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Pod quality and yield traits in snap bean (Phaseolus vulgaris L.) influence consumer preferences, crop adoption by farmers, and the ability of the product to be commercially competitive locally and globally. The objective of the study was to identify the quantitative trait loci (QTL) for pod quality and yield traits in a snap × dry bean recombinant inbred line (RIL) population. A total of 184 F6 RILs derived from a cross between Vanilla (snap bean) and MCM5001 (dry bean) were grown in three field sites in Kenya and one greenhouse environment in Davis, CA, USA. They were genotyped at 5,951 single nucleotide polymorphisms (SNPs), and composite interval mapping was conducted to identify QTL for 16 pod quality and yield traits, including pod wall fiber, pod string, pod size, and harvest metrics. A combined total of 44 QTL were identified in field and greenhouse trials. The QTL for pod quality were identified on chromosomes Pv01, Pv02, Pv03, Pv04, Pv06, and Pv07, and for pod yield were identified on Pv08. Co-localization of QTL was observed for pod quality and yield traits. Some identified QTL overlapped with previously mapped QTL for pod quality and yield traits, with several others identified as novel. The identified QTL can be used in future marker-assisted selection in snap bean.

Aims: We aimed to evaluate the impact of C-reactive protein (CRP) gene polymorphism, additional gene–gene interaction, and haplotypes on susceptibility to type 2 diabetes mellitus (T2DM). Methods: SNPstats online software (https://www.snpstats.net/start.htm) was employed to evaluate the association between CRP gene and T2DM risk. High-order interactions among SNPs was tested using generalized multifactor dimensionality reduction, and the testing balanced accuracy, training balanced accuracy and cross-validation consistency were calculated. The SHEsisPlus (http://shesisplus.bio-x.cn/SHEsis.html) online software was used for haplotype analysis. Results: A total of 730 T2DM patients and 765 controls were enrolled. The T allele of rs1205 is associated with increased susceptibility to T2DM, OR (95% CI) were 1.51 (1.13–2.01), 1.44 (1.10–1.89) and 1.25 (1.01–1.54) for codominant, dominant and over-dominant models, respectively. We also found that minor allele of rs2794521 is associated with decreased susceptibility to T2DM under codominant and recessive models, OR (95%CI) were 0.38 (0.18–0.79) and 0.37 (0.16–0.80) for codominant and recessive models, respectively. No significant gene–gene interaction existed among CRP gene SNPs, all interaction p- values were more than 0.05. Haplotype analyses suggested the CGCA haplotype containing rs1205-C, rs1130864-G, rs2794521- C and rs3093059- A allele was associated with decreased risk of T2DM, OR (95% CI) = 0.83 (0.68–0.98), P = 0.047. Conclusions: Minor allele of rs1205 was associated with increased T2DM risk. Minor allele of rs2794521 and the CGCA haplotype were associated with decreased T2DM risk. [ABSTRACT FROM AUTHOR]

Observational studies have suggested links between standing height, BMI, body fat percentage, and inguinal hernia risk, but with inconsistent results. We conducted Mendelian randomization (MR) method to investigate their causal relationships. Independent SNPs associated with standing height, BMI, and body fat percentage were extracted from GWAS data as instrumental variables (IVs). Two-sample MR initially explored causal relationships between these factors and inguinal hernia risk. Multivariable Mendelian randomization (MVMR) assessed the direct causal effects of exposures on inguinal hernia. Positive findings from the MVMR analysis were independently validated. The inverse-variance weighted Methods (IVW), weighted median(WM), and MR-Egger were used for the MR estimates. Sensitivity analyses were used to examine the stability and reliability of the results. Two-sample MR analysis revealed a suggestive causal association between height and inguinal hernia (OR = 1.091, 95% CI = 1.003–1.186, P = 0.042). BMI (OR = 0.846, 95% CI = 0.774–0.924, P < 0.001) and body fat percentage (OR = 0.793, 95% CI = 0.690–0.911, P = 0.001) were significantly protective factors. After MVMR adjustment, BMI (OR = 0.746,95%CI = 0.638–0.872, P < 0.001) remained protective. Independent validation yielded consistent result. Genetically predicted BMI is a significant protective factor for inguinal hernia, providing valuable guidance for individualized prevention strategies. [ABSTRACT FROM AUTHOR]

In order to describe large-scale spatial structure of sockeye salmon on the Asian part of the range, the variability of 45 SNP loci was analyzed in 22 samples from the Northwest coast of the Pacific Ocean. Three large regional population complexes were identified: Southwest Kamchatka, Kamchatka River basin, and the Northeast (comprising stocks from Koryak Highlands). Populations within the identified complexes are connected by gene migration and have a common origin, close geographic proximity, comparable climatic, landscape, and environmental conditions in the freshwater and early marine periods of sockeye salmon life. Populations confined to watersheds of the North coast of the Sea of Okhotsk (Palana and Okhota rivers), along with island populations, displayed distinctions from the isolated population complexes. It is hypothesized that the marked divergence observed in island populations is primarily caused by genetic drift occurring during long periods of isolation. The pronounced divergence of Palana River population may be the result of both genetic drift and natural selection, driven by the challenging smoltification and specific conditions of freshwater period in this watershed. At the same time in the Okhota River population, demographic factors such as genetic drift and bottlenecks played a key role. [ABSTRACT FROM AUTHOR]

Ketosis, evidenced by hyperketonemia with elevated blood β‐hydroxybutyrate (BHB) levels, is a significant metabolic disorder of dairy cattle, typically diagnosed within the first 6 weeks post‐calving when high energy levels are essential to milk production. Our study aimed to identify genetic markers linked to hyperketonemia (HYK) patterns in Holstein cows during early lactation and compare these to HYK‐negative cows. We screened 964 cows for HYK using a threshold of BHB ≥1.2 mmol/L during the first 2 weeks postpartum (screening period, SP). Cows that tested negative initially were retested the following week. Cows were deemed HYK‐negative (CON group) if BHB levels were below 1.2 mmol/L in both tests, while those with BHB levels exceeding this threshold at any test were treated and classified as HYK‐positive (HYK+). Post‐treatment, HYK+ cows were monitored for two‐week follow‐up period (FP) and classified based on their recovery: cured (CUR; consistently low BHB), recurrent (REC; fluctuating BHB levels), severe (SEV; high initial BHB that decreased), or chronic (CHR; persistently high BHB). Using 489 cows that were genotyped, a GWAS was conducted using GCTA software, revealing significant associations of several SNPs across different HYK patterns when compared to the CON group. These SNPs were primarily linked to genes affecting milk traits and were enriched in biological pathways relevant to protein glycosylation, inflammatory response, glucose homeostasis, and fatty acid synthesis. Our findings highlight genomic regions, potential candidate genes, and biological pathways related to ketosis, underscoring potential targets for improving health management in dairy cattle. These insights could lead to better strategies for managing ketosis through genetic selection, ultimately enhancing dairy cattle welfare and productivity. Further research with a larger number of cows is recommended to validate these findings and help confirm the implicated SNPs and genes. [ABSTRACT FROM AUTHOR]

A 44-year-old man with hypertension and dyslipidemia presented with pain in the buttocks. The patient was diagnosed with perianal ischiorectal fossa abscesses and cellulitis. He was subsequently diagnosed with a perineal subcutaneous abscess after a week, a right lower leg impetigo after a month, right periorchitis, a scrotal abscess, and Fournier's gangrene after two months. The patient was treated with various antimicrobials and underwent incisional drainage. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in all draining specimens. Her daughter and son, who lived with the patient, presented with subcutaneous abscesses caused by MRSA. Suspecting repeated infections and household infections by virulent types of MRSA, such as PVL-positive strains, we performed genetic analyses of his and his son's strains. The results showed that the genotype and toxin gene profiles [ST8/t008/SCCmec type IVc/Panton-Valentine leucocidin (PVL) (+)/arginine catabolic mobile element (ACME) (−)] of both strains matched. single nucleotide polymorphism (SNP) analysis confirmed genetic homology between the two, concluding that home transmission by the same clone had occurred. In addition, the strain in this case differed from USA300 [ST8/t008/SCCmec type IVa/PVL (+) ACME (+)], which is a PVL-positive MRSA worldwide, including Japan, and its genetic profile matches that of USA300-LV, which is detected mainly in South America. Furthermore, SNP analysis showed that this strain is similar to USA300-LV/J (derived from USA300-LV) detected on Ishigaki Island, Okinawa Prefecture, Japan. This is the first report of refractory infections and household transmission of USA300-LV/J. Therefore, it is necessary to closely monitor both the USA300 and the USA300-LV. [ABSTRACT FROM AUTHOR]

The dysfunction of the ABO glycosyltransferase (GT) enzyme, which is caused by mutations in the ABO gene, can lead to weak ABO phenotypes. In this study, we have discovered a novel weak ABO subgroup allele and investigated the underlying mechanism to causing its A weak phenotype. The ABO phenotyping and genotyping were performed by serological studies and direct DNA sequencing of ABO gene. The role of the novel single nucleotide polymorphism (SNP) was evaluated by 3D model, predicting protein structure changes, and in vitro expression assay. The total glycosyltransferase transfer capacity in supernatant of transfected cells was examined. The results of serological showed the subject was A weak phenotype. A novel SNP c.424A > G (p. M142V) based on ABO∗A1.02 was identified, and the genotype of the subject was AW-var/O.01 according to the gene analysis. In silico analysis showed that the SNP c.424A > G on the A allele may change the local conformation by damaging the hydrogen bonds and reduce the stability of GT. In vitro expression study showed that SNP p.M142V impaired H to A antigen conversion, although it did not affect the generation of A glycosyltransferase (GTA). One novel AW allele was identified and the SNP c.424A > G (p.M142V) can cause the A weak phenotype through damaging the hydrogen bonds and reducing stability of the GTA. [ABSTRACT FROM AUTHOR]

The relationship of single nucleotide polymorphisms (SNPs) in COL4A2 gene with risk and outcome of primary intracerebral hemorrhage (ICH) in the Chinese Han population remains unclear, which was investigated in this study. Primary ICH patients and non-stroke controls of Chinese Han ethnicity were enrolled. The genotypes of 8 tag-SNPs were determined using a custom-by-design 48-Plex SNPscan Kit. Poor 3-month outcome was defined as modified Rankin Scale score 4–6. Logistic regression was employed to examine association between COL4A2 variants and risk and poor outcome of primary ICH. 323 patients with primary ICH and 376 stroke-free controls were included. Compared to controls, the rs1049931 G and rs1049906 C alleles were associated with increased ICH risk (p = 0.027 and 0.033), and these two allele counts increased this risk after adjustments respectively (additive model: adjusted OR [aOR] 1.41, 95% CI 1.03–1.94, corrected p = 0.043; aOR 1.37, 95% CI 1.01–1.86, corrected p = 0.043). The rs1049931 AG/GG and rs1049906 CT/CC genotypes showed increased susceptibility to non-lobar hemorrhage (aOR 1.63, 95% CI 1.06–2.50, p = 0.025; aOR 1.63, 95% CI 1.07–2.47, p = 0.022). Haplotype analysis revealed an association between rs1049906-rs1049931 haplotype CG and ICH risk (OR 1.36, 95% CI 1.05–1.78, p = 0.021). Regarding clinical outcome, the rs3803230 C allele (dominant model: aOR 1.94, 95% CI 1.04–3.63, p = 0.037) and haplotype AC of rs7990214-rs3803230 (OR 1.98, 95% CI 1.13–3.46, p = 0.015) contributed to 3-month poor outcome. The COL4A2 polymorphisms are associated with an increased risk of primary ICH, mainly non-lobar hemorrhage, and with long-term poor outcome after ICH in Chinese Han population. [ABSTRACT FROM AUTHOR]

Background: Microvascular complications of diabetes including retinopathy, nephropathy, and neuropathy are those long-term complications that affect small blood vessels. Diabetic nephropathy (DN) is characterized by persistent microalbuminuria. A meta-analysis of case–control studies aims to examine the relationship between MnSOD (rs4880) and GPx1 (rs1050450) and the risk of DN. Methods: Various databases such as Web of Science, PubMed, Springer Link, Cochrane Library, Science Direct, Embase, and Google Scholar were utilized to extract relevant studies. The statistical software MedCalc version 22.009 was acquired to accomplish the meta-analysis of the included studies. Results: A significant association was found between two SNPs (rs4880 and rs1050450) and DN in the homozygous recessive model [95% confidence interval (CI) 0.97–2.41, odds ratio (OR) TT vs CC = 1.53, P = 0.06] and heterozygous model [95% CI 0.92–1.97, OR CT vs CC = 1.35, P = 0.12], while there was no association with the other genetic models. A significant association between rs4880 and DN was perceived in the Asian population [95% CI 1.24–2.03, OR = 1.6, P < 0.001], meanwhile the studies among Caucasian group showed insignificant association [95% CI 0.87–1.32, OR = 1.07, P = 0.5]. On the other hand, the association between rs1050450 and DN was significant [95% CI 3.80–13.01, OR = 7.04, P < 0.001] and insignificant [95% CI 0.96–2.28, OR = 1.48, P = 0.07] among Asian and Caucasian population, respectively. Conclusion: To date, this meta-analysis could be the first to contribute a panoramic exploration of the MnSOD and GPx1 polymorphic association with DN. The results of the study contemplate the data presently accessible from the literature and can be employed as an influential lead for future research. [ABSTRACT FROM AUTHOR]

Background and Objective Methods Results Conclusion A disintegrin and metalloprotease 33 (ADAM33) is associated with asthma susceptibility, and its genetic variations impact susceptibility and disease severity. However, the mechanisms remain unclear. This study aimed to investigate ADAM33 single nucleotide polymorphisms (SNPs) in childhood asthma susceptibility and explore their regulatory mechanisms.Eleven selected SNPs in ADAM33 were genotyped and identified the association with asthma susceptibility. In the validation cohort, we measured plasma sADAM33 levels and compared them with disease severity among children with different SNP genotypes. Computational predictions identified miRNAs targeting the SNP, and the impact of the SNP on miRNA regulation was confirmed using a dual luciferase reporter system. Finally, we validated the regulatory role of miRNAs on ADAM33 expression using an in vitro model with upregulated ADAM33 expression.Only rs3918400 was associated with asthma susceptibility. In the validation cohort, children with allergic asthma exhibited higher plasma sADAM33 levels. Among asthmatic children, those with the rs3918400 CT/TT genotype had higher sADAM33 levels, poorer asthma control, more severe airway hyper‐responsiveness, lower FEV1% and higher dust mite‐specific IgE activity compared to those with the CC genotype. miR‐3928‐5p bound strongly to the rs3918400 C allele and effectively reduced ADAM33 protein expression in CC genotype cells. However, the binding affinity of miR‐3928‐5p to the T allele was weaker, resulting in diminished negative regulation of protein expression.The rs3918400 SNP affects the negative regulation of ADAM33 by miR‐3928‐5p, potentially participating in a complex interplay of processes related to childhood asthma susceptibility. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

This study was performed on Micropterus salmoides to determine growth-linked gene and single nucleotide polymorphism (SNP) markers under carbohydrate diet and varying temperature through RNA-seq and whole-genome re-sequencing. The results showed that growth-related genes were primarily enriched in the fat digestion and absorption signaling pathway, playing a role in lipid transport and metabolism. Fatty acid binding protein 6, bile salt-activated lipase-like, lysophosphatidylcholine acyltransferase 2, phospholipase A2, minor isoenzyme-like, and phospholipase A2, group IB (pancreas) were identified as the crucial genes. The differentially expressed genes between high and low temperatures were enriched in the pentose phosphate pathway, with carbohydrate transport and metabolism were most affected by temperature. Major facilitator superfamily domain containing 10, phosphogluconate dehydrogenase, fructose-1,6-bisphosphatase 1a, and spinster homolog 3 transcript variant X1(spns3) were the shared genes affected by temperature. From all the common genes, 10 growth-associated SNP markers were identified. The TT genotype at rs7781 was associated with lower body weight, while AA genotype at rs31434173 and CC genotype at rs31435313 showed positive correlation with body weight. Analogously, the GG genotype at rs31436887 and AA genotype at rs31438769 also found to characterize better growth performance. At low temperature, individuals with the AA genotype at rs11506587 and rs31435313 exhibited the slowest growth. For the genotypes labeled with rs11510589, the GG individual grew faster than the AA individual, whereas the opposite phenomenon occurred in these genotypes when labeled with rs11511314. The genotypes at rs32970704 and rs32967921 showed no growth correlation. The AA genotype at rs31435313 in spns3 had the slowest growth under a carbohydrate-rich diet regardless of the temperature. Our study presents candidate genes and SNP markers associated with growth influenced by carbohydrate and temperature, providing basis for the development of M. salmoides strain that better accepts carbohydrate diets at varying temperature. [ABSTRACT FROM AUTHOR]

This study aimed to explore the potential association between Endothelin type A receptor (EDNRA) genetic polymorphisms and susceptibility to large artery atherosclerotic stroke (LAA), as well as the involvement of inflammation mechanisms. We recruited Han Chinese patients with LAA and age- and sex-matched controls. The distribution of alleles and genotypes for 16 single nucleotide polymorphisms (SNPs) in EDNRA was analyzed using dominant, recessive, and co-dominant genetic models between cases and controls. We quantified the mRNA and protein levels of EDNRA and NLRP3 genes, and concentrations of inflammatory factors (TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, and CCL18) in peripheral blood samples randomly selected from cases and controls. We also investigated the relationship between these SNPs, gene expression patterns and inflammatory factor levels. A total of 428 LAA cases and 434 controls were enrolled in this study. The results showed that rs5343 TT genotype of EDNRA was significantly associated with an increased risk of LAA (OR = 3.243, 95%CI = 1.608–6.542, P = 0.001). It also demonstrated a significant upregulation level of NLRP3 as well as higher concentrations of IL-10, IL-18, and CCL-18 in cases compared to controls. Besides, we discovered that the EDNRA polymorphisms were linked to NLRP3, IL-6, IL-10, and IL-18 levels in cases. There existed a positive correlation between EDNRA transcription levels and both NLRP3 transcript levels (r = 0.437, p < 0.001) and IL-18 concentrations (r = 0.212, p < 0.001). EDNRA is linked to susceptibility of LAA. This association may be attributed to the NLRP3-mediated inflammatory pathway. [ABSTRACT FROM AUTHOR]

Background : Garuga Roxb. is a genus endemic to southwest China and other tropical regions in Southeast Asia facing risk of extinction due to the loss of tropical forests and changes in land use. Conducting a genome survey of G. forrestii contribute to a deeper understanding and conservation of the genus. Results: This study utilized genome survey of G. forrestii generated approximately 54.56 GB of sequence data, with approximately 112 × coverage. K-mer analysis indicated a genome size of approximately 0.48 GB, smaller than 0.52GB estimated by flow cytometry. The heterozygosity is of about 0.54%, and a repeat rate of around 51.54%. All the shotgun data were assembled into 339,729 scaffolds, with an N50 of 17,344 bp. The average content of guanine and cytosine was approximately 35.16%. A total of 330,999 SSRs were detected, with mononucleotide repeats being the most abundant at 70.16%, followed by dinucleotide repeats at 20.40%. We conducted a preliminary ploidy assessment using Smudgeplot and observed a clear bimodal distribution in G. forrestii at 1/2 relative coverage depth and total coverage depth (2n), suggesting a potential diploid genome structure. A pseudo chromosome of G. forrestii and a gemone of Boswellia sacra were used as reference genome to perform a primer population resequencing analysis within three Garuga species. Principal component analysis (PCA) indicated three distinct groups, but genome wide phylogenetics represented conflicting both between the dataset of different reference genomes and between maternal and nuclear genome. Conclusion: In summary, the genome of G. forrestii is small, and the phylogenetic relationships within the Garuga genus are complex. The genetic data presented in this study holds significant value for comprehensive whole-genome analyses, the evaluation of population genetic diversity, investigations into adaptive evolution, the advancement of artificial breeding efforts, and the support of species conservation and restoration initiatives. Ultimately, this research contributes to reinforcing the conservation and management of natural ecosystems, promoting biodiversity conservation, and advancing sustainable development. [ABSTRACT FROM AUTHOR]

Identifying genetic regions and candidate genes that influence milk production traits is critical for understanding genetic inheritance and improving both the quality and quantity of milk in dairy cattle. Crossbred dairy cattle significantly contribute to increasing milk production and ensuring food security in the middle‐ and high‐altitude regions of Ethiopia. However, the genetic architecture underlying their milk yield and composition traits has not yet been thoroughly investigated. This study conducted a genome‐wide association study (GWAS) on 308 crossbred dairy cows from central, northeastern, and southern Ethiopia to identify genetic markers associated with key milk production traits. Using high‐density SNP chip data and the fixed and random model circulating probability unification (Farm CPU) method via the Memory‐efficient, Visualization‐enhanced, and Parallel‐accelerated R package (rMVP) (Version 1.0.7.), we analyzed traits including test‐day milk yield (TDMY), total protein (TP), casein (CN), whey (W), protein percentage (P), fat percentage (F), lactose percentage (L), total solids (TS), density (D), solids‐not‐fat (SNF), salt (S), and freezing point (FP). This study identified 16 significant SNPs associated with these traits, including rs41661899 on Chromosome 6, which was significantly associated with both TP and W, and rs42274954 on Chromosome 12, which was significantly associated with CN. Eight SNPs, such as rs43560693, rs109098713, rs111029661, rs134499665, rs133908307, rs133627532, rs42098411, and rs110066280, were found across multiple chromosomes (8, 10, 14, 15, 19, 21, 26, and 28, respectively) and were significantly associated with milk P. Additionally, SNPs rs110844447 and rs135995768 on Chromosomes 6 and 14 were significantly associated with D and FP, respectively. Three SNPs, including rs109564259, rs135552551, and rs41620904 on Chromosomes 6, 11, and 24, were significant associations with S. Candidate genes identified near and within these SNPs include TRAM1L1, DIAPH3, PEBP4, WDR89, BCAS3, RALGAPA1, HABP2, NRG3, HPSE, PCDH7, LINC02579, TRNAS‐GGA, and OR5CN1P. These findings enhance our understanding of the genetic architecture of milk‐related traits in Ethiopian dairy cattle and highlight the potential for marker‐assisted selection to improve milk production and composition in breeding programs. [ABSTRACT FROM AUTHOR]

Introduction and objectives: Recent studies have indicated a potential association of hypertension with Hashimoto's thyroiditis (HT) and other autoimmune diseases, yet the impact of antihypertensive drugs on HT risk is not well understood. Methods: We employed a drug-target Mendelian randomization approach to investigate the prolonged impact of 9 classes of antihypertensive medications on HT susceptibility in European and Asian populations. Genetic variants close to or within genes associated with the drug targets and systolic blood pressure (SBP) were utilized to mimic the effects of antihypertensive medications. We focused on drugs linked to a lower risk of coronary artery disease for our main analysis. We gathered genetic data on SBP and HT risk from comprehensive genomewide association studies available for European and Asian groups. For a supplementary analysis, we used expression quantitative trait loci (eQTLs) related to drug target genes as proxies. Results: Our analysis revealed that the use of calcium channel blockers (CCBs) is linked to a reduced risk of HT in both European (OR [95% CI]: 0.96 [0.95 to 0.98] per 1 mmHg decrease in SBP; p = 3.51×10-5) and Asian populations (OR [95% CI]: 0.28 [0.12, 0.66]; p = 3.54×10-3). Moreover, genetically mimicking the use of loop diuretics (OR [95% CI]: 0.94 [0.91, 0.97]; p = 3.57×10-5) and thiazide diuretics (0.98 [0.96, 0.99]; p = 3.83×10-3) showed a significant association with a decreased risk of HT only in European population. These outcomes were confirmed when eQTLs were employed to represent the effects of antihypertensive medications. Conclusion: The study suggests that CCBs and diuretics could potentially reduce the risk of HT in different populations. Additional research is needed to assess the feasibility of repurposing antihypertensive medications for the prevention of HT. [ABSTRACT FROM AUTHOR]

Enteritis caused by Vibrio is a highly die-off disease that severely impeded substantial production in seahorse aquaculture. In the present study, challenged with LD50 of concentration of Vibrio harveyi, a total of 161 of susceptible and 166 of resistant individuals were allocated into binary survival phenotypes, thus, to firstly investigate the genetic architecture by genome-wide association study (GWAS) analysis, as well as to evaluate the feasibility of genomic selection (GS) in enteritis disease resistance trait of the lined seahorse Hippocampus erectus. Results indicated that the heritability for resistance to Vibrio harveyi was estimated to be 0.10. And a set of 10 significant/suggestive SNPs in a multiple chromosomes localization were identified, explaining 7.76% to 13.28% of genetic variance. Associated 82 of candidate genes were clustered into signal transduction, cell proliferation, response of external stress, bacteria defence, and antiinflammatory processes. Moreover, the potential performance of genomic selection (GS) in application in selective breeding for enteritis disease resistance seahorses was assessed by genomic prediction (GP). In general, the predictive accuracy of the genomic estimated breeding value (GEBV) of BayesC exceeded the rrBLUP, BayesA, RKHS, and SVM models while with no significant difference. And the GWAS-informative SNPs was significantly superior in efficience than random selected markers by comparison of predictive performance on different selection strategies of SNPs. Overall, the genetic basis of enteritis disease resistance trait in the lined seahorse is a polygenic genetic architecture. SNPs associated with the important genes of cathepsin L1-like previously reported with respect to disease resistance are consider as potential molecular markers of genetic breeding. Furthermore, GS approach is an appropriate, effective, and less-cost application in breeding enteritis disease-resistant seahorses. [ABSTRACT FROM AUTHOR]

Simple Summary: The genetic polymorphisms in the ovocalyxin-32 gene were studied in the present work with regard to egg quality traits in indigenous chicken populations. In the same investigation, based on exons 1 and 6, the frequencies of G/T and A/G SNPs regarding the Hardy–Weinberg equilibrium (HWE) and their role in egg quality were determined. The T allele of the G/T SNP in exon 1 was associated with thinner shells and lower shell strength, while the A/G SNP in exon 1 resulted in eternal eggs with thicker shells in AG and AA genotypes. Regarding this, the A/G SNP in exon 6 was able to enhance shell and yolk quality in AG genotypes. These SNPs could be considered candidate genetic markers for marker-assisted selection (MAS) focusing on egg quality improvement, which has additive and dominance genetic effects on phenotypic variation. This study sought to evaluate the genetic variations of the ovocalyxin-32 gene and its association with egg quality traits in indigenous chicken populations, focusing on exons 1 and 6. Genotype frequencies of SNPs (G/T and A/G) within these exons were assessed for their conformity to the Hardy–Weinberg equilibrium (HWE) across several strains. While most strains exhibited close adherence to HWE expectations, some like light-brown and gray strains indicated substantial discrepancies, particularly for the TT genotype, which points towards the possible effects of genetic drift as well as selection pressures. This study also analyzed the influence of such SNPs on egg quality parameters. A thinner eggshell, reduced shell weight, and decreased breaking strength were associated with the G/T SNP in exon 1, suggesting a likely negative effect on egg quality in T allele carriers. Conversely, the AG genotype displayed better performance in shell thickness, weight and egg weight in the A/G SNP in exon 1, whilst yolk height was best improved by the AA genotype compared to breaking strength. For instance, in exon 6, the A/G SNP enhanced the shell and yolk quality among AG genotypes, while the CC genotype resulted in better eggshell characteristics with enlarged yolks because the C/T SNP was linked. Nonetheless, there were no significant deviations from the HWE despite these associations, which suggested that most breeds had a stable genetic background. Further, considering SNPs' additive and dominant effects in this research, it was indicated that additive effects account for phenotypic expressions given by the G/T SNP located at exon 1. In contrast, significant additive and dominant effects were observed under the A/G SNP situated at the exon. Generally, it therefore could be concluded from this study that specific SNPs within the ovocalyxin-32 gene may act as good markers for marker-assisted selection (MAS) that can improve desired characteristics—such as those of egg quality—in indigenous chicken breeds. This study demonstrated that both additive and dominance effects must be taken into account when performing genetic analyses, thereby emphasizing the complexity of phenotypic variation caused by genetic mechanisms in native chicken races. [ABSTRACT FROM AUTHOR]

Simple Summary: Expression quantitative trait locus (eQTL) analysis is crucial in revealing the genetic basis of complex traits, advancing the study of human diseases, optimizing the breeding of agricultural plants and animals, and gaining a deeper understanding of specific biological processes. The conventional analysis involves correlating genetic variants from whole-genome sequencing (WGS) data and gene expression, but to improve the power of eQTL detection, it is often necessary to expand the sample size as far as possible, ranging from hundreds to thousands. Large sample sizes for WGS are extremely costly, and this bottleneck is particularly evident in economically important agricultural animals. In contrast, the advantages of eQTL analyses from transcriptome data are obvious: cost-effective, simultaneous acquisition of variants and expression information. We propose to use transcriptome data alone for SNP calling and kmer generation, and then association analysis with gene expression. Here, 87 SNP-based and 35 kmer-based association results were obtained. Subsequently, comparison and validation of these two results revealed that they each have their own strengths and can complement each other, which promotes in-depth exploration of the regulatory relationship between genetic variants and gene expression. Traditional expression quantitative trait locus (eQTL) mapping associates single nucleotide polymorphisms (SNPs) with gene expression, where the SNPs are derived from large-scale whole-genome sequencing (WGS) data or transcriptome data. While WGS provides a high SNP density, it also incurs substantial sequencing costs. In contrast, RNA-seq data, which are more accessible and less expensive, can simultaneously yield gene expressions and SNPs. Thus, eQTL analysis based on RNA-seq offers significant potential applications. Two primary strategies were employed for eQTL in this study. The first involved analyzing expression levels in relation to variant sites detected between populations from RNA-seq data. The second approach utilized kmers, which are sequences of length k derived from RNA-seq reads, to represent variant sites and associated these kmer genotypes with gene expression. We discovered 87 significant association signals involving eGene on the basis of the SNP-based eQTL analysis. These genes include DYNLT1, NMNAT1, and MRLC2, which are closely related to neurological functions such as motor coordination and homeostasis, play a role in cellular energy metabolism, and function in regulating calcium-dependent signaling in muscle contraction, respectively. This study compared the results obtained from eQTL mapping using RNA-seq identified SNPs and gene expression with those derived from kmers. We found that the vast majority (23/30) of the association signals overlapping the two methods could be verified by haplotype block analysis. This comparison elucidates the strengths and limitations of each method, providing insights into their relative efficacy for eQTL identification. [ABSTRACT FROM AUTHOR]

Autoimmune polyglandular syndrome (APS) comprises a complex association of autoimmune pathological conditions. APS Type 1 originates from loss-of-function mutations in the autoimmune regulator (AIRE) gene. APS2, APS3 and APS4 are linked to specific HLA alleles within the major histocompatibility complex, with single-nucleotide polymorphisms (SNPs) in non-HLA genes also contributing to disease. In general, variability in the AIRE locus and the presence of heterozygous loss-of-function mutations can impact self-antigen presentation in the thymus. In this study, whole-exome sequencing (WES) was performed on a sixteen-year-old female APS3A/B patient to investigate the genetic basis of her complex phenotype. The analysis identified two variants (p.Arg111Trp and p.Thr101Ile) of the hepatitis A virus cell receptor 2 gene (HAVCR2) encoding for the TIM-3 (T cell immunoglobulin and mucin domain 3) protein. These variants were predicted, through in silico analysis, to impact protein structure and stability, potentially influencing the patient's autoimmune phenotype. While confocal microscopy analysis revealed no alteration in TIM-3 fluorescence intensity between the PBMCs isolated from the patient and those of a healthy donor, RT-qPCR showed reduced TIM-3 expression in the patient's unfractionated PBMCs. A screening conducted on a cohort of thirty APS patients indicated that the p.Thr101Ile and p.Arg111Trp mutations were unique to the proband. This study opens the pathway for the search of TIM-3 variants possibly linked to complex autoimmune phenotypes, highlighting the potential of novel variant discovery in contributing to APS classification and diagnosis. [ABSTRACT FROM AUTHOR]

Although farmed shrimp contribute to global food security and foreign exchange, the development of genomic resources such as single nucleotide polymorphisms for these shrimp is at slow pace. Public genomic resources like Genbank and Ensembl do not host polymorphism data for shrimp. Therefore, through analysis of the short RNA‐sequence reads generated on pooled‐individual samples, using the latest bioinformatics tools, this study documents data of single nucleotide polymorphisms in two shrimp species, Penaeus vannamei and Penaeus indicus, and presents these data in a searchable user‐friendly webtool, the dbVAST. The webtool also hosts the information about the possible effects that the variations could have on the functioning of the coded protein. This is the first open‐access SNP database of shrimp intended to benefit researchers and academicians by showcasing variations in shrimp transcripts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Existing epidemiological data indicated a correlation between thyroid cancer (THCA) and the risk of secondary primary malignancies (SPMs). However, the correlation does not always imply causality. Methods: The Mendelian randomization (MR) analyses were performed to investigate the causal relationships between THCA and SPMs based on international multicenter data. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. The Cancer Genome Atlas (TCGA) was used to explore potential mechanisms shared by THCA and bladder cancer (BLCA). Results: Summary datasets of genome-wide association studies (GWAS) on 30 types of cancers were obtained from the United Kingdom Biobank (UKB) and FinnGen database. Meta-analysis of the UKB and FinnGen results revealed that THCA was significantly positively correlated with BLCA (OR = 1.140; 95% CI, 1.072-1.212; P < 0.001). Four genes, including WNT3, FAM171A2, MLLT11, and ULBP1, were identified as key genes shared by both TCHA and BLCA. Correlation analysis indicated that THCA may increase the risk of secondary BLCA through augmentation of N2 neutrophil infiltration. Conclusions: This study showed that THCA was causally related to BLCA. It is recommended to conduct more rigorous screenings for BLCA during the followup of THCA patients. [ABSTRACT FROM AUTHOR]

Background: Behcet's syndrome (BS) is a variable-vessel vasculitis characterized by hyperactive innate immunity. The nuclear factor kappa B (NFKB) pathway is involved in the regulation of inflammatory responses including innate and adaptive immune responses. BS could be associated with NFKB hyperactivation. We aimed to study the association between the NFKB1 A > G (rs4648068) single-nucleotide polymorphism (SNP) and BS in Egyptian patients, in comparison to healthy controls, and to correlate the presence of rs4648068 SNP with the different activity domains of the disease. After ethical committee approval (Faculty of Medicine, Cairo University, Egypt, code MD-228-2022), the International Study Group Criteria for Behçet's Disease (ISG) criteria was used to recruit 60 BS patients, and the activity of the disease was assessed using Behcet's Disease Current Activity Form (BDCAF) and the Behcet Syndrome Activity Score (BSAS). Another 60 matched controls were recruited. DNA extraction was done followed by PCR amplification to detect the target SNP. Results: The GG genotype was significantly higher in BS versus controls (21.7% and 5%, respectively, p value = 0.015). Also, the G allele was significantly higher in BS versus controls (43.3% and 30%, respectively, p value = 0.033). Of the whole activity domains, only arthralgia was found to be significantly correlated with rs4648068 SNP. Conclusion: NFKB1 rs4648068 A > G SNP increases the risk of developing BS. Among patients with BS, the GG genotype is protective against developing arthralgia. There is no statistically significant relation between rs4648068 SNP and either other activity domains of BS or the different activity scores of the disease. [ABSTRACT FROM AUTHOR]

Background: Anadara granosa, commonly known as the blood clam, exhibits the unusual characteristic of having red blood among invertebrates. There is significant individual variation in blood color intensity among blood clams; individuals with vibrant red blood are deemed healthier and exhibit stronger stress resistance. However, the molecular basis underlying these red blood traits (RBTs) remains poorly understood. Results: In this study, we performed genome-wide association studies (GWAS) in a population of 300 A. granosa individuals, focusing on RBTs as measured by hemoglobin concentration (HC), total hemocyte count (THC), and heme concentration (HEME). Our analysis identified 18 single nucleotide polymorphisms (SNPs) correlated with RBTs, subsequently selected 117 candidate genes within a 100 kb flanking region of these SNPs, potentially involved in the RBTs of A. granosa. Moreover, we discovered two haplotype blocks specifically associated with THC and HEME. Further analysis revealed eight genes (Septin7, Hox5, Cbfa2t3, Avpr1b, Hhex, Eif2ak3, Glrk, and Rpl35a) that significantly influence RBTs. Notably, a heterozygous A/T mutation in the 3'UTR of Cbfa2t3 was found to promote blood cell proliferation. These genes suggest that the hematopoietic function plays a significant role in the variability of RBTs in A. granosa. Conclusions: Our findings reveal a conservation of the regulatory mechanisms of RBTs between blood clams and vertebrates. The results not only provide a scientific basis for selective breeding in blood clams, but also offer deeper insights into the evolutionary mechanisms of RBTs in invertebrates. [ABSTRACT FROM AUTHOR]

Erect panicles with enhanced grain numbers can rationally utilize solar energy for dry matter accumulation. Only in japonica cultivars an inactive natural nonsense mutant allele of DEP1 has been reported to pleiotropically improve panicle architecture, nitrogen use efficiency, nitrogen and dry matter translocation and strength of the stem. Genomic sequence comparison of DEP1 in indica, aus and aromatic genotypes of West Bengal led to the identification of four natural allelic variants based on three single nucleotide polymorphisms (SNPs) on intron 1, two SNPs on exon 5 and two deletions on intron 2. Among them, a yield favourable missense mutant allele of DEP1 with two amino acid substitutions from Patnai 23 has been identified, and an allele‐specific co‐dominant marker based on the SNP (A/G) at 333rd position of exon 5 was designed. Assessment of DEP1Patnai 23 allele for yield improvement was examined in RILs and NILs developed from Patnai23 × N22 as N22 carries wild‐type allele. The relative abundance of DEP1 transcript in young panicles was twice as high in Patnai 23 than in N22. RIL‐DEP1Patnai 23 and NIL‐DEP1Patnai 23 showed enhanced grain number per panicle and total yield per plant compared to RIL‐DEP1N22 and NIL‐DEP1N22 allele. This newly identified DEP1 allele and marker will accelerate MAS to improve rice yield precisely. [ABSTRACT FROM AUTHOR]

Aim: To clarify the association between genetic factors related to angiogenesis and feeling of incomplete bladder emptying among older community‐dwelling individuals. Method: A cross‐sectional study of 1762 (607 men and 1155 women) older Japanese individuals aged 60–79 years with data on rs3025020 was conducted, because vascular endothelial growth factor (VEGF), which contributes to the progression of angiogenesis, has been reported to be positively associated with the minor allele (T) of polymorphism rs3025020. Results: In the study population, 155 (103 men and 52 women) had feeling of incomplete bladder emptying. With rs3025020 (C/C) as the reference group, rs3025020 (T/T) was associated with a significantly higher odds ratio (OR) for feeling of incomplete bladder emptying. The adjusted ORs and 95% confidence intervals were 3.01(1.53, 5.93) in men and 2.48 (1.09, 5.66) in women, respectively. Conclusion: VEGF polymorphism rs3025020 was associated with feeling of incomplete bladder emptying among older community‐dwelling individuals. Development of angiogenesis could be associated with feeling of incomplete bladder emptying in older individuals. Geriatr Gerontol Int 2024; 24: 1039–1044. [ABSTRACT FROM AUTHOR]

Hollowness is a physiological disorder that frequently occurs during the growth and postharvest storage phases of fleshy radish roots, significantly diminishing quality, yield, and marketability. However, the molecular mechanism for hollowness remains elusive. To identify the QTLs and potential candidate genes for hollowness tolerance in radish, F2 and BC1 populations were constructed from hollowness-tolerant radish (C16) and hollowness-sensitive radish (C17) in the present study. Genetic analysis indicated that hollowness tolerance may be governed by two independent recessive genes. By employing bulked segregant analysis sequencing (BSA-seq), two significant candidate genomic intervals were pinpointed on chromosomes R04 (960 kb, 6.48–7.44 Mb) and R05 (600 kb, 31.44–32.04 Mb), which together harbor 107 annotated genes. Transcriptomic sequencing revealed that the downregulated differentially expressed genes (DEGs) were significantly enriched in biological processes related to cell death and the response to water stress, whereas the upregulated DEGs were significantly associated with the chitin catabolic process and the cell wall macromolecule metabolic process. A total of 46 intersecting genes were identified among these DEGs within the genomic intervals of interest. One gene with high expression (Rsa10025345) and two with low expression (Rsa10025320 and Rsa10018106) were detected in the tolerant variety C16. Furthermore, a SNP within Rsa10025320 resulting in an amino acid change (A188E) was characterized through sequence variation observed in both BSA-seq and RNA-seq data and further developed as a derived cleaved amplified polymorphic sequence (dCAPS) marker. Our study reveals potential target genes for tolerance to hollowness and paves the way for marker-assisted breeding of hollowness tolerance in red-skinned radishes. [ABSTRACT FROM AUTHOR]

Beclin 1 protein encoded by the BECN1 gene plays a critical role in the autophagy pathway which is utilized by the Hepatitis B virus (HBV) for its replication. HBV is known for the subversion of the host's autophagy process for its multiplication. The aim of this study was to determine the role of BECN1 intronic variants in HBV susceptibility. Intronic region variant rs9890617 was analyzed using Human splicing finder v3.1 and was found to alter splicing signals. A total of 712 individuals (494 HBV infected and 218 healthy controls) were recruited in the study and genotyped by applying Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR–RFLP). Statistical analysis revealed that the mutant allele T of rs9890617 was significantly associated with the overall disease risk in the allelic model (OR 1.41; 95%CI 1.00–1.99, p = 0.04). On stratifying the data based on the different stages of HBV infection, the mutant genotype showed a significant association with the chronic group in allelic (OR 1.62; 95%CI 1.11–2.39, p = 0.01), dominant (OR 1.64; 95%CI 1.07–2.52, p = 0.02), and co-dominant (OR 1.55; 95%CI 1.00–2.40, p = 0.04) models. Overall, this is the first study regarding beclin 1 variant rs9890617 and we found a significant association of the mutant T allele with the genetic predisposition to HBV infection. [ABSTRACT FROM AUTHOR]

Suicide is a leading cause of death worldwide. Suicide ideation (SI) is a known risk factor for suicide behaviour (SB). The current psychobiology and genetic predisposition to SI and SB are poorly defined. Despite convincing relevance of a genetic background for SI, there is no current implementable knowledge about the genetic makeup that identifies subjects at risk for it. One of the possible reasons for the absence of a clear-cut evidence is the polygenetic nature of SI along with the very large sample sizes that are needed to observe significant genetic association result. The CATIE sample was instrumental to the analysis. SI was retrieved as measured by the Calgary test. Clinical possible covariates were identified by a nested regression model. A principal component analysis helped in defining the possible genetic stratification factors. A GWAS analysis, polygenic risk score associated with a random forest analysis and a molecular pathway analysis were undertaken to identify the genetic contribution to SI. As a result, 741 Schizophrenic individuals from the CATIE were available for the genetic analysis, including 166,325 SNPs after quality control and pruning. No GWAS significant result was found. The random forest analysis conducted by combining the polygenic risk score and several clinical variables resulted in a possibly overfitting model (OOB error rate < 1%). The molecular pathway analysis revealed several molecular pathways possibly involved in SI, of which those involved in microglia functioning were of particular interest. A medium-small sample of SKZ individuals was analyzed to shed a light on the genetic of SI. As an expected result from the underpowered sample, no GWAS positive result was retrieved, but the molecular pathway analysis indicated a possible role of microglia and neurodevelopment in SI. [ABSTRACT FROM AUTHOR]

Genetic variants can affect gene expression by altering the level of N6-methyladenosine (m6A) modifications. A better understanding of the association of these genetic variants with susceptibility to cervical cancer (CC) can promote advances in disease screening and treatment. Genome-wide identification of m6A-associated functional SNPs for CC was performed using the TCGA and JENGER databases, incorporating the data from RNA-seq and MeRIP-seq. The screened risk-associated SNP rs1059288 (A>G), which is located in the 3′ UTR of TAPBP, was further validated in a case–control study involving 921 cases and 1077 controls. The results revealed a significant association between rs1059288 and the risk of CC (OR 1.48, 95% CI 1.13–1.92). Mechanistically, the presence of the risk G allele of rs1059288 was associated with increased m6A modification of TAPBP compared with the A allele. This modification was facilitated by the m6A methyltransferase METTL14 and the reading protein YTHDF2. Immunohistochemical staining of tissue microarrays containing 61 CC and 45 normal tissues showed an overexpression of TAPBP in CC. Furthermore, the upregulation of TAPBP promoted the growth and migration of CC cells as well as tumor-forming ability, inhibited apoptosis, and conferred increased resistance to commonly used chemotherapeutic drugs such as bleomycin, cisplatin, and doxorubicin. Knockdown of TAPBP inhibited the JAK/STAT/MICB signaling pathway in CC cells and upregulated certain immune genes including ISG15, IRF3, PTPN6, and HLA-A. These findings offer insights into the involvement of genetic variations in TAPBP in the development and progression of CC. [ABSTRACT FROM AUTHOR]

Increasing consumption of apples (Malus domestica Borkh.) produced in Norway requires the availability of superior cultivars and extended marketability. Favorable texture and slow softening are important traits for consumer appreciation and postharvest performance. Apple texture has been well characterized using both sensory evaluation and instrumental assessments, and major quantitative trait loci (QTL) have been detected. With texture being targeted as an important trait and markers being publicly available, marker-assisted selection has already been implemented into several breeding programs. When focusing solely on a limited set of markers linked to well-investigated major QTLs, most minor-effect QTLs are normally excluded. To find novel potential SNP markers suitable to assist in selection processes, we selected a subset of accessions from a larger apple collection established in Norway based on the favorable alleles of two markers previously associated with texture, enabling the investigation of a minor part of the variance initially masked by the effect of major loci. The subset was employed to conduct a genome-wide association study aiming to search for associations with texture dynamics and retainability. QTL regions related to texture at harvest, postharvest, and for the storage index were identified on chromosomes 3, 12, and 16. Specifically, the SNPs located on chromosome 12 were shown to be potential novel markers for selection of crispness retention during storage, a valuable storability trait. These newly detected QTLs and underlying SNPs will represent a potential set of markers for the selection of the most favorable accessions characterized by superior fruit texture properties in ongoing breeding programs. [ABSTRACT FROM AUTHOR]

The meta-analysis was used to summarize the results of previously performed studies on variability of 45 single-nucleotide polymorphism loci and 13 microsatellite loci in Asian sockeye salmon Oncorhynchus nerka populations from the eastern coast of Kamchatka and Chukotka. Allelic frequencies of both types of markers were analyzed using congruent statistical approaches in 53 sample sets from 13 sockeye salmon reproduction watersheds on the west coast of the Bering Sea and the western Pacific Ocean. The spatial structure of the species in considered part of its distribution range was assessed and four major regional population complexes were identified: the Koryak Plateau and Chukotka, the Karaginsky Gulf, the Kamchatka River Basin, and southeastern Kamchatka. The formation of the geographic structure of the sockeye salmon on the Asian Pacific coast is associated with the history of colonization of the region by the species and its adaptation to reproductive conditions in the river and lake-river systems of eastern Kamchatka and Chukotka. [ABSTRACT FROM AUTHOR]

Selection is a fundamental part of the plant breeding process, enabling the identification and development of varieties with desirable traits. Thanks to advances in genetics and biotechnology, the selection process has become more precise and efficient, resulting in faster breeding progress and better adaptation of crops to environmental challenges. Genetic parameters related to gene additivity and epistasis play a key role and can influence decisions on the suitability of breeding material. In this study, 188 rapeseed doubled haploid lines were assessed in field conditions for resistance to Leptosphaeria spp. Through next-generation sequencing, a total of 133,764 molecular markers (96,121 SilicoDArT and 37,643 SNP) were obtained. The similarity of the DH lines at the phenotypic and genetic levels was calculated. The results indicate that the similarity at the phenotypic level was markedly different from the similarity at the genetic level. Genetic parameters related to additive gene action effects and epistasis (double and triple) were calculated using two methods: based on phenotypic observations only and using molecular marker observations. All evaluated genetic parameters (additive, additive-additive and additive-additive-additive) were statistically significant for both estimation methods. The parameters associated with the interaction (double and triple) had opposite signs depending on the estimation method. [ABSTRACT FROM AUTHOR]

Background/Objectives: Genetic factors contribute to the physiopathology of obesity and its comorbidities. This study aimed to investigate the association of the SNPs ABCA1 (rs9282541), ADIPOQ (rs2241766), FTO (rs9939609), GRB14 (rs10195252), and LEPR (rs1805134) with various clinical, anthropometric, and biochemical variables. Methods: The study included 396 Mexican mestizo individuals with obesity and 142 individuals with normal weight. Biochemical markers were evaluated from peripheral blood samples, and SNP genotyping was performed using PCR with TaqMan probes. A genetic risk score (GRS) was computed using an additive model. Results: No significant associations were found between the SNPs ABCA1, ADIPOQ, FTO, and LEPR with obesity. However, the T allele of the GRB14 SNP was significantly associated with obesity (χ2 = 5.93, p = 0.01; OR = 1.52; 95% CI: 1.08–2.12). A multivariate linear regression model (adjusted R-squared: 0.1253; p < 0.001) predicting LDL-c levels among all participants (n = 538) identified significant (p < 0.05) beta coefficients for several anthropometric and biochemical variables, as well as for the GRS. Additionally, the interaction between the GRS and the waist-to-hip ratio (WHR) showed a negative beta coefficient (BC = −26.5307; p = 0.014). Participants with a WHR < 0.839 showed no effect of GRS on LDL-c concentration, while those with a WHR > 0.839 exhibited a greater effect of GRS (~9) at lower LDL-c concentrations (~50 mg/dL) and a lesser effect of GRS (~7) at higher LDL-c concentrations (~250 mg/dL). Conclusions: A significant interaction between genetics and WHR influences LDL-c in Mexicans, which may contribute to the prevention and clinical management of dyslipidemia and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Rice is one of the most important food crops in the world and is important for global food security. However, damage caused by striped stem borer (SSB) seriously threatens rice production and can cause significant yield losses. The development and use of resistant rice varieties or genes is currently the most effective strategy for controlling SSB. We genotyped 201 rice samples using 2849855 high-confidence single nucleotide polymorphisms (SNPs). We conducted a genome-wide association study (GWAS) based on observed variation data of 201 rice cultivars resistant to SSB. We obtained a quantitative trait locus (QTL)-qRSSB4 that confers resistance to SSB. Through annotation and analysis of genes within the qRSSB4 locus, as well as qRT-PCR detection in resistant rice cultivars, we ultimately selected the candidate gene LOC_;Os04g34140 (named OsRSSB4) for further analysis. Next, we overexpressed the candidate gene OsRSSB4 in Nipponbare through transgenic methods, resulting in OsRSSB4 overexpressing lines (OsRSSB4OE). In addition, we evaluated the insect resistance of OsRSSB4OE lines using wild type (Nipponbare) as a control. The bioassay experiment results of live plants showed that after 20 days of inoculation with SSB, the withering heart rate of OsRSSB4OE-34 and OsRSSB4OE-39 lines was only 8.3% and 0%, with resistance levels of 1 and 0, respectively; however, the withering heart rate of the wild-type reached 100%, with a resistance level of 9. The results of the in vitro stem bioassay showed that, compared with the wild-type, the average corrected mortality rate of the SSB fed on the OsRSSB4OE line reached 94.3%, and the resistance reached a high level. In summary, we preliminarily confirmed that OsRSSB4 positively regulates the defense of rice against SSB. This research findings reveal new SSB resistance gene resources, providing an important genetic basis for SSB resistance breeding in rice crops. [ABSTRACT FROM AUTHOR]

Background: Hypoxia, a condition where there is a lack of oxygen, is known to play a role in cancer progression. Objective: This study investigates the correlation between HIF1A gene-altered expression and hypoxia in Bangladeshi breast cancer (BC) cases and TCGA_BC datasets. Design: This case-control study compares BC cases to healthy controls to understand the relationship between gene changes and cancer. Method: This study used advanced analysis methods to examine the transcriptional landscape of BC, and quantitatively assessed its correlation using integrated multi-omics analysis. Results: In Bangladeshi BC cases, the T allele of HIF1A rs1154946 correlates notably (P -value <.001) with BC incidence. ELISA results confirmed a significant association (P -value <.005) between elevated HIF1A expression and BC-related hypoxia. Bioinformatics eQTL analysis validated the correlation between increased HIF1A expression and rs11549465 T allele (P -value <.01). Structural analyses suggested that rs11549465 (P582S) mutation may decrease protein stability (ΔΔG-value: −1.24 kcal/mole), potentially affecting HIF1A function. HIF1A enrichment analysis in BC underscores strong associations with oxygen levels, hypoxia, metabolic processes, apoptosis, and programed cell death (P -value <.001). Transcriptomic data demonstrated a robust correlation (P -value <.0001) between HIF1A expression and copy-number alterations, mutations, and abnormal methylation. Altered HIF1A expression showed strong negative correlations (P -value <.00001) with methylation and the expression of the ER (ESR1), in Whites. Survival analysis revealed marked differences in overall survival linked to high and low HIF1A expression (P -value <.00001). Furthermore, HIF1A expression significantly correlated (P -value <.000001) with hypoxia, TMB, MSI, and immune infiltration by CD8+ T cells, neutrophils, dendritic, and macrophages, providing deeper insights into the BC microenvironment. Conclusion: Thus, the HIF1A gene could serve as a promising biomarker for breast cancer progression, control, and survival across ethnicities, emphasizing its role in disease development and regulation. Plain Language Summary: Hypoxia is a known indicator of cancer progression. This study investigates the correlation between HIF1A gene-altered expression and hypoxia in Bangladeshi breast cancer (BC) cases and TCGA_BC datasets. This case-control study examined the transcriptional landscape of breast cancer, and quantitatively assessed its correlation using integrated multi-omics analysis. In Bangladeshi BC cases, the T allele of HIF1A rs1154946 correlates notably (P -value <.001) with BC incidence. ELISA results confirmed a significant association (P -value <.005) between elevated HIF1A expression and BC-related hypoxia. Bioinformatics eQTL analysis validated the correlation between increased HIF1A expression and rs11549465 T allele (P -value <.01). Structural analyses suggested that rs11549465 (P582S) mutation may decrease protein stability (ΔΔG-value: –1.24 kcal/mole), potentially affecting HIF1A function. HIF1A enrichment analysis in BC underscores strong associations with oxygen levels, hypoxia, metabolic processes, apoptosis, and programed cell death (P -value <.001). Transcriptomic data demonstrated a robust correlation (P -value <.0001) between HIF1A expression and copy-number alterations, mutations, and abnormal methylation. Altered HIF1A expression showed strong negative correlations (P -value <.00001) with methylation and the expression of the ER (ESR1), in Whites. Survival analysis revealed marked differences in overall survival linked to high and low HIF1A expression (P -value <.00001). Furthermore, HIF1A expression significantly correlated (P -value <.000001) with hypoxia, TMB, MSI, and immune infiltration by CD8+ T cells, neutrophils, dendritic, and macrophages, providing deeper insights into the BC microenvironment. Thus, the HIF1A gene could serve as a promising biomarker for breast cancer progression, control, and survival across ethnicities, emphasizing its role in disease development and regulation. [ABSTRACT FROM AUTHOR]

The present study aimed to enhance salicin and direct regeneration in willow (Salix safsaf Forssk) using the sodium nitroprusside (SNP) regulation of nitric oxide (NO) and vinasse for its nutrition effect in culture medium. Internodes of Salix safsaf were cultured on Murashige and Skoog (MS) medium supplemented with benzyl adenine (BA) (0.25 mg L−1) and different concentrations of SNP (0, 5, 10, 15, and 20 mg L−1) or vinasse (0, 5, 10, and 20%) to examine shoot regeneration, antioxidant defense enzyme activity, total phenolic compounds, flavonoids, and salicine contents. The reported data revealed that application of SNP at 15 mg L−1 and vinasse at 10% induced a significant effect in vitro Salix safsaf shoot regeneration. To confirm that, nitric oxide is required for auxin-mediated activation of cell division in a dose-dependent manner. A concentration of 15 mg L−1 SNP promotes regeneration and salicin accumulation (3162.16 mg/100 g) during signaling action. On the other hand, the cross talk effect of nitric oxide and vinasse combination in Salix safsaf significantly induced a synergistic effect on direct propagation more than vinasse alone. SNP significantly stimulates salicylate accumulation in a dose-dependent manner, but the data on the association of vinasse and SNP on salicylate up-regulation showed a significant reduction in salicin accumulation when SNP was combined with 10% vinasse, which directly affected the signaling action of SNP as secondary product stimulators. Vinasse's phenolic compounds affect directly on the reduction activity of SNP to suppress its signaling action, or indirectly by inhibiting the sequence cascade of the SNP signaling transduction process to decrease the accumulation of salicin contents. Data confirmed that vinasse and SNP stimulated the antioxidant enzymes activity throw quenching the stimulated reactive oxygen species that produced via SNP. Results show that modified media with SNP administration at 15 mg L−1 and the combination of vinasse at 10% and SNP at 15 mg L−1 are recommended for modifying tissue culture media for induced direct regeneration and salicin accumulation in tissue culture applications, which will be very useful for commercial salicin overproduction as a biological active ingredient in willows. [ABSTRACT FROM AUTHOR]

This study investigated the influence of single nucleotide polymorphisms (SNPs) in genes associated with the interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) on COVID-19 severity and their association with nonalcoholic fatty liver disease (MAFLD). We did not observe a significant association between the investigated SNPs and COVID-19 severity. While the IFNAR2 rs2236757 A allele was correlated with higher creatinine levels upon admission and the G allele was correlated with lower band neutrophils upon discharge, these findings require further investigation. The distribution of OAS gene polymorphisms (rs10774671 and rs10735079) did not differ between MAFLD patients and non-MAFLD patients. Our study population's distribution of ACE2 rs2074192 genotypes and alleles differed from that of the European reference population. Overall, our findings suggest that these specific SNPs may not be major contributors to COVID-19 severity in our patient population, highlighting the potential role of other genetic factors and environmental influences. [ABSTRACT FROM AUTHOR]

Temporal Lobe Epilepsy (TLE) is a chronic neurological disorder characterized by recurrent focal seizures originating in the temporal lobe. Despite the variety of antiseizure drugs currently available to treat TLE, about 30% of cases continue to have seizures. The etiology of TLE is complex and multifactorial. Increasing evidence indicates that Alzheimer's disease (AD) and drug-resistant TLE present common pathological features that may induce hyperexcitability, especially aberrant hyperphosphorylation of tau protein. Genetic polymorphic variants located in genes of the microtubule-associated protein tau (MAPT) and glycogen synthase kinase-3β (GSK3B) have been associated with the risk of developing AD. The APOE ε4 allele is a major genetic risk factor for AD. Likewise, a gene-dose-dependent effect of ε4 seems to influence TLE. The present study aimed to investigate whether the APOE ɛ4 allele and genetic variants located in the MAPT and GSK3B genes are associated with the risk of developing AD and drug-resistant TLE in a cohort of the Mexican population. A significant association with the APOE ε4 allele was observed in patients with AD and TLE. Additional genetic interactions were identified between this allele and variants of the MAPT and GSK3B genes. [ABSTRACT FROM AUTHOR]

Currently, the molecular background based on mitochondrial DNA (mtDNA) analysis of canine testicular tumours is underestimated. The available data mostly focus on histopathological evaluations, with a few reports of nuclear genome (nDNA) studies. Tumourigenesis represents a highly complex and diverse genetic disorder, which can also encompass defects in mtDNA. The aim of this study was to identify molecular changes in whole mitochondrial genome sequences obtained from dogs affected by testicular tumours. Samples of blood, tumour, and healthy tissue were collected from each animal, and mtDNA (ultimately 45 samples) was subsequently sequenced. Thereafter, protein analyses were performed to assess the impact of the identified molecular alterations on the amino acid level. The total number of observed changes included 722 SNPs, 12 mutations, 62 indels, 5 indel mutations, and 35 heteroplasmic sites. The highest number of mtDNA variants in protein-coding genes COX1, COX3, ATP6, ND1, ND4, and ND5 was observed. Interestingly, SNPs were found in 10 out of 22 tRNA genes. Most of the identified mtDNA defects were synonymous changes at the amino acid level. Also, polymorphisms and heteroplasmy were frequently observed in the variable number of tandem repeat (VNTR) regions, especially in its fragment spanning 16,138–16,358 bp. Based on the obtained results, it was possible to select 11 polymorphisms that occurred in all the tested samples (benign, malignant) and an additional five SNPs identified only in benign neoplasms. The comprehensive analysis of malignant testicular tumours demonstrated a significant diversity in their molecular profiles, with changes ranging from 17 to 101 per sample. [ABSTRACT FROM AUTHOR]

Multiple genes might interact to determine the age at onset of bipolar disorder. We investigated gene-gene interactions related to age at onset of bipolar disorder in the Korean population, using genome-wide association study (GWAS) data. The study population consisted of 303 patients with bipolar disorder. First, the top 1000 significant single-nucleotide polymorphisms (SNPs) associated with age at onset of bipolar disorder were selected through single SNP analysis by simple linear regression. Subsequently, the QMDR method was used to find gene-gene interactions. The best 10 SNPs from simple regression were located in chromosome 1, 2, 3, 10, 11, 14, 19, and 21. Only five SNPs were found in several genes, such as FOXN3 , KIAA1217 , OPCML , CAMSAP2 , and PTPRS. On QMDR analyses, five pairs of SNPs showed significant interactions with a CVC exceeding 1/5 in a two-locus model. The best interaction was found for the pair of rs60830549 and rs12952733 (CVC = 1/5, P < 1E−07). In three-locus models, four combinations of SNPs showed significant associations with age at onset, with a CVC of >1/5. The best three-locus combination was rs60830549, rs12952733, and rs12952733 (CVC = 2/5, P < 1E−6). The SNPs showing significant interactions were located in the KIAA1217 , RBFOX3 , SDK2 , CYP19A1 , NTM , SMYD3 , and RBFOX1 genes. Our analysis confirmed genetic interactions influencing the age of onset for bipolar disorder and identified several potential candidate genes. Further exploration of the functions of these promising genes, which may have multiple roles within the neuronal network, is necessary. • Genetic interactions are crucial for the sub-phenotype of psychiatric disorder. • Age at onset of bipolar disorder was influenced by gene-gene interactions. • The SNPs showing significant interactions were located in the KIAA1217 , RBFOX3 , SDK2 , CYP19A1 , NTM , SMYD3 , and RBFOX1 genes. [ABSTRACT FROM AUTHOR]

This study investigated carotenoid content and fruit color variation in 306 pepper accessions from diverse Capsicum species. Red-fruited accessions were predominant (245 accessions), followed by orange (35) and yellow (20). Carotenoid profiles varied significantly across accessions, with capsanthin showing the highest mean concentration (239.12 μg/g), followed by β-cryptoxanthin (63.70 μg/g) and zeaxanthin (63.25 μg/g). Total carotenoid content ranged from 7.09 to 2566.67 μg/g, emphasizing the diversity within the dataset. Correlation analysis revealed complex relationships between carotenoids, with strong positive correlations observed between total carotenoids and capsanthin (r = 0.94 ***), β-cryptoxanthin (r = 0.87 ***), and zeaxanthin (r = 0.84 ***). Principal component analysis (PCA) identified two distinct carotenoid groups, accounting for 67.6% of the total variance. A genome-wide association study (GWAS) identified 91 significant single nucleotide polymorphisms (SNPs) associated with fruit color (15 SNPs) and carotenoid content (76 SNPs). These SNPs were distributed across all chromosomes, with varying numbers on each. Among individual carotenoids, α-carotene was associated with 28 SNPs, while other carotenoids showed different numbers of associated SNPs. Candidate genes encoding diverse proteins were identified near significant SNPs, potentially contributing to fruit color variation and carotenoid accumulation. These included pentatricopeptide repeat-containing proteins, mitochondrial proton/calcium exchangers, E3 ubiquitin-protein ligase SINAT2, histone–lysine N-methyltransferase, sucrose synthase, and various enzymes involved in metabolic processes. Seven SNPs exhibited pleiotropic effects on multiple carotenoids, particularly β-cryptoxanthin and capsanthin. The findings of this study provide insights into the genetic architecture of carotenoid biosynthesis and fruit color in peppers, offering valuable resources for targeted breeding programs aimed at enhancing the nutritional and sensory attributes of pepper varieties. [ABSTRACT FROM AUTHOR]

Background: African mahogany species (Khaya sp.) have been introduced to Brazil gaining increasing economic interest over the last years, as they produce high quality wood for industrial applications. To this date, however, the knowledge available on the genetic basis of African mahogany plantations in Brazil is limited, which has driven this study to examine the extent of genetic diversity and structure of three cultivated species (Khaya grandifoliola, Khaya senegalensis and Khaya ivorensis) and their prospects for forest breeding. Results: In total, 115 individuals were genotyped (48 of K. grandifoliola, 34 of K. senegalensis and 33 of K. ivorensis) for 3,330 filtered neutral loci obtained from genotyping-by-sequencing for the three species. The number of SNPs varied from 2,951 in K. ivorensis to 4,754 in K. senegalensis. Multiloci clustering, principal component analysis, Bayesian structure and network analyses showed a clear genetic separation among the three species. Structure analysis also showed internal structure within each species, highlighting genetic subgroups that could be sampled for selecting distinct genotypes for further breeding, although the genetic distances are moderate to low. Conclusion: In our study, SNP markers efficiently assessed the genomic diversity of African mahogany forest plantations in Brazil. Our genetic data clearly separated the three Khaya species. Moreover, pairwise estimates of genetic distances among individuals within each species showed considerable genetic divergence among individuals. By genotyping 115 pre-selected individuals with desirable growth traits, allowed us not only to recommend superior genotypes but also to identify genetically distinct individuals for use in breeding crosses. [ABSTRACT FROM AUTHOR]

Background: Fusarium head blight (FHB), caused by Fusarium graminearum, is a major disease of wheat in North America. FHB infection causes fusarium damaged kernels (FDKs), accumulation of deoxynivalenol (DON) in the grain, and a reduction in quality and grain yield. Inheritance of FHB resistance is complex and involves multiple genes. The objective of this research was to identify QTL associated with native FHB and DON resistance in a 'D8006W'/'Superior', soft white winter wheat population. Results: Phenotyping was conducted in replicated FHB field disease nurseries across multiple environments and included assessments of morphological and FHB related traits. Parental lines had moderate FHB resistance, however, the population showed transgressive segregation. A 1913.2 cM linkage map for the population was developed with SNP markers from the wheat 90 K Infinium iSelect SNP array. QTL analysis detected major FHB resistance QTL on chromosomes 2D, 4B, 5A, and 7A across multiple environments, with resistance from both parents. Trait specific unique QTL were detected on chromosomes 1A (visual traits), 5D (FDK), 6B (FDK and DON), and 7D (DON). The plant height and days to anthesis QTL on chromosome 2D coincided with Ppd-D1 and were linked with FHB traits. The plant height QTL on chromosome 4B was also linked with FHB traits; however, the Rht-B1 locus did not segregate in the population. Conclusions: This study identified several QTL, including on chromosome 2D linked with Ppd-D1, for FHB resistance in a native winter wheat germplasm. [ABSTRACT FROM AUTHOR]

Salinity stress is one of the major abiotic stresses that significantly impacts plant growth and performance. Therefore, this study investigated the role of foliar-applied ascorbic acid (AsA) at a concentration of 2 mM as a mitigative approach to salt stress in barley during its vegetative stage. The research aimed to elucidate the genetic responses induced by AsA that potentially confer enhanced tolerance to salinity. A controlled environment experiment was conducted, wherein barley plants were subjected to salt stress and treated with a foliar application of AsA. Natural phenotypic variation showed an increment for all agronomical traits after the foliar application of AsA compared to saline environment (control). Highly significant markers were detected by using a genome-wide association study (GWAS) that are associated with all of the studied traits, underscoring the protective role of AsA under salt stress. Furthermore, the study identified several novel stress-responsive genes influenced by AsA treatment, pointing to complex genetic networks underlying salt stress mitigation. For instance, the gene HORVU.MOREX.r3.2HG0199440 at position (622,219,977–622,220,459 bp) on 2H, which is annotated as V-type ATP synthase beta chain, helps to maintain cellular redox balance during stress conditions. This research paves the way for future work on the practical applications of AsA in agriculture, especially in breeding programs aimed at enhancing salt stress tolerance in barley and similar cereals. [ABSTRACT FROM AUTHOR]

The unique chaperone-like properties of C19orf53, discovered in 2020 as a "hero" protein, make it an intriguing subject for research in relation to ischemic stroke (IS). Our pilot study aimed to investigate whether C19orf53 SNPs are associated with IS. DNA samples from 2138 Russian subjects (947 IS and 1308 controls) were genotyped for 7 C19orf53 SNPs using probe-based PCR. Dominant (D), recessive (R), and log-additive (A) regression models in relation to the effect alleles (EA) were used to interpret associations. An increased risk of IS was associated with rs10104 (EA G; Pbonf(R) = 0.0009; Pbonf(A) = 0.0004), rs11666524 (EA A; Pbonf(R) = 0.003; Pbonf(A) = 0.02), rs346158 (EA C; Pbonf(R) = 0.006; Pbonf(A) = 0.045), and rs2277947 (EA A; Pbonf(R) = 0.002; Pbonf(A) = 0.01) in patients with obesity; with rs11666524 (EA A; Pbonf(R) = 0.02), rs346157 (EA G; Pbonf(R) = 0.036), rs346158 (EA C; Pbonf(R) = 0.005), and rs2277947 (EA A; Pbonf(R) = 0.02) in patients with low fruit and vegetable intake; and with rs10104 (EA G; Pbonf(R) = 0.03) and rs11666524 (EA A; Pbonf(R) = 0.048) in patients with low physical activity. In conclusion, our pilot study provides comprehensive genetic and bioinformatic evidence of the involvement of C19orf53 in IS risk. [ABSTRACT FROM AUTHOR]

Pregnancy-associated glycoproteins (PAGs) are a polygenic family with many scattered genes and pseudogenes resulting from the duplication or fusion of a pseudogene with expression beginning in the trophoblast during the peri-implantation period and continuing in the trophectoderm. In this study, single-nucleotide polymorphism (SNP) and insertion/deletion (InDels) in the open reading frame (nine exons) of crossbreed pigs are reported for the first time. Novel SNPs/InDels were researched using genomic DNA templates isolated from the leukocytes of crossbreed pigs (N = 25), which were amplified, gel-out-purified, and sequenced. Sixteen SNPs and one InDel (g.6961_6966 Ins TGCCAA) were identified in the crossbreed pigs. In silico analysis revealed that among 16 SNPs, only 10 SNPs cause amino acid (aa) substitutions, and InDel codes asparagine (N298) and alanine (A299). The results provide a novel broad-based database (main pattern) that will be critical for future research into the possible correlations between the SNP genotypes of the pPAG2-L subfamily in pigs of various breeds whose reproductive traits are known. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the contribution of genetic factors, i.e., the level of expression and polymorphisms of Toll-like receptors (TLR), to the susceptibility of latent tuberculosis infection in a Russian cohort of individuals infected with HIV. The patients (n = 317) with confirmed HIV infection were divided into two groups according to the results of the STANDARD E TB-Feron test: 63 cases with a latent TB infection and 274 controls without LTBI. Total DNA and RNA were isolated from whole-blood samples. SNP genotyping and expression levels of five TLR genes (TLR1, TLR2, TLR4, TLR6, and TLR8) were determined by means of real-time PCR. There were no significant differences in the expression levels of the TLRs between the case and control groups. In addition, we did not observe any significant association between the analyzed SNPs and the susceptibility of Latent tuberculosis infection (LTBI) in patients with HIV. However, patients from an entire cohort with the rs4986790-GG (TLR4) and rs5743708-GG (TLR2) genotypes were characterized by lower CD4 T-cell counts compared to carriers of alternative alleles. Moreover, we found a significant risk of a hazardous drop in the CD4 T-cell count below 350 cells/mm3 associated with the rs4986790-G (TLR4) allele. Latent tuberculosis infection in individuals infected with HIV does not significantly modify the level of TLR gene expression. [ABSTRACT FROM AUTHOR]

Background and Objective: To explore the association between protein quantitative trait loci (pQTL‐SNPs) and the risk of LUAD. Methods: "Blood +" high depth blood proteomics analysis was performed on plasma from female LUAD patients and female healthy controls, and combined with proteomics data from tumors and adjacent non‐tumor tissues of female LUAD patients to screen proteins uniformly expressed in plasma and tissues. pQTL‐SNPs were then screened through multiple databases and subjected to multilevel screening. The associations between selected pQTL‐SNPs and LUAD risk were evaluated by Female Lung Cancer Consortium in Asia GWAS (FLCCA GWAS). Enzyme linked immunosorbent assay (ELISA) is used to determine the levels of candidate protein. Results: A total of 7 pQTL‐SNPs were significantly associated with altered LUAD risk (p < 0.05). Meanwhile, the expression of their corresponding target proteins were all decreased in both plasma and tumor tissues of LUAD cases, which may play a role of tumor suppressor proteins. After mutation of 3 pQTL‐SNPs (rs7683000, rs73224660, and rs2776937), the expression of corresponding target proteins BST1 and NRP1 decreased, and as potential tumor suppressor proteins, which may promote tumorigenesis and further increasing the risk of developing LUAD (OR >1, p < 0.05); while after mutation the other pQTL‐SNP rs62069916, the corresponding target protein APOH expression was increased, while as a potential tumor suppressor protein, which may inhibit tumorigenesis and further reduced the risk of developing LUAD (OR <1, p < 0.05). In addition, the expression of NRP1 and APOH were significant decreased in LUAD cell lines and validated in plasma of LUAD patients. Conclusion: A total of 4 pQTL‐SNPs (rs7683000, rs73224660, rs2776937, and rs62069916) may associate with altered LUAD risk by regulating the expression of target proteins (BST1, NRP1, and APOH) after mutation. [ABSTRACT FROM AUTHOR]