Four single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin

AbstractSecretion of pertussis toxin (PT) is the preeminent virulence trait of the human pathogen Bordetella pertussis, causing whooping cough. Bordetella bronchiseptica, although it harbors an intact 12-kb ptx–ptl operon, does not express PT due to an inactive ptx promoter (Pptx), which contains 18 SNPs (single nucleotide polymorphisms) relative to B. pertussis Pptx. A systematic analysis of these SNPs was undertaken to define the degree of mutational divergence necessary to activate B. bronchiseptica Pptx. A single change (C−13T), which created a better − 10 element, was capable of activating B. bronchiseptica Pptx sufficiently to allow secretion of low but measureable levels of active PT. Three additional changes in the BvgA-binding region, only in the context of C−13T mutant, raised the expression of PT to B. pertussis levels. These results illuminate a logical evolutionary pathway for acquisition of this key virulence trait in the evolution of B. pertussis from a B. bronchiseptica-like common ancestor.

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Toll-Like Receptor 4 Polymorphism Associated with the Response to Whole-Cell Pertussis Vaccination in Children from the KOALA Study

Clinical and Vaccine Immunology ◽

10.1128/cvi.00175-07 ◽

2007 ◽

Vol 14 (10) ◽

pp. 1377-1380 ◽

Cited By ~ 14

Author(s):

Sander Banus ◽

Renske W. B. Bottema ◽

Christine L. E. Siezen ◽

Rob J. Vandebriel ◽

Johan Reimerink ◽

...

Keyword(s):

Antibody Response ◽

Pertussis Toxin ◽

Immunoglobulin G ◽

Nucleotide Polymorphisms ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Single Nucleotide ◽

Whole Cell ◽

Specific Immunoglobulin ◽

Lower Titer

ABSTRACT We examined the association between haplotype tagging single-nucleotide polymorphisms in TLR4 and the pertussis toxin-specific immunoglobulin G response after whole-cell pertussis (wP) vaccination in 515 1-year-old children from the KOALA study. A lower titer was associated with the minor allele of rs2770150, supporting a role for Toll-like receptor 4 in the antibody response to wP vaccination.

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Genome characteristic of Bordetella parapertussis isolated from Iran

10.1101/2022.01.05.475152 ◽

2022 ◽

Author(s):

Azadeh Safarchi ◽

Samaneh Saedi ◽

Chin Yen Tay ◽

Binit Lamichhan ◽

Masoumeh Nakhost Lotfi ◽

...

Keyword(s):

Whooping Cough ◽

Clinical Syndrome ◽

Reference Laboratory ◽

Nucleotide Polymorphisms ◽

Biochemical Tests ◽

Single Nucleotide ◽

Bordetella Parapertussis ◽

Evolutionary Changes ◽

Nasal Swabs ◽

Relationship Of

Pertussis also known as whooping cough is a respiratory infection in humans particularly in infants and usually caused by Bordetella pertussis. However, Bordetella parapertussis can also cause a similar clinical syndrome. During 2012 to 2015, from nasal swabs sent from different provinces to the pertussis reference laboratory of Pasture Institute of Iran for pertussis confirmation, seven B. parapertussis isolates were identified by bacterial culture, biochemical tests, and the presence of IS1001 insertion in the genome by real-time PCR. Furthermore, the expression of pertactin (Prn) as one the major virulence factor for bacterial adhesion was investigated using western blot. Moreover, the genomic characteristic of one recently collected isolate, IRBP134, from a seven-month infant was investigated using Illumina NextSeq sequencing protocol. The results revealed the genome with G+C content 65% and genome size 4.7 Mbp. A total of 81 single nucleotide polymorphisms (SNPs) and 13 short insertion and deletions were found in the genome compared to the B. parapertussis 12822 as a reference genome showing ongoing evolutionary changes in our isolate. A phylogeny relationship of IRBP134 was also investigated using global B. parapertussis available genomes.

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The genetics of Cannabis – genomic variations of key synthases and their effect on cannabinoids content

Genome ◽

10.1139/gen-2020-0087 ◽

2020 ◽

Author(s):

Aparna Singh ◽

Andriy Bilichak ◽

Igor Kovalchuk

Keyword(s):

Cannabis Sativa ◽

Deep Understanding ◽

Biosynthesis Pathway ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Systematic Analysis ◽

Genomic Variations ◽

Coding Regions ◽

The World ◽

History Of

Despite being a controversial crop, Cannabis sativa L. has a long history of cultivation throughout the world. Following recent legalisation in Canada, it is emerging as an important plant for both medicinal and recreational purposes. Recent progress in genome sequencing of both cannabis and hemp varieties allows for systematic analysis of genes coding for enzymes involved in the cannabinoid biosynthesis pathway. Single nucleotide polymorphisms in the coding regions of cannabinoid synthases play important role in determining plant chemotype. Deep understanding of how these variants affect enzymes activity and accumulation of cannabinoids will allow breeding of novel cultivars with desirable cannabinoid profile. Here we present a short overview of the major cannabinoid synthases and present the data on the analysis of their genetic variants and their effect on cannabinoid content using several in-house sequenced Cannabis cultivars.

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An Exploration of ABCG2 and SLC2A9 Gene Interactions with Gout

Journal of the Medical Association of Thailand ◽

10.35755/jmedassocthai.2020.11.11281 ◽

2020 ◽

Vol 103 (11) ◽

pp. 1163-1170

Keyword(s):

Interaction Analysis ◽

Conditional Logistic Regression ◽

Gene Interactions ◽

Nucleotide Polymorphisms ◽

Base Pairs ◽

Thai Population ◽

Single Nucleotide ◽

Systematic Analysis ◽

Study Results ◽

Matched Case

Background: Currently, there is no systematic analysis of single nucleotide polymorphisms (SNPs) in the urate transporter genes (ABCG2 and SLC2A9), and the influence of their combination and gene-gene (G×G) interactions on gout is still unknown in the Thai population. Objective: To investigate the interaction between ABCG2 and SLC2A9 with gout. Materials and Methods: A matched case-control study with 116 Thai adults (58 gout patients and 58 control subjects) was done. Genotyping using a TaqMan SNP Genotyping Assays was performed. G×G interactions for gout risk were analyzed using an interaction analysis in multiple conditional logistic regression. Results: The results show that the rs2231142 (G/T+T/T) variants in ABCG2 was associated with gout. On the contrary, the rs2280205 (G/A+A/A) and rs6820230 (C/T–T/T) variant in SLC2A9 were not associated with gout. The result indicated that the participants carrying ABCG2 variant with SLC2A9 wild-type (i.e., original base pairs) had a significant association with gout. The present study results also revealed that epistatic interaction pairs (rs2231142:rs6820230 and rs2231142:rs2280205) were strongly associated with gout. Conclusion: The authors concluded that the ABCG2 and SLC2A9 interactions were a significant association with gout. The stronger combined effect of SNPs in the ABCG2 and SLC2A9 genes via G×G interaction may help to predict gout risk and its prognosis. However, further studies with larger sample sizes should be performed to confirm these results. Keywords: Gene-gene interactions, Gout, ABCG2 gene, SLC2A9 gene

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Stepwise Arms Race Between AvrPik and Pik Alleles in the Rice Blast Pathosystem

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-02-14-0046-r ◽

2014 ◽

Vol 27 (8) ◽

pp. 759-769 ◽

Cited By ~ 21

Author(s):

Weihuai Wu ◽

Ling Wang ◽

Shu Zhang ◽

Zekang Li ◽

Yu Zhang ◽

...

Keyword(s):

Rice Blast ◽

Management Strategies ◽

Natural Populations ◽

Arms Race ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Evolutionary Pathway ◽

Allele Specific ◽

Stepwise Mutation ◽

Selection For

A stepwise mutation that occurred in both pathogens and their respective hosts has played a seminal role in the co-evolutionary arms race evolution in diverse pathosystems. The process driven by rice blast AvrPik and Pik alleles was investigated through population genetic and evolutionary approaches. The genetic diversity of the non-signal domain of AvrPik was higher than that in its signal peptide domain. Positive selection for particular AvrPik alleles in the northeastern region of China was stronger than in the south. The perfect relationship between the functional lineages and AvrPik allele-specific pathotypes was established by ruling out the nonfunctional lineages derived from additional copies. Only four alleles conditioning stepwise pathotypes were detected in natural populations, which were likely created by only one evolutionary pathway with three recognizable mutation steps. Two non-stepwise pathotypes were determined by two blocks in a network constructed by all 16 possible alleles, indicating that a natural evolution process can be artificially changed by a combination of specific single-nucleotide polymorphisms. Assuming that AvrPik evolution has been largely driven by host selection, the co-evolutionary stepwise relationships between AvrPik and Pik was established. The experimental validation of stepwise mutation is required for the development of sustainable management strategies against plant disease.

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Phenotypic expression and founder effect of PANK2 c.1583C>T (p.T528M) mutation in Serbian pantothenate kinase-associated neurodegeneration patients

Archives of Biological Sciences ◽

10.2298/abs181227009s ◽

2019 ◽

Vol 71 (2) ◽

pp. 275-280

Author(s):

Marina Svetel ◽

Monika Hartig ◽

Dragana Cvetkovic ◽

Cyrielle Beaubois ◽

Jasmina Maksic ◽

...

Keyword(s):

Founder Effect ◽

Autosomal Recessive ◽

Common Ancestor ◽

Phenotypic Expression ◽

Autosomal Recessive Disorder ◽

Clinical Findings ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Pantothenate Kinase ◽

The Brain

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder characterized by dystonia, parkinsonism, cognitive and visual impairment, and iron accumulation in the brain. Many cases of PKAN result from mutations in the PANK2 gene that encodes pantothenate kinase 2, a key regulatory enzyme in the biosynthesis of coenzyme A. We previously detected six Serbian patients with clinically suggestive PKAN, all of whom had PANK2 c.1583C>T (p.T528M) mutation either in the homozygous or in the heterozygous state. In this study we explored the phenotypic expression and a possible founder effect of this substitution. We performed the analysis of linkage disequilibrium (LD) and organization in haplotypes of 23 single nucleotide polymorphisms (SNPs) adjacent to the PANK2 gene in all of the six patients and their parents, as well as in control healthy child-parents trios. The age of PANK2 c.1583C>T mutation was determined using the r2 degeneration method. Clinical findings in our patients were markedly similar. Different LD structures between patients and controls is revealed, and PANK2 c.1583T allele was significantly associated with a particular haplotype. The age of PANK2 c.1583C>T mutation was estimated to be about 15 generations. Our results suggest that PANK2 c.1583C>T in Serbian PKAN patients represents a founder mutation descended from one common ancestor.

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Nuclear receptors in disease: the oestrogen receptors

Essays in Biochemistry ◽

10.1042/bse0400157 ◽

2004 ◽

Vol 40 ◽

pp. 157-167 ◽

Cited By ~ 18

Author(s):

Maria Nilsson ◽

Karin Dahlman-Wright ◽

Jan-Åke Gustafsson

Keyword(s):

Nuclear Receptors ◽

Target Genes ◽

Receptor Subtype ◽

Target Tissue ◽

Oestrogen Receptors ◽

Nucleotide Polymorphisms ◽

Cell Type ◽

Single Nucleotide ◽

Beneficial Effects ◽

The Family

For several decades, it has been known that oestrogens are essential for human health. The discovery that there are two oestrogen receptors (ERs), ERalpha and ERbeta, has facilitated our understanding of how the hormone exerts its physiological effects. The ERs belong to the family of ligand-activated nuclear receptors, which act by modulating the expression of target genes. Studies of ER-knockout (ERKO) mice have been instrumental in defining the relevance of a given receptor subtype in a certain tissue. Phenotypes displayed by ERKO mice suggest diseases in which dysfunctional ERs might be involved in aetiology and pathology. Association between single-nucleotide polymorphisms (SNPs) in ER genes and disease have been demonstrated in several cases. Selective ER modulators (SERMs), which are selective with regard to their effects in a certain cell type, already exist. Since oestrogen has effects in many tissues, the goal with a SERM is to provide beneficial effects in one target tissue while avoiding side effects in others. Refined SERMs will, in the future, provide improved therapeutic strategies for existing and novel indications.

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