Single Nucleotide Polymorphism Analysis Research Articles

Genomic analysis of Salmonella Heidelberg isolated from the Brazilian poultry farms.

The rapid expansion of broiler chicken production in Brazil has presented significant sanitation challenges within the poultry industry. Among these challenges, Salmonella enterica subsp. enterica serotype Heidelberg stands as a contributor to global salmonellosis outbreaks. This study analyzed 13 draft genomes of Salmonella Heidelberg isolated from the pre-slaughter broiler chickens farms in Brazil. By conducting in silico analysis of these genomes, the study investigated genome similarity based on single nucleotide polymorphisms (SNPs) and identified genes encoding resistance to antimicrobials, sanitizers, and virulence factors. Furthermore, mobile genetic elements (MGE) were identified to assess their potential role in propagating genes through horizontal gene transfer. A risk classification was also applied based on the resistomes. The genomes revealed a high prevalence of genes conferring resistance to aminoglycosides, fosfomycin, sulfonamides, tetracycline, and genes linked to quaternary ammonium resistance. The study also uncovered six Salmonella pathogenicity islands (SPI) and over 100 genes encoding virulence factors. The association of MGE with antibiotic-resistant genes sul2 and blaCMY-2 raised concerns about the potential transfer to other bacteria, posing a substantial risk for spreading resistance mechanisms according to established risk protocols. Additionally, SNP analysis indicated close phylogenetic relationships among some isolates, suggesting a common origin. This study enhances our understanding of Salmonella Heidelberg strains by identifying key risk factors for transmission and revealing the association between resistance genes and MGEs. This insight provides a foundation for developing and implementing effective control, monitoring, and treatment strategies in the poultry industry.

Genome resource announcement for emerging pathogen Bipolaris gigantea, isolated from Microstegium vimineum

Bipolaris gigantea is a pathogen of the invasive grass Microstegium vimineum and an emerging pathogen of other hosts such as hemp and barley, causing characteristic eyespot foliar lesions. The fungus is characterized by long pale hyaline conidia measuring about 300 to 350 μm. Previously, this pathogen was classified in the Drechslera genus, and recently reassigned as Bipolaris based on molecular identification. Here, we generated a high-quality draft genome sequence of B. gigantea isolate BGF using long and short read DNA sequencing. The assembled genome, 30.23 Mb in size with a BUSCO completeness score of 98.4%, exhibited synteny with the common grass pathogen B. sorokiniana isolate 10943. Average nucleotide identity (ANI) and single nucleotide polymorphisms (SNP) analyses revealed high sequence identity with B. gigantea isolates from Cannabis sativa fields in Kentucky. This research provides a genomic resource that will contribute to future studies to understand the host range evolution and pathogenicity of this novel pathogen.

Single nucleotide polymorphism discrimination and genotyping based on cascade strand displacement reaction mediated label-free Cas12a system

Single nucleotide polymorphism (SNP) discrimination plays an important role in precision medicine by providing insights into an individual’s genetic information. The low abundance of the mutant target and the minimal impact caused by SNP on the whole nucleic acid sequence remain a challenge during discrimination. Herein, a cascade strand displacement reaction mediated label-free Cas12a sensing platform is established for SNP analysis. Split G-quadruplex (G4) motif is recruited as label-free signal output for Cas12a sensing system, and hence overcomes relying of fluorescence labeled substrates like conventional method. The established platform exhibits excellent single base difference discrimination ability attributing to the cascade strand displacement process, during which, single-base mismatch will affect the strand-exchange rate significantly. The limit of detection reaches 1 copy / test after integration with isothermal preamplification. The proposed method can discriminate as low as 0.1 % single base variation and perform robustly in biological matrixes. Human buccal swab samples are successfully genotyped with high accuracy.

Analysis of Single Nucleotide Polymorphisms of Liver X Receptor Alpha (LXR-α) Gene in Diabetic Kidney Disease.

Introduction Genetic factors significantly contribute to the progression of diabetic kidney disease (DKD), which is one of the world's most common causes of chronic kidney disease (CKD). Inflammation, glucose homeostasis, and lipid metabolism are all significantly influenced by the liver X receptor alpha (LXR-α) gene. Single nucleotide polymorphisms in the liver X receptor alpha gene may result in the altered function of the gene, making the individual susceptible to DKD. The purpose of this article is to examine the frequency of expression of single nucleotide polymorphisms (SNPs) in exon 7 of the LXR-α gene in people with type 2 diabetes (T2DM) and DKD. Gaining an understanding of these genetic differences could improve risk assessmentand therapy approaches while providing fresh perspectives on the molecular mechanisms underlying DKD. Aims and objectives To identify specific SNPs in the LXR-αgene in T2DMand DKD patients. Methods The study was conducted between May 2022 and May 2023 and it involved 120 T2DM and 120 DKD patients. All the clinical history of the study participants were recorded. Blood samples were collected from the participants and genomic DNA was isolated and was followed by polymerase chain reaction (PCR) using exon 7 specified primers of LXR-α gene. To find mutations in the LXR-α gene, the PCR products were subsequently analyzed using the capillary-based Sanger sequencing technique. Results A total of seven SNPs were detected in T2DM patients, and 20 SNPs were detected in DKD patients. SNP rs7120118 was found with the highest frequency of 100 (83.33%) in T2DM patients and 80 (66.66%) in DKD patients. SNP rs1956299169 was found to have the second highest frequency of 60 (50%) among T2DM patients and SNP rs1252683195 was found to have a frequency of 20 (16.7%). Othercommon SNPs were rs1956299169, with 40 (33.33%) in DKD and 60 (50%) in T2DM, and rs12574081, with 20 (16.71%) in T2DM and 10 (8.33%) in T2DM. Conclusion The study detects the highest and the most common SNP rs7120118, which may be associated with T2DM and DKD. Thereby, ithelps to conduct furtherassociation studies with larger populations and to diagnose the disease.

Single nucleotide polymorphism (SNP) analysis reveals ancestry and genetic diversity of cultivated and wild grapevines in Croatia

BackgroundCroatia is a geographically small country with a remarkable diversity of cultivated and spontaneous grapevines. Local germplasm has been characterised by microsatellite markers, but a detailed analysis based on single nucleotide polymorphisms (SNPs) is still lacking. Here we characterize the genetic diversity of 149 accessions from three germplasm repositories and four natural sites using 516,101 SNPs to identify complete parent-offspring trios and their relations with spontaneous populations, offering a proof-of-concept for the use of reduced-representation genome sequencing in population genetics and genome-wide association studies (GWAS).ResultsPrincipal component analysis revealed a clear discontinuity between cultivated (V. vinifera subsp. sativa) and spontaneous grapevines, supporting the notion that the latter represent local populations of the wild progenitor (V. vinifera subsp. sylvestris). ADMIXTURE identified three ancestry components. Two sativa components are alternatively predominant in cultivars grown either in northern Adriatic Croatia and Continental Croatia or in Dalmatia (i.e. central and southern Adriatic Croatia). A sylvestris component, which is predominant in accessions from spontaneous populations, is a minor ancestry component in cultivated accessions. TREEMIX provided evidence of unidirectional migration from the vineyards to natural sites, suggesting that gene flow has gone preferentially from the introduced domesticated germplasm into local wild populations rather than vice versa. Identity-by-descent analysis indicated an extensive kinship network, including 14 complete parent-offspring trios, involving only cultivated accessions, six full-sibling relationships and invalidated a presumed pedigree of one of the most important varieties in Croatia, ‘Plavac Mali’. Despite this strong population structure, significant association was found between 143 SNPs and berry skin colour and between 2 SNPs and leaf hairiness, across two previously known genomic regions.ConclusionsThe clear genetic separation between Croatian cultivars and sylvestris ruled out the hypothesis that those cultivars originated from local domestication events. On the other hand, the evidence of a crop-to-wild gene flow signals the need for an urgent adoption of conservation strategies that preserve the residual genetic integrity of wild relatives. The use of this reduced-representation genome sequencing protocol in grapevine enables an accurate pedigree reconstruction and can be recommended for GWAS experiments.

Association between ATG16L1 rs2241880(T300A) and rs4663421 and ANCA‑associated vasculitis in the Guangxi population of China: Propensity score matching analysis.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a rare autoimmune disease with an unclear pathogenesis. The present study investigated the associations between autophagy-related protein 16-like 1 (ATG16L1) rs2241880(T300A) and rs4663421 and AAV. A total of 177 patients with AAV and 216 healthy controls were included. Propensity score matching was used to match the two groups of subjects in terms of sex, age and ethnicity. Analyses of the relationships between these genetic polymorphisms and AAV susceptibility, including comparisons of allele and genotype frequency distribution, linkage disequilibrium analysis and analysis of single nucleotide polymorphism (SNP) interactions between two loci were performed. The association between the loci and laboratory test results and renal pathology were also analysed. A total of 154 pairs of patients with AAV and healthy controls was successfully matched. Neither polymorphism was associated with AAV susceptibility. However, SNP interaction in the model constructed with the two loci was statistically significant (P=0.018), and the combination of the AA genotype of rs2241880(T300A) and GG genotype of rs4663421 was associated the highest disease risk. The differences in the Birmingham Vasculitis Activity Score (BVAS), C-reactive protein (CRP) levels and 24-h urine protein level between patients with the rs2241880(T300A) AA + AG genotypes and the GG genotype were statistically significant (P<0.05). Furthermore, significant differences in the severity of glomerulosclerosis and global sclerosis were detected between individuals with the AA + AG genotype and those with the GG genotype at the rs2241880(T300A) locus (P<0.05). Similarly, there were statistically significant differences in degree of segmental sclerosis between individuals with CC + CG genotypes and those with GG genotypes at the rs2243421 locus (P<0.05). In summary, the single gene polymorphisms of these loci were not associated with genetic susceptibility to AAV. However, SNP interactions may serve a role in the risk of AAV. The rs2241880(T300A) polymorphism may be associated with BVAS, CRP levels and 24-h urine protein level in AAV. These SNPs may be associated with glomerulosclerosis and segmental sclerosis.

Chromatin interaction maps of human arterioles reveal new mechanisms for the genetic regulation of blood pressure.

Arterioles are small blood vessels located just upstream of capillaries in nearly all tissues. The constriction and dilation of arterioles regulate tissue perfusion and are primary determinants of systemic blood pressure (BP). Abnormalities in arterioles are central to the development of major diseases such as hypertension, stroke, and microvascular complications of diabetes. Despite the broad and essential role of arterioles in physiology and disease, current knowledge of the functional genomics of arterioles is largely absent, partly because it is challenging to obtain and analyze human arteriole samples. Here, we report extensive maps of chromatin interactions, single-cell expression, and other molecular features in human arterioles and uncover new mechanisms linking human genetic variants to gene expression in vascular cells and the development of hypertension. Compared to large arteries, arterioles exhibited a higher proportion of pericytes which were strongly associated with BP traits. BP-associated single nucleotide polymorphisms (SNPs) were enriched in chromatin interaction regions in arterioles, particularly through enhancer SNP-promoter interactions, which were further linked to gene expression specificity across tissue components and cell types. Using genomic editing in animal models and human induced pluripotent stem cells, we discovered novel mechanisms linking BP-associated noncoding SNP rs1882961 to gene expression through long-range chromatin contacts and revealed remarkable effects of a 4-bp noncoding genomic segment on hypertension in vivo. We anticipate that our rich data and findings will advance the study of the numerous diseases involving arterioles. Moreover, our approach of integrating chromatin interaction mapping in trait-relevant tissues with SNP analysis and in vivo and in vitro genome editing can be applied broadly to bridge the critical gap between genetic discoveries and physiological understanding.

Investigating the Association between Catechol-O-Methyltransferase Gene Activity and Pain Perception in South African Patients with Different Temporomandibular Disorders Diagnoses.

Background: Temporomandibular disorders (TMD) affect a significant portion of the population, with profound psychological, behavioral, and social repercussions. Recent investigations have explored the genetic basis underlying pain perception in individuals with TMD, aiming to elucidate the role of specific genetic factors in modulating the condition. Notably, genetic variations have been implicated in the pathogenesis of TMD, particularly genes involved in pain perception pathways. One of the primary candidates is the Catechol-O-Methyltransferase (COMT) gene, which plays a crucial role in the catecholaminergic system and has been associated with the regulation of nociceptive processes. This study seeks to investigate the correlation between COMT gene activity and pain perception among South African patients diagnosed with varying forms of TMD. Methodology: In this study, a total of 196 participants were enrolled, comprising 97 patients diagnosed with TMD and 99 control participants. The control group was meticulously matched with the TMD group for age, gender, and ethnicity. Data collection involved clinical and radiological investigations, and saliva sampling. The English version of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I was utilized to evaluate all TMD participants, focusing on standard diagnostic measures based on clinical signs and symptoms of TMD, which primarily describe common physical manifestations of the disorder. Genomic DNA was extracted from saliva samples, enabling the analysis of single-nucleotide polymorphisms (SNPs) in the COMT gene, specifically targeting polymorphisms rs165774, rs9332377, rs6269, rs4646310, rs165656, and rs4680. Results: The current study demonstrated a pronounced gender disparity, with 80.41% of the participants being female and 19.59% male, suggesting that women in South Africa either exhibit a higher susceptibility to TMD or are more likely to seek treatment for the condition compared to men. The highest prevalence of TMD was observed in the white population (58.76%). Additionally, over 65% of TMD patients were diagnosed with at least two Axis I diagnoses, a figure that increased to 89% for those diagnosed with three Axis I diagnoses. The findings further indicated significant associations between several single-nucleotide polymorphisms (SNPs) in the Catechol-O-Methyltransferase (COMT) gene-specifically rs165656, rs9332377, rs4646310, rs6269, and rs165774-and both TMD and TMD-related pain. Myofascial pain with referral and myalgia showed a strong association with the COMT SNPs rs9332377 and rs4646310. Furthermore, COMT SNP rs4646310 was also associated with disability related to TMD. Conclusions: This study substantiates the hypothesis that pain is prevalent in a considerable proportion of patients affected by TMD. Furthermore, the findings reveal a significant association between COMT gene activity and pain perception in South African patients diagnosed with TMD.

Single nucleotide polymorphism (SNP) characterisation of mouse inbred strains bred at MRC-National Institute for Medical Research.

Inbred mouse strains have long proved useful as tools for biomedical research. They remove the effects of genetic background as an experimental variable. Within all mouse colonies, genetic drift is a recognised phenomenon and monitoring and documenting changes is important for experimental design and consistency. This communication documents the initial characterisation through SNP analysis of the inbred mouse strains bred and used at the time at the Medical Research Council National Institute for Medical Research (MRC-NIMR), Mill Hill, now The Crick Institute. These inbred strains were part of the foundation colonies for the many genetically modified mouse strains made at Mill Hill. We found small genetic changes in four of the nine inbred strains. Although phenotypic differences have not yet been found between the NIMR and the correspondent parental strains, I cannot discard that these may arise or have already arisen. This work has also authenticated the 129/SvJEvNimr-Gpi1c strain that was widely used at MRC-NIMR for gene targeting. All these inbred strains have been renamed according to The International Committee on Standardized Genetic Nomenclature for Mice.

DNA polymorphisms in inflammatory and endocrine signals linked to frailty are also associated with obesity: data from the FRASNET cohort.

Obesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity. We aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures. SNPs related to frailty and linked to the renin-angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21-23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults. Frailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies.

First report on whole genome sequencing and comparative genomics of Salmonella enterica serovar Abortusequi isolated from Donkey in India.

Salmonella enterica subspecies enterica serovar Abortusequi (S. Abortusequi) is a leading cause of abortion in equines that hinders the rapid growth of equine industry. S. Abortusequi infection in equids has re-emerged over last ten years. In the present study, S. Abortusequi was isolated and characterized from donkeys during an abortion storm in the southern peninsular region of India. Further, whole genome sequencing and phylogenomic analysis revealed that the present isolate was clustered among S. Abortusequi clade. The core genome MLST (cgMLST) analysis based on hierarchical clustering and single nucleotide polymorphism (SNP) core-genome dendrogram of the present isolate against 10S. Abortusequi isolates revealed that the present isolate established a distinct clade compared to all previously reported isolates. A comparison of cgMLST and SNP analyses revealed the same clustering concordance between isolates. In addition, comparative genomics and phylogenetic analysis was carried out with six S. Abortusequi serovars showed a higher number of core genes than accessory genes. Further, comparative analysis of phenotype and genotype antimicrobial resistance revealed a concordance of 32% and discordance of 68% respectively.

Testing source elevation versus genotype as predictors of sugar pine performance in a post‐fire restoration planting

AbstractClimate change is motivating a reassessment of how seeds are selected for reforestation, as rapid environmental change can lead to local maladaptation in trees. Genetic association studies and past seed source climate both have the potential to help identify appropriate planting stock, but these techniques have not been compared and tested as part of an operational planting program. In this study, we combined an analysis of single nucleotide polymorphisms (SNPs) associated with environmental gradients in sugar pine (Pinus lambertiana) with an analysis of post‐fire seedling survival and growth in a restoration experiment. Our genotype–environment association (GEA) tests of 92 individuals from varying climates within CA revealed 829 SNPs (out of 300,604) with significant association with climate gradients, especially April snowpack. Of these, 323 either had annotations that suggested potential functional importance or were identified by two different methods. We then built Bayesian models of survival and growth for all seedlings in a separate post‐fire planting experiment, to test the relative predictive ability of source elevation (a common proxy for source climate) versus the proportion of seedling alleles expected to be locally advantageous based on GEA. Across three sites within the King Fire scar in Eldorado National Forest in 2017, 2018, and 2019, 1774 seedlings were planted. Of these, 206 had enough green needles in 2020 to allow sample collection, and 161 were successfully genotyped. We found that source elevation was generally better at predicting seedling performance than genotype indices, perhaps because of the limited scope of the association analysis. Seed sources from 500 to 1800 ft (152.4–548.6 m) lower in elevation, and one seed zone further south generally performed as well or better than local seed sources. This result, and those of similar previous studies, suggest that “climate matching” using past climate information for existing seed sourcing units is a reasonable starting point for finding seedlings suited to already‐altered planting site climate conditions. However, further tests with more extensive genomic and performance data may improve the utility of genotype information for seed selection.

Transcriptional and genetic characteristic of chimera pea generation via double ethyl methanesulfonate-induced mutation revealed by transcription analysis.

Ethyl methanesulfonate (EMS)-induced mutagenesis is a prominent method for generating plant mutants, often resulting in chimera plants; however, their transcriptional and genetic characteristic remain elusive. In this investigation, chimera pea (Pisum sativum L.) specimens, labeled GY1 and GY2, exhibiting a distinctive phenotype with yellow and green leaves were meticulously cultivated via sequential double EMS mutagenesis. The observed color disparity between the yellow and green leaves was attributed to a significant reduction in chlorophyll content coupled with heightened lutein levels in both chimeric variants. Transcriptome profiling revealed the enrichment of differentially expressed genes in both GY1 and GY2, specifically implicating Kyoto Encyclopedia of Genes and Genomes pathways linked to amino acid biosynthesis and ribosome development, alongside Gene Ontology (GO) biological processes linked with stress response mechanisms. Few structural genes associated with chlorophyll and lutein biosynthesis exhibited discernible differential expression. Despite these functional similarities, distinctive nuances were evident between specimens, with GY1 exhibiting enrichment in GO pathways related to chloroplast development and GY2 showing enrichment for ribosome development pathways. Single-nucleotide polymorphism (SNP) analysis uncovered a shared pool of 599 and 598 polymorphisms in the yellow and green leaves of GY1 and GY2, respectively, likely stemming from the initial EMS mutagenesis step. Further investigation revealed an increased number of unique SNPs in the yellow leaves following the second EMS application, whereas the green leaves exhibited sparse and unique SNP occurrences, suggestive of potential evasion from secondary mutagenesis. This inherent genetic variability underpins the mechanism underlying the formation of chimera plants. Predominant base mutations induced by EMS were characterized by G/A and C/T transitions, constituting 74.1% of the total mutations, aligning with established EMS mutation induction paradigms. Notably, genes encoding the eukaryotic translation initiation factor eIIso4G and the ubiquitin ligase RKP, known to modulate leaf color in model plants, harbored two SNPs in the yellow leaves of both GY1 and GY2, implicating their putative role in the yellow leaf phenotype. Collectively, this study provides novel insights into the transcriptional and genetic characteristics of chimera plants via EMS-induced mutagenesis.

Investigation of the outbreak of Clostridium perfringens using single nucleotide polymorphism analysis for genotyping in Toyama, Japan, 2023.

Clostridium perfringens, which produces C. perfringens enterotoxin (CPE), is a major causative agent of food poisoning owing to its gastrointestinal symptoms. Genotyping is important for identifying the etiological agent in outbreaks of C. perfringens. We attempted to genotype strains isolated from an outbreak of food poisoning in Toyama in 2023 using single nucleotide polymorphism (SNP) analysis. The strains of C. perfringens were isolated from a piece of curry food consumed by all patients and from the feces of the patients and employees. The cpe gene was detected in isolates from patients and curry food. The cpe-negative isolates were found in patients who consumed curry foods and in employees. The results of the SNP analysis suggest that the patient- and curry-derived isolates were likely from the same source but were unlikely to be related to the employee-derived isolates. The results of the SNP and pulsed-field gel electrophoresis (PFGE) analyses were consistent, indicating that the patient- and curry-derived isolates came from the same source. SNP analysis, a whole-genome-based genotyping method, is a promising alternative to the traditional PFGE method. Further studies are needed to accumulate more experience with genotyping using SNP analysis for the epidemiological investigation of outbreaks of C. perfringens.

Prevalence of the cefazolin inoculum effect (CzIE) in nasal colonizing methicillin-susceptible Staphylococcus aureus in patients from intensive care units in Colombia and use of a modified rapid nitrocefin test for detection.

The cefazolin inoculum effect (CzIE) has been associated with poor clinical outcomes in patients with methicillin-susceptible Staphylococcus aureus (MSSA) infections. We aimed to investigate the point prevalence of the CzIE among nasal colonizing MSSA isolates from ICU patients in a multicenter study in Colombia (2019-2023). Patients underwent nasal swabs to assess for S. aureus colonization on admission to the ICU, and some individuals had follow-up swabs. We performed cefazolin MIC by broth microdilution using standard and high inoculum and developed a modified nitrocefin-based rapid test to detect the CzIE. Whole-genome sequencing was carried out to characterize BlaZ types and allotypes, phylogenomics, and Agr-typing. A total of 352 patients were included; 46/352 (13%) patients were colonized with S. aureus and 22% (10/46) and 78% (36/46) with MRSA and MSSA, respectively. Among 36 patients who contributed with 43 MSSA colonizing isolates, 21/36 (58%) had MSSA exhibiting the CzIE. BlaZ type A and BlaZ-2 were the predominant type and allotype in 56% and 52%, respectively. MSSA belonging to CC30 were highly associated with the CzIE, and single-nucleotide polymorphism (SNP) analyses supported possible transmission of MSSA exhibiting the CzIE among some patients of the same unit. The modified nitrocefin rapid test had 100%, 94.4%, and 97.7% sensitivity, specificity, and accuracy, respectively. We found a high point prevalence of the CzIE in MSSA colonizing the nares of critically ill patients in Colombia. A modified rapid test was highly accurate in detecting the CzIE in this patient population.

SNP Markers: Analysis of Genetic Diversity and Identification of Genomic Regions in Pantaneiro Sheep and Texel Sheep Under Natural Selection.

Sheep farming is growing substantially in Brazil, driven by the increasing demand for sheep meat. This rising demand has heightened the focus on sheep, making them the subject of numerous studies, including those centered on genetic analysis. A notable research area involves Pantaneiro sheep, which are indigenous to the Pantanal region of Mato Grosso do Sul and other locations. These sheep are of particular interest due to their adaptation to the unique environmental conditions of the Pantanal, a floodplain characterized by its distinctive climatic and ecological features. This study primarily aimed to conduct a comprehensive genomic analysis of Pantanal sheep subjected to natural selection within the Pantanal region and compare different sample herds using methodological approaches. Genomic analysis was performed to examine genetic diversity and structure via GGP50K single nucleotide polymorphism (SNP) analysis. A sample of 192 adult sheep over 4 years old was categorized into seven populations based on location: Six populations comprised Pantaneiro sheep with one Texel sheep population. Outlier SNPs were assessed to pinpoint regions under natural selection, with comparisons between the Pantaneiro and the commercial Texel breeds. All data analyses were conducted using the R programming language, employing specialized genetic analysis packages. These outlier SNPs were detected using three methodologies, PCAdapt, OutFLANK, and FDIST2/fsthet, with false discovery rate (FDR) corrections applied to ensure result accuracy. Each method was evaluated, and the genes associated with the identified SNPs were cross-referenced with the most recent sheep genome database, focusing specifically on genes with known phenotypic traits. Analysis of a sample comprising 192 adult individuals revealed greater genetic variability within the Pantaneiro breed than the Texel breed, highlighting the adaptation of the Pantaneiro breed to the unique Pantanal environment. Conversely, the Texel breed exhibited significantly higher levels of inbreeding, attributed to its controlled breeding practices. Outlier SNPs were detected with notable variation across different methodologies, underscoring the importance of FDR correction in ensuring the reliability and concentration of identified outliers. These outlier SNPs facilitated the identification of genes associated with key phenotypic traits, including hair growth, tissue regeneration, pigmentation regulation, and muscle capacity. The integrated analysis of methodologies demonstrated significant efficiency in elucidating the genomic landscape of Pantanal sheep, highlighting the genetic richness inherent in sheep from the Pantanal region of Mato Grosso do Sul. The techniques employed effectively identified outlier SNPs associated with phenotypically relevant genes. These findings, which reveal greater genetic variability and adaptability, underscore the potential of these animals for future research and their significance within Brazilian sheep farming. The Texel breed served as a valuable comparative group, illustrating the limited genetic variability in highly controlled breeding environments.

DNA Microarray Technology Principles and Applications in Genetic Research

DNA microarray technology, a high-throughput gene analysis tool, has played a crucial role in genetic research. This paper explores the fundamental principles of DNA microarray technology, including its working mechanisms, sample preparation, and types of chips. It emphasizes the applications of DNA microarrays in detecting genetic variations and analyzing gene expression profiles, illustrating examples in single nucleotide polymorphism (SNP) analysis and genome-wide association studies (GWAS). The paper also discusses the technical details of high-throughput gene expression measurement and differential expression analysis. Additionally, it analyzes the main advantages of DNA microarray technology, such as high throughput and sensitivity, while also noting its limitations, including data interpretation complexity and technical costs. Finally, the paper looks forward to future development trends in DNA microarray technology, particularly its potential applications in personalized medicine.

Missense mutations in the CITED2 gene may contribute to congenital heart disease

BackgroundCongenital heart disease (CHD) is a lifelong abnormality present from birth. Multiple studies have shown that mutations in genes involved in heart development could cause congenital heart disease. The CITED2 gene works as a transcription factor in the hypoxic pathway for the development of the heart. Therefore, five CHD types, ventricular septal defect, atrial septal defect, atrioventricular septal defect, tetralogy of fallot, and patent ductus arteriosus, were evaluated by conducting a targeted single nucleotide polymorphism (SNP) analysis of the CITED2 gene variant rs375393125 (T > C). This study aimed to identify the association of CITED2 gene mutations in CHD patients.MethodsThree hundred fifty samples, 250 from patients and 100 from controls, were collected for this genetic analysis. Allele-specific PCR and gel electrophoresis were used to identify the target missense mutations. The genotypic results of the CHDs were further validated through Sanger sequencing.ResultsThe frequency of the homozygous mutant (CC) in CHD patients was 48.4%, and of the heterozygous mutant (TC) genotype was 11.4%; these percentages are higher than controls (1%). The control samples had only one heterozygous TC and no homozygous CC genotype. The chi-square value was obtained at 103.9 with a probability of 0.05, more significant than the significance value of 21.03. The odds ratio was 43.7, which is > 1. The calculated value of ANOVA was 11.6, which was more significant than the F critical value of 3.7. As a result of sequencing, the mutant sample of each selected CHD type was found heterozygous or homozygous, and the results were like those obtained through conventional PCR.ConclusionThe samples of CHD patients showed mutations. Therefore, the CITED2 gene SNP might be associated with CHD.

RiceSNP-BST: a deep learning framework for predicting biotic stress-associated SNPs in rice.

Rice consistently faces significant threats from biotic stresses, such as fungi, bacteria, pests, and viruses. Consequently, accurately and rapidly identifying previously unknown single-nucleotide polymorphisms (SNPs) in the rice genome is a critical challenge for rice research and the development of resistant varieties. However, the limited availability of high-quality rice genotype data has hindered this research. Deep learning has transformed biological research by facilitating the prediction and analysis of SNPs in biological sequence data. Convolutional neural networks are especially effective in extracting structural and local features from DNA sequences, leading to significant advancements in genomics. Nevertheless, the expanding catalog of genome-wide association studies provides valuable biological insights for rice research. Expanding on this idea, we introduce RiceSNP-BST, an automatic architecture search framework designed to predict SNPs associated with rice biotic stress traits (BST-associated SNPs) by integrating multidimensional features. Notably, the model successfully innovates the datasets, offering more precision than state-of-the-art methods while demonstrating good performance on an independent test set and cross-species datasets. Additionally, we extracted features from the original DNA sequences and employed causal inference to enhance the biological interpretability of the model. This study highlights the potential of RiceSNP-BST in advancing genome prediction in rice. Furthermore, a user-friendly web server for RiceSNP-BST (http://rice-snp-bst.aielab.cc) has been developed to support broader genome research.

Causal relationship between varicose veins and mean corpuscular hemoglobin concentration based on Mendelian randomization study

BackgroundIncreased hemoglobin concentrations may increase the risk of varicose veins. However, the underlying relationship between them was not yet understood.MethodsMendelian randomization (MR) analysis was performed to investigate causal effect between mean corpuscular hemoglobin concentration (MCHC, exposure factor) and varicose veins (outcome). Afterward, sensitivity analysis was used to ensure the reliability of MR analysis results. Then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of SNPs were performed. A search tool for recurring instances of neighbouring genes (STRING) database was used to construct a protein-protein interaction (PPI) network.ResultsTherefore, the inverse-variance weighted (IVW) results showed there existed a causal relationship between MCHC and varicose veins (p = 0.0026), with MCHC serving as a significant risk factor. (odd ratio [OR] = 1.2321). In addition, the validity of the results of the forward MR analysis was verified by sensitivity analysis. Further, a PPI network of 92 single-nucleotide polymorphisms (SNPs) which used for forward MR analysis related genes was constructed. And they were found to be closely associated with the peroxisome proliferator-activated receptor (PPAR) signalling pathway and cellular response to external stimulus by enrichment analysis. In addition, we clarified that the effect of varicose veins on MCHC was minimal by reverse MR analysis, suggesting that the results of forward MR analysis were not disturbed by reverse results.ConclusionThis study found a causal relationship between varicose veins and MCHC, which provided strong evidence for the effect of hemoglobin on varicose veins, and a new thought for the diagnosis and prevention of varicose veins in the future.