Single Nucleotide Polymorphisms In Genes Research Articles

Identifying Oncogenic Missense Single Nucleotide Polymorphisms in Human SAT1 Gene Using Computational Algorithms and Molecular Dynamics Tools.

The human SAT1 gene encodes spermidine/spermine N1-acetyltransferase 1 (SSAT1), a regulatory biological catalyst of polyamine catabolism. Numerous essential biological processes, such as cellular proliferation, differentiation, and survival, depend on polyamines like spermidine and spermine. Thus, SSAT1 is involved in key cellular activities such as proliferation and survival of cells and mediates various diseases including cancer. A plethora of studies established the involvement of missense single nucleotide polymorphisms (SNPs) in numerous pathological conditions due to their ability to adversely affect the structure and subsequent function of the protein. To date, an in silico study to identify the pathogenic missense SNPs of the human SAT1 gene has not been accomplished yet. This study aimed to filter the missense SNPs that were functionally detrimental and pathogenic. The rs757435207 (I21N) was ascertained to be the most deleterious and pathogenic by all algorithmic tools. Stability and evolutionary conservation analysis tools also stated that I21N variant decreased the stability and was located in the highly conserved residue. Molecular dynamics simulation revealed that I21N caused substantial alterations in the conformational stability and dynamics of the SSAT1 protein. Consequently, the I21N variant could disrupt the native functional roles of the SSAT1 enzyme. Therefore, the I21N variant was identified and concluded to be an oncogenic missense variant of the human SAT1 gene. Overall, the findings of this study would be a great directory of future experimental research to develop personalized medicine.

Targeted Obesity Genes Single Nucleotide Polymorphisms, Diet, Lifestyles, and Obesity Indices: Nutrigenetics as a Predictive Model

Targeted Obesity Genes Single Nucleotide Polymorphisms, Diet, Lifestyles, and Obesity Indices: Nutrigenetics as a Predictive Model

Relationship between Selected SNPs (g.16024A/G, g.16039T/C and g.16060A/C) of the FASN Gene and the Fat Content and Fatty Acid Profile in the Milk of Three Breeds of Cows.

Fat is an important energy and nutritional component of milk and consists of fatty acids. FASN (fatty acid synthase) is an enzyme that regulates the synthesis of fatty acids in the milk and meat of cattle. It was hypothesized that knowing the relationships between the genotypes of the tested single nucleotide polymorphisms (SNPs) and the content of fat and specific fatty acids would make it possible to improve milk quality in the selection process during cattle breeding. This study aimed to analyze the relationships of SNPs (g.16024A/G, g.16039T/C) of the FASN gene and their genotypes with the fat and fatty acid content of the milk of the following breeds: Polish Red-White (ZR), Polish Red (RP), and Polish Holstein-Friesian Red-White (RW). The SNP g.16060A/C was included in the study, although its effect on the fat composition of cow's milk has not yet been widely studied. Milk was obtained during test milkings. SNP genotyping was performed using the real-time PCR (HRM) method. The milk from ZR and RP cows was more often characterized by a more favorable fatty acid profile than the milk from RW cows. This information can be used by cattle breeders and consumers of so-called functional food.

Relationship Between Cytotoxic T-Lymphocyte-associated Antigen-4: Programmed Death-1 Genes Polymorphisms and Susceptibility to Pediatric B-Cell Acute Lymphoblastic Leukemia.

Programmed death-1 (PD1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have a vital role in immune checkpoint pathways. Single nucleotide polymorphisms (SNPs) of PD1 and CTLA4 have been reported to be associated with susceptibility to certain autoimmune diseases and cancers. The potential association between SNPs in these immune checkpoint genes and risk of acute lymphoblastic leukemia (ALL) still unclear. The aim of this study is to clarify the effect of PD1 and CTLA4 SNPs on the risk of developing ALL and the prognosis of the disease. The study was performed on 100 pediatric B-ALL patients and 100 controls. The PD1 and CTLA4 SNPs were examined by RFLP technique. The study revealed that CTLA4 (rs11571316) was associated with high risk of B-ALL developments OR 1.492 (CI: 1157 to 1924) ( P =0.002). PD1 (rs36084323) GA genotype was significantly associated with protective effect against nonremission ( P =0.007). PD1 (rs36084323) A allele were associated with protective effect against relapse ( P =0.008). CTLA4 and PD1 genotypes did not have significant impact on B-ALL patients outcome. The current study displayed for the first time that genetic variations of the CTLA-4, was associated with susceptibility to B-ALL and that PD1 (rs36084323) GA genotype was significantly associated with protective effect against nonremission, while PD1 (rs36084323) A allele was associated with protective effect against relapse.

A longitudinal population-based study identifies THBS2 as a susceptibility gene for intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a common degenerative disease associated with ageing. Additionally, IDD is recognized as one of the leading causes of low back pain and disability in the working-age population and is the first step in the process leading to degenerative spinal changes. However, the genetic factors and regulatory mechanisms of IDD remain unknown. Therefore, we selected eight single nucleotide polymorphisms of genes to reveal the progression of IDD in a 7-year longitudinal study of the general population in Japan. IDD was evaluated in the Wakayama Spine Study (WSS), which is a population-based cohort study. Overall, 574 participants from the general population cohort who underwent whole spine magnetic resonance imaging and provided clinical information were included in this longitudinal survey. The progression of IDD was affected only by THBS2 at the lumbar region, T12-L1 (p = 0.0044) and L3-4 (p = 0.0045). The significant interaction between THBS2 and age with IDD negatively affected the thoracic spines and passively influenced both the thoracolumbar junction and thoracic spines. The higher progression per year of Pfirrmann's score was rapid in young people with age; however, this decelerated the IDD progression per year in different ages. Our longitudinal study found the genes associated with IDD progression and that genetic factors' impact on IDD differs depending on disc level and age.

Alterations in methylation and SNPs of OPRM1 gene show lack of association with heroin (nyaope) consumption in South African males of African ancestry

Nyaope is a highly addictive heroin derivative that elicits its effects via the -opioid receptor. Gene mutations and (cytosine-phospho-guanosine) CpG methylation, alter the function of the -opioid receptor gene (OPRM1) and protein. The single nucleotide polymorphisms (SNPs) rs1799971 (118 A>G) and intronic rs3778150 (T>C) in the OPRM1 have previously been associated with heroin use. The SNP rs1799971 can influence methylation levels of OPRM1 and alter mRNA and protein expression. This study compared the degree of OPRM1 methylation and allele frequency of SNPs rs1799971 and rs3778150 in black South African male nyaope users (n=200) to age-and gender-matched controls (n=55).DNA was extracted from whole blood samples, and analysed by methylation-specific PCR and sequencing to determine methylation frequencies across 29 CpGs within the OPRM1promoter gene region. SNPsrs1799971 (118 A>G) and rs3778150 (T>C) were assessed using SNP genotyping Taqman assays.Using a positive methylation assignment method, most CpGs were significantly more unmethylated in nyaope users than in controls. Using a partial methylation assignment method, most CpGs displayed significantly higher percentages of partial methylation in nyaope users than in controls. The AG genotype frequency for SNP (118 A>G), was higher in controls than in nyaope users while other genotypes (AA & GG) for SNP rs1799971 and (TT, CT, CC) SNP rs3778150 were broadly similar in both groups. There was no correlation observed between nyaope consumption and the presence of SNP rs1799971 and/or rs3778150 in the study populations.This study provided evidence that methylation may not be associated with the intake of nyaope and that SNPs rs1799971 and rs3778150 did not alter the methylation status of the OPRM1 promoter gene or contribute to nyaope addiction in a black South African male population.

Variations in the LINGO2 and GLIS3 Genes and Gene-Environment Interactions Increase Gestational Diabetes Mellitus Risk in Chinese Women.

Gestational diabetes mellitus (GDM) has been found to be a common complication in pregnant women, known to escalate the risk of negative obstetric outcomes. In our study, we genotyped 1,566 Chinese pregnant women for two single nucleotide polymorphisms (SNPs) in the LINGO2 gene and one SNP in the GLIS3 gene, utilizing targeted next-generation sequencing. The impact of two interacting genes, and the interaction of genes with the environment─including exposure to particulate matter (PM2.5), ozone (O3), and variations in prepregnancy body mass index (BMI)─on the incidence of GDM were analyzed using logistic regression. Our findings identify the variants LINGO2 rs10968576 (P = 0.022, OR = 1.224) and rs1412239 (P = 0.018, OR = 1.231), as well as GLIS3 rs10814916 (P = 0.028, OR = 1.172), as risk mutations significantly linked to increased susceptibility to GDM. Further analysis underscores the crucial role of gene-gene and gene-environment interactions in the development of GDM among Chinese women (P < 0.05). Particularly, the individuals carrying the rs10968576 G-rs1412239 G-rs10814916 C haplotype exhibit increased susceptibility to GDM during the prepregnancy period when interacting with PM2.5, O3, and BMI (P = 8.004 × 10-7, OR = 1.206; P = 6.3264 × 10-11, OR = 1.280; P = 9.928 × 10-7, OR = 1.334, respectively). In conclusion, our research emphasizes the importance of the interaction between specific gene variations─LINGO2 and GLIS3─and environmental factors in influencing GDM risk. Notably, we found significant associations between these gene variations and GDM risk across various environmental exposure periods.

Genetic variants of LEAP2 are associated with anthropometric traits and circulating insulin-like growth factor-1 concentration: A UK Biobank study.

To test the hypothesis that liver-expressed antimicrobial peptide 2 (LEAP2) genetic variants might influence the susceptibility to human obesity. Using data from the UK Biobank, we identified independent LEAP2 gene single nucleotide polymorphisms (SNPs) and examined their associations with obesity traits and serum insulin-like growth factor-1 (IGF-1) concentration. These associations were evaluated for both individual SNPs and after combining them into a genetic risk score (GRSLEAP2) using linear and logistic regression models. Sex-stratified analyses were also conducted. Five SNPs showed positive associations with obesity-related traits. rs57880964 was associated with body mass index (BMI) and waist-to-hip ratio adjusted for BMI (WHRadjBMI), in the total population and among women. Four independent SNPs were positively associated with higher serum IGF-1 concentrations in both men and women. GRSLEAP2 was associated with BMI and WHRadjBMI only in women and with serum IGF-1 concentration in both sexes. These findings reveal sex-specific associations between key LEAP2 gene variants and several obesity traits, while also indicating a strong independent association of LEAP2 variants with serum IGF-1 concentration.

The first report of single nucleotide polymorphisms in the open reading frame of the prion-like protein gene in rabbits.

Natural cases of prion disease have not been reported in rabbits, and prior attempts to identify a prion conversion agent have been unsuccessful. However, recent applications of prion seed amplifying experimental techniques have sparked renewed interest in the potential susceptibility of rabbits to prion disease infections. Among several factors related to prion disease, polymorphisms within the prion-like protein gene (PRND), a member of the prion protein family, have been reported as significantly associated with disease susceptibility in various species. Therefore, our study aimed to investigate polymorphisms in the PRND gene of rabbits and analyze their genetic characteristics. Genomic DNA was extracted from 207 rabbit samples to investigate leporine PRND polymorphisms. Subsequently, amplicon sequencing targeting the coding region of the leporine PRND gene was conducted. Additionally, linkage disequilibrium (LD) analysis was employed to assess the connection within and between loci. The impact of non-synonymous single nucleotide polymorphisms (SNPs) on the Doppel protein was evaluated using PolyPhen-2. We found nine novel SNPs in the leporine PRND gene: c.18A > G, c.76G > C, c.128C > T, c.146C > T, c.315A > G, c.488G > A, c.525G > C, c.544G > A, and c.579A > G. Notably, seven of these PRND SNPs, excluding c.525G > C and c.579A > G, exhibited strong LD values exceeding 0.3. In addition, LD analysis confirmed a robust link between PRNP SNP c.234C > T and PRND SNPs at c.525G > C and c.579A > G. Furthermore, according to PolyPhen-2 and SIFT analyses, the four non-synonymous SNPs were predicted to have deleterious effects on the function or structure of the Doppel protein. However, PANTHER and Missense3D did not indicate such effects. In this paper, we have identified novel SNPs in the rabbit PRND gene and predicted their potential detrimental effects on protein function or structure through four non-synonymous SNPs. Additionally, we observed a genetic linkage between SNPs in the PRND and PRNP genes. These findings may provide insights into understanding the characteristics of rabbits as partially resistant species. To the best of our knowledge, this study is the first to genetically characterize PRND SNPs in rabbits.

Azole Resistance in Veterinary Clinical Aspergillus fumigatus Isolates in the Netherlands

Aspergillus fumigatus is a saprophytic fungal pathogen that causes opportunistic infections in animals and humans. Azole resistance has been reported globally in human A. fumigatus isolates, but the prevalence of resistance in isolates from animals is largely unknown. A retrospective resistance surveillance study was performed using a collection of clinical A. fumigatus isolates from various animal species collected between 2015 and 2020. Agar-based azole resistance screening of all isolates was followed by in vitro antifungal susceptibility testing and cyp51A gene sequencing of the azole-resistant isolates. Over the 5 year period 16 (11.3%) of 142 A. fumigatus culture-positive animals harbored an azole-resistant isolate. Resistant isolates were found in birds (15%; 2/13), cats (21%; 6/28), dogs (8%; 6/75) and free-ranging harbor porpoise (33%; 2/6). Azole-resistance was cyp51A mediated in all isolates: 81.3% (T-67G/)TR34/L98H, 12.5% TR46/Y121F/T289A. In one azole-resistant A. fumigatus isolate a combination of C(-70)T/F46Y/C(intron7)T/C(intron66)T/M172V/E427K single-nucleotide polymorphisms in the cyp51A gene was found. Of the animals with an azole-resistant isolate and known azole exposure status 71.4% (10/14) were azole naive. Azole resistance in A. fumigatus isolates from animals in the Netherlands is present and predominantly cyp51A TR-mediated, supporting an environmental route of resistance selection. Our data supports the need to include veterinary isolates in resistance surveillance programs. Veterinarians should consider azole resistance as a reason for therapy failure when treating aspergillosis and consider resistance testing of relevant isolates.

Evaluating Single-Nucleotide Polymorphisms in Inflammasome Proteins and Serum Levels of IL-18 and IL-1β in Kidney Interstitial Damage in Anti-Neutrophilic Cytoplasmic Antibody-Associated Vasculitis.

The inflammasome regulates the innate inflammatory response and is involved in autoimmune diseases. In this study, we explored the levels of IL-18 and IL-1β in serum and urine and the influence of various single-nucleotide polymorphisms (SNPs) on kidney lesions at diagnosis in patients with ANCA-associated vasculitis (AAV) and their clinical outcomes. Ninety-two patients with renal AAV were recruited, and blood and urine were collected at diagnosis. Serum and urine cytokine levels were measured by ELISA. DNA was extracted and genotyped using TaqMan assays for SNPs in several inflammasome genes. Lower serum IL-18 (p = 0.049) and the IL-18 rs187238 G-carrier genotype (p = 0.042) were associated with severe fibrosis. The IL-18 rs1946518 TT genotype was associated with an increased risk of relapse (p = 0.05), whereas GG was related to better renal outcomes (p = 0.031). The rs187238 GG genotype was identified as a risk factor for mortality within the first year after AAV diagnosis, independent of the requirement for dialysis or lung involvement (p = 0.013). We suggest that decreased cytokine levels could be a surrogate marker of scarring and chronicity of the renal lesions, together with the rs187238 GG genotype. If our results are validated, the rs1946518 TT genotype predicts the risk of relapse and renal outcomes during follow-up.

Association of LEP rs2167270 and LEPR rs1137100 genetic variants with obesity in the Jordanian population cohort

Background Previous Genome Wide Association Studies (GWAS) of obesity susceptibility genes in different populations have confirmed the association of some variants with obesity, body mass index (BMI), and some related metabolic traits. To our knowledge, the current study is the first to investigate the genetic basis of obesity in the Jordanian population. The aim of our study is to investigate the occurrence and frequency of obesity-related genes in Jordanian individuals and any possible relationship between SNP genetic markers and phenotypic characteristics of studied individuals. Methods A total of 150 Jordanian unrelated adults, including 83 obese, 26 overweight, and 41 normal-weight subjects, were genotyped using the high resolution melt analysis (HRMA) and tested for the association of single nucleotide polymorphisms (SNPs), rs2167270 in LEP gene and rs1137100 in LEPR gene, with obesity risk, obesity/overweight risk, BMI, weight, height, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and blood level glucose. Results A significant association between obesity risk and the rs2167270 mutation in LEP gene was observed under a dominant model (odds ratio (OR) = 2.5147, 95% CI =1.0629 to 5.9494, p = 0.0358). A marginal (not significant) association between BMI and the rs2167270 mutation in LEP gene (p = 0.075), was also detected. Moreover, an association between rs2167270 mutation in LEP gene and glucose blood level was observed (p = 0.038). Total cholesterol and LDL-cholesterol also presented a weak association with the rs1137100 mutation in LEPR gene, with p = 0.071 and p = 0.078, respectively. Additionally, no significant association between LDL-cholesterol and the rs2167270 mutation in LEP gene was observed (p = 0.091). By contrast, there was no association between weight or height and the SNPs mutation evaluated in this study (p &gt; 0.05). Conclusions These results suggest that some SNPs in some obesity-related genes may contribute to obesity risk and its related anthropometric and metabolic traits in Jordanian population. To confirm these results, further studies on a larger Jordanian cohort should be carried out.

Chronic heart failure associated genetic polymorphisms

The genetic associations between single-nucleotide polymorphisms of genes and chronic heart failure in phenotypically similar groups of patients were examined. The known information about single-nucleotide polymorphisms associated with the main pathogenetic links of chronic heart failure is systematized. Using electronic databases (PubMed, Web of Science, eLibrary), a search and synthesis of scientific works was conducted, followed by the formation of groups of genes homogeneous in their functionality (i.e., genes of the metabolic cascade, coagulation cascade, and neuroendocrine cascade). From 50 literary sources analyzed, 15 of the most specific genes were identified (ApoA1, ApoE, ApoC3, GNB3, FTO, PON-1, ET(A), EDNRA, F13, ITGB3, PAI-1, VEGF, ACE, AGT, AGTR1), contributing in metabolic processes, the hemostatic system, endothelial function, and regulation of the renin–angiotensin–aldosterone system and associated with the development of chronic heart failure. The most significant contribution of these genes in the development of regulatory and structural disorders characteristic of the pathogenetic phenotype of chronic heart failure has been proven. The results are ambiguous. Thus, in individuals who have a polymorphic gene variant in their genotype associated with the risk of developing a disease, the possibility of its manifestation is considerably higher; however, this does not confirm the development of the disease. Moreover, a correlation was noted between ejection fraction in patients with chronic heart failure and gene polymorphisms associated with renin–angiotensin–aldosterone system dysfunction and metabolic cascade. Chronic heart failure is a polygenic disease. Hence, this allows for further research into groups of coordinately functioning genes that are part of genetic regulatory networks, enabling a more complete understanding of the etiology and pathophysiological mechanisms of this nosology with the aim of subsequent early identification of individuals belonging to the risk group and the creation of a set of measures for individual prevention diseases. We believe that the development of chronic heart failure with low ejection fraction is primarily responsible for gene polymorphisms associated with disorders of the renin–angiotensin–aldosterone system and for the development of chronic heart failure with preserved ejection fraction — gene polymorphisms associated with metabolic cascade disorders.

Polymorphisms in the Dopaminergic Receptor D3 Gene Correlate with Disease Progression Rate in Relapsing-Remitting Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a common chronic autoimmune disease of the central nervous system. In MS, disability progresses unpredictably. Dopamine (DA) is a modulator of immune functions, and compelling evidence supports its involvement in both pathogenesis and treatment of MS. Although single nucleotide polymorphisms (SNPs) in dopaminergic receptor (DR) genes have been extensively studied, their role in MS progression remains unexplored. Therefore, the aim of this explorative study is to investigate the potential association between functional SNPs in DR genes and MS progression. Caucasian patients with relapsing-remitting (RR) MS were enrolled, and disease progression assessed by the Multiple Sclerosis Severity Score (MSSS). Out of the 59 RRMS patients enrolled, those with the G/G genotype for rs6280 and rs1800828 SNPs in DRD3 showed significantly higher MSSSs compared to those with ancestral and heterozygous genotypes. If confirmed in a larger prospective study, the reported findings could contribute to a better understanding of MS pathophysiological mechanisms, opening the way for the identification of marker(s) for assessing MS progression as well as novel therapeutic strategies. A personalized approach to MS management has the potential to improve the overall well-being of MS patients and alleviate the burden on their caregivers.

Probing the Association of EPCAM Gene Single Nucleotide Polymorphisms with Genetic Disorders

Background: Mutations in the EPCAM gene can lead to the absence of this protein from epithelial cell surfaces, resulting in various disorders such as Lynch syndrome, congenital tufting enteropathy, cholestatic liver disease, and a range of cancers. Therefore, analyzing mutations in this gene is significant from diagnostic and prognostic perspectives. This study examines the effect of various mutations in the EPCAM gene on different attributes of the encoded protein. Objective: The objective of this study was to analyze the impact of single nucleotide polymorphisms (SNPs) in the EPCAM gene on the protein's structural and functional properties, aiming to identify potential predictive biomarkers for EPCAM-associated diseases. Methods: The study focused on the EPCAM gene transcript EPCAM-201, with ENSEMBL transcript ID ENST00000263735.9 and NCBI Reference Sequence NM_002354.3. The gene sequence was retrieved from the NCBI database, and SNPs were selected from the ENSEMBL database. A total of 21 variants were selected to design twenty-one cases. These cases were analyzed using various bioinformatics tools, including EXPASY for nucleotide sequence translation, HOPE server for 3D structure analysis, CELLO2GO for sub-cellular localization, and PROTPARAM for physicochemical parameter prediction. Data collection adhered to the principles outlined in the Declaration of Helsinki. Statistical analyses were conducted using SPSS version 25, with descriptive statistics and appropriate tests to determine the significance of the observed variations. Results: Analysis revealed that sixteen SNPs, namely rs994384264, rs1280024892, rs1294456118, rs149875996, rs767811939, rs750826481, rs754293486, rs748292053, rs1460762372, rs1294456118, rs149875996, rs754293486, rs748292053, rs771063031, rs776854951, and rs267606785, significantly altered the 3D structure of mutated proteins. Among these SNPs, rs994384264 and rs149875996 also affected the sub-cellular localization of proteins. Additionally, four mutations—rs1280024892, rs1460762372, rs987919056, and rs771029207—caused alterations in extinction coefficient, isoelectric point (pI), aliphatic index, and instability index. Conclusion: These single nucleotide variants might serve as predictive biomarkers for EPCAM-associated diseases, aiding in diagnosis and prognosis. Variants predicted in this study require further experimental validation to confirm their clinical utility.

Early Detection of Candidate Genes for Body Weight in Indonesian Cattle Breeds with Genome-Wide Association Study (GWAS)

Abstract Genome-wide association study (GWAS) was used to detect candidate genes affecting economic traits in livestock. GWAS can detect single nucleotide polymorphisms (SNPs) in all chromosome regions. This study aimed to determine the genetic markers for body weight by GWAS in native cattle breeds of Indonesia. The Illumina Bovine 50K BeadChip was used to determine the candidate genes in three mixed-sex Indonesian cattle breeds of Bali (16 animals), Madura (16 animals), and Ongole grade (13 animals). All animals were raised at the Pasuruan Regency, East Java, Indonesia breeding station. The GWAS was performed in pooled sample of animals (45 animals) with the general linear model (GLM) method using SNP markers with minimum allele frequency (MAF) values more than 0.05 by TASSEL 5.0. software. Therefore, the body weight of cattle at 1 to 3 years of age was collected for each animal for computing Manhattan plot graphics. This research found that SUGT1, SF3A3, and DSCAM genes were detected as potential genetic markers for body weight in cattle breeds of Indonesia. The SUGT1 and DSCAM genes were monomorphic in Bali cattle (Bos javanicus). In addition, both genes were significantly associated (P&lt;0.05) with the body weight of Ongole-grade cattle (Bos indicus) at three years of age. However, the SF3A3 gene was significantly (P&lt;0.05) associated with body weight of Madura cattle (Bos indicus) at 2 and 3 years of age. In conclusion, the GWAS of pool animals reveals three candidate genes significantly associated with body weight in many cattle breeds of Indonesia. Further study to detect SNPs in candidate genes with sequencing method is essential to apply these findings practically.

A multiplex SNaPshot assay for the detection of single nucleotide polymorphism associated with clinical severity of enterovirus infections

Non-polio enterovirus infections are known to cause a variety of diseases and neurological complications. It is also known that the severity of these diseases largely differs among individuals with different genotypes and alleles. The Single Nucleotide Polymorphisms (SNPs) within specific genes have a considerable effect on the immune response to enteroviruses and on the outcome of disease, leading to variations in complications and infection susceptibility. Knowing the distribution of such SNPs can be valuable for individual case management and studying epidemiological parameters of enterovirus infections. In this feasibility study, a multiplex version of the primer extension-based technique called the SNaPshot Assay has been developed to examine SNPs in various relevant genes for predicting the clinical severity of enterovirus infections. It is already established that this technique is precise, consistent, scalable, and likely to exhibit high throughput. The multiplex SNaPshot can investigate multiple genetic susceptibility markers simultaneously, and the assay can be used to identify vulnerable populations, understand the epidemiology of infections, and manage the outbreaks of enteroviruses. Based on the literature, 15 SNPs were identified which are suspected for higher susceptibility to the worst outcomes after enterovirus infection and the assay was developed. Blood samples of 100 healthy volunteers were collected and tested for assay feasibility as well as to know the proportions of 15 selected SNPs. After the analysis, seven SNPs have been identified and suggested to be considered for future assays. Based on the pilot test results, it appears that positivity for any three out of the identified seven SNPs might indicate a higher risk, and future studies correlated with clinical studies among patients with and without severe diseases utilizing this assay will provide robust parameters to determine at-risk individuals more accurately.

The impact of SLCO1B1 single nucleotide polymorphism and non-genetic factors on statin-induced myopathy

Abstract Funding Acknowledgements None. Background Statins, also known as HMG CoA Reductase Inhibitors, are a class of drugs considered the drug of choice for treating hypercholesterolemia. Statins are well tolerated; however, they may cause severe myopathy in 20% to 30% of patients, due to the individual variation regarding its efficacy and related adverse effects. Of these, comes the Single Nucleotide Polymorphism (SNP) T521C of the SLCO1B1 gene that encodes the protein involved in the trafficking of statins from the blood to hepatocytes which is called Organic Anion Transport Protein 1B1 (OATP1B1). The T521C single nucleotide polymorphism (SNP) results in a substitute of valine with alanine resulting in a decreased or lack of functional protein. Purpose The aim is to determine the frequency of the high-risk C allele and to define its impact on statin-induced myopathy in Syrian patients on statins. In addition to the non-genetic factors that may affect the ability to develop statin-induced myopathy. Methods This was an observational case-control study that had ethical approval from Damascus University (No.433/ 2020). The case group included 44 patients on statins who experienced myopathy, 18 patients who had increased creatinine kinase levels (CK), and 26 patients with normal CK levels, while the control group encompassed 56 patients who were taking statins and had no muscular adverse events. The DNA was extracted from each sample and then genotyped using standard sequencing of specific PCR products using a specific pair of primers. Results The age of patients in the case arm ranged between 27 and 84 years with an average ± SD of (58.2 ± 12.7 years), 70% of them were males. In comparison with (53.34 ± 12.4 years) in the control arm, 66% of them were males without a statistically significant differences (p=0.672, 0.057) respectively. The statin type and dose have a statistically non-significant effect, the average statin dose in the case arm and the control arm was 26.02 mg and 31.27 mg respectively (p=0.072). While the statin type treatment varied as 59% used atorvastatin and 39% used rosuvastatin in the case group compared with 71% used atorvastatin and 27% used rosuvastatin in the control group, without a statistically significant difference (p=0.252). The frequency of the C allele reaches 19.3% and is distributed in three genotypes: wild-type TT (68%), heterozygote TC (25%), and homozygote CC (7%) in the case arm, while it does not exceed 8% in the control arm with the absence of the CC genotype. Only a statistically significant difference was found in the frequency of the CC genotype between these two groups (p=0.047). Conclusion Our study is the first to identify the frequency of the 521T&amp;gt;C SNP of the SLCO1B1 gene in Syrian patients taking statins. Our data reveals a high prevalence of risk allele C in the patients who suffer from statin-induced myopathy with a statically significant difference from the control arm (p=0.026).

Phenotypic and Genetic Diversity of Xanthomonads Isolated from Pepper (Capsicum spp.) in Taiwan from 1989 to 2019.

Bacterial spot caused by Xanthomonas spp. is an economically important disease of pepper causing significant yield losses in Taiwan. Monitoring the pathogen population on a continuous basis is necessary for developing disease management strategies. We analyzed a collection of xanthomonad strains isolated from pepper in Taiwan between 1989 and 2019. Among the sequenced genomes, 65 were identified as Xanthomonas euvesicatoria, and 10 were X. perforans. Thirty-five X. euvesicatoria and 10 X. perforans strains were copper tolerant, whereas only four X. euvesicatoria and none of the X. perforans strains were tolerant to streptomycin. Nine X. euvesicatoria strains were amylolytic, which is considered an unusual characteristic for X. euvesicatoria. Bayesian analysis of the population structure based on core gene single-nucleotide polymorphisms clustered the strains into five clusters for X. euvesicatoria and three clusters for X.perforans. One X. perforans cluster, designated as TP-2019, appears to be a novel genetic cluster based on core genes, accessory gene content, and effector profile. This knowledge of pathogen diversity with whole genomic information will be useful in future comparative studies and in improving breeding programs to develop disease-resistant cultivars and other disease management options.

The First Genetic Characterization of the SPRN Gene in Pekin Ducks (Anas platyrhynchos domesticus).

Prion diseases are fatal neurodegenerative disorders characterized by an accumulation of misfolded prion protein (PrPSc) in brain tissues. The shadow of prion protein (Sho) encoded by the shadow of prion protein gene (SPRN) is involved in prion disease progress. The interaction between Sho and PrP accelerates the PrPSc conversion rate while the SPRN gene polymorphisms have been associated with prion disease susceptibility in several species. Until now, the SPRN gene has not been investigated in ducks. We identified the duck SPRN gene sequence and investigated the genetic polymorphisms of 184 Pekin ducks. We compared the duck SPRN nucleotide sequence and the duck Sho protein amino acid sequence with those of several other species. Finally, we predicted the duck Sho protein structure and the effects of non-synonymous single nucleotide polymorphisms (SNPs) using computational programs. We were the first to report the Pekin duck SPRN gene sequence. The duck Sho protein sequence showed 100% identity compared with the chicken Sho protein sequence. We found 27 novel SNPs in the duck SPRN gene. Four amino acid substitutions were predicted to affect the hydrogen bond distribution in the duck Sho protein structure. Although MutPred2 and SNPs&GO predicted that all non-synonymous polymorphisms were neutral or benign, SIFT predicted that four variants, A22T, G49D, A68T, and M105I, were deleterious. To the best of our knowledge, this is the first report about the genetic and structural characteristics of the duck SPRN gene.