scholarly journals New insights into genotype–phenotype correlation in individuals with different level of general non-specific reactivity of an organism

2016 ◽  
Vol 13 (4) ◽  
pp. 33-42 ◽  
Author(s):  
Alexander Mulik ◽  
Valery Novochadov ◽  
Alexander Bondarev ◽  
Sofya Lipnitskaya ◽  
Irina Ulesikova ◽  
...  
Keyword(s):  
Pain Sensitivity ◽  
Genetic Basis ◽  
Pain Threshold ◽  
Molecular Mechanisms ◽  
Human Organism ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Specific Reactivity ◽  
High Level ◽  
Very High

Summary The objective of the study was to investigate the genetic basis of general non-specific reactivity of an organism. Systematic search in PubMedCentral, PDB, KEGG and SNP databases identified a set of genes and their polymorphisms that can determine pain sensitivity and therefore the level of general non-specific reactivity of the human organism. Six SNPs were selected for genotyping kit design; 230 healthy volunteers were enrolled in the study. It was revealed that very high pain threshold was associated with allele A in rs1851048 and allele C in rs6777055. High level of general non-specific reactivity of an organism was associated with allele G in rs2562456 (OR=1.804, CI=1.139-2.857, p=0.011) and allele C in rs6923492 (OR=1.582, CI=1.071-2.335, p=0.021). Low level of general non-specific reactivity of an organism was associated with allele T in rs6923492 (OR=0.351, CI=0.154-0.799, p=0.010). A set of genes and single-nucleotide polymorphisms associated with the pain sensitivity and indirectly with the level of general non-specific reactivity of human organism were determined. The identified correlations reveal some molecular mechanisms of general non-specific reactivity of an organism variability and can guide further research in this area.

scholarly journals Strain-Specific Genotyping of Bifidobacterium animalis subsp. lactis by Using Single-Nucleotide Polymorphisms, Insertions, and Deletions

2009 ◽  
Vol 75 (23) ◽  
pp. 7501-7508 ◽  
Author(s):  
Elizabeth P. Briczinski ◽  
Joseph R. Loquasto ◽  
Rodolphe Barrangou ◽  
Edward G. Dudley ◽  
Anastasia M. Roberts ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Sequence Similarity ◽  
Nucleotide Polymorphisms ◽  
Strain Specificity ◽  
Typing Method ◽  
Single Nucleotide ◽  
Bifidobacterium Animalis ◽  
Molecular Approaches ◽  
Commercial Applications ◽  
High Level

ABSTRACT Several probiotic strains of Bifidobacterium animalis subsp. lactis are widely supplemented into food products and dietary supplements due to their documented health benefits and ability to survive within the mammalian gastrointestinal tract and acidified dairy products. The strain specificity of these characteristics demands techniques with high discriminatory power to differentiate among strains. However, to date, molecular approaches, such as pulsed-field gel electrophoresis and randomly amplified polymorphic DNA-PCR, have been ineffective at achieving strain separation due to the monomorphic nature of this subspecies. Previously, sequencing and comparison of two B. animalis subsp. lactis genomes (DSMZ 10140 and Bl-04) confirmed this high level of sequence similarity, identifying only 47 single-nucleotide polymorphisms (SNPs) and four insertions and/or deletions (INDELs) between them. In this study, we hypothesized that a sequence-based typing method targeting these loci would permit greater discrimination between strains than previously attempted methods. Sequencing 50 of these loci in 24 strains of B. animalis subsp. lactis revealed that a combination of nine SNPs/INDELs could be used to differentiate strains into 14 distinct genotypic groups. In addition, the presence of a nonsynonymous SNP within the gene encoding a putative glucose uptake protein was found to correlate with the ability of certain strains to transport glucose and to grow rapidly in a medium containing glucose as the sole carbon source. The method reported here can be used in clinical, regulatory, and commercial applications requiring identification of B. animalis subsp. lactis at the strain level.

scholarly journals Multicenter Study on Differential Human Neutrophil Antigen 2 Expression and Underlying Molecular Mechanisms

2020 ◽  
Vol 47 (5) ◽  
pp. 385-395
Author(s):  
Brigitte K. Flesch ◽  
Angelika Reil ◽  
Núria Nogués ◽  
Carme Canals ◽  
Peter Bugert ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Human Neutrophil ◽  
Molecular Mechanisms ◽  
Normal Population ◽  
Regulatory Elements ◽  
Population Exposure ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Immune Neutropenia ◽  
The Impact

Background: The human neutrophil antigen 2 (HNA-2), which is expressed on CD177, is undetectable in 3–5% of the normal population. Exposure of these HNA-2null individuals to HNA-2-positive cells can cause immunization and pro­duction of HNA-2 antibodies, which can induce immune neutropenia and transfusion-related acute lung injury. In HNA-2-positive individuals, neutrophils are divided into a CD177pos. and a CD177neg. subpopulation. The molecular background of HNA-2 deficiency and the bimodal expression pattern, however, are not completely decoded. Study Design: An international collaboration was conducted on the genetic analysis of HNA-2-phenotyped blood samples, including HNA-2-deficient individuals, mothers, and the respective children with neonatal immune neutropenia and regular blood donors. Results: From a total of 54 HNA-2null individuals, 43 were homozygous for the CD177*787A>T substitution. Six carried the CD177*c.1291G>A single nucleotide polymorphism. All HNA-2-positive samples with >40% CD177pos. neutrophils carried the *787A wild-type allele, whereas a lower rate of CD177pos. neutrophils was preferentially associated with *c.787AT heterozygosity. Interestingly, only the *c.787A allele sequence was detected in complementary DNA (cDNA) sequence analysis carried out on all *c.787AT heterozygous individuals. However, cDNA analysis after sorting of CD177pos. and CD177neg. neutrophil subsets from HNA-2-positive individuals showed identical sequences, which makes regulatory elements within the promoter unlikely to affect CD177 gene transcription in different CD177 neutrophil subsets. Conclusion: This comprehensive study clearly demonstrates the impact of single nucleotide polymorphisms on the expression of HNA-2 on the neutrophil surface but challenges the hypothesis of regulatory epigenetic effects being implicated in the bimodal CD177 expression pattern.

scholarly journals Genetics of Lactose Intolerance: An Updated Review and Online Interactive World Maps of Phenotype and Genotype Frequencies

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2689
Author(s):  
Augusto Anguita-Ruiz ◽  
Concepción M. Aguilera ◽  
Ángel Gil
Keyword(s):  
Genetic Basis ◽  
Human Populations ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Genetic Mechanisms ◽  
Visualization Tools ◽  
Available Information ◽  
Static World ◽  
Interactive Resources

In humans the ability to digest milk lactose is conferred by a β-galactosidase enzyme called lactase-phlorizin hydrolase (LPH). While in some humans (approximately two-thirds of humankind) the levels of this enzyme decline drastically after the weaning phase (a trait known as lactase non-persistence (LNP)), some other individuals are capable of maintaining high levels of LPH lifelong (lactase persistence (LP)), thus being able to digest milk during adulthood. Both lactase phenotypes in humans present a complex genetic basis and have been widely investigated during the last decades. The distribution of lactase phenotypes and their associated single nucleotide polymorphisms (SNPs) across human populations has also been extensively studied, though not recently reviewed. All available information has always been presented in the form of static world maps or large dimension tables, so that it would benefit from the newly available visualization tools, such as interactive world maps. Taking all this into consideration, the aims of the present review were: (1) to gather and summarize all available information on LNP and LP genetic mechanisms and evolutionary adaptation theories, and (2) to create online interactive world maps, including all LP phenotype and genotype frequency data reported to date. As a result, we have created two online interactive resources, which constitute an upgrade over previously published static world maps, and allow users a personalized data exploration, while at the same time accessing complete reports by population or ethnicity.

scholarly journals Identification of root rot resistance QTLs in pea using Fusarium solani f. sp. pisi-responsive differentially expressed genes

2020 ◽  
Author(s):  
Bruce A. Williamson-Benavides ◽  
Richard Sharpe ◽  
Grant Nelson ◽  
Eliane T. Bodah ◽  
Lyndon D. Porter ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Fusarium Solani ◽  
Root Rot ◽  
Genetic Basis ◽  
Gene Pyramiding ◽  
Interval Mapping ◽  
Differentially Expressed ◽  
Nucleotide Polymorphisms ◽  
Resistance Qtls ◽  
Single Nucleotide

AbstractPisum sativum (pea) yields have declined significantly over the last decades, predominantly due to susceptibility to root rot diseases. One of the main causal agents of root rot is the fungus Fusarium solani f. sp. pisi (Fsp), leading to yield losses ranging from 15 to 60%. Determining and subsequently incorporating the genetic basis for resistance in new cultivars offers one of the best solutions to control this pathogen; however, no green-seeded pea cultivars with complete resistance to Fsp have been identified. To date, only partial levels of resistance to Fsp has been identified among pea genotypes. SNPs mined from Fsp-responsive differentially expressed genes (DEGs) identified in a preceding study were utilized to identify QTLs associated with Fsp resistance using composite interval mapping in two recombinant inbred line (RIL) populations segregating for partial root rot resistance. A total of 769 DEGs with single nucleotide polymorphisms (SNPs) were identified, and the putative SNPs were evaluated for being polymorphic across four partially resistant and four susceptible P. sativum genotypes. The SNPs with validated polymorphisms were used to screen two RIL populations using two phenotypic criteria: root disease severity and plant height. One QTL, WB.Fsp-Ps 5.1 that mapped to chromosome V explained 14.76 % of the variance with a confidence interval of 10.36 cM. The other four QTLs located on chromosomes II, III, and V, explained 5.26–8.05 % of the variance. The use of SNPs derived from Fsp-responsive DEGs for QTL mapping proved to be an efficient way to identify molecular markers associated with Fsp resistance in pea. These QTLs are potential candidates for marker-assisted selection and gene pyramiding to obtain high levels of partial resistance in pea cultivars to combat root rot caused by Fsp.

scholarly journals Re-Identification of Individuals in Genomic Data-Sharing Beacons via Allele Inference

2017 ◽  
Author(s):  
Nora von Thenen ◽  
Erman Ayday ◽  
A. Ercument Cicek
Keyword(s):  
Data Sharing ◽  
Genomic Data ◽  
Nucleotide Polymorphisms ◽  
Privacy Risk ◽  
High Confidence ◽  
Single Nucleotide ◽  
Order Markov Chain ◽  
Adversary Model ◽  
Very High ◽  
Membership Information

AbstractGenomic datasets are often associated with sensitive phenotypes. Therefore, the leak of membership information is a major privacy risk. Genomic beacons aim to provide a secure, easy to implement, and standardized interface for data sharing by only allowing yes/no queries on the presence of specific alleles in the dataset. Previously deemed secure against re-identification attacks, beacons were shown to be vulnerable despite their stringent policy. Recent studies have demonstrated that it is possible to determine whether the victim is in the dataset, by repeatedly querying the beacon for his/her single nucleotide polymorphisms (SNPs). In this work, we propose a novel re-identification attack and show that the privacy risk is more serious than previously thought. Using the proposed attack, even if the victim systematically hides informative SNPs (i.e., SNPs with very low minor allele frequency -MAF-), it is possible to infer the alleles at positions of interest as well as the beacon query results with very high confidence. Our method is based on the fact that alleles at different loci are not necessarily independent. We use the linkage disequilibrium and a high-order Markov chain-based algorithm for the inference. We show that in a simulated beacon with 65 individuals from the CEU population, we can infer membership of individuals with 95% confidence with only 5 queries, even when SNPs with MAF less than 0.05 are hidden. This means, we need less than 0.5% of the number of queries that existing works require, to determine beacon membership under the same conditions. We further show that countermeasures such as hiding certain parts of the genome or setting a query budget for the user would fail to protect the privacy of the participants under our adversary model.

scholarly journals Third-generation sequencing-based mapping and visualization of single nucleotide polymorphism, meiotic recombination, illegitimate mutation and repeat-induced point mutation

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Wan-Chen Li ◽  
Hou-Cheng Liu ◽  
Ying-Jyun Lin ◽  
Shu-Yun Tung ◽  
Ting-Fang Wang
Keyword(s):  
Point Mutation ◽  
Meiotic Recombination ◽  
Molecular Mechanisms ◽  
Cytosine Methylation ◽  
Defense Mechanism ◽  
Nucleotide Polymorphisms ◽  
Tetrad Analysis ◽  
Single Nucleotide ◽  
A Genome ◽  
Repeat Induced Point Mutation

Abstract Generation of new genetic diversity by crossover (CO) and non-crossover (NCO) is a fundamental process in eukaryotes. Fungi have played critical roles in studying this process because they permit tetrad analysis, which has been used by geneticists for several decades to determine meiotic recombination products. New genetic variations can also be generated in zygotes via illegitimate mutation (IM) and repeat-induced point mutation (RIP). RIP is a genome defense mechanism for preventing harmful expansion of transposable elements or duplicated sequences in filamentous fungi. Although the exact mechanism of RIP is unknown, the C:G to T:A mutations might result from DNA cytosine methylation. A comprehensive approach for understanding the molecular mechanisms underlying these important processes is to perform high-throughput mapping of CO, NCO, RIP and IM in zygotes bearing large numbers of heterozygous variant markers. To this aim, we developed ‘TSETA’, a versatile and user-friendly pipeline that utilizes high-quality and chromosome-level genome sequences involved in a single meiotic event of the industrial workhorse fungus Trichoderma reesei. TSETA not only can be applied to most sexual eukaryotes for genome-wide tetrad analysis, it also outcompetes most currently used methods for calling out single nucleotide polymorphisms between two or more intraspecies strains or isolates.

scholarly journals Genomic Determinants of Hypertension With a Focus on Metabolomics and the Gut Microbiome

2020 ◽  
Vol 33 (6) ◽  
pp. 473-481
Author(s):  
Panayiotis Louca ◽  
Cristina Menni ◽  
Sandosh Padmanabhan
Keyword(s):  
Blood Pressure ◽  
Genetic Basis ◽  
Salt Water ◽  
Nucleotide Polymorphisms ◽  
Pressure Regulation ◽  
Single Nucleotide ◽  
Multiple Factors ◽  
Single Marker ◽  
Genomic Studies ◽  
Diet And Lifestyle

Abstract Epidemiologic and genomic studies have progressively improved our understanding of the causation of hypertension and the complex relationship with diet and environment. The majority of Mendelian forms of syndromic hypotension and hypertension (HTN) have all been linked to mutations in genes whose encoded proteins regulate salt–water balance in the kidney, supporting the primacy of the kidneys in blood pressure regulation. There are more than 1,477 single nucleotide polymorphisms associated with blood pressure and hypertension and the challenge is establishing a causal role for these variants. Hypertension is a complex multifactorial phenotype and it is likely to be influenced by multiple factors including interactions between diet and lifestyle factors, microbiome, and epigenetics. Given the finite genetic variability that is possible in humans, it is likely that incremental gains from single marker analyses have now plateaued and a greater leap in our understanding of the genetic basis of disease will come from integration of other omics and the interacting environmental factors. In this review, we focus on emerging results from the microbiome and metabolomics and discuss how leveraging these findings may facilitate a deeper understanding of the interrelationships between genomics, diet, and microbial ecology in humans in the causation of essential hypertension.

scholarly journals ATXN7 Gene Variants and Expression Predict Post-Operative Clinical Outcomes in Hepatitis B Virus-Related Hepatocellular Carcinoma

2016 ◽  
Vol 39 (6) ◽  
pp. 2427-2438 ◽  
Author(s):  
Chuangye Han ◽  
Long Yu ◽  
Xiaoguang Liu ◽  
Tingdong Yu ◽  
Wei Qin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcomes ◽  
Pcr Amplification ◽  
Predictive Biomarkers ◽  
Therapeutic Effects ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
B Virus ◽  
Serum Alpha Fetoprotein ◽  
High Level

Background/Aims: Hepatocellular carcinoma (HCC) is a lethal disease with nearly equal morbidity and mortality. Thus, the discovery and application of more useful predictive biomarkers for improving therapeutic effects and prediction of clinical outcomes is of crucial significance. Methods: A total of 475 HBV-related HCC patients were enrolled. Ataxin 7 (ATXN7) single nucleotide polymorphisms (SNPs) were genotyped by Sanger DNA sequencing after PCR amplification. The associations between ATXN7 SNPs and mRNA expression with the prognosis of HBV-related HCC were analyzed. Results: In all, rs3774729 was significantly associated with overall survival (OS) of HBV-related HCC (P = 0.013, HR = 0.66, 95% CI: 0.48-0.94). And patients with the AA genotype and a high level of serum alpha fetoprotein (AFP) had significantly worse OS when compared to patients with AG/GG genotypes and a low level of AFP (adjusted P = 0.007, adjusted HR = 1.83, 95% CI = 1.18-2.82). Furthermore, low expression of ATXN7 was significantly associated with poor recurrence-free survival (RFS) and OS (P = 0.007, HR = 2.38, 95% CI = 1.27-4.45 and P = 0.025, HR = 1.75, 95% CI = 1.18-2.62). Conclusion: ATXN7 may be a potential predictor of post-operative prognosis of HBV-related HCC.

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