Identification Of Single Nucleotide Polymorphisms Research Articles

Chromosome-scale reference genome of an ancient landrace: unveiling the genetic basis of seed weight in the food legume crop pigeonpea (Cajanus cajan).

Pigeonpea (Cajanus cajan) is a nutrient-rich and versatile food legume crop of tropical and subtropical regions. In this study, we describe the de novo assembly of a high-quality genome for the ancient pigeonpea landrace 'D30', achieved through a combination of Pacific Biosciences high-fidelity (PacBio HiFi) and high-throughput chromatin conformation capture (Hi-C) sequencing technologies. The assembled 'D30' genome has a size of 813.54Mb, with a contig N50 of 10.74Mb, a scaffold N50 of 73.07Mb, and a GC content of 35.67%. Genomic evaluation revealed that the 'D30' genome contains 99.2% of Benchmarking Universal Single-Copy Orthologs (BUSCO) and achieves a 29.06 long terminal repeat (LTR) assembly index (LAI). Genome annotation indicated that 'D30' encompasses 431.37Mb of repeat elements (53.02% of the genome) and 37 977 protein-coding genes. Identification of single-nucleotide polymorphisms (SNPs), insertions/deletions (indels), and structural variations between 'D30' and the published genome of pigeonpea cultivar 'Asha' suggests that genes affected by these variations may play important roles in biotic and abiotic stress responses. Further investigation of genomic regions under selection highlights genes enriched in starch and sucrose metabolism, with 42.11% of these genes highly expressed in seeds. Finally, we conducted genome-wide association studies (GWAS) to facilitate the identification of 28 marker-trait associations for six agronomic traits of pigeonpea. Notably, we discovered a calmodulin-like protein (CcCML) that harbors a dominant haplotype associated with the 100-seed weight of pigeonpea. Our study provides a foundational resource for developing genomics-assisted breeding programs in pigeonpea.

Novel loci linked to serum lipid traits are identified in a genome-wide association study of a highly admixed Brazilian population - the 2015 ISA Nutrition

BackgroundCardiovascular diseases (CVDs) comprise major causes of death worldwide, leading to extensive burden on populations and societies. Alterations in normal lipid profiles, i.e., dyslipidemia, comprise important risk factors for CVDs. However, there is lack of comprehensive evidence on the genetic contribution to dyslipidemia in highly admixed populations. The identification of single nucleotide polymorphisms (SNPs) linked to blood lipid traits in the Brazilian population was based on genome-wide associations using data from the São Paulo Health Survey with Focus on Nutrition (ISA-Nutrition).MethodsA total of 667 unrelated individuals had genetic information on 330,656 SNPs available, and were genotyped with Axiom™ 2.0 Precision Medicine Research Array. Genetic associations were tested at the 10− 5 significance level for the following phenotypes: low-density lipoprotein cholesterol (LDL-c), very low-density lipoprotein cholesterol (VLDL-c), high-density lipoprotein cholesterol (HDL-c), HDL-c/LDL-c ratio, triglycerides (TGL), total cholesterol, and non-HDL-c.ResultsThere were 19 significantly different SNPs associated with lipid traits, the majority of which corresponding to intron variants, especially in the genes FAM81A, ZFHX3, PTPRD, and POMC. Three variants (rs1562012, rs16972039, and rs73401081) and two variants (rs8025871 and rs2161683) were associated with two and three phenotypes, respectively. Among the subtypes, non-HDL-c had the highest proportion of associated variants.ConclusionsThe results of the present genome-wide association study offer new insights into the genetic structure underlying lipid traits in underrepresented populations with high ancestry admixture. The associations were robust across multiple lipid phenotypes, and some of the phenotypes were associated with two or three variants. In addition, some variants were present in genes that encode ncRNAs, raising important questions regarding their role in lipid metabolism.

Identification of Single-Nucleotide Polymorphisms in Differentially Expressed Genes Favoring Soybean Meal Tolerance in Higher-Growth Zebrafish (Danio rerio).

Genetic variability within the same fish species could confer soybean meal (SBM) tolerance in some individuals, thus favoring growth. This study investigates the single-nucleotide polymorphisms (SNPs) in differentially expressed genes (DEGs) favoring SBM tolerance in higher-growth zebrafish (Danio rerio). In a previous work, nineteen families of zebrafish were fed a fish meal diet (100FM control diet) or SBM-based diets supplemented with saponin (50SBM + 2SPN-experimental diet), from juvenile to adult stages. Individuals were selected from families with a genotype-by-environment interaction higher (170 ± 18mg) or lower (76 ± 10mg) weight gain on 50SBM + 2SPN in relation to 100FM. Intestinal transcriptomic analysis using RNA-seq revealed six hundred and sixty-five differentially expressed genes in higher-growth fish fed 50SBM + 2SPN diet. In this work, using these results, 47 SNPs in DEGs were selected. These SNPs were genotyped by Sequenom in 340 zebrafish that were fed with a 50SBM + 2SPN diet or with 100FM diet. Marker-trait analysis revealed 4 SNPs associated with growth in 3 immunity-related genes (aif1l, arid3c, and cst14b.2) in response to the 50SBM + 2SPN diet (p-value < 0.05). Two SNPs belonging to aif1l y arid3c produce a positive (+19mg) and negative (-26mg) effect on fish growth, respectively. These SNPs can be used as markers to improve the early selection of tolerant fish to SBM diet or other plant-based diets. These genes can be used as biomarkers to identify SNPs in commercial fish, thus contributing to the aquaculture sustainability.

Causal relationships between inflammatory cytokines and myopia: an analysis of genetic and observational studies.

This study aims to explore the causal relationship between inflammatory markers and myopia through the use of bidirectional Mendelian randomization (MR) and myopia animal models. The authors utilized data from a comprehensive and publicly accessible genome-wide association study (GWAS) for our analysis, which includes 460536 European ancestry control subjects and 37362 myopia patients. Utilizing a two-sample Mendelian randomization analysis framework, 27 inflammatory markers were investigated as exposure variables with myopia serving as the outcome variable. Nine MR analysis techniques were employed, with inverse-variance weighting (IVW) as the principal MR analysis method. Heterogeneity was assessed using Cochrane's Q test. The identification of single-nucleotide polymorphisms (SNPs) and outliers linked to myopia was achieved via MR-PRESSO. The expression of interleukin-2 (IL-2) in the vitreous of guinea pigs subjected to experimentally induced form-deprivation myopia (FDM) was examined. Elevated concentrations of IL-2 and IL-2ra were found to be associated [IVW estimate odds ratio (OR): 1.003, 95% CI: 1.001-1.005, P=0.001] and strongly associated (IVW estimate OR: 1.002, 95% CI: 1.000-1.003, P=0.049) with an increased risk of myopia, respectively. Conversely, lower levels of C-reactive protein (CRP) (IVW estimate OR: 0.996, 95% CI: 0.994-0.999, P=0.002) and tumour necrosis factor alpha (IVW estimate OR: 0.995, 95% CI: 0.994-0.996, P<0.001) were robustly linked to a heightened risk of myopia. IL-2 expression was notably upregulated in the vitreous of guinea pigs with experimentally induced FDM. Elevated levels of inflammatory factors, especially IL-2 and IL-2ra, have a potential causal relationship with myopia susceptibility, providing new insights into the pathogenesis of myopia.

Paradoxical Psoriasis in Patients Receiving Therapy with Tumor Necrosis Factor Inhibitors: Potential Pathogenic Mechanisms and the Role of Genetic Factors.

TNF inhibitors (TNFi) have revolutionized the therapeutic management of various chronic immune-mediated inflammatory diseases. Despite their known benefits, these therapies are related to paradoxical adverse effects (PAEs), including paradoxical psoriasis (PP). Although the underlying mechanism remains somewhat unclear, some theories suggest that genetic factors, particularly certain single-nucleotide polymorphisms (SNPs), may play an important role. The present review aimed to research and analyze recent findings regarding the pathomechanisms involved in the appearance of PP and the association between various genetic factors and PP in individuals treated with TNFi. We performed a literature search and found that certain genes (IL23R, TNF, FBXL19, CTLA4, SLC12A8, TAP1) are strongly associated with the occurrence of PP in pediatric and adult patients during therapy with TNFi. The identification of the specific SNPs involved in the appearance of PP and other PAEs in patients treated with TNFi for various diseases and in different populations may later favor the recognition of those patients at a high risk of developing such adverse effects and could guide personalized therapeutic strategies in future years.

Causal relationship between gut microbiota and puerperal sepsis: a 2-sample Mendelian randomization study.

Some recent observational studies have shown that gut microbiota composition is associated with puerperal sepsis (PS) and no causal effect have been attributed to this. The aim of this study was to determine a causal association between gut microbiota and PS by using a two-sample Mendelian randomization (MR) analysis. This study performed MR analysis on the publicly accessible genome-wide association study (GWAS) summary level data in order to explore the causal effects between gut microbiota and PS. Gut microbiota GWAS (n = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for PS were obtained from the UK Biobank (PS, 3,940 cases; controls, 202,267 cases). Identification of single nucleotide polymorphisms associated with each feature were identified based on a significance threshold of p < 1.0 × 10-5. The inverse variance weighted (IVW) parameter was used as the primary method for MR and it was supplemented by other methods. Additionally, a set of sensitivity analytical methods, including the MR-Egger intercept, Mendelian randomized polymorphism residual and outlier, Cochran's Q and the leave-one-out tests were carried out to assess the robustness of our findings. Our study found 3 species of gut microbiota, Lachnospiraceae FCS020, Lachnospiraceae NK4A136, and Ruminococcaceae NK4A214, to be associated with PS. The IVW method indicated an approximately 19% decreased risk of PS per standard deviation increase with Lachnospiraceae FCS020 (OR = 0.81; 95% CI 0.66-1.00, p = 0.047). A similar trend was also found with Lachnospiraceae NK4A136 (OR = 0.80; 95% CI 0.66-0.97, p = 0.024). However, Ruminococcaceae NK4A214 was positively associated with the risk of PS (OR = 1.33, 95% CI: 1.07-1.67, p = 0.011). This two-sample MR study firstly found suggestive evidence of beneficial and detrimental causal associations of gut microbiota on the risk of PS. This may provide valuable insights into the pathogenesis of microbiota-mediated PS and potential strategies for its prevention and treatment.

Identification of Novel Functional Single Nucleotide Polymorphisms in the BRCA1 Gene of Breast Cancer Patients

Identification of Novel Functional Single Nucleotide Polymorphisms in the BRCA1 Gene of Breast Cancer Patients

Impact of TYMS gene polymorphism on the outcome of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients - identification of novel single nucleotide polymorphism: Cross-sectional study.

The current work aims to evaluate the association between genetic mutations in thymidylate synthetase (TYMS gene in exon1 and partial regions of promotor and intron 1 [877 bp, 657,220-658,096 bp]) and the therapeutic outcomes for rheumatoid arthritis (RA) Iraqi patients. An observational cross-sectional study involving 95 RA patients with established RA patients based on their methotrexate treatment responsiveness. Genetic sequencing of the TYMS gene was performed for all patients according to the instruction manuals of the sequencing company (Macrogen Inc. Geumchen, South Korea). Four polymorphisms were identified by sequencing 95 randomly selected patients in the noncoding region of TYMS. Three of these polymorphisms were found in the NCBI database's dbSNP (rs2853741, rs2606241, and rs2853742 SNPs), and one SNP polymorphism is novel (657334). The CTAT (657334, rs2853741, rs2606241, and rs2853742 SNPs) haplotype was significantly associated with responder with odd ratio, 95% confidence interval: 0.506, 0.281-0.912 (P value = .022). In contrast, the other haplotypes were not associated with MTX responsiveness. In the multivariate analysis, after adjusting to the effect of age, sex, smoking, and disease duration, the TCrs2853741 genotype was associated with non-responders (P value = .030). In contrast, the ACrs260641 genotype, after adjusting to the effect of age, sex, and smoking, was associated with non-responders (P value = .035). Genetic polymorphism of the TYMS gene, especially in TCrs2853741 and ACrs260641, predicts non-responder to MTX treatment in RA, while the presence of the CTAT haplotype predicts a good response to MTX treatment.

Custom-Designed Probes for the Accurate Determination of Epidermal Growth Factor Receptor Mutations and Their Allelic Configuration.

The identification of single nucleotide polymorphisms (SNPs) is of paramount importance for disease diagnosis and clinical prognostication. In the context of nonsmall cell lung cancer (NSCLC), the emergence of resistance mutations, exemplified by the epidermal growth factor receptor (EGFR) T790 M and C797S, is intricately linked to the therapeutic efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Herein, a highly efficient and specific SNP detection platform for T790 M and C797S mutations has been engineered through the integration of an asymmetric polymerase chain reaction (PCR) and an ingeniously tailored four-way junction (4WJ) probe. Notably, a molecular beacon (MB) probe was judiciously designed to discern the allelic configuration of these mutations. The administration of first- and third-generation EGFR-TKIs demonstrates therapeutic efficacy solely when the mutations are in the trans configuration, characterized by a low fluorescence signal. In contrast, significant fluorescence by the MB probe is indicative of the C797S mutation being in a cis arrangement with T790M, thereby rendering the cells refractory to the therapeutic interventions of both first- and third-generation EGFR-TKIs. The assay is capable of concurrently detecting two point-mutations and ascertaining their allelic positions in a single test within 1.5 h, enhancing both efficiency and simplicity. It also exhibits high accuracy in the identification of clinical samples, offering promising implications for therapeutic guidelines. By enabling tailored treatment plans based on specific genetic profiles, our approach not only advances the precision of NSCLC treatment strategies but also marks a significant contribution to personalized medicine.

Insights into genetic diversity and functional significance of the bHLH genes in cotton fiber development

This study investigated the identification and distribution of single nucleotide polymorphisms (SNPs) within basic Helix-Loop-Helix (bHLH) transcription factors (TFs) across diverse cotton (Gossypium hirsutum) accessions, including wild, landrace, and improved varieties. Comprehensive genomic analyses revealed substantial SNP diversity in wild cotton, distinct from that observed in landraces and improved accessions. Comparative analysis showed notable variations in SNP abundance and impact levels across different accessions, with missense SNPs being prevalent. Nucleotide substitution patterns highlighted the dominance of G>A and A>G substitutions. Population genetic analyses unveiled significant genetic diversity within wild accessions and distinct clustering between wild and improved accessions. Temporal expression profiling of bHLH genes during cotton fiber development demonstrated dynamic expression patterns, emphasizing their roles in fiber initiation, elongation, and cellulose biosynthesis. Moreover, association analysis identified SNPs significantly associated within bHLH genes, particularly GhbHLH149, with fiber quality traits, indicating their potential functional significance. Population genetic analyses further revealed evidence of positive selection on GhbHLH149 during cotton improvement. This study provides a comprehensive understanding of SNP diversity, gene expression dynamics, and genetic selection in bHLH genes, offering valuable insights for future cotton breeding efforts aimed at improving fiber quality traits in cotton.

Double base mismatches mediated catalytic hairpin assembly for enzyme-free single-base mutation detection: integrating signal recognition and amplification in one.

Single nucleotide polymorphism (SNP) biosensors are emerging rapidly for their promising applications in human disease prevention diagnosis, treatment, and prognosis. However, it remains a bottleneck in equipping simple and stable biosensors with the traits of high sensitivity, non-enzyme, and low cost. Double base mismatches mediated chain displacement reactions have attracted fascinating advantages of tailorable thermodynamics stability, non-enzyme, and excellent assembly compliance to involvement in SNP identification. As the base mismatch position and amount in DNA sequence can be artificially adjusted, it provides plenty of selectivity and specificity for exploring perfect biosensors. Herein, abiosensor with double base mismatches mediated catalytic hairpin assembly (CHA) is designed via one base mismatch in the toehold domain and the other base mismatch in the stem sequence of hairpin 1 (H1) by triggering CHA reaction to achieve selective amplification of the mutation target (MT) and fluorescence resonance energy transfer (FRET) effect that is composed of Cy3 and Cy5 terminally attached H1 and hairpin 2 (H2). Depending on the rationally designed base mismatch position and toehold length, the fabricated biosensors show superior SNP detection performance, exhibiting a good linearity with high sensitivity of 6.6 fM detection limitand a broad detection abundance of 1%. The proposed biosensor can be used to detect the KRAS mutation gene in real samples and obtain good recoveries between 106 and 116.99%. Remarkably, these extendible designs of base mismatches can be used for more types of SNP detection, providing flexible adjustment based on base mismatch position and toehold length variations, especially for their thermodynamic model for DNA-strand displacement reactions.

An overview of autosomal STRs and identity SNPs in a Norwegian population using massively parallel sequencing

In recent years, probabilistic genotyping software has been adapted for the analysis of massively parallel sequencing (MPS) forensic data. Likelihood ratios (LR) are based on allele frequencies selected from populations of interest. This study provides an outline of sequence-based (SB) allele frequencies for autosomal short tandem repeats (aSTRs) and identity single nucleotide polymorphisms (iSNPs) in 371 individuals from Southern Norway. 27 aSTRs and 94 iSNPs were previously analysed with the ForenSeq™ DNA Signature Prep Kit (Verogen). The number of alleles with frequencies less than 0.05 for sequenced-based alleles was 4.6 times higher than for length-based alleles. Consistent with previous studies, it was observed that sequence-based data (both with and without flanks) exhibited higher allele diversity compared to length-based (LB) data; random match probabilities were lower for SB alleles confirming their advantage to discriminate between individuals. Two alleles in markers D22S1045 and Penta D were observed with SNPs in the 3´ flanking region, which have not been reported before. Also, a novel SNP with a minor allele frequency (MAF) of 0.001, was found in marker TH01. The impact of the sample size on minor allele frequency (MAF) values was studied in 88 iSNPs from Southern Norway (n = 371). The findings were then compared to a larger Norwegian population dataset (n = 15,769). The results showed that the smaller Southern Norway dataset provided similar results, and it was a representative sample. Population structure was analyzed for regions within Southern Norway; FST estimates for aSTR and iSNPs did not indicate any genetic structure. Finally, we investigated the genetic differences between Southern Norway and two other populations: Northern Norway and Denmark. Allele frequencies between these populations were compared, and we found no significant frequency differences (p-values > 0.0001). We also calculated the pairwise FST values per marker and comparisons between Southern and Northern Norway showed small differences. In contrast, the comparisons between Southern Norway and Denmark showed higher FST values for some markers, possibly driven by distinct alleles that were present in only one of the populations. In summary, we propose that allele frequencies from each population considered in this study could be used interchangeably to calculate genotype probabilities.

Identification and analysis of oncogenic non-synonymous single nucleotide polymorphisms in the human NRAS gene: An exclusive in silico study

BackgroundN-ras protein is encoded by the NRAS gene and operates as GDP-GTP-controlled on/off switching. N-ras interacts with cellular signaling networks that regulate various cellular activities including cell proliferation and survival. The nonsynonymous single nucleotide polymorphism (nsSNPs)-mediated alteration can substantially disrupt the structure and activity of the corresponding protein. N-ras has been reported to be associated with numerous diseases including cancers due to the nsSNPs. A comprehensive study on the NRAS gene to unveil the potentially damaging and oncogenic nsSNPs is yet to be accomplished. Hence, this extensive in silico study is intended to identify the disease-associated, specifically oncogenic nsSNPs of the NRAS gene. ResultsOut of 140 missense variants, 7 nsSNPs (I55R, G60E, G60R, Y64D, L79F, D119G, and V152F) were identified to be damaging utilizing 10 computational tools that works based on different algorithms with high accuracy. Among those, G60E, G60R, and D119G variants were further filtered considering their location in the highly conserved region and later identified as oncogenic variants. Interestingly, G60E and G60R variants were revealed to be particularly associated with lung adenocarcinoma, rhabdomyosarcoma, and prostate adenocarcinoma. Therefore, D119G could be subjected to detailed investigation for identifying its association with specific cancer. ConclusionThis in silico study identified the deleterious and oncogenic missense variants of the human NRAS gene that could be utilized for designing further experimental investigation. The outcomes of this study would be worthwhile in future research for developing personalized medicine.

Exploring TSLP and IL-33 Serum Levels and Genetic Variants: Unveiling Their Limited Potential as Biomarkers for Mild Asthma in Children.

As the burden of mild asthma is not well understood, the significance of expanding research in the group of patients with mild asthma is emphasized. Thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL-33) are involved in the pathogenesis of atopy and the immune response to inhaled environmental insults, such as allergens, in asthmatic patients. Objectives: The objective of this study was to explore the correlation between specific polymorphisms within the genes encoding TSLP and IL-33, as well as the concentrations of TSLP and IL-33 in the serum, and the occurrence of pediatric mild asthma. Methods: The analysis encompassed 52 pediatric patients diagnosed with mild bronchial asthma, including both atopic and non-atopic cases, and a control group of 26 non-asthmatic children. Recruitment was conducted through a comprehensive questionnaire. Parameters such as allergic sensitization, serum levels of circulating TSLP and IL-33, and the identification of single-nucleotide polymorphisms in TSLP (rs11466750 and rs2289277) and IL-33 (rs992969 and rs1888909) were assessed for all participants. Results: Significantly lower mean serum TSLP concentrations were observed in asthmatic subjects compared to the control group, with atopic asthma patients showing even lower TSLP levels than non-atopic counterparts. No significant differences were found in mean serum IL-33 concentrations between the two groups. Considering the allele model, for both tested SNPs of IL-33, we observed that patients with asthma, atopic asthma, and atopy statistically less frequently possess the risk allele. Conclusions: Our study findings suggest that IL-33 and TSLP do not serve as ideal biomarkers for mild asthma in children. Their effectiveness as biomarkers might be more relevant for assessing disease severity rather than identifying asthma in pediatric patients. Further research focusing on the association between TSLP and IL-33 gene polymorphisms and asthma is expected to significantly advance disease management.

Identification of potential candidate genes associated with milk protein differences in Holstein cows: a meta-analysis integrating GWAS and RNA-Seq transcriptome

Despite the identification of candidate genes influencing milk protein, the connections between genes and regulatory pathways remains elusive. This study aimed integrate findings from genome-wide association studies (GWAS) and RNA sequencing (RNA-Seq) through meta-analysis to pinpoint single nucleotide polymorphisms (SNPs) and genes responsible for high and low protein yield in cows. Previous GWAS and RNA-Seq analyses had identified 663 SNPs and 1106 genes ( P &lt; 0.05). Twenty SNPs from GWAS, 10 genes from RNA-Seq, and 49 SNP/gene associations from both datasets, were identified using meta-analysis. Meta-analysis validated several SNPs previously identified through GWAS, such as rs135549651 ( P = 2.6 × 10−256), rs109146371 ( P = 3.1 × 10−208), rs109350371 ( P = 4.0 × 10−207), and rs109774038 ( P = 8.6 × 10−587). Genes identified in RNA-Seq experiments, including NR4A1 ( P = 3.2 × 10−7), ATF3 ( P = 9.6 × 10−7), CDH16 ( P = 9.9 × 10−7), VEGFA ( P = 1.0 × 10−6), and SAA3 ( P = 7.3 × 10−11), were confirmed. The combined GWAS and RNA-Seq datasets highlighted CCND2 ( P = 8.9 × 10−111), MAPK15 ( P = 1.3 × 10−151), and CPSF1 ( P = 1.2 × 10−306) as the most significant genes. Additionally, significant gene ontology (GO) terms, including ionizing radiation ( P = 1.5 × 10−4), nuclear pore cytoplasmic filaments ( P = 9.4 × 10−5), and phenylalanine 4-monooxygenase activity ( P = 1.4 × 10−5), were identified. In conclusion, the integration of GWAS and RNA-Seq, coupled with GO enrichment, allowed identification of candidate SNPs and genes with higher accuracy. These findings improve our knowledge about genomic architecture of milk protein and enhance evaluation of Holstein cows.

Exploring the Relationship Between Growth Hormone Secretagogue Receptor (GHSR) Gene and Body Proportions in Bangkok Chickens: Insights from DNA Sequencing and Hin6I Enzyme-Restricted PCR-RFLP Analysis

The purpose of this study was to determine the diversity of the growth hormone secretagogue receptor (GHSR) gene and also to analyze the association of the GHSR gene with the body proportions of Bangkok chickens. A total of 125 Bangkok chickens were reared, and blood samples were taken. Bangkok chickens were kept in colony cages with ad libitum feeding and drinking. The GHSR gene polymorphism was determined using the PCR-RFLP method. The restriction enzyme used in this study was Hin6I. The data analyzed were indicators of body proportions, which included data on body weight, carcass weight, and commercial cut weight. Single nucleotide polymorphism (SNP) identification using the Molecular Evolutionary Genetics Analysis 7 program with reference number AB095994.1. Allele frequency values, genotype frequencies, and Hardy-Weinberg balance values were also analyzed. The association between the GHSR gene and the traits observed in Bangkok chickens was analyzed using the T-test. The results of the study showed that the GHSR gene in Bangkok chickens had two genotypes, namely TT and CT. The values for Ho and He were 0.224 and 0.198, respectively. The genotype frequencies of TT and CT were 0.776 and 0.224, respectively. The two genotypes were associated with body weight, carcass weight, and commercial weight (p &lt; 0.05). For all measured criteria, the TT genotype showed a higher weight value than the CT genotype. The GHSR gene has the potential to be used as a genetic marker for the selection process on body weight, carcass weight, and commercial weight traits.

Identification of Damaging and Deleterious Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) in the Orang Asli, Jakun

The study of genetics and its relation to different disorders has recently been getting remarkable attention worldwide. Non-synonymous single-nucleotide polymorphisms (nsSNPs) are coding variants that introduce amino acid alterations to proteins. Since nsSNPs have various effects on protein structure and function, these changes can significantly impact human health. The primary purpose of this research is to examine the relationship between diseases and Jakun nsSNP mutations. A total of 10 samples with 24,604 nsSNPs were used in the study. Several in silico bioinformatics tools were used to classify the high-risk nsSNPs that might affect the structure and function of proteins in the Jakun tribe. The in silico tools PROVEAN, SIFT and PolyPhen2 identified 1395 high-risk nsSNPs. Further analysis with the DAVID annotation tool revealed that these related genes are associated with cardiovascular diseases, myocardial infarction, Alzheimer's and obesity. Other bioinformatics tools were then used to infer the protein structures of these high-risk nsSNPs. From SNP&amp;GO and PhD-SNPs, the results conclude that there are four damaging nsSNPs in the Jakun tribe. The damaging nsSNPs and the mutation positions are MTHFR (A222V), ESR2 (G445S), ACSM3 (G460R) and UGT3A1 with two mutation sites, C121G and C67G. This study using in silico tools can be the basis for increasing medical discoveries, reducing lab costs and helping with clinical trials for further studies by providing genetically related information.

Abstract 883: Genetic characteristics between males and females with urothelial bladder cancer

Abstract Urothelial bladder cancer (UBC) affects the epithelial cells of the urinary tract and is the most common type of bladder cancer worldwide. Statistically, males are four times more likely to develop UBC than females. It is known that decreased expression of the KDM6A gene, coded on the X chromosome, corresponds with a higher incidence of UBC. KDM6A mutations are known to be more prevalent in females with non-muscle-invasive UBC. These mutations are targetable by inhibiting EZH2, an enzyme coded by its namesake gene. On the environmental side, males are at a higher risk of developing carcinogenic complications due to smoking and environmental toxins. However, this discrepancy fails to exist when comparing males and females who smoke similar levels. Though environmental factors may play a role in influencing behavior and altering levels of risk to develop UBC, research suggests that they do not single-handedly explain sex-based disparities in UBC. In this study, we characterize the molecular mechanisms associated with altered overall survival by uncovering previously unreported data on the expression of KDM6A and FGFR3, a commonly altered oncogene, in UBC patients. Our in silico approach consisted of broad survival data analysis through cBioPortal (n=1486), sequencing-based gene expression data through ICGC Portal (n=295), and single nucleotide polymorphism identification with the PLCO Atlas (n=69,429). The 5-year overall survival (OS) curves of 13 therapeutic and/or significantly altered genes between males and females were analyzed. BRCA2 was the only gene associated with worse survival for females with alterations. Interestingly, males with alterations to the following genes had significantly better OS outcomes: ERCC2, KDM6A, BRCA2, FGFR3. However, there was no gene whose alterations were associated with significantly better OS outcomes for females. KDM6A and FGFR3, two genes whose alterations are typically associated with worse OS outcomes in males, exhibit the opposite effect. Additionally, males exhibited significantly worse OS outcomes when presenting with CDKN2A and CDKN2B alterations, while females exhibited significantly worse OS outcomes when presenting with CDKN2A and NTRK1. A majority of European males had SNPs on the following genes: CDKN2B, ERBB2, CREBBP, while a majority of European females had SNPs on BRCA2. Differential expression also revealed 714 genes that were significantly expressed in one sex when compared to the other. Therefore, we suggest that there are unique molecular differences between sex that conflict with previous analyses; further research should be conducted to explore the effect of sex via the tumor-suppressive characteristics of KDM6A as well as oncogenic properties of FGFR3. Citation Format: Rishi Nair, Roy Khalife, Anthony Magliocco. Genetic characteristics between males and females with urothelial bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 883.

Identification of SNPs and candidate genes associate with growth performance in all-female mandarin fish (Siniperca chuatsi) by a genome-wide association study

The all-female mandarin fish (Dinggui I, Siniperca Chuatsi) was recently approved by Ministry of Agriculture and Rural Affairs of the People's Republic of China as a new strain of mandarin fish (GS-04-001-2021). Select breeding of fast-growing lines is an important goal of the mandarin fish industry. However, single nucleotide polymorphisms (SNPs) associated with growth of Dinggui I mandarin fish remains unclear. Therefore, a genome-wide association study (GWAS) was performed on 5 growth traits (body weight, body length, whole length, body height and body thickness) of 192 mandarin fish. A total of 49,940 SNPs were identified by ddRAD-seq. Among them, a total of 6 significant SNPs were detected on multiple chromosomes. The proportion of phenotypic variance explained for these SNPs ranged from 9.66% to 19.47% for growth traits. Specifically, 4 SNPs were associated with all traits. Several candidate genes (AKT2, CCNT2, EPB41L2 and CAMKMT) were identified based on these SNPs. The loci were verified in 100 individuals, indicating the reliability of candidate SNPs. Our results contribute to understanding of growth traits and the development of molecular marker-assisted selection in all-female mandarin fish.

Identification of single nucleotide polymorphisms (SNPs) in selected rice phosphate transporter (OsPHT) genes

Phosphorus (P) is one of the fundamental elements for plant growth and development. Due to the scarcity of viable P in the soil for plants, P deficiency was often the culprit that restrained plant’s wellbeing. Plasma membrane phosphate transporters (PHT) are a group of proteins responsible for phosphate (Pi) uptake from soil and further allocation to plant organs and tissues. The PHT can be further categorized into constitutively expressed low-affinity Pi transporter or high-affinity Pi transporter that are induced upon Pi starvation. Significant variability in P use efficiency has been observed among different rice varieties. Genotypic differences such as single nucleotide polymorphisms (SNPs) could be responsible for the variation observed aside from the well-studied phenotypic responses. Nevertheless, the occurrence of the SNPs in OsPHT genes remain unexplored. Therefore, the objective of this study was to analyse and profile the SNPs in five selected high affinity OsPHT genes which are responsible for P uptake under P deficiency. The SNPs mining was conducted using Rice SNP-Seek Database against 3024 rice varieties with Oryza sativa japonica cultivar Nipponbare as the reference sequence. Results showed that a total of zero, seven, three, one and ten non-synonymous SNPs was identified in OsPHT1;2, OsPHT1;3, OsPHT1;6, OsPHT1;9 and OsPHT1;10, respectively. A base substitution of C to A at position 16028497 of chromosome 10 of OsPHT1;3 was found to change tyrosine to a stop codon. This could result in a truncated protein which has only 213 amino acids as compared 526 amino acids in the complete protein. The large number of non-synonymous SNPs in OsPHT1;10 could explain the redundant function of this gene in the translocation and uptake of P in rice. In short, the identified SNPs especially the non-synonymous SNPs could potentially disrupt the biosynthesis of phosphate in rice which requires further investigation.