Single Nucleotide Polymorphisms (SNPs) in genes of the innate immunity in cystic fibrosis patients: correlation with lung function and Pseudomonas aeruginosa colonisation

Variation in surfactant protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage. The association between serum SP-D (sSP-D) and expiratory lung function was assessed in a cross-sectional design in a Danish twin population ( n = 1,512, 18–72 yr old). The adjusted heritability estimates for expiratory lung function, associations between SP-D gene ( SFTPD) single-nucleotide polymorphisms or haplotypes, and expiratory lung function were assessed using twin study methodology and mixed-effects models. Significant inverse associations were evident between sSP-D and the forced expiratory volume in 1 s and forced vital capacity in the presence of current tobacco smoking but not in nonsmokers. The two SFTPD single-nucleotide polymorphisms, rs1923536 and rs721917, and haplotypes, including these single-nucleotide polymorphisms or rs2243539, were inversely associated with expiratory lung function in interaction with smoking. In conclusion, SP-D is phenotypically and genetically associated with lung function measures in interaction with tobacco smoking. The obtained data suggest sSP-D as a candidate biomarker in risk assessments for subclinical tobacco smoke-induced lung damage. The data and derived conclusion warrant confirmation in a longitudinal population following chronic obstructive pulmonary disease initiation and development.

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The Effect of Synonymous Single-Nucleotide Polymorphisms on an Atypical Cystic Fibrosis Clinical Presentation

Life ◽

10.3390/life11010014 ◽

2020 ◽

Vol 11 (1) ◽

pp. 14

Author(s):

Giovana Bampi ◽

Anabela Ramalho ◽

Leonardo Santos ◽

Johannes Wagner ◽

Lieven Dupont ◽

...

Keyword(s):

Cystic Fibrosis ◽

Single Nucleotide Polymorphisms ◽

Protein Expression ◽

Protein Function ◽

Low Frequency ◽

Exon Skipping ◽

Cftr Gene ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Exon 11

Synonymous single nucleotide polymorphisms (sSNPs), which change a nucleotide, but not the encoded amino acid, are perceived as neutral to protein function and thus, classified as benign. We report a patient who was diagnosed with cystic fibrosis (CF) at an advanced age and presented very mild CF symptoms. The sequencing of the whole cystic fibrosis transmembrane conductance regulator (CFTR) gene locus revealed that the patient lacks known CF-causing mutations. We found a homozygous sSNP (c.1584G>A) at the end of exon 11 in the CFTR gene. Using sensitive molecular methods, we report that the c.1584G>A sSNP causes cognate exon skipping and retention of a sequence from the downstream intron, both of which, however, occur at a relatively low frequency. In addition, we found two other sSNPs (c.2562T>G (p.Thr854=) and c.4389G>A (p.Gln1463=)), for which the patient is also homozygous. These two sSNPs stabilize the CFTR protein expression, compensating, at least in part, for the c.1584G>A-triggered inefficient splicing. Our data highlight the importance of considering sSNPs when assessing the effect(s) of complex CFTR alleles. sSNPs may epistatically modulate mRNA and protein expression levels and consequently influence disease phenotype and progression.

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Comparative genome analysis of a multidrug-resistant Pseudomonas aeruginosa sequence type 277 clone that harbours two copies of the blaSPM-1 gene and multiple single nucleotide polymorphisms in other resistance-associated genes

10.1101/693440 ◽

2019 ◽

Author(s):

Ana Paula Barbosa do Nascimento ◽

Fernando Medeiros Filho ◽

Hério Sousa ◽

Hermes Senger ◽

Rodolpho Mattos Albano ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Resistance ◽

Single Nucleotide Polymorphisms ◽

Multidrug Resistant ◽

Sequence Type ◽

Genomic Islands ◽

Genome Comparison ◽

Nucleotide Polymorphisms ◽

Emerging Pathogens ◽

Single Nucleotide

AbstractPseudomonas aeruginosa is one of the most common pathogens related to healthcare-associated infections. The Brazilian isolate, named CCBH4851, is a multidrug-resistant clone belonging to the sequence type 277. The antimicrobial resistance mechanisms of the CCBH4851 strain are associated with the presence of blaSPM-1 gene, encoding a metallo-beta-lactamase, in addition to other exogenously acquired genes. Whole-genome sequencing studies focusing on emerging pathogens are essential to identify physiological key aspects that may lead to the exposure of new targets for therapy. This study was designed to characterize the genome of Pseudomonas aeruginosa CCBH4851 through the detection of genomic features and genome comparison with other Pseudomonas aeruginosa strains. The CCBH4851 closed genome showed features that were consistent with data reported for the specie. However, comparative genomics revealed the absence of genes important for pathogenesis. On the other hand, CCBH4851 genome contained acquired genomic islands that carry additional virulence and antimicrobial resistance-related genes. The presence of single nucleotide polymorphisms in the core genome, mainly those located in resistance-associated genes, suggests that these mutations could influence the multidrug-resistant behavior of CCBH4851. Overall, the characterization of Pseudomonas aeruginosa CCBH4851 complete genome revealed several features that could directly impact the profile of virulence and antibiotic resistance of this pathogen in infectious outbreaks.

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CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity

BMC Medical Genetics ◽

10.1186/1471-2350-5-26 ◽

2004 ◽

Vol 5 (1) ◽

Cited By ~ 9

Author(s):

Carol J Blaisdell ◽

Timothy D Howard ◽

Augustus Stern ◽

Penelope Bamford ◽

Eugene R Bleecker ◽

...

Keyword(s):

Cystic Fibrosis ◽

Single Nucleotide Polymorphisms ◽

Disease Severity ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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Sequence diversity of the mucABD locus in Pseudomonas aeruginosa isolates from patients with cystic fibrosis

Microbiology ◽

10.1099/mic.0.29175-0 ◽

2006 ◽

Vol 152 (11) ◽

pp. 3261-3269 ◽

Cited By ~ 70

Author(s):

Alessandra Bragonzi ◽

Lutz Wiehlmann ◽

Jens Klockgether ◽

Nina Cramer ◽

Dieter Worlitzsch ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

De Novo ◽

Nucleotide Polymorphisms ◽

Aquatic Habitats ◽

Environmental Isolates ◽

Single Nucleotide ◽

Genome Wide ◽

Airway Colonization

The mucA gene of the muc operon, which is instrumental in the control of the biosynthesis of the exopolysaccharide alginate, is a hotspot of mutation in Pseudomonas aeruginosa, a micro-organism that chronically colonizes the airways of individuals with cystic fibrosis (CF). The mucA, mucB and mucD genes were sequenced in nine environmental isolates from aquatic habitats, and in 37 P. aeruginosa strains isolated from 10 patients with CF, at onset or at a late stage of chronic airway colonization, in order to elucidate whether there was any association between mutation and background genotype. The 61 identified single nucleotide polymorphisms (SNPs) segregated into 18 mucABD genotypes. Acquired and de novo stop mucA mutations were present in 14 isolates (38 %) of five mucABD genotypes. ΔG430 was the most frequent and recurrent mucA mutation detected in four genotypes. The classification of strains by mucABD genotype was generally concordant with that by genome-wide SpeI fragment pattern or multilocus SNP genotypes. The exceptions point to intragenic mosaicism and interclonal recombination as major forces for intraclonal evolution at the mucABD locus.

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