scholarly journals Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
JA Guerra-Assunção ◽  
AC Crampin ◽  
RMGJ Houben ◽  
T Mzembe ◽  
K Mallard ◽  
...  
Keyword(s):  
Large Scale ◽  
Nucleotide Polymorphisms ◽  
Recent Infection ◽  
Transmission Networks ◽  
Tuberculosis Transmission ◽  
Recent Transmission ◽  
High Prevalence ◽  
Pathogen Variation ◽  
Lineage 2

To improve understanding of the factors influencing tuberculosis transmission and the role of pathogen variation, we sequenced all available specimens from patients diagnosed over 15 years in a whole district in Malawi. Mycobacterium tuberculosis lineages were assigned and transmission networks constructed, allowing ≤10 single nucleotide polymorphisms (SNPs) difference. We defined disease as due to recent infection if the network-determined source was within 5 years, and assessed transmissibility from forward transmissions resulting in disease. High-quality sequences were available for 1687 disease episodes (72% of all culture-positive episodes): 66% of patients linked to at least one other patient. The between-patient mutation rate was 0.26 SNPs/year (95% CI 0.21–0.31). We showed striking differences by lineage in the proportion of disease due to recent transmission and in transmissibility (highest for lineage-2 and lowest for lineage-1) that were not confounded by immigration, HIV status or drug resistance. Transmissions resulting in disease decreased markedly over time.

scholarly journals Transmission of Multidrug/Rifampicin-Resistant Mycobacterium Tuberculosis in Chongqing, China: A Retrospective Observational Study Using Whole-Genome Sequencing

2021 ◽  
Author(s):  
Bing Zhao ◽  
Chunfa Liu ◽  
Jiale Fan ◽  
Aijing Ma ◽  
Wencong He ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Resistance Mutations ◽  
Treatment Information ◽  
Recent Transmission ◽  
Drugs Analysis ◽  
Lineage 2 ◽  
And Cluster Analysis

Abstract Background: Multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) is a global barrel for ‘Stop TB plan’. China has the second highest MDR/RR-TB burden in whole world wide. Understanding the transmission dynamic is facilitated for disease control. Methods: Whole genome sequencing (WGS) data from patients of Chongqing tuberculosis control institute were used for phylogenetic classifications, resistance predictions, and cluster analysis as indicator for recent transmission (RT). Factors associated with MDR/RR-TB were defined by a logistic regression model. Results: A total of 223 cases of MDR/RR-TB were recorded between Jan 1, 2018 and Dec 31, 2020, and 200 cases obtained relevant treatment information. The patients who are older than 55 year old were more likely to suffering from death. 178 MDR/RR strains were obtained WGS data, 152 were classified as lineage 2 strains. 80 (44.9%, 80 of 178) strains were in 20 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms (SNPs), indicating RT. Patients who were infected with lineage 2 strains is a significant factor driving the epidemic towards MDR/RR-TB. Resistance mutations of first-line tuberculosis drugs analysis found that 79 (98.8%) of all 80 strains defined as RT have same mutations among each clusters totally. 55% (44 of 80) of the MDR/RR-TB strains accumulated additional drug resistance mutations along the transmission chain, especially fluoroquinolones (FQs) (63.6%, 28 of 44). Conclusions: The age is the most significant factor that causes death of MDR/RR-TB patients. RT of MDR/RR strains is not only drove the MDR/RR-TB epidemic, but also accumulated more serious resistance along the transmission chains.

scholarly journals Non-B DNA: a major contributor to small- and large-scale variation in nucleotide substitution frequencies across the genome

2021 ◽  
Vol 49 (3) ◽  
pp. 1497-1516
Author(s):  
Wilfried M Guiblet ◽  
Marzia A Cremona ◽  
Robert S Harris ◽  
Di Chen ◽  
Kristin A Eckert ◽  
...  
Keyword(s):  
Large Scale ◽  
Nucleotide Substitution ◽  
Genetic Diseases ◽  
Nucleotide Polymorphisms ◽  
Dna Structures ◽  
Cellular Processes ◽  
Genome Wide ◽  
Dna Types ◽  
Flanking Regions

Abstract Approximately 13% of the human genome can fold into non-canonical (non-B) DNA structures (e.g. G-quadruplexes, Z-DNA, etc.), which have been implicated in vital cellular processes. Non-B DNA also hinders replication, increasing errors and facilitating mutagenesis, yet its contribution to genome-wide variation in mutation rates remains unexplored. Here, we conducted a comprehensive analysis of nucleotide substitution frequencies at non-B DNA loci within noncoding, non-repetitive genome regions, their ±2 kb flanking regions, and 1-Megabase windows, using human-orangutan divergence and human single-nucleotide polymorphisms. Functional data analysis at single-base resolution demonstrated that substitution frequencies are usually elevated at non-B DNA, with patterns specific to each non-B DNA type. Mirror, direct and inverted repeats have higher substitution frequencies in spacers than in repeat arms, whereas G-quadruplexes, particularly stable ones, have higher substitution frequencies in loops than in stems. Several non-B DNA types also affect substitution frequencies in their flanking regions. Finally, non-B DNA explains more variation than any other predictor in multiple regression models for diversity or divergence at 1-Megabase scale. Thus, non-B DNA substantially contributes to variation in substitution frequencies at small and large scales. Our results highlight the role of non-B DNA in germline mutagenesis with implications to evolution and genetic diseases.

scholarly journals High Prevalence of Clonorchis sinensis and Other Zoonotic Trematode Metacercariae in Fish from a Local Market in Yen Bai Province, Northern Vietnam

2020 ◽  
Vol 58 (3) ◽  
pp. 333-338 ◽  
Author(s):  
Fuhong Dai ◽  
Sung-Jong Hong ◽  
Jhang Ho Pak ◽  
Thanh Hoa Le ◽  
Seung-Ho Choi ◽  
...  
Keyword(s):  
Freshwater Fish ◽  
Clonorchis Sinensis ◽  
Local Market ◽  
Recent Infection ◽  
Northern Vietnam ◽  
High Prevalence ◽  
Artificial Digestion ◽  
Infection Source ◽  
Haplorchis Pumilio

A small survey was performed to investigate the recent infection status of Clonorchis sinensis and other zoonotic trematode metacercariae in freshwater fish from a local market of Yen Bai city, Yen Bai province, northern Vietnam. A total of 118 fish in 7 species were examined by the artificial digestion method on March 2016. The metacercariae of 4 species of zoonotic trematodes, i.e., C. sinensis, Haplorchis pumilio, Haplorchis taichui, and Centrocestus formosanus, were detected. The metacercariae of C. sinensis were found in 62 (69.7%) out of 89 fish (5 species), and their intensity of infection was very high, 81.2 per fish infected. Prevalences of 3 intestinal flukes, H. pumilio, H. taichui and C. formosanus, were 75.0%, 47.6%, and 31.7% in positive fish species, respectively, with the metacercarial intensities of 15.5, 10.3, and 2.2 per fish infected. From the above results, it has been confirmed that various species of freshwater fish continue to play the role of the infection source of C. sinensis and other zoonotic trematodes in Yen Bai city, Yen Bai province, northern Vietnam. It is of particular note that the prevalence and intensity of C. sinensis metacercariae are much higher than those reported in previous studies in fish in northern Vietnam.

scholarly journals Association Analysis of Genetic Variants with Type 2 Diabetes in a Mongolian Population in China

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Haihua Bai ◽  
Haiping Liu ◽  
Suyalatu Suyalatu ◽  
Xiaosen Guo ◽  
Shandan Chu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Large Scale ◽  
Risk Allele ◽  
Association Studies ◽  
Northern China ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genome Wide

The large scale genome wide association studies (GWAS) have identified approximately 80 single nucleotide polymorphisms (SNPs) conferring susceptibility to type 2 diabetes (T2D). However, most of these loci have not been replicated in diverse populations and much genetic heterogeneity has been observed across ethnic groups. We tested 28 SNPs previously found to be associated with T2D by GWAS in a Mongolian sample of Northern China (497 diagnosed with T2D and 469 controls) for association with T2D and diabetes related quantitative traits. We replicated T2D association of 11 SNPs, namely, rs7578326 (IRS1), rs1531343 (HMGA2), rs8042680 (PRC1), rs7578597 (THADA), rs1333051 (CDKN2), rs6723108 (TMEM163), rs163182 and rs2237897 (KCNQ1), rs1387153 (MTNR1B), rs243021 (BCL11A), and rs10229583 (PAX4) in our sample. Further, we showed that risk allele of the strongest T2D associated SNP in our sample, rs757832 (IRS1), is associated with increased level of TG. We observed substantial difference of T2D risk allele frequency between the Mongolian sample and the 1000G Caucasian sample for a few SNPs, including rs6723108 (TMEM163) whose risk allele reaches near fixation in the Mongolian sample. Further study of genetic architecture of these variants in susceptibility of T2D is needed to understand the role of these variants in heterogeneous populations.

scholarly journals Genetic Determinants for Bacterial Osteomyelitis: A Focused Systematic Review of Published Literature

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoping Xie ◽  
Jiangbi Li ◽  
Feng Gu ◽  
Ke Zhang ◽  
Zilong Su ◽  
...  
Keyword(s):  
Systematic Review ◽  
Large Scale ◽  
Biological Effects ◽  
Bone Destruction ◽  
Bioinformatic Analysis ◽  
Vital Role ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Single Nucleotide

Background: Osteomyelitis is an inflammatory process characterized by progressive bone destruction. Moreover, chronic bacterial osteomyelitis is regarded as a difficult-to-treat clinical entity due to its long-standing course and frequent infection recurrence. However, the role of genetic factors in the occurrence and development of bacterial osteomyelitis is poorly understood.Methods: We performed a systematic review to assess the frequency of individual alleles and genotypes of single-nucleotide polymorphisms (SNPs) among patients with bacterial osteomyelitis and healthy people to identify whether the SNPs are associated with the risk of developing bacterial osteomyelitis. Then, gene ontology and Kyoto Encyclopedia of Gene and Genomes analyses were performed to identify the potential biological effects of these genes on the pathogenesis of bacterial osteomyelitis.Result: Fourteen eligible studies containing 25 genes were analyzed. In this review, we discovered that the SNPs in IL1B, IL6, IL4, IL10, IL12B, IL1A, IFNG, TNF, PTGS2, CTSG, vitamin D receptor (VDR), MMP1, PLAT, and BAX increased the risk of bacterial osteomyelitis, whereas those in IL1RN and TLR2 could protect against osteomyelitis. The bioinformatic analysis indicated that these osteomyelitis-related genes were mainly enriched in inflammatory reaction pathways, suggesting that inflammation plays a vital role in the development of bacterial osteomyelitis. Furthermore, functional notation for 25 SNPs in 17 significant genes was performed using the RegulomeDB and NCBI databases. Four SNPs (rs1143627, rs16944, rs2430561, and rs2070874) had smaller scores from regulome analysis, implying significant biological function.Conclusion: We systematically summarized several SNPs linked to bacterial osteomyelitis and discovered that these gene polymorphisms could be a genetic factor for bacterial osteomyelitis. Moreover, further large-scale cohort studies are needed to enhance our comprehensive understanding of the development of osteomyelitis to provide earlier individualized preventions and interventions for patients with osteomyelitis in clinical practice.

scholarly journals Search for associations between polymorphic variants of human acid chitinase gene and bronchial asthma in children of Novosibirsk

2022 ◽  
Vol 36 (4) ◽  
pp. 92-98
Author(s):  
S. I. Makarova ◽  
D. V. Mitrofanov ◽  
A. B. Shintyapina ◽  
E. G. Komova ◽  
V. V. Zelenskaya ◽  
...  
Keyword(s):  
Bronchial Asthma ◽  
Chitinase Gene ◽  
Nucleotide Polymorphisms ◽  
Fungal Cell ◽  
Single Nucleotide ◽  
High Prevalence ◽  
Human Acid ◽  
Polymorphic Variants ◽  
Asthma In Children

High prevalence of bronchial asthma among the population (about 300 million people all over the world) provides rationale for the search for candidate genes of disease. Human acidic chitinase (CHIA (AMCase)), encoded by the CHIA gene, is involved in the degradation of chitin, a component of the fungal cell wall and arthropod exoskeleton, which, if present in food or house dust, is a provoking factor for the bronchial asthma (BA) development. Functionally significant mutations in the CHIA gene may apparently increase the risk of susceptibility to BA.Aim. The aim of the study was to assess the associations of single nucleotide polymorphisms (SNPs) rs12033184 and rs3806448 in the CHIA gene with bronchial asthma in children in Novosibirsk.Material and Methods. The study was organized as case-control. A total of 537 blood samples were used. SNPs were determined by real-time PCR. The associations of polymorphic variants with the disease were assessed by the odds ratio.Results. No associations of rs12033184 and rs3806448 with BA were found.Conclusion. The role of acidic chitinase gene in the development of BA in residents of Novosibirsk was found to be less significant than in the Indian population where it was previously shown to be associated with the disease.

Role of genes involved in the regulation of apoptosis in the pathogenesis of genital endometriosis. A literature review

2021 ◽  
Vol 70 (4) ◽  
pp. 99-113
Author(s):  
Nelly Y. Andreyeva ◽  
Maria I. Yarmolinskaya ◽  
Tatiana E. Ivashchenko
Keyword(s):  
Future Research ◽  
Nucleotide Polymorphisms ◽  
Scientific Publications ◽  
Single Nucleotide ◽  
High Prevalence ◽  
Apoptotic Pathways ◽  
Keyword Searches ◽  
Cell Death Cascade ◽  
Selection Of

BACKGROUND: The high prevalence, the lack of reliable data on the etiology, as well as the complexity of diagnosis and treatment of genital endometriosis indicate the urgency of the problem. AIM: The aim of this study was to analyze and summarize scientific publications devoted to the study of single-nucleotide polymorphisms involved in apoptosis and their association with endometriosis. MATERIALS AND METHODS: Based on keyword searches for gene, SNP, apoptosis, and endometriosis, a selection of papers published in open sources (PubMed and Google Scholar) in the period from 2010 to 2020 was performed. RESULTS AND CONCLUSIONS: An analysis of the main and auxiliary apoptotic pathways was performed, with the protein regulators and their genes detailed in accordance with the implementation of the programmed cell death cascade in genital endometriosis. The review identified the significance of a number of proteins (TNF-, FADD, CASP3, CASP7, CASP10) in the pathogenesis of hyperproliferative diseases. However, many apoptotic regulators (BCL2, BIK, BMF, HRK, BAD, Survivin) in genital endometriosis were found to have been understudied, which makes future research in this direction promising.

The Role of Sense of Direction and Other Factors During Navigation in a Large-Scale, Unconstrained Environment

2013 ◽  
Author(s):  
Elisabeth J. Ploran ◽  
Ericka Rovira ◽  
James C. Thompson ◽  
Raja Parasuraman
Keyword(s):  
Large Scale ◽  
Sense Of Direction

Magnetic Properties of xCeO2•(50 − x) PbO•50B2O3 Glasses and Glass Ceramics

2017 ◽  
Vol 13 (1) ◽  
pp. 4486-4494 ◽  
Author(s):  
G.El Damrawi ◽  
F. Gharghar
Keyword(s):  
Magnetic Properties ◽  
Large Scale ◽  
Glass Ceramics ◽  
Magnetic Behavior ◽  
Crystal Formation ◽  
Dual Roles ◽  
Effective Agent ◽  
Ordered Structures ◽  
Essential Change

Cerium oxide in borate glasses of composition xCeO2·(50 − x)PbO·50B2O3 plays an important role in changing both microstructure and magnetic behaviors of the system. The structural role of CeO2 as an effective agent for cluster and crystal formation in borate network is clearly evidenced by XRD technique. Both structure and size of well-formed cerium separated clusters have an effective influence on the structural properties. The cluster aggregations are documented to be found in different range ordered structures, intermediate and long range orders are the most structures in which cerium phases are involved. The nano-sized crystallized cerium species in lead borate phase are evidenced to have magnetic behavior.  The criteria of building new specific borate phase enriched with cerium as ferrimagnetism has been found to keep the magnetization in large scale even at extremely high temperature. Treating the glass thermally or exposing it to an effective dose of ionized radiation is evidenced to have an essential change in magnetic properties. Thermal heat treatment for some of investigated materials is observed to play dual roles in the glass matrix. It can not only enhance alignment processes of the magnetic moment but also increases the capacity of the crystallite species in the magnetic phases. On the other hand, reverse processes are remarked under the effect of irradiation. The magnetization was found to be lowered, since several types of the trap centers which are regarded as defective states can be produced by effect of ionized radiation. 

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