously unappreciated role of non-coding VNTRs in human health and gene regulation.
Topics: Humans; Calcium Channels; Colorectal Neoplasms; Genome, Human; Glaucoma; Minisatellite Repeats; Polymorphism, Genetic; Eukaryotic Initiation Factor-3
PubMed: 37527660
DOI: 10.1016/j.cell.2023.07.002 -
International Journal of Molecular... Jul 2023The hominid-specific retrotransposon SINE-VNTR-Alu (SVA) is a composite element that has contributed to the genetic variation between individuals and influenced genomic...
The hominid-specific retrotransposon SINE-VNTR-Alu (SVA) is a composite element that has contributed to the genetic variation between individuals and influenced genomic structure and function. SVAs are involved in modulating gene expression and splicing patterns, altering mRNA levels and sequences, and have been associated with the development of disease. We evaluated the genome-wide effects of SVAs present in the reference genome on transcript sequence and expression in the CNS of individuals with and without the neurodegenerative disorder Amyotrophic Lateral Sclerosis (ALS). This study identified SVAs in the exons of 179 known transcripts, several of which were expressed in a tissue-specific manner, as well as 92 novel exonisation events occurring in the motor cortex. An analysis of 65 reference genome SVAs polymorphic for their presence/absence in the ALS consortium cohort did not identify any elements that were significantly associated with disease status, age at onset, and survival. However, there were transcripts, such as transferrin and , that were differentially expressed between those with or without disease, and expression levels were associated with the genotype of proximal SVAs. This study demonstrates the functional consequences of several SVA elements altering mRNA splicing patterns and expression levels in tissues of the CNS.
Topics: Humans; Amyotrophic Lateral Sclerosis; Minisatellite Repeats; Short Interspersed Nucleotide Elements; Alu Elements; RNA, Messenger
PubMed: 37511314
DOI: 10.3390/ijms241411548 -
Genome Biology Jul 2023Roughly 3% of the human genome is composed of variable-number tandem repeats (VNTRs): arrays of motifs at least six bases. These loci are highly polymorphic, yet current...
Roughly 3% of the human genome is composed of variable-number tandem repeats (VNTRs): arrays of motifs at least six bases. These loci are highly polymorphic, yet current approaches that define and merge variants based on alignment breakpoints do not capture their full diversity. Here we present a method vamos: VNTR Annotation using efficient Motif Sets that instead annotates VNTR using repeat composition under different levels of motif diversity. Using vamos we estimate 7.4-16.7 alleles per locus when applied to 74 haplotype-resolved human assemblies, compared to breakpoint-based approaches that estimate 4.0-5.5 alleles per locus.
Topics: Humans; Minisatellite Repeats
PubMed: 37501141
DOI: 10.1186/s13059-023-03010-y -
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 -
Journal of Microbiological Methods Aug 2023Numerous genotyping techniques based on different principles and with different costs and levels of resolution are currently available for understanding the transmission...
Numerous genotyping techniques based on different principles and with different costs and levels of resolution are currently available for understanding the transmission dynamics of brucellosis worldwide. We aimed to compare the population structure of the genomes of 53 Brazilian Brucella abortus isolates using eight different genotyping methods: multiple-locus variable-number tandem-repeat analysis (MLVA8, MLVA11, MLVA16), multilocus sequence typing (MLST9, MLST21), core genome MLST (cgMLST) and two techniques based on single nucleotide polymorphism (SNP) detection (parSNP and NASP) from whole genomes. The strains were isolated from six different Brazilian states between 1977 and 2008 and had previously been analyzed using MLVA8, MLVA11, and MLVA16. Their whole genomes were sequenced, assembled, and subjected to MLST9 MLST21, cgMLST, and SNP analyses. All the genotypes were compared by hierarchical grouping method based on the average distances between the correlation matrices of each technique. MLST9 and MLST21 had the lowest level of resolution, both revealing only four genotypes. MLVA8, MLVA11, and MLVA16 had progressively increasing levels of resolution as more loci were analyzed, identifying 6, 16, and 44 genotypes, respectively. cgMLST showed the highest level of resolution, identifying 45 genotypes, followed by the SNP-based methods, both of which had 44 genotypes. In the assessed population, MLVA was more discriminatory than MLST and was easier and cheaper to perform. SNP techniques and cgMLST provided the highest levels of resolution and the results from the two methods were in close agreement. In conclusion, the choice of genotyping technique can strongly affect one's ability to make meaningful epidemiological conclusions but is dependent on available resources: while the VNTR based techniques are more indicated to high prevalence scenarios, the WGS methods are the ones with the best discriminative power and therefore recommended for outbreaks investigation.
Topics: Humans; Brucella abortus; Genotyping Techniques; Genotype; Multilocus Sequence Typing; Brucellosis; Minisatellite Repeats; Phylogeny
PubMed: 37343840
DOI: 10.1016/j.mimet.2023.106772 -
BMC Infectious Diseases May 2023Immigration is considered as a risk factor of tuberculosis (TB). Qom province receives millions of pilgrims and significant numbers of immigrants each year. Most of the...
BACKGROUND
Immigration is considered as a risk factor of tuberculosis (TB). Qom province receives millions of pilgrims and significant numbers of immigrants each year. Most of the immigrants to Qom, arrive from neighboring TB-endemic countries. This study aimed to identify the current circulating Mycobacterium tuberculosis genotypes in Qom province using 24-locus MIRU-VNTR genotyping.
METHODS
Eighty six M. tuberculosis isolates were collected during 2018-2022 from patients referring to Qom TB reference laboratory. The DNA of isolates was extracted and followed by 24 loci MIRU-VNTR genotyping which performed using the web tools available on MIRU-VNTRplus.
RESULTS
Of 86 isolates, 39 (45.3%) were of Delhi/CAS genotype, 24 (27.9%) of NEW-1, 6 (7%) of LAM, 6 (7%) of Beijing, 2 (2.3%) of UgandaII, 2 (2.3%) of EAI, 1 of S (1.2%) and 6 (7%) did not match with profiles present in MIRUVNTRplus database.
CONCLUSIONS
About half of the isolates belong to Afghan immigrants; which warns health policy makers about the future situation of TB in Qom. Also, the similarity of Afghan and Iranian genotypes provides evidence that immigrants partake in the circulation of M. tuberculosis. This study underpin the studies about the circulating M. tuberculosis genotypes, their geographical distribution, the association of TB risk factors with these genotypes and the impact of immigration on the situation of TB in Qom province.
Topics: Humans; Mycobacterium tuberculosis; Iran; Tuberculosis; Genotype; Emigrants and Immigrants; Minisatellite Repeats; Bacterial Typing Techniques
PubMed: 37231348
DOI: 10.1186/s12879-023-08325-6 -
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