Single Nucleotide
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Zhiying Zhang ◽  
Lifeng Ma ◽  
Xiaowei Fan ◽  
Kun Wang ◽  
Lijun Liu ◽  

AbstractHigh-altitude polycythemia (HAPC) is characterized by excessive proliferation of erythrocytes, resulting from the hypobaric hypoxia condition in high altitude. The genetic variants and molecular mechanisms of HAPC remain unclear in highlanders. We recruited 141 Tibetan dwellers, including 70 HAPC patients and 71 healthy controls, to detect the possible genetic variants associated with the disease; and performed targeted sequencing on 529 genes associated with the oxygen metabolism and erythrocyte regulation, utilized unconditional logistic regression analysis and GO (gene ontology) analysis to investigate the genetic variations of HAPC. We identified 12 single nucleotide variants, harbored in 12 genes, associated with the risk of HAPC (4.7 ≤ odd ratios ≤ 13.6; 7.6E − 08 ≤ p-value ≤ 1E − 04). The pathway enrichment study of these genes indicated the three pathways, the PI3K-AKT pathway, JAK-STAT pathway, and HIF-1 pathway, are essential, which p-values as 3.70E − 08, 1.28 E − 07, and 3.98 E − 06, respectively. We are hopeful that our results will provide a reference for the etiology research of HAPC. However, additional genetic risk factors and functional investigations are necessary to confirm our results further.

2021 ◽  
pp. 1-30
L.E. González-Salazar ◽  
O. Granados-Portillo ◽  
I. Medina-Vera ◽  
E. Pichardo-Ontiveros ◽  
A. Vigil-Martínez ◽  

Abstract Background & aims: Branched-chain amino acids (BCAAs) are considered markers of insulin resistance (IR) in subjects with obesity. In this study, we evaluated whether the presence of a single nucleotide polymorphism (SNP) of the branched-chain aminotransferase 2 (BCAT2) gene can modify the effect of a dietary intervention (DI) on the plasma concentration of BCAAs in subjects with obesity and IR. Methods: A prospective cohort study of adult subjects with obesity, body mass index (BMI) ≥ 30 kg/m2, IR (HOMA-IR ≥ 2.5) no diagnosed chronic disease, underwent a DI with an energy restriction of 750 kcal/d and nutritional education for one month. Anthropometric measurements, body composition, blood pressure, resting energy expenditure (REE), oral glucose tolerance test (OGTT) results, serum biochemical parameters and the plasma amino acid profile were evaluated before and after the DI. SNPs were assessed by the TaqMan SNP genotyping assay. Results: A total of 82 subjects were included, 15 subjects with a BCAT2 SNP had a greater reduction in leucine, isoleucine, valine, and the sum of BCAAs. Those subjects also had a greater reduction in skeletal muscle mass, fat free mass, total body water, blood pressure, muscle strength and biochemical parameters after one month of the DI and adjusting for age and sex. Conclusions: This study demonstrated that the presence of the BCAT2 SNP promotes a greater reduction in plasma BCAA concentration after adjusting for age and sex, in subjects with obesity and IR after a one-month energy-restricted DI.

2021 ◽  
Weijia Cheng ◽  
Kai Wu ◽  
Xiaonan Song ◽  
Wang Wei ◽  
Weixing Du ◽  

Abstract BackgroundMolecular markers for monitoring resistance could help improve malaria treatment policies. Delayed clearance of Plasmodium falciparum by Artemisinin-based Combination Therapies (ACTs) has been reported in several countries. In addition to the PfKelch13 (pfk13), new drug resistance genes, the ubiquitin-specific protease 1 (pfubp1) and the eadaptor protein complex 2 mu subunit (pfap2mu) have been identified as being linked to ACTs. This study investigated the prevalence of single-nucleotide polymorphisms (SNPs) in clinical Plasmodium falciparum isolates pfubp1 and pfap2mu imported from Africa and Southeast Asia (SEA) to Wuhan, China, to provide baseline data for antimalarial resistance monitoring in this region.MethodsPeripheral Blood samples were collected in Wuhan, China, from August 2011 to December 2019. The SNPs of Pfubp1 and pfap2mu of P. falciparum were determined by nested PCR and Sanger sequencing. ResultsIn total, 296 samples were collected. Subsequently, 92.23% (273/296) were successfully amplified and sequenced for the Pfubp1. There were 60.07% (164/273) wild strains and 39.93% (109/273) mutant strains. For the pfap2mu gene, it was divided into three fragments for amplification, 82.77% (245/296), 90.20% (267/296) and 94.59% (280/296) were sequenced successfully respectively. Genotypes reportedly associated with ACTs resistance detected in this study included pfubp1 D1525E as well as E1528D and pfap2mu S160N. The mutation prevalence rates were 10.99% (30/273), 13.19% (36/273) and 11.24% (30/267), respectively. ConclusionsThe existence of mutation sites of known clearance genes detected in the isolates in this study, including D1525E and E1528D in the pfubp1 gene, and S160N in the pfap2mu gene, further proved the risk of ACTs resistance. Constant vigilance is therefore needed to protect the effectiveness of ACTs, and to prevent the spread of drug-resistant P. falciparum. Further studies in malaria-endemic countries are needed to further validate potential genetic markers for monitoring parasite populations in Africa and SEA.

2021 ◽  
Vol 19 (2) ◽  
pp. 245-257
Pham Thanh Hai ◽  
Bui Xuan Phuong ◽  
Tran Huu Coi ◽  
Phung Thanh Tung ◽  
Ngo Quang Duc ◽  

The H'mong short tail dog is breed indigenous dogs, distributed in mountainousareas of northern Vietnam. H'mong short tail dog possesses many valuable properties such as intelligence, agility, good health, good shape, human friendliness, ease of training and it can fully meet the needs of war Dogs intelligence, strength, good parenting, people friendly and more importantly, still keeping wild characteristics of hunting dogs. The total 45 samples (blood) collected from 45 individuals in two provinces of Northern Vietnam (Ha Giang and Lao Cai), were used to assess genetic diversity based on sequencing hypervariable – 1 region (HV1) in D-loop genes. In the current study showed that genetic diversity of H'mong short tail dog was high with nucleotide diversity (Pi = 0.00801), haplotype diversity (Hd = 0.96162) and average number of nucleotide differences (Kt = 5.18384). Furthermore, 25 different haplotypes were recorded and divided into four main groups: A, B, C, and E. Of which, seven new haplotypes in haplogroups A (An1 to An7) and 18 haplotypes have been published in the world. In addition, H'mong short tail dog was found rare haplogroups (B1, C2, E1 and E4). Notably, there is none individuals contain haplotype of haplogroups (D and F). H'mong short tail dog were identified 38 single nucleotide polymorphisms, including 32 nucleotide base substitution/base insertion and 6 nucleotide indel mutation. Almost mutation was transversion (31/32) and only one nucleotide transition mutations. Phylogenetic tree shown that H'mong short tail dog have close relationship with dogs origin from East Asia (China, Japan and Korea).

2021 ◽  
Vol 12 ◽  
Xiaosen Jiang ◽  
Zheng Xu ◽  
Tongda Zhang ◽  
Yuan Li ◽  
Wei Li ◽  

Helicobacter pylori exhibit specific geographic distributions that are related to clinical outcomes. Despite the high infection rate of H. pylori throughout the world, the genetic epidemiology surveillance of H. pylori still needs to be improved. This study used the single nucleotide polymorphisms (SNPs) profiling approach based on whole genome sequencing (WGS) to facilitate genomic population analyses of H. pylori and encourage the dissemination of microbial genotyping strategies worldwide. A total number of 1,211 public H. pylori genomes were downloaded and used to construct the typing tool, named HpTT (H. pylori Typing Tool). Combined with the metadata, we developed two levels of genomic typing, including a continent-scale and a country scale that nested in the continent scale. Results showed that Asia was the largest isolate source in our dataset, while isolates from Europe and Oceania were comparatively more widespread. More specifically, Switzerland and Australia are the main sources of widespread isolates in their corresponding continents. To integrate all the typing information and enable researchers to compare their dataset against the existing global database easily and rapidly, a user-friendly website ( was developed with both genomic typing tools and visualization tools. To further confirm the validity of the website, ten newly assembled genomes were downloaded and tested precisely located on the branch as we expected. In summary, the H. pylori typing tool (HpTT) is a novel genomic epidemiological tool that can achieve high-resolution analysis of genomic typing and visualizing simultaneously, providing insights into the genetic population structure, evolution analysis, and epidemiological surveillance of H. pylori.

2021 ◽  
Masoud Tahani ◽  
Mohamad Taghi Goodarzi ◽  
Ali Asghar Ahmadi ◽  
Mohammad Hossein Hasani ◽  
Alireza Farrahi ◽  

Abstract Genetic modifications in the adiponectin receptor 2 (AdipoR2) gene can affect phenotypes associated with insulin resistance and diabetes. The purpose of this study was to evaluate the possible role of genetic modifications in the AdipoR2 gene, to determine the frequency of genotypes and polymorphism alleles of this gene at rs11061971 (+ 219 A > T), and to investigate its correlation with type 2 diabetes (T2D) and its related metabolic profile. In this case-control study, the single-nucleotide polymorphism (SNP) of interest in 116 T2D patients and 102 controls was evaluated using RFLP PCR and FOK 1 enzyme. Fasting blood sugar, cholesterol, triglyceride, insulin, HDL-C, LDL-C and HbA1c were also measured and their correlation with the studied genetic modifications was assessed. The collected data were analyzed using Chi-square test and Hardy-Weinberg equation. There was a significant association in AT and TT genotypes in rs11061971 (+ 219 A > T) with T2D. However, no significant difference was observed in the frequency of alleles between the case and control groups. In addition, in LDL-C and total cholesterol in the control group, there was a significant difference between AA and TT genotypes as well as with AA and AT genotypes. However, no correlation was found between the other serum studied parameters and the genotype of individuals in the rs1106197171 polymorphism. The role of rs11061971 (+ 219 A > T) polymorphism in T2D incidence seems to be strong. This study showed that AT and TT genotypes versus AA genotype increase the risk of diabetes.

2021 ◽  
Vol 8 ◽  
Jianqiang Zhao ◽  
Heng Chen ◽  
Chengui Zhuo ◽  
Shudong Xia

Several observational studies have shown that cannabis use has negative effects on the cardiovascular system, but the causality of this relationship has not been confirmed. The aim of the current study was to estimate the effects of genetically determined cannabis use on risk of cardiovascular diseases. Ten single-nucleotide polymorphisms related to cannabis use were employed as instruments to estimate the association between genetically determined cannabis use and risk of cardiovascular diseases using a two-sample Mendelian randomization (MR) method. Summary statistics data on exposure and outcomes were obtained from different genome-wide association meta-analysis studies. The results of this MR analysis showed no causal effects of cannabis use on the risk of several common cardiovascular diseases, including coronary artery disease, myocardial infarction, stroke and ischemic stroke subtypes, atrial fibrillation (AF), and heart failure. Various sensitivity analyses yielded similar results, and no heterogeneity and directional pleiotropy were observed. After adjusting for tobacco use and body mass index, multivariable MR analysis suggested a causal effect of cannabis use on small vessel stroke (SVS) [odds ratio (OR) 1.17; 95% CI 1.02–1.35; p = 0.03] and AF (OR 1.06; 95% CI 1.01–1.10; p = 0.01), respectively. This two-sample MR study did not demonstrate a causal effect of genetic predisposition to cannabis use on several common cardiovascular outcomes. After adjusting for tobacco use and body mass index, the multivariable MR analysis suggested a detrimental effect of cannabis use on the risk of SVS and AF, respectively.

Hanla A. Park ◽  
Sonja Neumeyer ◽  
Kyriaki Michailidou ◽  
Manjeet K. Bolla ◽  
Qin Wang ◽  

Abstract Background Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Results Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07–1.30, P = 0.11 × 10–2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78–1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

2021 ◽  
Vol 8 ◽  
Yichang Zhao ◽  
Xiaoyang Yuan ◽  
Yang Zhong ◽  
Yutao Zhang ◽  
Shushan Zhang ◽  

Background: Corin is a transmembrane serine protease that activates pro-forms of atrial and brain natriuretic peptides. Numerous studies have indicated that corin played an important role in cardiovascular diseases (CVDs). However, there have been few studies about the correlation between single-nucleotide polymorphisms (SNPs) in the 3' untranslated region (3'UTR) of CORIN and CVDs. The aims of this study were to investigate the associations of three SNPs (rs3749585, rs4695253, and rs12641823) in the 3'UTR of CORIN with CVDs and to find the seed regions of microRNAs (miRNAs) that bind to SNPs of CORIN.Methods and Results: A case–control study (n = 3,537) was performed in a Han population of northeastern China. CVDs included essential hypertension (EH), atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD). Genotyping was performed using high-resolution melt analysis. In the EH-control study, rs3749585T was significantly associated with the risk of EH after adjusting for sex and age in allelic (padj = 0.049; OR: 1.113) and dominant (padj = 0.015, OR: 1.233) models. Rs4695253T was significantly associated with the risk of EH in the recessive model after adjusting for sex and age (padj = 0.005, OR: 2.084). Rs3749585T was significantly and negatively associated with AF in the dominant and additive models after adjusting for sex, age, EH, HF, T2DM, and CAD (dominant: padj = 0.009, OR: 0.762; additive: padj = 0.048, OR: 0.873). In the HF-control study and CAD-control study, none of the three SNPs was associated with HF and CAD after adjusting for covariates in any models (padj > 0.05). The levels of high-density lipoprotein (HDL) in rs4695253CC+CT were lower than the levels of HDL in rs4695253TT (42.47 ± 10.30 vs. 48.0 ± 10.24 mg/dl, padj = 0.008). The levels of total cholesterol (TC) in rs4695253CC+CT were lower than the levels of TC in rs4695253TT (164.01 ± 49.15 vs. 180.81 ± 43.92 mg/dl, padj = 0.036). Luciferase assay revealed that the relative luciferase activity of rs3749585CC-transfected cells was significantly decreased by miR-494-3p, in comparison to cells transfected with rs3749585TT (p < 0.001). A significant decrease in the relative luciferase activity of rs3749585TT reporter was observed as compared with rs3749585CC reporter in the presence of miR-1323 or miR-548o-3p (p = 0.017 and 0.012, respectively).Conclusions: We found significant associations between rs3749585T and rs4695253T and EH, between rs4695253T and the levels of TC and HDL, and between rs3749585T and AF. Hsa-miR-494-3p may serve as a potential therapeutic target for EH and AF patients in the future.

2021 ◽  
Jeremy S. Brown

The Streptococcus pneumoniae capsule is essential for disease pathogenesis, suggesting that even minor genetic changes within the cps locus could potentially have important consequences. Arends et al. have identified 79 different non-synonymous SNPs in the cps locus of 338 19A serotype strains, and shown significant variations between strains in nucleotide sugars content and capsule shedding. Further work is required to characterise whether any of these changes have important functional consequences on capsule/host interactions.

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