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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 -
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 -
Journal, Genetic Engineering &... May 2023Date palm, oasis pivot, plays a vital socio-economic part in the southern area of Morocco. However, with climate change and drought intensity and frequency increasing,...
BACKGROUND
Date palm, oasis pivot, plays a vital socio-economic part in the southern area of Morocco. However, with climate change and drought intensity and frequency increasing, the Moroccan palm grove is threatened with significant genetic degradation. Genetic characterization of this resource is key element for the development of effective conservation and management strategies in the current circumstances of climate change and various biotic and abiotic stresses. To evaluate the genetic diversity of date palm populations collected from different Moroccan oases, we used simple sequence repeats (SSR) and directed amplification of mini-satellite DNA (DAMD) markers. Our results showed that used markers could efficiently assess genetic diversity in Phoenix dactylifera L.
RESULTS
A total of 249 and 471 bands were respectively scored for SSR and DAMD, of which 100% and 92.9% were polymorphic. The polymorphic information content (PIC = 0.95), generated by the SSR primer was nearly identical to that generated by the DAMD primer (PIC = 0.98). The resolving power (Rp) was higher in DAMD than SSR (29.46 and 19.51, respectively). Analysis of the molecular variance (AMOVA) based on the combined data sets for both markers revealed a higher variance within populations (75%) than among populations (25%). Principal coordinate analysis (PCoA) and the ascendant hierarchical classification showed that the population of Zagora and Goulmima regions were the closest populations. The STRUCTURE analysis clustering of the 283 tested samples into seven clusters based on their genetic composition.
CONCLUSION
The results drawn from this study will orient genotypes selection strategies for a successful future breeding and conservation program, particularly under climate change context.
PubMed: 37217693
DOI: 10.1186/s43141-023-00516-7 -
Neuropsychopharmacology Reports Sep 2023One potential cause of suicide is serotonergic dysfunction. Sex differences have been reported to modulate the effects of serotonergic polymorphisms. Monoamine oxidase A... (Meta-Analysis)
Meta-Analysis
BACKGROUND
One potential cause of suicide is serotonergic dysfunction. Sex differences have been reported to modulate the effects of serotonergic polymorphisms. Monoamine oxidase A (MAOA) is an enzyme that degrades serotonin and is located on the X chromosome. A previous study indicated that the upstream (u) variable number of tandem repeat (VNTR) in the MAOA gene promoter may be associated with suicide. However, a meta-analysis showed that this polymorphism may not be related to suicide. According to a recent study, compared with the uVNTR, the distal (d)VNTR and the haplotypes of the two VNTRs modulate MAOA expression.
METHODS
We examined the two VNTRs in the MAOA gene promoter in 1007 subjects who committed suicide and 844 healthy controls. We analyzed the two VNTRs using fluorescence-based polymerase chain reaction assays. We conducted a meta-analysis for the two VNTRs to update it.
RESULTS
Our results demonstrated that neither the genotype-based associations nor allele/haplotype frequencies of the two VNTRs were significantly associated with suicide. In the meta-analysis, we did not indicate relationships between uVNTR and suicide nor did we identify articles analyzing dVNTR in suicide.
CONCLUSION
Overall, we did not find a relationship between the two VNTRs in the MAOA promoter and suicide completion; thus, warranting further studies are required.
Topics: Female; Humans; Male; Minisatellite Repeats; Monoamine Oxidase; Polymorphism, Genetic; Promoter Regions, Genetic; Suicide
PubMed: 37202909
DOI: 10.1002/npr2.12344 -
Scientific Reports Apr 2023The objective of this study was to genotype Mycobacterium tuberculosis complex isolated from humans and cattle in northern Iran. Over the course of one year, a total of...
The objective of this study was to genotype Mycobacterium tuberculosis complex isolated from humans and cattle in northern Iran. Over the course of one year, a total of 120 human and 21 cattle isolates were tested using region of difference (RD)-based polymerase chain reaction (PCR) and mycobacterial interspersed repetitive unites-variable number tandem repeats (MIRU-VNTR). In M. tuberculosis, out of 120 isolates investigated, the most common genotype detected was NEW-1 (53.3%), followed by CAS/ Delhi (24.1%), Haarlem (5%), Beijing (4.16%), Uganda I (4.16%), S (3.3%), Ural (0.83%), TUR (0.83%), Uganda II (0.83%), Lam (0.83%) and Cameroon (0.83%). The HGDI rate was 0.9981 and the clustering rate was 10.83. Of the isolates, QUB26 had the highest allele diversity (h: 0.76), while the loci Mtub29 and MIRU24 had the lowest (h: 0). In M. Bovis, out of 123 collected tissue samples, 21 (17%) grew on culture media. The HGDI rate was 0.71 and clustering rate was 85.7%. The locus ETRC had the highest allele diversity (h: 0.45). The findings of this study suggest that there is high genetic diversity among M. tuberculosis isolates in Khorasan Razavi Province, which is consistent with similar results from other studies in other provinces in Iran and neighboring countries. This indicates that the prevalent genotypes in this study are spreading in the Middle East region. Furthermore, considering that M. Bovis isolates were identified in two clusters, it seems that all of them have a common origin and are circulating among the livestock farms in the province.
Topics: Humans; Cattle; Animals; Mycobacterium tuberculosis; Genotype; Iran; Minisatellite Repeats; Tuberculosis; Bacterial Typing Techniques
PubMed: 37185604
DOI: 10.1038/s41598-023-33740-9 -
PloS One 2023Cassava Bacterial Blight (CBB) is a destructive disease widely distributed in the different areas where this crop is grown. Populations studies have been performed at...
Cassava Bacterial Blight (CBB) is a destructive disease widely distributed in the different areas where this crop is grown. Populations studies have been performed at local and national scales revealing a geographical genetic structure with temporal variations. A global epidemiology analysis of its causal agent Xanthomonas phaseoli pv. manihotis (Xpm) is needed to better understand the expansion of the disease for improving the monitoring of CBB. We targeted new tandem repeat (TR) loci with large repeat units, i.e. minisatellites, that we multiplexed in a scheme of Multi-Locus Variable number of TR Analysis (MLVA-8). This genotyping scheme separated 31 multilocus haplotypes in three clusters of single-locus variants and a singleton within a worldwide collection of 93 Xpm strains isolated over a period of fifty years. The major MLVA-8 cluster 1 grouped strains originating from all countries, except the unique Chinese strain. On the contrary, all the Xpm strains genotyped using the previously developed MLVA-14 microsatellite scheme were separated as unique haplotypes. We further propose an MLVA-12 scheme which takes advantage of combining TR loci with different mutation rates: the eight minisatellites and four faster evolving microsatellite markers, for global epidemiological surveillance. This MLVA-12 scheme identified 78 haplotypes and separated most of the strains in groups of double-locus variants (DLV) supporting some phylogenetic relationships. DLV groups were subdivided into closely related clusters of strains most often sharing the same geographical origin and isolated over a short period, supporting epidemiological relationships. The main MLVA-12 DLV group#1 was composed by strains from South America and all the African strains. The MLVA-12 scheme combining both minisatellite and microsatellite loci with different discriminatory power is expected to increase the accuracy of the phylogenetic signal and to minimize the homoplasy effects. Further investigation of the global epidemiology of Xpm will be helpful for a better control of CBB worldwide.
Topics: Minisatellite Repeats; Manihot; Phylogeny; Genotype; Microsatellite Repeats; Bacterial Typing Techniques
PubMed: 37167330
DOI: 10.1371/journal.pone.0285491 -
Microbiology Spectrum Jun 2023Mixed infections of Mycobacterium tuberculosis, defined as the coexistence of multiple genetically distinct strains within a single host, have been associated with...
Mixed infections of Mycobacterium tuberculosis, defined as the coexistence of multiple genetically distinct strains within a single host, have been associated with unfavorable treatment outcomes. Different methods have been used to detect mixed infections, but their performances have not been carefully evaluated. To compare the sensitivity of whole-genome sequencing (WGS) and variable-number tandem repeats (VNTR) typing to detect mixed infections, we prepared 10 artificial samples composed of DNA mixtures from two strains in different proportions and retrospectively collected 1,084 clinical isolates. The limit of detection (LOD) for the presence of a minor strain was 5% for both WGS and VNTR typing. The overall clinical detection rate of mixed infections was 3.7% (40/1,084) for the two methods combined, WGS identified 37/1,084 (3.4%), and VNTR typing identified 14/1,084 (1.3%), including 11 also identified by WGS. Multivariate analysis demonstrated that retreatment patients had a 2.7 times (95% confidence interval [CI], 1.2 to 6.0) higher risk of mixed infections than new cases. Collectively, WGS is a more reliable tool to identify mixed infections than VNTR typing, and mixed infections are more common in retreated patients. Mixed infections of M. tuberculosis have the potential to render treatment regimens ineffective and affect the transmission dynamics of the disease. VNTR typing, currently the most widely used method for the detection of mixed infections, detects mixed infections only by interrogating a small fraction of the M. tuberculosis genome, which necessarily limits sensitivity. With the introduction of WGS, it became possible to study the entire genome, but no quantitative comparison has yet been undertaken. Our systematic comparison of the ability of WGS and VNTR typing to detect mixed infections, using both artificial samples and clinical isolates, revealed the superior performance of WGS at a high sequencing depth (~100×) and found that mixed infections are more common in patients being retreated for tuberculosis (TB) in the populations studied. This provides valuable information for the application of WGS in the detection of mixed infections and the implications of mixed infections for tuberculosis control.
Topics: Humans; Mycobacterium tuberculosis; Coinfection; Retrospective Studies; Polymorphism, Single Nucleotide; Tuberculosis; Minisatellite Repeats; Bacterial Typing Techniques
PubMed: 37098911
DOI: 10.1128/spectrum.03570-22