scholarly journals A Workflow for Selection of Single Nucleotide Polymorphic Markers for Studying of Genetics of Ischemic Stroke Outcomes

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 328
Author(s):  
Gennady Khvorykh ◽  
Andrey Khrunin ◽  
Ivan Filippenkov ◽  
Vasily Stavchansky ◽  
Lyudmila Dergunova ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Ischemia ◽  
Candidate Gene Approach ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Stroke Outcomes ◽  
Genomic Variations ◽  
Human Genes ◽  
Human Genomic ◽  
Selection Of

In this paper we propose a workflow for studying the genetic architecture of ischemic stroke outcomes. It develops further the candidate gene approach. The workflow is based on the animal model of brain ischemia, comparative genomics, human genomic variations, and algorithms of selection of tagging single nucleotide polymorphisms (tagSNPs) in genes which expression was changed after ischemic stroke. The workflow starts from a set of rat genes that changed their expression in response to brain ischemia and results in a set of tagSNPs, which represent other SNPs in the human genes analyzed and influenced on their expression as well.

Selection of Genes and Single Nucleotide Polymorphisms for Fine Mapping Starting From a Broad Linkage Region

2007 ◽  
Vol 10 (6) ◽  
pp. 871-885 ◽  
Author(s):  
An Windelinckx ◽  
Robert Vlietinck ◽  
Jeroen Aerssens ◽  
Gaston Beunen ◽  
Martine A. I. Thomis
Keyword(s):  
Linkage Disequilibrium ◽  
Candidate Gene ◽  
Candidate Genes ◽  
Fine Mapping ◽  
Complex Disease ◽  
Gene Selection ◽  
Candidate Gene Approach ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Selection Of

AbstractFine mapping of linkage peaks is one of the great challenges facing researchers who try to identify genes and genetic variants responsible for the variation in a certain trait or complex disease. Once the trait is linked to a certain chromosomal region, most studies use a candidate gene approach followed by a selection of polymorphisms within these genes, either based on their possibility to be functional, or based on the linkage disequilibrium between adjacent markers. For both candidate gene selection and SNP selection, several approaches have been described, and different software tools are available. However, mastering all these information sources and choosing between the different approaches can be difficult and time-consuming. Therefore, this article lists several of these in silico procedures, and the authors describe an empirical two-step fine mapping approach, in which candidate genes are prioritized using a bioinformatics approach (ENDEAVOUR), and the top genes are chosen for further SNP selection with a linkage disequilibrium based method (Tagger). The authors present the different actions that were applied within this approach on two previously identified linkage regions for muscle strength. This resulted in the selection of 331 polymorphisms located in 112 different candidate genes out of an initial set of 23,300 SNPs.

scholarly journals Examination of Genetic Variants Revealed from a Rat Model of Brain Ischemia in Patients with Ischemic Stroke: A Pilot Study

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1938
Author(s):  
Andrey V. Khrunin ◽  
Gennady V. Khvorykh ◽  
Alexandra V. Rozhkova ◽  
Evgeniya A. Koltsova ◽  
Elizaveta A. Petrova ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Ischemia ◽  
Rat Model ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Single Nucleotide ◽  
Functional Annotations ◽  
Great Progress ◽  
Specific Association ◽  
Bioinformatic Approach

Although there has been great progress in understanding the genetic bases of ischemic stroke (IS), many of its aspects remain underexplored. These include the genetics of outcomes, as well as problems with the identification of real causative loci and their functional annotations. Therefore, analysis of the results obtained from animal models of brain ischemia could be helpful. We have developed a bioinformatic approach exploring single nucleotide polymorphisms (SNPs) in human orthologues of rat genes expressed differentially under conditions of induced brain ischemia. Using this approach, we identified and analyzed nine SNPs in 553 Russian individuals (331 patients with IS and 222 controls). We explored the association of SNPs with both IS outcomes and with the risk of IS. SNP rs66782529 (LGALS3) was associated with negative IS outcomes (p = 0.048). SNPs rs62278647 and rs2316710 (PTX3) were associated significantly with IS (p = 0.000029 and p = 0.0025, respectively). These correlations for rs62278647 and rs2316710 were found only in women, which suggests a sex-specific association of the PTX3 polymorphism. Thus, this research not only reveals some new genetic associations with IS and its outcomes but also shows how exploring variations in genes from a rat model of brain ischemia can be of use in searching for human genetic markers of this disorder.

scholarly journals Selection of X-chromosome Inactivation Model

2017 ◽  
Vol 16 ◽  
pp. 117693511774727 ◽  
Author(s):  
Jian Wang ◽  
Rajesh Talluri ◽  
Sanjay Shete
Keyword(s):  
X Chromosome ◽  
X Chromosome Inactivation ◽  
Association Test ◽  
Chromosome Inactivation ◽  
Simulation Studies ◽  
Nucleotide Polymorphisms ◽  
Unified Approach ◽  
Cancer Genetic ◽  
Single Nucleotide ◽  
Selection Of

To address the complexity of the X-chromosome inactivation (XCI) process, we previously developed a unified approach for the association test for X-chromosomal single-nucleotide polymorphisms (SNPs) and the disease of interest, accounting for different biological possibilities of XCI: random, skewed, and escaping XCI. In the original study, we focused on the SNP-disease association test but did not provide knowledge regarding the underlying XCI models. One can use the highest likelihood ratio (LLR) to select XCI models (max-LLR approach). However, that approach does not formally compare the LLRs corresponding to different XCI models to assess whether the models are distinguishable. Therefore, we propose an LLR comparison procedure (comp-LLR approach), inspired by the Cox test, to formally compare the LLRs of different XCI models to select the most likely XCI model that describes the underlying XCI process. We conduct simulation studies to investigate the max-LLR and comp-LLR approaches. The simulation results show that compared with the max-LLR, the comp-LLR approach has higher probability of identifying the correct underlying XCI model for the scenarios when the underlying XCI process is random XCI, escaping XCI, or skewed XCI to the deleterious allele. We applied both approaches to a head and neck cancer genetic study to investigate the underlying XCI processes for the X-chromosomal genetic variants.

scholarly journals Interaction between COX-1 and COX-2 increases susceptibility to ischemic stroke in a Chinese population

2019 ◽  
Author(s):  
Lei Zhao ◽  
Jinghuan Fang ◽  
Muke Zhou ◽  
Jie Zhou ◽  
Lihua Yu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Gene Interaction ◽  
Additive Effect ◽  
Large Artery ◽  
Nucleotide Polymorphisms ◽  
Vessel Occlusion ◽  
Single Nucleotide ◽  
Ischemic Stroke Risk ◽  
Cox 2 ◽  
Cox 1

Abstract Background Mutations of cyclooxygenase gene (COX gene) may increase the susceptibility of ischemic stroke. We investigated five variants (rs5788, rs1330344, rs3842788, rs20417, and rs689466) of two COX genes to explain the association between these polymorphisms and ischemic stroke risk determine whether gene–gene interaction between these genes increase the susceptibility of ischemic stroke or its subtypes. Methods A total of 1981 study subjects (1078 cases and 903 control subjects) were recruited. The interaction of multiple factors was investigated using Multifactor Dimensionality Reduction and additive effect of single nucleotide polymorphisms on ischemic stroke or its subtypes were analyzed by multiple factor logistic regression. Results At COX-1(rs1330344), AA genotype carriers had a lower susceptibility of ischemic stroke (OR=0.657, 95%CI= 0.437-0.988, P = 0.044), and A allele carriers had a lower susceptibility of ischemic stroke (OR=0.812, 95%CI= 0.657-0.978, P = 0.029). At COX-1(rs3842788), AA genotype carriers had a higher susceptibility of ischemic stroke (OR =5.203, 95% CI=1.519-5.159, P =0.016). At COX-2 (rs689466), AA genotype carriers had a higher susceptibility of large-artery atherosclerosis (OR =1.404, 95% CI=1.019-1.934, P =0.038). COX-1(rs1330344, rs3842788) and COX-2 rs689466 interacted in SVO, but had no additive effect with ischemic stroke or its subtypes. Conclusions At rs1330344, AA genotype may reduce the susceptibility of ischemic stroke. At rs3842788, AA genotype may increase the susceptibility of ischemic stroke. At rs689466, AA genotype may increase the susceptibility of large-artery atherosclerosis (LAA). COX-1(rs1330344, rs3842788) and COX-2 rs689466 interacted in small vessel occlusion (SVO), but had no additive effect with ischemic stroke or its subtypes.

scholarly journals A Novel Test System for Genotyping rs43703016 Single-nucleotide Substitutions in the Bovine CSN3 Gene

2019 ◽  
pp. 1-5
Author(s):  
Svetlana Kovalchuk ◽  
Arina Tagmazyan ◽  
Eugene Klimov
Keyword(s):  
Nucleotide Substitution ◽  
Milk Proteins ◽  
Test System ◽  
Nucleotide Polymorphisms ◽  
Dna Testing ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
Allele Specific ◽  
Selection Of

Aims: Caseins are among the main milk proteins that determine many of its properties. Bovine kappa-casein (CSN3) is associated with the qualitative composition of milk, as well as with the quality of cheese obtained from this milk. The rs43703016 single-nucleotide substitution (g.88532332A>C; Asp148Ala) in exon 4 of the bovine CSN3 gene plays an important role in the production of quality hard cheeses. Various methods for the DNA testing of this substitution have been developed in the last three decades. Emergent DNA technologies provide an opportunity to modernize methods of genotyping single-nucleotide polymorphisms. Results: We have developed and verified a method to differentiate A/C alleles of the rs43703016 substitution in the bovine CSN3 gene by real-time PCR using allele-specific fluorescent probes. Conclusion: Our new method allows fast genotyping of animals, and may be used for selection of cows carrying the CC genotype, which determines good cheese-making properties of milk.

scholarly journals Functional Inflammatory Genotypes in Ischemic Stroke: Could We Use Them to Predict Age of Onset and Long-Term Outcome?

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Stella Marousi ◽  
Anna Antonacopoulou ◽  
Haralambos Kalofonos ◽  
Panagiotis Papathanasopoulos ◽  
Marina Karakantza ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cox Regression ◽  
Age Of Onset ◽  
Adverse Outcome ◽  
Nucleotide Polymorphisms ◽  
Term Outcome ◽  
Single Nucleotide ◽  
Long Term Outcome ◽  
Tnf Α

Functional single-nucleotide polymorphisms (SNPs) of inflammatory cytokines have been previously related to the occurrence of an ischemic stroke (IS). We investigated whether five functional SNPs (i.e., TNF-α-308G>A, IL6-174G>C, IL12B 1188A>C, IL4-589C>T, and IL10-1082G>A) might be associated with the age of onset and 6-month outcome of an acute IS. A probe-free real-time PCR methodology was used to genotype 145 consecutively admitted cases with a first-ever IS. Simple Kaplan-Mayer and adjusted Cox regression analyses showed no association between inflammatory genotypes and the age of IS onset. IL6-174G>C, IL12B 1188A>C, IL4-589C>T, and IL10-1082G>A were not found to significantly contribute to the long-term outcome of the disease. However, carriage of the TNF-α-308 GG genotype was significantly associated with reduced odds for an adverse outcome. Larger studies are needed to confirm our results.

scholarly journals Genome-Wide Association Study of Body Weight Traits in Chinese Fine-Wool Sheep

Animals ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 170 ◽  
Author(s):  
Zengkui Lu ◽  
Yaojing Yue ◽  
Chao Yuan ◽  
Jianbin Liu ◽  
Zhiqiang Chen ◽  
...  
Keyword(s):  
Body Weight ◽  
Muscle Development ◽  
Genome Wide Association Study ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Economic Trait ◽  
Significance Levels ◽  
Genomic Regions ◽  
Selection Of

Body weight is an important economic trait for sheep and it is vital for their successful production and breeding. Therefore, identifying the genomic regions and biological pathways that contribute to understanding variability in body weight traits is significant for selection purposes. In this study, the genome-wide associations of birth, weaning, yearling, and adult weights of 460 fine-wool sheep were determined using resequencing technology. The results showed that 113 single nucleotide polymorphisms (SNPs) reached the genome-wide significance levels for the four body weight traits and 30 genes were annotated effectively, including AADACL3, VGF, NPC1, and SERPINA12. The genes annotated by these SNPs significantly enriched 78 gene ontology terms and 25 signaling pathways, and were found to mainly participate in skeletal muscle development and lipid metabolism. These genes can be used as candidate genes for body weight in sheep, and provide useful information for the production and genomic selection of Chinese fine-wool sheep.

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