Single Nucleotide Polymorphism Analysis Research Articles

Where do obesity and male infertility collide?

The parallel rise in obesity and male infertility in modern societies necessitates the identification of susceptibility genes underlying these interconnected health issues. In our study, we conducted a comprehensive search in the OMIM database to identify genes commonly associated with male infertility and obesity. Subsequently, we performed an insilico analysis using the REVEL algorithm to detect pathogenic single nucleotide polymorphisms (SNPs) in the coding region of these candidate genes. To validate our findings in vivo, we conducted a comprehensive analysis of SNPs and gene expression of candidate genes in 200 obese infertile subjects and 240 obese fertile individuals using ARMS-PCR. Additionally, we analyzed 20 fertile and 22 infertile obese individuals using Realtime-qPCR. By removing duplicated queries, we obtained 197 obesity-related genes and 102 male infertility-related genes from the OMIM database. Interestingly, the APOB gene was found in common between the two datasets. REVEL identified the rs13306194 variant as potentially pathogenic with a calculated score of 0.524. The study identified a significant association between the AA (P value = 0.001) genotype and A allele (P value = 0.003) of the APOB rs13306194 variant and infertility in obese men. APOB expression levels were significantly lower in obese infertile men compared to obese fertile controls (p < 0.01). Moreover, the AA genotype of rs13306194 APOB was associated with a significant decrease in APOB gene expression in obese infertile men (p = 0.05). There is a significant association between the Waist-to-Hip Ratio (WHR) and LH with infertility in the obese infertile group. These results are likely to contribute to a better understanding of the causes of male infertility and its association with obesity.

HPV16 Genomes: In Silico Analysis of E6 and E7 Oncoproteins in 20 South American Variants

Background: Human papillomavirus (HPV) is the main risk factor for the development of squamous cell cervical cancer, and E6 oncoprotein and E7 oncoprotein are important components of the viral genome and its oncogenic potential. It is known that different viral variants of HPV16 have different pathology and impact on the development of neoplasia, although few studies have been performed on South American variants. Objective: Therefore, the present study aimed to analyze in silico the genomic diversity of HPV16 in 20 complete genome variants of South America in the National Center for Biotechnology Information (NCBI) database. Methods: We performed a descriptive study to characterize the polymorphic regions of the E6 and E7 genes in HPV16 variants, using software for genomic data and single nucleotide polymorphism (SNP) analysis and others for phylogenetic analysis. Results: The variants analyzed included six SNPs linked to cancer (A131G, G145T, C335T, T350G, C712A, and T732C) and significant variation (798 nucleotide substitutions). Despite this, the variants showed low genetic diversity. Eighteen variants of unclear significance (VUS) were identified, 10 of which were in the coding E6 regions and 8 in the coding E7 regions. The prevalence of lineage D variants is of concern due to their pathology in cervical cancer and requires more research and epidemiological vigilance regarding their prevalence in the population. Conclusion: study may contribute to future research on South American variants of HPV16, their pathogenicity, and the development of treatments.

Influence of UGT2B7, UGT1A4 and ABCG2 Polymorphisms on the Pharmacokinetics and Therapeutic Efficacy of Lamotrigine in Patients with Epilepsy.

A substantial inter-individual variability has been observed in the pharmacokinetics of lamotrigine. The aim of the study was to investigate the impact of genetic polymorphism of the metabolizing enzymes (UGT2B7, UGT1A4) and transporter (ABCG2) on the pharmacokinetics and therapeutic efficacy of lamotrigine in patients with epilepsy. The genetic analysis of single-nucleotide polymorphisms was conducted using polymerase chain reaction sequence. High-performance liquid chromatography/tandem mass spectrometry was employed to measure the plasma concentrations of lamotrigine. The efficacy of lamotrigine was assessed by evaluating the reduction rate of epileptic seizure frequency. This study included a cohort of 331 patients who were treated with lamotrigine as monotherapy. A linear correlation was observed between the lamotrigine concentration and daily dose taken (r = 0.58, p < 2.2e-16). Statistically significant differences were found in both the median plasma concentration and dose-adjusted concentration (C/D ratio) when comparing the ineffective to the effective group (p < 0.05). Multivariate analysis showed that UGT1A4 rs2011425, ABCG2 rs2231142 polymorphisms and age had a significant relationship with the lamotrigine concentrations (p < 0.05). Age was a predictive factor for C/D ratio (p < 0.001). Lamotrigine concentration and weight were good predictive factors for effective seizure outcomes (odds ratio [OR] = 0.715, 95% CI 0.658-0.776, p < 0.001; OR = 0.926, 95% CI 0.901-0.951, p < 0.001, respectively). The cut-off values of lamotrigine trough concentrations for clinical outcomes in the age-related groups were determined as 2.49μg/ml (area under the receiver-operating characteristic curve [AUC]: 0.828, 95% CI 0.690-0.966), 2.70μg/ml (AUC: 0.805, 95% CI 0.745-0.866) and 3.25μg/ml (AUC: 0.807, 95% CI 0.686-0.928) for the adult group, adolescent group, and toddler and school-age group, respectively. UGT1A4 rs2011425 and ABCG2 rs2231142 were correlated with lamotrigine concentrations. Lower lamotrigine trough concentration was found in the ineffective group and the troughs were associated with seizure outcomes.

Potential Single Nucleotide Polymorphisms markers for radiation dermatitis in head and neck cancer patients: ameta-analysis.

To identify potential Single Nucleotide Polymorphisms (SNPs) of susceptibility for the development of acute radiation dermatitis in head and neck cancer patients, and also to verify the association between SNPs and the severity of RD. This systematic review was reported according to the PRISMA guideline. The proportion meta-analysis was performed to identify the prevalence of genetic markers by geographical region and radiation dermatitis severity. The meta-analysis was performed to verify the association between genetic markers and RD severity. The certainty of the evidence was assessed by GRADE. Thirteen studies were included. The most prevalent SNPs were XRCC3 (rs861639) (36%), TGFβ1 (rs1800469) (35%), and RAD51 (rs1801321) (34%). There are prevalence studies in Europe and Asia, with asimilar prevalence for all SNPs (29-40%). The prevalence was higher in patients who developed radiation dermatitis ≤2 for any subtype of genes (75-76%). No SNP showed astatistically significant association with very low certainty of evidence. The most prevalent SNPs may be predictors of acute RD. The analysis of SNP before starting radiation therapy may be apromising method to predict the risk of developing radiation dermatitis and allow radiosensitive patients to have acustomized treatment. This current review provides new research directions.

Genome-wide meta-analysis of short-tandem repeats for Parkinson's disease risk using genotype imputation

Abstract Idiopathic Parkinson’s disease is determined by a combination of genetic and environmental factors. Recently, the first genome-wide association study on short-tandem repeats in Parkinson’s disease reported on eight suggestive short-tandem repeat-based risk loci (α=5.3×10-6), of which four were novel, i.e. they had not been implicated in Parkinson’s disease risk by genome-wide association analyses of single-nucleotide polymorphisms before. Here, we tested these eight candidate short-tandem repeats in a large, independent Parkinson’s disease case-control dataset (n=4,757). Furthermore, we combined the results from both studies by meta-analysis resulting in the largest Parkinson’s disease genome-wide association study of short-tandem repeats to date (n=43,844). Lastly, we investigated whether leading short-tandem repeat risk variants exert functional effects on gene expression regulation based on methylation quantitative trait locus data in human post-mortem brain (n=142). None of the eight previously reported short-tandem repeats were significantly associated with Parkinson’s disease in our independent dataset after multiple testing correction (α=6.25x10-3). However, we observed modest support for short tandem repeats near CCAR2 and NCOR1 in the updated meta-analyses of all available data. While the genome-wide meta-analysis did not reveal additional study-wide significant (α=6.3×10-7) short-tandem repeat signals, we identified seven novel suggestive Parkinson’s disease short-tandem repeat risk loci (α=5.3×10-6). Of these, especially a short-tandem repeat near MEIOSIN showed consistent evidence for association across datasets. CCAR2, NCOR1 and one novel suggestive locus identified here (LINC01012) emerged from colocalization analyses showing evidence for a shared causal short-tandem repeat variant affecting both Parkinson’s disease risk and cis DNA methylation in brain. Larger studies, ideally using short-tandem repeats called from whole-sequencing data, are needed to more fully investigate their role in Parkinson’s disease.

Large-scale genome-wide SNP analysis reveals the rugged (and ragged) landscape of global ancestry, phylogeny, and demographic history in chicken breeds.

The worldwide chicken gene pool encompasses a remarkable, but shrinking, number of divergently selected breeds of diverse origin. This study was a large-scale genome-wide analysis of the landscape of the complex molecular architecture, genetic variability, and detailed structure among 49 populations. These populations represent a significant sample of the world's chicken breeds from Europe (Russia, Czech Republic, France, Spain, UK, etc.), Asia (China), North America (USA), and Oceania (Australia). Based on the results of breed genotyping using the Illumina 60K single nucleotide polymorphism (SNP) chip, a bioinformatic analysis was carried out. This included the calculation of heterozygosity/homozygosity statistics, inbreeding coefficients, and effective population size. It also included assessment of linkage disequilibrium and construction of phylogenetic trees. Using multidimensional scaling, principal component analysis, and ADMIXTURE-assisted global ancestry analysis, we explored the genetic structure of populations and subpopulations in each breed. An overall 49-population phylogeny analysis was also performed, and a refined evolutionary model of chicken breed formation was proposed, which included egg, meat, dual-purpose types, and ambiguous breeds. Such a large-scale survey of genetic resources in poultry farming using modern genomic methods is of great interest both from the viewpoint of a general understanding of the genetics of the domestic chicken and for the further development of genomic technologies and approaches in poultry breeding. In general, whole genome SNP genotyping of promising chicken breeds from the worldwide gene pool will promote the further development of modern genomic science as applied to poultry.

Comparison of IncK-blaCMY-2 Plasmids in Extended-Spectrum Cephalosporin-Resistant Escherichia coli Isolated from Poultry and Humans in Denmark, Finland, and Germany.

Escherichia coli carrying IncK-blaCMY-2 plasmids mediating resistance to extended-spectrum cephalosporins (ESC) has been frequently described in food-producing animals and in humans. This study aimed to characterize IncK-blaCMY-2-positive ESC-resistant E. coli isolates from poultry production systems in Denmark, Finland, and Germany, as well as from Danish human blood infections, and further compare their plasmids. Whole-genome sequencing (Illumina) of all isolates (n = 46) confirmed the presence of the blaCMY-2 gene. Minimum inhibitory concentration (MIC) testing revealed a resistant phenotype to cefotaxime as well as resistance to ≥3 antibiotic classes. Conjugative transfer of the blaCMY-2 gene confirmed the resistance being on mobile plasmids. Pangenome analysis showed only one-third of the genes being in the core with the remainder being in the large accessory gene pool. Single nucleotide polymorphism (SNP) analysis on sequence type (ST) 429 and 1286 isolates showed between 0-60 and 13-90 SNP differences, respectively, indicating vertical transmission of closely related clones in the poultry production, including among Danish, Finnish, and German ST429 isolates. A comparison of 22 ST429 isolates from this study with 80 ST429 isolates in Enterobase revealed the widespread geographical occurrence of related isolates associated with poultry production. Long-read sequencing of a representative subset of isolates (n = 28) allowed further characterization and comparison of the IncK-blaCMY-2 plasmids with publicly available plasmid sequences. This analysis revealed the presence of highly similar plasmids in ESC-resistant E. coli from Denmark, Finland, and Germany pointing to the existence of common sources. Moreover, the analysis presented evidence of global plasmid transmission and evolution. Lastly, our results indicate that IncK-blaCMY-2 plasmids and their carriers had been circulating in the Danish production chain with an associated risk of spreading to humans, as exemplified by the similarity of the clinical ST429 isolate to poultry isolates. Its persistence may be driven by co-selection since most IncK-blaCMY-2 plasmids harbor resistance factors to drugs used in veterinary medicine.

An enzyme-free and ratiometric biosensor for single nucleotide polymorphism with portable electrochemical system

Portable, low-cost and efficient biosensing systems are valuable for single nucleotide polymorphisms (SNPs) analysis, particularly in resource-limited fields. Herein, a rapid, enzyme-free and ratiometric SNPs biosensor with portable electrochemical system enabling simultaneous recognition and signal amplification is proposed. To demonstrate its versatility and effectiveness, we have selected the human cancer-related KRAS gene and the soybean mosaic virus resistance Rsv3 gene as our analysis models. Our biosensor is constructed based on a combination of strand displacement reactions and hybridization chain reactions (HCR). This unique design enables to differentiate between mutant (MT) and wild (WD) sequences based on the differential release of HCR products on the electrode surfaces. Importantly, this enzyme-free SNPs biosensor concurrently achieves both SNPs recognition and signal amplification, significantly reducing the reaction time to just 40 minutes. Furthermore, we have developed a miniaturized biosensor system that incorporates screen printed gold electrodes (SPGE) and smartphones. This system is integrated with a ratiometric strategy with an limit of detection as low as 1.2 fM, enhancing accuracy and eliminating external interference. This simple SNPs biosensing system possesses high reliability, positioning it as a versatile biosensor for the determination of various SNPs mutations.

Genetic Profile of &lt;I&gt;Brucella melitensis&lt;/I&gt; Strains Isolated on the Territory of the Russian Federation, Based on Analysis of Single Nucleotide Polymorphisms Following Whole Genome Sequencing

The aim of the work was to conduct a comparative phylogenetic analysis based on wgSNP of complete genomes of Brucella melitensis strains circulating in the territory of the Russian Federation.Materials and methods. wgSNP typing of 412 B. melitensis strains of the main genetic lineages of brucella from different regions of the world, including 64 strains isolated in the regions of the European and Asian parts of the Russian Federation, was performed. DNA sequencing was conducted on the “Ion GeneStudio S5 Plus” platform (“Life Technologies”, USA) using the “Ion Plus Fragment Library Kit library preparation” (“Life Technologies”, USA), according to the “Ion 520™ &amp; Ion 530™ Kit – Chef” protocol (Revision D.0).Results and discussion. It has been established that the strains circulating in Russia belong mainly to genotype II, which has a wide geographical distribution across the territory of Eurasia. At the same time, subgenotype IIh prevails in the regions of Siberia, and Iii – in the European territory of the country. For the first time, sets of specific SNPs have been identified that allow for intraspecific differentiation of B. melitensis strains. The obtained results made it possible to determine the probable routes of introduction of the causative agent of brucellosis into the territory of the Russian Federation from China and the countries of the Middle East. The prospect of using an optimized wgSNP typing scheme to solve urgent problems in the field of molecular epidemiology of brucellosis is demonstrated. It includes determining the genotype and subgenotype of the pathogen associated with the probable geographical region of origin of infection, and identifying the genetic relations between strains with high accuracy.

Cereulide production capacities and genetic properties of 31 emetic Bacillus cereus group strains

The highly potent toxin cereulide is a frequent cause of foodborne intoxications. This extremely resistant toxin is produced by Bacillus cereus group strains carrying the plasmid encoded cesHPTABCD gene cluster. It is known that the capacities to produce cereulide vary greatly between different strains but the genetic background of these variations is not clear.In this study, cereulide production capacities were associated with genetic characteristics. For this, cereulide levels in cultures of 31 strains were determined after incubation in tryptic soy broth for 24 h at 24 °C, 30 °C and 37 °C. Whole genome sequencing based data were used for an in-depth characterization of gene sequences related to cereulide production. The taxonomy, population structure and phylogenetic relationships of the strains were evaluated based on average nucleotide identity, multi-locus sequence typing (MLST), core genome MLST and single nucleotide polymorphism analyses. Despite a limited strain number, the approach of a genome wide association study (GWAS) was tested to link genetic variation with cereulide quantities.Our study confirms strain-dependent differences in cereulide production. For most strains, these differences were not explainable by sequence variations in the cesHPTABCD gene cluster or the regulatory genes abrB, spo0A, codY and pagRBc. Likewise, the population structure and phylogeny of the tested strains did not comprehensively reflect the cereulide production capacities. GWAS yielded first hints for associated proteins, while their possible effect on cereulide synthesis remains to be further investigated.

Identification and Distribution of the 'Candidatus Liberibacter asiaticus'-Asian Citrus Psyllid Pathosystem in Saudi Arabia.

Citrus greening disease was first reported in Saudi Arabia during the 1970s when characteristic foliar and fruit symptoms were observed in commercial citrus groves. However, 'Candidatus Liberibacter asiaticus' (CLas) was not detected in symptomatic trees until 1981 to 1984 when CLas-like cells were observed by transmission electron microscopy in leaves collected from symptomatic citrus groves in southwestern Saudi Arabia. Despite the anticipated establishment of the CLas-Asian citrus psyllid (ACP) (Diaphorina citri Kuwayama) pathosystem, CLas presence has not been verified in suspect trees nor have ACP infestations been documented. Given the recent expansion of citrus production in Saudi Arabia, a systematic country-wide survey was carried out to determine the potential CLas distribution in the 13 citrus-growing regions of the country. Citrus trees were surveyed for the presence of CLas-psyllid vector(s) and characteristic disease symptoms in commercial and urban citrus trees. Adult psyllids collected from infested citrus trees were identified as ACP based on morphological characteristics. Real-time quantitative PCR amplification (qPCR) of the CLas β-subunit of the ribonucleotide reductase (RNR) gene from citrus leaf and fruit samples and/or ACP adults revealed that trees were positive for CLas detection in 10 of the 13 survey regions; however, CLas was undetectable in ACP adults. Phylogenetic and single nucleotide polymorphism (SNP) analyses of a PCR-amplified, cloned fragment of the CLas 16S rRNA gene (∼1.1 kbp) indicated Saudi Arabian isolates were most closely related to Florida, U.S.A., isolates. Analysis of climate variables indicated that the distribution of the ACP-CLas pathosystem observed in Saudi Arabia was consistent with published predictions of terrains most likely to support establishment.

Genetic diversity and antimicrobial susceptibility of Streptococcus suis from diseased Swiss pigs collected between 2019 – 2022

Streptococcus suis is an important pathogen causing severe disease in pigs and humans, giving rise to economic losses in the pig production industry. Out of 65S. suis isolates collected from diseased pigs in Switzerland between 2019 and 2022, 57 isolates were thoroughly examined by phenotypic and whole genome sequence (WGS) based characterization. The isolates’ genomes were sequenced allowing for a comprehensive analysis of their distribution in terms of serovar, sequence type (ST), clonal complex (CC), and classical virulence markers. Antimicrobial resistance (AMR) genes were screened, and phenotypic susceptibility to eight classes of antimicrobial agents was examined. Serovar 6, devoid of any resistance genes, was found to be most prevalent, followed by serovars 1, 3, 1/2, and 9. Thirty STs were identified, with ST1104 being the most prevalent. Serovar 2 and serovar 1/2 were associated with CC1, potentially containing the most virulent variants. Based on single nucleotide polymorphism (SNP) analyses, fifteen isolates belonged to one of seven putative transmission clusters each consisting of two or three isolates. High phenotypic AMR rates were detected for tetracyclines (80%) and macrolides (35%) and associated with the resistance genes tet(O) and erm(B), respectively. In contrast, susceptibility to β-lactam antibiotics and phenicols was high. Determination of phenotypic AMR profiling, including the minimum inhibitory concentrations (MICs) of the tested antimicrobial agents, sets a baseline for future studies. The study provides valuable insights into the genetic diversity and antimicrobial susceptibility of Swiss S. suis isolates, facilitating the identification of emerging clones relevant to public health concerns.

Expansion and transmission dynamics of high risk carbapenem-resistant Klebsiella pneumoniae subclones in China: An epidemiological, spatial, genomic analysis

AimsCarbapenem-resistant Klebsiella pneumonia (CRKP) is a global threat that varies by region. The global distribution, evolution, and clinical implications of the ST11 CRKP clone remain obscure. MethodsWe conducted a multicenter molecular epidemiological survey using isolates obtained from 28 provinces and municipalities across China between 2011 and 2021. We integrated sequences from public databases and performed genetic epidemiology analysis of ST11 CRKP. ResultsAmong ST11 CRKP, KL64 serotypes exhibited considerable expansion, increasing from 1.54% to 46.08% between 2011 and 2021. Combining our data with public databases, the phylogenetic and phylogeography analyses indicated that ST11 CRKP appeared in the Americas in 1996 and spread worldwide, with key clones progressing from China’s southeastern coast to the inland by 2010. Global phylogenetic analysis showed that ST11 KL64 CRKP has evolved to a virulent, resistant clade with notable regional spread. Single-nucleotide polymorphism (SNP) analysis identified BMPPS (bmr3, mltC, pyrB, ppsC, and sdaC) as a key marker for this clade. The BMPPS SNP clade is associated with high mortality and has strong anti-phagocytic and competitive traits in vitro. ConclusionsThe high-risk ST11 KL64 CRKP subclone showed strong expansion potential and survival advantages, probably owing to genetic factors.

Genomic insights into anthropozoonotic tuberculosis in captive sun bears (Helarctos malayanus) and an Asiatic black bear (Ursus thibetanus) in Cambodia

Contact between humans and wildlife presents a risk for both zoonotic and anthropozoonotic disease transmission. In this study we report the detection of human strains of Mycobacterium tuberculosis in sun bears and an Asiatic black bear in a wildlife rescue centre in Cambodia, confirming for the first time the susceptibility of these bear species to tuberculosis when in close contact with humans. After genotyping revealed two different strains of M. tuberculosis from cases occurring between 2009 and 2019, 100 isolates from 30 sun bear cases, a single Asiatic black bear case, and a human case were subjected to whole genome sequencing. We combined single nucleotide polymorphism analysis and exploration of mixed base calls with epidemiological data to indicate the evolution of each outbreak. Our results confirmed two concurrent yet separate tuberculosis outbreaks and established a likely transmission route in one outbreak where the human case acted as an intermediatory between bear cases. In both outbreaks, we observed high rates of transmission and progression to active disease, suggesting that sun bears are highly susceptible to tuberculosis if exposed under these conditions. Overall, our findings highlight the risk of bi-directional transmission of tuberculosis between humans and captive bears in high human tuberculosis burden regions, with implied considerations for veterinary and public health. We also demonstrate the use of standard genomic approaches to better understand disease outbreaks in captive wildlife settings and to inform control and prevention measures.

Genomic and common garden data reveal significant genetic differentiation in the endangered San Fernando Valley spineflower Chorizanthe parryi var. fernandina

AbstractSan Fernando Valley spineflower (Chorizanthe parryi var. fernandina [S. Watson] Jeps.) (Polygonaceae) is an herbaceous annual plant, endemic to California, and until rediscovered in 1999 had been thought to be extinct for almost seven decades. Historically documented at 10 locations, it currently persists at 2, separated by approximately 27 km. State listed as endangered, a description of its genetic diversity and structure is of conservation interest. After determining a lack of variation in ploidy, we examined genetic variation from samples within both populations: a common garden study for potentially adaptive genetic variation in selected growth and phenological traits and analysis of single nucleotide polymorphisms identified through restriction-site associated DNA sequencing. Both measures indicated that this highly restricted taxon nevertheless harbors substantial levels of genetic diversity and has significant between- and within-population genetic structure. Combining approaches from population genomics and common garden studies provided more insight into the patterns and basis of genetic diversity than is typical for studies of non-model species. Although local adaptation was not specifically studied (i.e., via reciprocal transplant studies), the differences determined from these two independent lines of evidence indicate that mixing gene pools between populations is not recommended at this time. Further, with significant differences revealed among subpopulations, we caution against mixing genotypes across subpopulations for the most part, and without much more evidence that this would not pose a risk of outbreeding depression. The importance of supporting pollinator health and diversity is highlighted. With genetic diversity—particularly with an annual species—being dynamic, fluctuating with the usual processes and with contributions from the soil seedbank, we recommend periodic resampling to monitor genetic diversity and structure. Climate change is anticipated to contribute to this variability.

Analysis of SIRT1 Gene SNPs and Clinical Characteristics in Medication-Related Osteonecrosis of the Jaw.

Certain genetic factors, including single-nucleotide polymorphisms (SNPs) in the SIRT1 gene, have been linked to medication-related osteonecrosis of the jaw (MRONJ). This study examined four SNPs in the SIRT1 gene and implemented multivariate statistical analysis to analyze genetic and clinical factors in MRONJ patients. Genomic DNA was isolated from peripheral blood samples of 63 patients of European origin treated for MRONJ, and four SNP genotypes in the gene encoding the SIRT-1 protein were determined by Sanger sequencing. The allele frequencies measured in the MRONJ population were compared with allele frequencies measured in the European population in the National Center for Biotechnology Information Allele Frequency Aggregator (NCBI ALFA) database. Genetic and clinical factors were examined with multivariate statistical analysis. A C:A allele distribution ratio of 77.8:22.2 was measured in the rs932658 SNP. In the ALFA project, a C:A allele distribution ratio of 59.9:40.1 was detected in the European population, which was found to be a significant difference (p = 4.5 × 10-5). Multivariate statistical analysis revealed a positive correlation (0.275) between the genotype of SNP rs932658 and the number of stages improved during appropriate MRONJ therapy. It is concluded that allele A in SNP rs932658 in the SIRT1 gene acts as a protective factor in MRONJ.

Traces of pandemic fluoroquinolone-resistant Escherichia coli clone ST131 transmitted from human society to aquatic environments and wildlife in Japan

Transmission of antimicrobial-resistant bacteria among humans, animals, and the environment is a growing concern worldwide. The distribution of an international high-risk fluoroquinolone-resistant Escherichia coli clone, ST131, has been documented in clinical settings. However, the transmission of ST131 from humans to surrounding environments remains poorly elucidated. To comprehend the current situation and identify the source of ST131 in nature, we analyzed the genetic features of ST131 isolates from the aquatic environment (lake/river water) and wildlife (fox, raccoon, raccoon dog, and deer) and compared them with the features of isolates from humans in Japan using accessory and core genome single nucleotide polymorphism (SNP) analyses. We identified ST131 isolates belonging to the same phylotype and genome clusters (four of eight clusters were concomitant) with low SNP distance between the human isolates and those from the aquatic environment and wildlife. These findings warn of ST131 transmission between humans and the surrounding environment in Japan.

Unveiling the population genetic structure of Iranian horses breeds by whole-genome resequencing analysis.

Preserving genetic diversity is pivotal for enhancing genetic improvement and facilitating adaptive responses to selection. This study focuses on identifying key genetic variants, including single nucleotide polymorphisms (SNPs), insertion/deletion polymorphisms (INDELs), and copy number variants (CNVs), while exploring the genomic evolutionary connectedness among seven Iranian horses representing five indigenous breeds: Caspian, Turkemen, DareShuri, Kurdish, and Asil. Using whole-genome resequencing, we generated 2.7Gb of sequence data, with raw reads ranging from 1.2Gb for Caspian horses to 0.38Gb for Turkoman horses. Post-filtering, approximately 1.9Gb of reads remained, with ~ 1.5Gb successfully mapped to the horse reference genome (EquCab3.0), achieving mapping rates between 76.4% (Caspian) and 98.35% (Turkoman). We identified 2,909,816 SNPs in Caspian horses, constituting around 0.1% of the genome. Notably, 71% of these SNPs were situated in intergenic regions, while 8.5 and 6.8% were located upstream and downstream, respectively. A comparative analysis of SNPs between Iranian and non-Iranian horse breeds showed that Caspian horses had the lowest number of shared SNPs with Turkoman horses. Instead, they showed a closer genetic relationship with DareShuri, Quarter, Arabian, Standardbred, and Asil breeds. Hierarchical clustering highlighted Caspian horses as a distinct cluster, underscoring their distinctive genomic signature. Caspian horses exhibit a unique genetic profile marked by an enrichment of private mutations in neurological genes, influencing sensory perception and awareness. This distinct genetic makeup shapes mating preferences and signifies a separate evolutionary trajectory. Additionally, significant non-synonymous single nucleotide polymorphisms (nsSNPs) in reproductive genes offer intervention opportunities for managing Caspian horses. These findings reveal the population genetic structure of Iranian horse breeds, contributing to the advancement of knowledge in areas such as conservation, performance traits, climate adaptation, reproduction, and resistance to diseases in equine science.

Computational Analysis of Single Nucleotide Polymorphisms in Human HIC1 Gene.

Background A putative tumor suppressor gene called HIC1 (hypermethylated in cancer) is situated at 17p13.3, a locus where the allelic loss occurs often in human malignancies, including breast cancer. Hypermethylated in cancer 1 protein is a protein that in humans is encoded by the HIC1 gene and it's aHomo sapiens(Human). This gene functions as a growth regulatory and tumor repressor gene. The molecular function of HIC1 gene includes DNA-binding transcription factor activity, sequence-specific DNA binding, DNA binding, histone deacetylase binding, protein binding, metal ion binding, nucleic acid binding, DNA-binding transcription repressor activity, RNA polymerase II-specific, DNA-binding transcription factor activity, RNA polymerase II-specific. The biological process of HIC1 gene includes multicellular organism development, negative regulation of Wnt signaling pathway, positive regulation of DNA damage response, signal transduction by p53 class mediator regulation of transcription, DNA-templated, negative regulation of transcription by RNA polymerase II, Wnt signaling pathway, transcription, DNA-templated, intrinsic apoptotic signaling pathway in response to DNA damage, cellular response to DNA damage stimulus. The study aimed to predict the stability and structure of the protein that will arise from single nucleotide polymorphisms (SNPs) in the human HIC1 gene. Methodology To investigate the possible negative effects associated with these SNPs, bioinformatic analysis is typically essential. The following tools were employed for forecasting harmful SNPs: scale-invariant feature transform (SIFT), Protein Analysis Through Evolutionary Relationships (PANTHER), nonsynonymous SNP by Protein Variation Effect Analyzer (PROVEAN), and nonsynonymous SNP by Single Nucleotide Polymorphism Annotation Platform (SNAP). Results The present study identified a total of 36 SNPs using the SIFT approach, which were shown to have functional significance. Twenty-six were determined to be tolerable, whereas 10 were shown to be detrimental. Out of 20 SNPs, seven (P370A, P646S, R654P, A476T, S400S, D666N, D7V) SNPs were predicted as "Possibly damaging" and seven (L9F, G468R, G490R, L482R, S12W, G489D, S12P) were identified as "probably benign", and six (R725G, G620S, A56V, E463D, D394N, L338V) were identified as "probably damaging" according to the predictions made by PANTHER tools. The majority of the pixels on the strip were red, indicating that the gene changes may have dangerous consequences. These results highlight the need for more research to fully comprehend how these mutations affect the hic1 protein's function, which is essential for the emergence of different types of cancer. Conclusion The current research has provided us with essential information about how SNPs might be used as a diagnostic marker for cancer, given that SNPs may be candidates for cellular changes caused by mutations linked to cancer.

Outbreak of NDM-5-producing Klebsiella pneumoniae ST307: an emerging high-risk antimicrobial resistance clone in Shanghai, China.

The high-risk clone Klebsiella pneumoniae ST307, associated with various carbapenem resistance genes, exhibits a global distribution and prevalence. However, in China, it has remained sporadic and has rarely been detected. In this study, we reported an outbreak caused by nine ST307 CRKP isolates harboring blaNDM-5 in Shanghai, China, in 2022. We employed antimicrobial susceptibility testing, conjugation assay, whole-genome sequencing (WGS) and comparative genomics, phylogenetic analysis, and fitness and virulence comparison to further characterize the isolates causing the outbreak. Besides blaNDM-5, these nine isolates co-carried blaCTX-M-15 and blaDHA-1, exhibiting nearly identical resistance profiles with high-level resistance to carbapenems and ceftazidime/avibactam, while showing susceptibility to colistin and tigecycline. blaNDM-5 was located on an IncX3 plasmid of 45,403 bp with a high frequency of conjugative ability. Phylogenetic and single-nucleotide polymorphism (SNP) analysis indicated the nature of clonal transmission with a maximum of five SNPs between these nine isolates, and they were closely related to strains obtained from the United States. ST307 isolates in our study showed a relatively lower virulence but higher growth rates and certain adaptability compared with ST11 isolates. Clinical investigation revealed that shared nursing staff in a mixed emergency intensive care unit ward and doctors' movement between wards might be responsible for the outbreak. The nonexistence before and sudden emergence of ST307 suggested that the currently circulating ST307 clone was a newly introduced superbug in our hospital. In conclusion, we revealed that blaNDM-5-producing ST307 CRKP isolates, a globally significant high-risk clone, are spreading in China, posing a substantial threat to public health.IMPORTANCEThe high-risk clone ST307, associated with various carbapenemases, including KPC, NDM, and OXA, has a global distribution. However, it is rarely reported in China, let alone causing outbreaks. Here, we found an outbreak caused by the clonal transmission of nine ST307 CRKP isolates. Clinical investigation revealed that shared nurses in a mixed emergency intensive care unit ward and doctors' movement between wards might be responsible for the outbreak. In our study, the nine NDM-5-producing ST307 isolates exhibited high-level resistance to carbapenems and ceftazidime-avibactam, high conjugative ability to Escherichia coli J53, and certain adaptability to environment, phylogenetically closet to the United States. All these features make ST307 clone the next successful clone comparable to ST11 clone in China. Therefore, it is imperative for us to vigilantly monitor the prevalence of carbapenem-resistant Klebsiella pneumoniae and promptly implement measures to control the spread of K. pneumoniae ST307 in China.