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Rapid advancements in technologies provide various tools to analyze fruit crop genomes to better understand genetic diversity and relationships and aid in breeding. Genome-wide single nucleotide polymorphism (SNP) genotyping arrays offer highly multiplexed assays at a relatively low cost per data point. We report the development and validation of 1.4M SNP Axiom® Citrus HD Genotyping Array (Citrus 15AX 1 and Citrus 15AX 2) and 58K SNP Axiom® Citrus Genotyping Arrays for Citrus and close relatives. SNPs represented were chosen from a citrus variant discovery panel consisting of 41 diverse whole-genome re-sequenced accessions of Citrus and close relatives, including eight progenitor citrus species. SNPs chosen mainly target putative genic regions of the genome and are accurately called in both Citrus and its closely related genera while providing good coverage of the nuclear and chloroplast genomes. Reproducibility of the arrays was nearly 100%, with a large majority of the SNPs classified as the most stringent class of markers, "PolyHighResolution" (PHR) polymorphisms. Concordance between SNP calls in sequence data and array data average 98%. Phylogenies generated with array data were similar to those with comparable sequence data and little affected by 3 to 5% genotyping error. Both arrays are publicly available.

BACKGROUND: Multiple clinical observational studies have suggested a close relationship of serum trace elements and nutrients with osteonecrosis, but it remains unclear whether there is a genetic causal effect between serum trace elements and nutrients on osteonecrosis. OBJECTIVE: To investigate the causal effects of serum trace elements and nutrients on osteonecrosis using the Mendelian randomization approach. METHODS: The exposure factors of serum trace elements and vitamins with mononucleotide polymorphisms were obtained from the published UK Biobank database and publicly available databases of genome-wide association studies. The outcome event of osteonecrosis was derived from the FinnGen Biobank database. Mendelian randomization methods were employed to explore the causal relationship between seven trace elements and three nutrients with osteonecrosis. Causal inference was conducted using inverse variance weighting, MR-Egger, and weighted median methods. F-statistic was calculated to ensure the robustness of instrumental variables. Cochran's Q test and leave-one-out method were used for heterogeneity testing. MR-Egger regression and MR-PRESSO were employed for horizontal pleiotropy testing. PhenoScanner database was utilized to remove mononucleotide polymorphisms with horizontal pleiotropy to ensure the reliability of the results. RESULTS AND CONCLUSION: Causal relationships were found between serum selenium, phosphate, vitamin C, vitamin E, and osteonecrosis through Mendelian randomization analysis. Serum selenium, vitamin C, and vitamin E were found to have a protective effect on osteonecrosis, while excessive intake of phosphate increased the risk of osteonecrosis. No heterogeneity or horizontal pleiotropy was observed during the study, and Mendelian randomization statistical power (Power value > 80%) indicated the reliability of the aforementioned four results. These findings have important clinical implications for the development of targeted preventive and therapeutic measures for osteonecrosis. [ABSTRACT FROM AUTHOR]

Background: Temporomandibular joint disorder (TMD), a prevalent orofacial disorder with complex aetiologies and considerable socioeconomic costs. This underscores the critical importance of developing a comprehensive understanding of the risk factors associated with TMD, as existing research is hindered by deficiencies in establishing causal relationships and the limitations of traditional research methodologies. Objectives: This research explores the causal link between certain risk factors and temporomandibular joint disorder (TMD) through Mendelian randomization (MR), providing multidimensional perspectives in addressing this worldwide health issue. Methods: Utilizing instrumental variables, we applied advanced statistical methods, including the weighted median, inverse variance weighted (IVW) and MR‐Egger, to evaluate the impact of twelve potential risk factors on TMD. Results: Our results identified a significant positive association of TMD with malocclusion (p <.001), sleeping disorders (p =.006), anxiety (p =.002), major depression (p =.0002), daily cigarettes consumption (p =.029) and autoimmune diseases (p =.039). Conversely, a negative association was observed with educational attainment (p =.003). Conclusion: These findings suggest that malocclusion, sleeping disorders, anxiety, major depression, daily cigarettes consumption and autoimmune diseases, could potentially increase TMD risk while educational attainment might mitigate its increase. No direct causal relationships were established between serum 25‐hydroxyvitamin D levels, menopause, frequent alcohol consumption, coffee intake and severely worn dentition and TMD. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association between vitamin D receptor (VDRs) and calcium-sensitive receptor (CaSR) gene polymorphisms and calcium-containing kidney stones (CCKS) in Dai populations. Methods: A total of 160 CCKS patients and 87 healthy controls were included in this study. CCKS was confirmed using urological computed tomography (CT), plain abdominal radiograph, or surgical lithotomy. Stone samples obtained during surgery were analyzed using infrared spectroscopy. Venous blood and 24-h urine samples were collected and analyzed using Sanger sequencing and high-performance liquid chromatography, respectively. Genetic variants in the VDR gene (rs7975232, rs2228570, rs731236, and rs1544410) and CaSR gene (rs7652589, rs1801725, and rs1042636) were identified through sequence analysis. Results: Analysis of genotype and allele frequencies revealed that the rs7975232 polymorphism in the VDR gene and the rs7652589 allele in the CaSR gene were significantly associated with CCKS. Furthermore, patients carrying the AC and AA genotypes of rs7975232 showed a higher incidence of hypocitraturia compared to those with other genotypes (p < 0.05). The AA and GG genotypes of rs1042636 and the AA genotype of rs7652589 were significantly associated with hypercalciuria (p < 0.05). Conclusion: CCKS in this study population may be closely related to hypocitraturia caused by the VDR locus rs7975232 polymorphism and hypercalciuria caused by the CaSR locus rs1042636 and rs7652589 polymorphism. [ABSTRACT FROM AUTHOR]

Background: Livestock farmers face financial losses every year because milk yield and components are severely affected by udder diseases. These udder infections attract the immune response from the host and lead to the influx of neutrophils into milk to fight infection and thus the number of somatic cell count (SCC) is increased. The SCC value of milk could be used as an important indicator in detecting clinical mastitis in dairy animals. Also, the milk yield and milk quality (e.g. fat) are negatively affected by the increased SCC. The SCC is used to estimate the somatic cell score (SCS)of the milk, which is used as an indirect measure to detect subclinical mastitis. Therefore, the purpose of this study was to investigate the presence of a significant SNP rs868996547, on the suppressor of cytokine signaling 2 gene (SOCS2) which is related to milk yield and milk quality in Awassi sheep. Methods: In this study, milk production data was obtained from 210 healthy Awassi ewes with different parties and ages. The general linear model (GLM) process analysis of variance (ANOVA) was used to determine fixed effects on milk traits. The DNA extraction was done using a blood DNA extraction kit from Qiagen. To validate the presence of SNP a customized SNP detection developed by Thermofisher Scientific was used. The presence of the SNP in the SOCS2 gene was detected with genotypes (C/T, T/T, and C/C) and T being the mutated allele and it had a significant (p < 0.015) effect on the milk yield (p < 0,015;0.091), fat (p < 0,001;0,003), fat/protein ratio (p < 0.001;0,037) and log10SCC value (p < 0,006;0,015) of Awassi ewes. However, the protein, total solid, and lactose percentages in the wild type and the mutated ewes found having no significant difference (P > 0.05). Conclusion: Our result showed the increase in SCC or SCS of the milk significantly affected the milk yield and composition. Parity and age had significant effects on ewes' milk yield (p < 0.001). In conclusion, we investigated the presence of SOCS2 gene of Awassi ewes in the study flock and its effect on milk yield, fat, and somatic cell count, and the change in milk composition and milk yield because of SCC. [ABSTRACT FROM AUTHOR]

Background: Genetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population. Methods: A case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders. Results: Our study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527–4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes. Conclusion: This study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes. Trial registration: www.chictr.org.cn ID: ChiCTR2300071579 2023-05-18. [ABSTRACT FROM AUTHOR]

We reported a performance during an implementation of prenatal cell-free (cf) DNA screening using single nucleotide polymorphism (SNP) approach in our accredited laboratory.Prospective audit with prompt intervention was set for the processing of 2,502 samples from singleton pregnancy from August 2017 to July 2019. Risks of trisomy 21 (T21), T18, T13, monosomy X (XO), and other sex chromosome aneuploidies (SCAs) were clarified by a proprietary bioinformatics algorithm.Laboratory failure occurred in 192 samples (7.7 %) as a result of inadequate sequencing (n=144), fundamental limitation of the testing (n=19), and obvious human error (n=29). Faulty setting of the calibration curve was the most common human error (n=22/29). After a redraw (n=110), 79 (71.8 %) were settled. Overall, 2,389/2,502 samples (95.5 %) were reportable. Thirty-five samples were high-risk for T21 (n=19), T18 (n=5), T13 (n=1), XO (n=3), and other SCAs (n=7), respectively. Positive predictive values calculated from either prenatal confirmatory tests or postnatal findings were 93.8 % (n=16), 100 % (n=4), 50 % (n=2), and 83.3 % (n=6) for T21, T18, XO, and other SCAs, respectively, with high sensitivity and specificity (>99.9 %). Vanishing twin was detected from 1 out of 4 samples with detected additional haplotypes.An overall performance of SNP-based prenatal cf-DNA screening during our initial implementation can be optimized with proactive approach. The technical know-how was a significant limiting factor for adopting the technology. The lessons learnt may be of interest to the academic laboratory considering adopting their own test instead of sending blood to a testing service of a supplier. [ABSTRACT FROM AUTHOR]

The spinal muscular atrophy (SMA) phenotype strongly correlates with the SMN2 gene copy number. However, the severity and progression of the disease vary widely even among affected individuals with identical copy numbers. This study aimed to investigate the impact of genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways on SMA susceptibility and clinical progression. Genotyping for 31 genetic variants across 20 genes was conducted in 54 SMA patients and 163 healthy controls. Our results revealed associations between specific polymorphisms and SMA susceptibility, disease type, age at symptom onset, and motor and respiratory function. Notably, the TNF rs1800629 and BDNF rs6265 polymorphisms demonstrated a protective effect against SMA susceptibility, whereas the IL6 rs1800795 was associated with an increased risk. The polymorphisms CARD8 rs2043211 and BDNF rs6265 were associated with SMA type, while SOD2 rs4880, CAT rs1001179, and MIR146A rs2910164 were associated with age at onset of symptoms after adjustment for clinical parameters. In addition, GPX1 rs1050450 and HMOX1 rs2071747 were associated with motor function scores and lung function scores, while MIR146A rs2910164, NOTCH rs367398 SNPs, and GSTM1 deletion were associated with motor and upper limb function scores, and BDNF rs6265 was associated with lung function scores after adjustment. These findings emphasize the potential of genetic variability in oxidative stress, inflammatory processes, and neurodevelopmental pathways to elucidate the complex course of SMA. Further exploration of these pathways offers a promising avenue for developing personalized therapeutic strategies for SMA patients. [ABSTRACT FROM AUTHOR]

Objective: To analyze the genotypes of VZV in Jiangsu province to identify vaccine strains and wild strains, providing a molecular biological background for the effective prevention and control of varicella. Method: Stratified sampling was used to collect herpes fluid or throat swab from patients diagnosed with varicella. ORF22 was carried out, and the restriction enzyme site of ORF38, ORF54 and ORF62 were detected. Results: All 207 virus strains were Clade 2 type by sequencing the PCR products of ORF22. The sequencing results showed that five SNP sites changed compared to the Dumas reference strain(Clade 1). From A to G at 37,902, from T to c at 38,055, from A to C at 38,081, and from G to A at 38,177, from G to A at 39,394. The prevalent VZV genotypes in Jiangsu is consistent with the P-Oka. The restriction enzyme site analysis of PCR amplification products from ORF38 (PstI), ORF54 (BglI), ORF62 (SmaI) showed that all 207 virus strains were wild-type. There were two different types of the wild strains, and 183 strains (88.4%) were PstI (+), BglI (+), SmaI (-). The wild strains between different regions showed no significant differences (χ2 = 0.05, P = 0.982). Conclusions: The prevalent VZV genotypes are Clade 2 and the prevalent virus strains are wild strains in Jiangsu Province, the primary wild strain observed is mainly PstI (+), BglI (+), SmaI (-). [ABSTRACT FROM AUTHOR]

Background and objective: Genetic polymorphism studies in families and twins indicated the heritability of depression. However, the association between genes with genetic polymorphism and depression provides various findings and remains unclear. Therefore, we conducted a systematic review and meta-analysis to determine the genes with their polymorphism associated with the symptomatic depression known as major depressive disorder (MDD). Materials and methods: PubMed and Scopus were searched for relevant studies published before May 22, 2023 (1968–2023), and 62 were selected for this review. The study's bias risk was investigated using the Newcastle–Ottawa scale. Gene functional enrichment analysis was investigated for molecular function (MF) and biological process (BP) and pathways. A meta-analysis of the studied genes that were replicative in the same single nucleotide polymorphism was conducted using a random-effect model. Results: The 49 genes involved in MDD were studied and engaged in several pathways, such as tryptophan metabolism or dopaminergic and serotonergic synapses. Based on gene overlapping in MF and BP, 13 genes with polymorphisms were identified as related to MDD. Most of them were only studied once. Solute carrier family 6 member 4 (SLC6A4) overlapping between MF and BP and brain-derived neurotrophic factor (BDNF) as unique to BP were replicative studied and used in the meta-analysis. The polymorphism of SLC6A4 SS and LS genotypes increased the occurrence of MDD development but not significantly [odd ratio (OR) = 1.39; 95% confidence interval (CI) = 0.87–2.22; P = 0.16 and OR = 1.13; 95% CI = 0.84–1.53; P = 0.42, respectively]. A similar result was observed for BDNF rs6265 GG (OR = 1.26; 95% CI = 0.78–2.06; P = 0.35) and BDNF rs6265 AA genotypes (OR = 1.12; 95% CI = 0.77–1.64; P = 0.56). These studies indicated low bias and significant heterogeneity. Conclusion: At least 13 studied genes with polymorphisms were involved in MDD development according to MF and BP, but not significantly. These results suggest that MDD development risk factors might require genetic and other factors for interaction and induction. [ABSTRACT FROM AUTHOR]

AbstractThe association between the MCM6-13910-C/T polymorphism and lactose intolerance in individuals of European descent is well known. However, the notion that having a single versus a double allelic mutation might influence one’s phenotype has been hypothesized. This study investigated whether patients with the three genotypes C/C, C/T, T/T differed in response to a lactose tolerance test (LTT) in a Danish setting. Anonymized data on 603 individuals with results for both genetic test and LTT were investigated. Mean delta glucose values were plotted for the time points of the LTT (0, 15, 30, 45 and 60 min) for the C/C, C/T and T/T genotype, respectively. Further, the agreement between the three genotypes and the diagnostic interpretation of the LTT were examined using a cut-off of > 1.4 mmol/L rise in glucose. In subjects with the C/C genotype, mean glucose delta levels were markedly lower compared to both the C/T and T/T genotypes at all time points. Overall, a difference between mean glucose delta values among the C/T and T/T genotype could not be shown. Using a LTT cut-off of > 1.4 mmol/L, the proportions of lactose intolerant LTT results for each genotype were as follows: 58% among C/C, 5% among C/T, and 7% among T/T. In a Danish healthcare setting, the C/C genotype was on average associated with a smaller glucose response during a LTT when compared to the C/T and T/T genotypes. A marked difference in the LTT response among the C/T and T/T genotype was not observed. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes (T1D) is an organ-specific autoimmune disorder characterized by the destruction of pancreatic β cells, leading to absolute insulin deficiency. The genes NLRP3, ICAM-1, PTPN22, and INS are reportedly associated with T1D in other populations. However, the genetic pattern of T1D in the Pakistani population is not clear. This study aimed to find the association of polymorphisms in the PTPN22, INS, NLRP3, and ICAM-1 genes with T1D susceptibility in the Pakistani population. Methodology: This case-control study includes 100 T1D patients (3–14 years), recruited randomly from the pediatric endocrinology department of Fatima Memorial Hospital, Lahore, Pakistan and 100 age-matched healthy controls were selected from different localities of the same population. The polymorphisms in PTPN22 (rs601, rs33996649, rs2488457), INS (rs80356664), NLRP3 (rs10754558, rs35829419), and ICAM-1 (rs1799969, rs5498) genes were genotyped by Sanger sequencing. The genotypic and allelic frequencies, haplotypes, and linkage disequilibrium were computed using the genetic toolset PLINK to investigate their relationship to T1D. Results: The results indicate that the occurrence of the GT genotype of the rs33996649 variant is significantly higher in children with T1D compared to a control group of healthy individuals (P = 0.001, OR: 2.0, 95% CI = 0.15–0.45). Furthermore, the CT genotype of rs2488457 was notably associated with T1D patients (P = 0.007, OR: 2.8, 95% CI = 0.56–0.67). The CG genotype of rs80356664 showed a slight association with T1D (P = 0.03, OR: 1.9, 95% CI = 0.35–0.59). The prevalence of the AT genotype of rs10754558 showed a strong association with T1D (P = 0.005, OR: 3.4, 95% CI = 0.45–0.69). The TG genotype of rs5498 was also strongly associated with T1D (P = 0.009, OR: 2.8, 95% CI = 0.75–0.89). Conclusion: The present study provides evidence that SNPs in the PTPN22, INS, NLRP3, and ICAM-1 genes are associated with the development of T1D. Further research is needed to explore their potential use in genetic screening and personalized medication. Significance: That is already known on this topic?: The genes NLRP3, ICAM-1, PTPN22, and INS have been associated with Type 1 diabetes (T1D) in ‎various populations. However, there is limited knowledge about their specific genetic patterns in the ‎Pakistani population, necessitating this study to explore these associations. What this study hopes to add?: This study hopes to provide valuable data by identifying significant associations between ‎polymorphisms in the PTPN22, INS, NLRP3, and ICAM-1 genes and T1D susceptibility in Pakistani ‎children. How this study might affect research, practice, or policy?: The findings could enhance genetic screening protocols and personalized medicine in Pakistan by ‎identifying key genetic variants, assessing their impact on disease presentation, and discovering ‎novel disease pathways. This can lead to new drug development and inform policies on early ‎intervention programs and resource allocation for ASD services. [ABSTRACT FROM AUTHOR]

Introduction: Antimicrobial resistance (AMR) in Brucella melitensis, the causative agent of brucellosis, is of growing concern, particularly in low and middle-income countries. This study aimed to explore the genetic basis of AMR in B. melitensis strains from India. Methods: Twenty-four isolates from humans and animals were subjected to antimicrobial susceptibility testing and whole-genome sequencing. Results: Resistance to doxycycline (20.80%), ciprofloxacin (16.67%), cotrimoxazole (4.17%), and rifampicin (16.67%) was observed. Genome analysis revealed efflux-related genes like mprF, bepG, bepF, bepC, bepE, and bepDacross all isolates, however, classical AMR genes were not detected. Mutations in key AMR-associated genes such as rpoB, gyrA, and folP were identified, intriguingly present in both resistant and susceptible isolates, suggesting a complex genotype-phenotype relationship in AMR among Brucella spp. Additionally, mutations in efflux genes were noted in resistant and some susceptible isolates, indicating their potential role in resistance mechanisms. However, mutations in AMR-associated genes did not consistently align with phenotypic resistance, suggesting a multifactorial basis for resistance. Discussion: The study underscores the complexity of AMR in B. melitensis and advocates for a holistic multi-omics approach to fully understand resistance mechanisms. These findings offer valuable insights into genetic markers associated with AMR, guiding future research and treatment strategies. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a major public health problem worldwide, currently ranking third in cancer incidence and second in mortality. Multiple genes and environmental factors have been involved in the complex and multifactorial process of CRC carcinogenesis. VDR is an intracellular hormone receptor expressed in both normal epithelial and cancer colon cells at various levels. Several VDR gene polymorphisms, including FokI and BsmI, have been evaluated for their possible association with CRC susceptibility. The aim of our study was to investigate these two SNPs for the first time in Romanian CRC patients. FokI (rs228570 C>T) and BsmI (rs1544410 A>G) were genotyped by real-time polymerase chain reaction (RT-PCR) in 384-well plates using specific TaqMan predesigned probes on a ViiA™ 7 RT-PCR System. A total of 441 subjects (166 CRC patients and 275 healthy controls) were included. No statistically significant difference was observed between CRC patients and controls when we compared the wild-type genotype with heterozygous and mutant genotypes for both FokI (OR 0.85, 95% CI: 0.56–1.28; OR 0.95, 95% CI: 0.51–1.79, respectively) and BsmI (OR 0.97, 95% CI: 0.63–1.49; OR 1.10, 95% CI: 0.65–1.87, respectively) or in the dominant and recessive models. Also, we compared allele frequencies, and no correlation was found. Moreover, the association between these SNPs and the tumor site, TNM stage, and histological type was examined separately, and there was no statistically significant difference. In conclusion, our study did not show any association between FokI and BsmI SNPs and CRC susceptibility in a Romanian population. Further studies including a larger number of samples are needed to improve our knowledge regarding the influence of VDR polymorphism on CRC susceptibility. [ABSTRACT FROM AUTHOR]

Sustainable fisheries management is important for the continued harvest of the world's marine resources, especially as they are increasingly challenged by a range of climatic and anthropogenic factors. One of the pillars of sustainable fisheries management is the accurate identification of the biological units, i.e., populations. Here, we developed and implemented a genetic baseline for Atlantic herring harvested in the Norwegian offshore fisheries to investigate the validity of the current management boundaries. This was achieved by genotyping > 15,000 herring from the northern European seas, including samples of all the known populations in the region, with a panel of population‐informative SNPs mined from existing genomic resources. The final genetic baseline consisted of ~1000 herring from 12 genetically distinct populations. We thereafter used the baseline to investigate mixed catches from the North and Norwegian Seas, revealing that each management area consisted of multiple populations, as previously suspected. However, substantial numbers (up to 50% or more within a sample) of herring were found outside of their expected management areas, e.g., North Sea autumn‐spawning herring north of 62° N (average = 19.2%), Norwegian spring‐spawning herring south of 62° N (average = 13.5%), and western Baltic spring‐spawning herring outside their assumed distribution area in the North Sea (average = 20.0%). Based upon these extensive observations, we conclude that the assessment and management areas currently in place for herring in this region need adjustments to reflect the populations present. Furthermore, we suggest that for migratory species, such as herring, a paradigm shift from using static geographic stock boundaries towards spatial dynamic boundaries is needed to meet the requirements of future sustainable management regimes. [ABSTRACT FROM AUTHOR]

Objective: Cell‐free DNA (cfDNA) is used as a biomarker after transplantation to detect graft injury, relying on the donor fraction (DF). We have established a PCR‐based approach allowing us to separately quantify absolute values of dd‐cfDNA and recipient‐derived cfDNA (rd‐cfDNA). We aimed to present typical clinical scenarios after heart transplantation (HTx) to illustrate the advantages of absolute cfDNA values over DF. Methods: We used the cfDNA results of our cohort (509 samples of 52 patients followed during the first year after HTx) as background and determined the trajectories of cfDNA in specific clinical situations. We profiled an uncomplicated clinical course, viral and bacterial infections, acute and chronic rejection, and false‐negative and false‐positive rejections in six patients (five adults, one child). Results: There was a substantial discrepancy between relative (DF) and absolute cfDNA‐levels in several clinical situations. Rd‐ and dd‐cfDNA were independently elevated during episodes of rejection and infection and were better suited to depict treatment response than DF alone. Conclusions: Absolute quantification of cfDNA may offer clinically relevant information additive to DF in various situations after HTx and could be helpful for more accurate monitoring of diagnosis and treatment of rejection. [ABSTRACT FROM AUTHOR]

Background: Recipient's VEGF‐A polymorphisms have been reported to be associated with the risk of acute allograft rejection. However, an association of the donor's VEGF‐A gene polymorphism with rejection remained unelucidated till now. Methods: In this study, VEGF‐A gene SNPs at nine loci were analyzed in 160 kidney donors and recipients with rejection (rejectors, n = 80) and without rejection (non‐rejectors, n = 80). Blood VEGF‐A mRNA, plasma VEGF level, and intragraft VEGF expression were also analyzed by RT‐PCR, ELISA, and immunohistochemistry, respectively. Results: On comparing between the donor and rejectors, the polymorphic genotypes of VEGF –634 C>G [GG genotype, p < 0.0001; OR (95% CI) = 17.74 (5.16–60.96)]; VEGF –1154 G>A [AG genotype, p < 0.0001, OR (95% CI) = 16.07 (3.68–70.15)]; VEGF +936 C>T [CT genotype, p < 0.0001, OR (95% CI) = 178.64 (23.28–1370.9), and TT genotype, p < 0.0001; OR (95% CI) = 3149 (278.91–35 553)]; VEGF –1455 T>C [CC genotype, p value = 0.0464, OR (95% CI) = 3.13 (1.07–9.10)]; VEGF –2578 C>A [CA genotype, p = 0.0426, OR (95% CI) = 4.62 (1.03–20.59), and AA genotype, p value < 0.0001, OR (95% CI) = 21.89 (4.94–97.04)]; VEGF –2549 18 bp Insertion/Deletion [ID genotype, p value < 0.0001, OR (95% CI) = 27.27 (3.61–205.73) and DD genotype, p value < 0.0001, OR (95% CI) = 25.18 (3.30–191.89) were significantly associated with acute rejection risk. On comparing rejectors versus non‐rejectors, GA genotype of VEGF –1190 G>A and TC genotype of VEGF –1455 T>C were associated with the risk of rejection. On comparing donor VEGF between rejectors and non‐rejectors, CG genotype of VEGF –634 C>G, AG of VEGF –1154 G>A; GA of VEGF –1190 G>A were associated with rejection. The blood VEGF‐A mRNA and plasma VEGF levels were higher in the rejectors group compared to non‐rejectors. Conclusions: Besides the recipient's VEGF SNPS, the donor's VEGF SNPs are also associated with the risk of acute rejection and may be closely monitored in evaluation to determine the risk of rejection. [ABSTRACT FROM AUTHOR]

Objectives Mechanisms of non-typhoidal Salmonella (NTS) resistance to azithromycin have rarely been reported. Here we investigate the epidemiology and genetic features of 10 azithromycin-resistant NTS isolates. Methods A total of 457 NTS isolates were collected from a tertiary hospital in Guangzhou. We performed antimicrobial susceptibility tests, conjugation experiments, efflux pump expression tests, whole-genome sequencing and bioinformatics analysis to conduct the study. Results The results showed that 10 NTS isolates (2.8%) were resistant to azithromycin with minimum inhibitory concentration values ranging from 128 to 512 mg/L and exhibited multidrug resistance. The phylogenetic tree revealed that 5 S. London isolates (AR1–AR5) recognized at different times and departments were closely related [3–74 single-nucleotide polymorphisms (SNPs)] and 2 S. Typhimurium isolates (AR7 and AR8) were clones (<3 SNPs) at 3-month intervals. The azithromycin resistance was conferred by mph (A) gene found on different plasmids, including IncFIB, IncHI2, InFII, IncC and IncI plasmids. Among them, IncFIB, InFII and IncHI2 plasmids carried different IS 26 -class 1 integron (intI1) arrangement patterns that mediated multidrug resistance transmission. Conjugative IncC plasmid encoded resistance to ciprofloxacin, ceftriaxone and azithromycin. Furthermore, phylogenetic analysis demonstrated that mph (A)-positive plasmids closely related to 10 plasmids in this study were mainly discovered from NTS, Escherichia coli , Klebsiella pneumonia and Enterobacter hormaechei. The genetic environment of mph (A) in 10 NTS isolates was IS 26 - mph (A)- mrx (A)- mphR (A)-IS 6100 /IS 26 that co-arranged with intI1 harbour multidrug-resistant (MDR) gene cassettes on diverse plasmids. Conclusions These findings highlighted that the dissemination of these plasmids carrying mph (A) and various intI1 MDR gene cassettes would seriously restrict the availability of essential antimicrobial agents for treating NTS infections. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, VEGFA, and CYP2C8. With the development of molecular biology, newer methods such as miRNA and gene expression studies have been introduced in MRONJ, in addition to methods that can examine the base sequence of the DNA. Describing the complex genetic background of MRONJ can help further understand its pathophysiology as well as identify new therapeutic targets to better manage this adverse drug reaction. [ABSTRACT FROM AUTHOR]

New selection methods, using trait-specific markers (marker-assisted selection (MAS)) and/or genome-wide markers (genomic selection (GS)), are becoming increasingly widespread in breeding programs. This new era requires innovative and cost-efficient solutions for genotyping. Reduction in sequencing cost has enhanced the use of high-throughput low-cost genotyping methods such as genotyping-by-sequencing (GBS) for genome-wide single-nucleotide polymorphism (SNP) profiling in large breeding populations. However, the major weakness of GBS methodologies is their inability to genotype targeted markers. Conversely, targeted methods, such as amplicon sequencing (AmpSeq), often face cost constraints, hindering genome-wide genotyping across a large cohort. Although GBS and AmpSeq data can be generated from the same sample, an efficient method to achieve this is lacking. In this study, we present the Genome-wide & Targeted Amplicon (GTA) genotyping platform, an innovative way to integrate multiplex targeted amplicons into the GBS library preparation to provide an all-in-one cost-effective genotyping solution to breeders and research communities. Custom primers were designed to target 23 and 36 high-value markers associated with key agronomical traits in soybean and barley, respectively. The resulting multiplex amplicons were compatible with the GBS library preparation enabling both GBS and targeted genotyping data to be produced efficiently and cost-effectively. To facilitate data analysis, we have introduced Fast-GBS.v3, a user-friendly bioinformatic pipeline that generates comprehensive outputs from data obtained following sequencing of GTA libraries. This high-throughput low-cost approach will greatly facilitate the application of DNA markers as it provides required markers for both MAS and GS in a single assay. [ABSTRACT FROM AUTHOR]

Background: Irisin was found to correlate with coronary artery disease (CAD) in diabetic patients. This study investigated the association of irisin and FNDC5 (SNP rs3480) with the presence and severity of CAD in T2DM. Methods: This cross-sectional study included 100 patients with T2DM divided into two groups, DM group (n = 50), including patients without CAD and CAD group (n = 50), including those confirmed to have CAD by coronary angiography. Irisin was measured. SNP rs3480 genotyping of FNDC5 was done. Results: Irisin levels were significantly lower in the CAD group (p < 0.001). The CAD group had significantly higher HbA1c and lower HDL (p < 0.001). Patients with controlled DM had significantly higher irisin levels (p < 0.001). single nucleotide polymorphism (SNP) rs3480 was not associated with irisin levels, and the FNDC5 rs3480 AA reference allele was significantly associated with significant CAD. Conclusion: Irisin appears to be protective against developing CAD in diabetic patients. Irisin level was an independent predictor of significant CAD in diabetic patients combined with the FNDC5 rs3480 genotype. Clinical trial registration number: NCT04957823 [ABSTRACT FROM AUTHOR]

The TMPRSS2 protease plays a key role in the entry of the SARS-CoV-2 into cells. The TMPRSS2 gene is highly polymorphic in humans, and some polymorphisms may affect the susceptibility to COVID-19 or disease severity. rs75603675 (c.23G > T) is a missense variant that causes the replacement of glycine with valine at position 8 (p.G8V) in the TMPRSS2 isoform 1. According to GnomAD v4.0.0 database, the allele frequency of the rs75603675 on a global scale is 38.10 %, and range from 0.92 % in East Asian to 40.77 % in non-Finnish European (NFE) population. We analyzed the occurrence of the rs75603675 in two cohorts of patients, the first with severe/critical COVID-19 enrolled in a French hospital (42 patients), and the second with predominantly asymptomatic/pauci-symptomatic/mild COVID-19 enrolled in an Italian hospital (69 patients). We found that the TMPRSS2 -c.23T minor allele frequency was similar in the two cohorts, 46.43 % and 46.38 %, respectively, and higher than the frequency in the NFE population (40.77 %). Chi-square test provided significant results (p < 0.05) when the genotype data (TMPRSS2 -c.23T/c.23T homozygotes + TMPRSS2 -c.23G/c.23T heterozygotes vs. TMPRSS2 -c.23G/c.23G homozygotes) of the two patient groups were pooled and compared to the expected data for the NFE population, suggesting a possible pathogenetic mechanism of the p.G8V substitution. We explored the possible effects of the p.G8V substitution and found that the N-terminal region of the TMPRSS2 isoform 1 contains a signal for clathrin/AP-2-dependent endocytosis. In silico analysis predicted that the p.G8V substitution may increase the accessibility to the endocytic signal, which could help SARS-CoV-2 enter cells. • Polymorphism rs75603675 is a missense variant that causes the replacement of glycine with valine at position 8 in TMPRSS2 • Minor allele of rs75603675 is associated with increased susceptibility to COVID-19 in a retrospective cohort analysis. • G8V substitution affects the stability of the N-terminal region of the TMPRSS2 as revealed by molecular dynamic simulation. • In silico analysis shows that an endocytic signal may be more exposed in TMPRSS2-p.8V variant, helping the virus enter cells. [ABSTRACT FROM AUTHOR]

Increased cardiovascular risk has been associated with certain platelet morphological parameters, and several single nucleotide polymorphisms (SNPs) have been reported to be linked. Still, little is known about their role among children with type 1 diabetes mellitus (T1DM). So, we aimed to investigate platelet parameters and lipid profile changes in relation to rs7961894 SNP in children with T1DM. Eighty children with T1DM and eighty apparently healthy controls participated in this cross-sectional study. Platelet count, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), HbA1c, triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol were measured, and atherogenic indices were calculated. Using a real-time polymerase chain allelic discrimination technique, rs7961894 SNP was genotyped. Children with T1DM had significantly higher MPV, PDW, TC, and LDL-C compared to controls. 25% of patients had rs7961894 CT genotype with significantly higher MPV, PDW, PCT, LDL-C, triglycerides, Castelli's risk index II (CRI II), and atherogenic index of plasma (AIP) compared to CC genotyped patients. MPV correlated significantly with CRI II and AIP, PDW with CRI II, while PCT correlated substantially with HbA1c, LDL-C, CRI II, and AIP. rs7961894 CT genotype was a significant dependent predictor of the changes in MPV, PDW, and PCT in multivariate regression analysis. Conclusion: In children with T1DM, rs7961894 CT genotype is significantly linked to MPV, PDW, and PCT changes, which showed a substantial relationship to CRI II and AIP, highlighting the importance of monitoring these patients to identify potential cardiovascular risks early. What is Known: • Platelets and dyslipidemia are involved in atherosclerosis pathogenesis • Changes in platelet activity and morphological parameters in diabetes mellitus are contradictory • rs7961894 single nucleotide polymorphism is associated with significant changes in mean platelet volume (MPV) with no available data in children What is New: • Children with type 1 diabetes mellitus exhibited significantly higher values of MPV and platelet distribution width (PDW) • rs7961894 CT genotype was a dependent predictor of the changes in MPV, PDW, and plateletcrit (PCT) values • Diabetic children with the rs7961894 CT genotype showed substantial alterations in lipid parameters with a strong correlation between MPV, PDW, and PCT and Castelli's risk index II and the atherogenic index of plasma [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the causal link between the gut microbiota and periodontitis, and to delineate and quantify the intermediary role of immune cells, so as to provide new insights into the pathogenesis, prevention and treatment of periodontitis. Materials and methods: We employed a two-sample Mendelian randomization (MR) approach to analyze the genetic predictors of gut microbiota composition (covering 412 gut microbiota taxa and functions) and periodontitis (involving 4,784 cases and 272,252 controls) derived from genome-wide association study (GWAS) datasets. A subsequent two-step MR analysis was conducted to evaluate the extent to which immune cell traits (encompassing 731 immune cell characteristics) mediate the influence of gut microbiota on periodontitis risk. Results: Our analysis implicated nine gut microbiota taxa as causal factors in periodontitis susceptibility (p < 0.05). Notably, the Genus Roseburia was identified as exerting a protective effect against periodontitis, partially mediated through the upregulation of CD86 expression on granulocytes, with an 8.15% mediation effect observed. Conclusions: Our findings establish a causal relationship between the gut microbiota and periodontitis, highlighting the protective role of Roseburia against this condition. A notable proportion of this protective effect is mediated via the upregulation of CD86 on granulocytes. Clinical relevance: It can provide new ideas for the pathogenesis, prevention and treatment for periodontitis through exploring the causal link between the gut microbiota and periodontitis, and describing and quantifying the intermediary role of immune cells. [ABSTRACT FROM AUTHOR]

Small ruminant lentivirus (SRLV) infections are spread in the flocks of sheep and goats all over the world, causing economic loss. Although only a fraction of infected animals develop disease symptoms, all of them may shed the virus, causing uncontrolled spread of the infection. Antibodies against the virus can be detected in the blood of infected animals and are the main marker of infection. Additionally, in most infected animals, proviral DNA can also be detected, but at different levels. Due to the lack of treatment or vaccines, the most effective strategy to prevent SRLV infections are control programmes introduced by several countries based on the elimination of seropositive individuals from the flock. An alternative approach, which has currently become the rationale, is an identification of host factors which may predispose certain individuals or breeds to resistance or susceptibility to small ruminant lentivirus infection. In our work, attention was paid to goats of the Carpathian breed infected with SRLV. Available RNA-seq results from the blood of 12 goats with a determined level of SRLV proviral load were used to analyse single nucleotide polymorphisms (SNPs) by the variant calling method. Six SNPs within five genes (POU2AF1, BCAT2, TMEM154, PARP14, UBASH3A) were selected for genotyping to determine their association with the level of small ruminant lentivirus proviral DNA in a group of 60 goats. Interestingly, in seronegative individuals, only the TT genotype of the PARP14 gene was observed, while the TMEM154 CC genotype was found only in seropositive goats. Both genes may be considered potential markers for resistance/susceptibility to SRLV infection. In contrast, polymorphisms identified in POU2AF1 and UBASH3A genes seemed to be deleterious for respective protein functions; therefore, these genes are less likely to be recognised as resistance/susceptibility markers of SRLV infection. [ABSTRACT FROM AUTHOR]

Leaves are vital organs for photosynthesis, gas exchange, and light energy absorption in plants and play a crucial role in synthesizing essential nutrients. Watermelon is a widely cultivated crop worldwide and has a range of leaf shapes, including non-lobed (entire), semi-lobed, and highly lobed varieties. However, few studies have focused on lobed leaf traits in watermelons. Therefore, our study aimed to elucidate the genetic basis of leaf lobing regulation in watermelons, focusing on lines cultivated in Korea. We analyzed the F2 progeny derived from crosses between the highly lobed SIT463ST and the non-lobed PS137 watermelon line. We discovered that lobed leaf traits in watermelons are controlled by a single incomplete dominant gene. Additionally, we used next-generation sequencing-based bulked segregant analysis sequencing to identify a candidate genomic region spanning 24.06–24.09 Mb (25 kb) on Chr. 4. Three single nucleotide polymorphism markers (LL-4-238, LL-4-956, and LL-4-252) were developed that were closely associated with the non-lobed leaf margin shape in the F2 population. Analysis of the expression levels of these genes in the fine mapping region revealed only synonymous substitutions in the coding regions, suggesting that mutations in potential promoter regions may regulate gene expression, thereby affecting leaf morphology. These findings provide valuable insights into the molecular factors underlying non-lobed leaf traits in watermelons and offer potential targets for genetic improvement. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the utility of 24 single nucleotide polymorphism (SNP) loci associated with iris color and hair color in phenotypic identification of the Han Chinese population in Fujian Province. The selected SNPs, known for their strong correlation with specific human phenotypic features, provide valuable reference data for developing a molecular phenotypic identification system. Methods: A multiplex genotyping assay system was established with primers for the 24 SNPs linked to iris color and hair color synthesized based on existing literature. In total, 235 unrelated individuals of Han Chinese ethnicity in Fujian Province were included in this study. PowerStats v12 was employed to calculate forensic parameters associated with the 24 SNP loci, including gene frequencies, genotype frequencies, minor allele frequencies, discrimination power (DP), polymorphism information content (PIC), and observed heterozygosity (Ho). Hardy- Weinberg equilibrium tests were conducted for each locus. The SNP genotyping results were uploaded to the HIrisPlex model (https://HIrisPlex.erasmusmc.nl/) to predict iris and hair colors, and the inferred results were compared with manually assessed images. The accuracy of pigment phenotype inference was evaluated by using ROC curves in SPSS 26.0 software. Results: The accuracy rates of inferring brown iris and black hair phenotypes were 99.6% and 99.5%. The area under the curve (AUC) values were 0.923 and 0.980, respectively. Conclusions: The 24 SNP loci demonstrated high accuracy in inferring iris color and hair color; it seems to be a useful tool for forensic phenotypic identification and anthropological or evolutionary applications. Establishment of suitable pigment classification criteria and optimized prediction models is based on revealing more phenotypic genetic markers. [ABSTRACT FROM AUTHOR]

Context Thiazide-induced hyponatremia is one of the most common forms of hyponatremia, but its pathogenesis is incompletely understood. Recent clinical data suggest links with prostaglandin E2 (PGE2) and a single nucleotide polymorphism (SNP) in the prostaglandin transporter gene (SLCO2A1), but it is unknown if these findings also apply to the general population. Objective To study the associations between serum sodium, thiazide diuretics, urinary excretions of PGE2, and its metabolite (PGEM), and the rs34550074 SNP in SLCO2A1 in the general population. Design Prospective population-based cohort study (Rotterdam Study). Setting General population. Participants 2178 participants (65% female, age 64 ± 8 years) Intervention(s) None. Main Outcome Measure(s) Serum sodium levels. Results Higher urinary PGE2 excretion was associated with lower serum sodium: difference in serum sodium for each 2-fold higher PGE2 −0.19 mmol/L [95% confidence interval (CI) −0.31 to −0.06], PGEM −0.29 mmol/L (95% CI −0.41 to −0.17). This association was stronger in thiazide users (per 2-fold higher PGE2 −0.73 vs −0.12 mmol/L and PGEM −0.6 vs −0.25 mmol/L, P for interaction <.05 for both). A propensity score matching analysis of thiazide vs non-thiazide users yielded similar results. The SNP rs34550074 was not associated with lower serum sodium or higher urinary PGE2 or PGEM excretion in thiazide or non-thiazide users. Conclusion Serum sodium is lower in people with higher urinary PGE2 and PGEM excretion, and this association is stronger in thiazide users. This suggests that PGE2-mediated water reabsorption regulates serum sodium, which is relevant for the pathogenesis of hyponatremia in general and thiazide-induced hyponatremia specifically. [ABSTRACT FROM AUTHOR]

Coke oven emissions (COEs) contain a variety of polycyclic aromatic hydrocarbons (PAHs), which can cause damage to the human cardiovascular system. In addition, myocardial mitochondria are susceptible to damage in hypertensive patients. However, it is not clear whether genetic variation, in single nucleotide polymorphisms (SNPs) in PINK1 affects COEs exposure-induced abnormal blood pressure. We surveyed and tested 518 workers exposed to COEs and statistically analyzed them with SPSS 21.0 software. SBP was greater in the high-exposure group than in the low-exposure group. Generalized linear model analysis showed that the interaction of PINK1 rs3738136 (GA+AA) and COEs had an effect on SBP [β(95%CI) = -6.537(−12.072, −1.002), p = 0.021] and DBP [β(95%CI) = -4.811(−8.567, −1.056), p = 0.012]. This study is the first to identify the role of PINK1 rs3738136 in COE- induced abnormal blood pressure, and to prove that the abnormal blood pressure of workers is the result of environmental and genetic factors. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the association between statins and the risk of osteoarthritis through Mendelian randomization analysis using summary data from large-scale population-based genome-wide association studies (GWAS). METHODS: Firstly, single nucleotide polymorphism data related to statins were obtained from the latest 9th edition of the FinnGen database, while data of osteoarthritis, knee osteoarthritis and hip osteoarthritis were obtained from the IEU Open GWAS, UK Biobank, and ArcOGEN (Genetics of Osteoarthritis) databases, respectively. The inverse variance weighted method was used as the primary analysis approach to evaluate the causal effects. The weighted median method, simple median method, weighted mode-based method, and MR-Egger regression were used as supplementary analyses. The causal relationship between statins and the risk of osteoarthritis, knee osteoarthritis and hip osteoarthritis was assessed using odds ratios (OR) with 95% confidence intervals (CI). Sensitivity analyses were conducted to validate the reliability of the results, including the Cochran’s Q test for heterogeneity and the MR-Egger-intercept test for horizontal pleiotropy, as well as leave-one-out analysis to identify potentially influential single nucleotide polymorphisms. RESULTS AND CONCLUSION: The inverse variance weighted analysis demonstrated a negative causal relationship between genetically predicted statins and the risk of osteoarthritis (OR=0.998, 95% CI: 0.996-0.999, P=0.01), knee osteoarthritis (OR=0.964, 95% CI: 0.940-0.989, P=0.005), and hip osteoarthritis (OR=0.928, 95% CI: 0.901-0.955, P=4.28×10-7). MR-Egger intercept analysis did not detect potential horizontal pleiotropy (osteoarthritis: P=0.658; knee osteoarthritis: P=0.600; hip osteoarthritis: P=0.141). The results of this study provide evidence that statins reduce the risks of osteoarthritis, knee osteoarthritis and hip osteoarthritis as described in observational studies. Further research is needed to explore the specific mechanisms of statin treatment for osteoarthritis. [ABSTRACT FROM AUTHOR]

Exploring genetic resources through genomic analyses has emerged as a powerful strategy to develop common bean (Phaseolus vulgaris L.) cultivars that are both productive and well-adapted to various environments. This study aimed to identify genomic regions linked to morpho-agronomic traits in Mesoamerican and Andean common bean accessions and to elucidate the proteins potentially involved in these traits. We evaluated 109 common bean accessions over three agricultural years, focusing on traits including the grain yield (YDSD), 100-seed weight (SW), number of seeds per pod (SDPD), number of pods per plant (PDPL), first pod insertion height (FPIH), plant height (PLHT), days to flowering (DF), and days to maturity (DPM). Using multilocus methods such as mrMLM, FASTmrMLM, FASTmrEMMA, ISIS EM-BLASSO, and pLARmEB, we identified 36 significant SNPs across all chromosomes (Pv01 to Pv11). Validating these SNPs and candidate genes in segregating populations is crucial for developing more productive common bean cultivars through marker-assisted selection. [ABSTRACT FROM AUTHOR]

Background: Intervertebral disc (IVD) degenerative disease is a multifactorial disease for which genetics plays an integral role. Several genes, and their variants, associated with the development and progression of IVD degenerative disease have been identified. While several studies have investigated these genes in Asian and European populations, no available evidence exists for the South African population. Therefore, this study aimed to investigate these parameters. Methods and results: Biological samples were collected in the form of buccal swabs from patients and DNA was extracted using a standard salt-lysis protocol. DNA purity and quantity was assessed by spectrophotometry, and subsequent genotyping was performed using the MassARRAY®System IPLEX extension reaction. For associations between variants and the presence of IVD degenerative disease, odds ratios (OR), confidence intervals (CI), chi-squared analysis and logistic regression was calculated. Age and sex were adjusted for, and Bonferroni’s correction was applied. This study found statistically significant associations for five of the evaluated single nucleotide polymorphisms (SNPs) with IVD degenerative disease, whereby IL-1α rs1304037 and rs1800587, ADAMTs-5 rs162509, and MMP-3 rs632478 demonstrated increased odds of a positive diagnosis for IVD degenerative disease, while decreased odds of IVD degenerative disease were seen for GDF-5 rs143383. Conclusion: To the best of our knowledge, this study represents the first of its kind to investigate the association of gene variants associated with IVD degenerative disease within the South African population. This study has shown that 5 of these gene variants were significantly associated with the presence of IVD degenerative disease, reflecting their integral roles in development and possible progression of the disease. [ABSTRACT FROM AUTHOR]

Historically, the genetic diversity of insular species and populations has generally been considered to be lower with respect to their continental counterparts. In this study, I compare for first time the genetic diversity of two gecko species, Phyllodactylus angelensis and P. magnus, that inhabit contrasting environments in Mexico (island and mainland, respectively). Utilizing genomic data for both species generated through genotyping by sequencing (GBS), I performed paired comparisons of various genetic diversity indices analyzing thousands of single nucleotide polymorphism (SNP) variants. The majority of genetic diversity indices demonstrated very similar values between both species, while the observed heterozygosity and genetic diversity within populations was higher for the insular species. The results do not support the generalized assumption of lower genetic diversity in island species. Key aspects such as the effective population size of founders, gene flow, and shared life histories may be involved in explaining the observed pattern. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionTo investigate the association of hypoxia-inducible factor-1α (HIF-1α), Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) gene polymorphisms with idiopathic scleritis in a Chinese Han population.Ten single nucleotide polymorphisms (SNP) of HIF-1α, tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 3 (STAT3), signal transducer and activator of transcription 4 (STAT4), and retinoid-related orphan nuclear receptors-γ (ROR-γ) were selected for this study. A total of 496 idiopathic scleritis patients and 1009 controls were genotyped by the MassARRAY platform and iPLEX Gold Genotyping Assay. The allele and genotype frequencies were analyzed by Chi-square test and Fisher's exact test. Stratified analyses were performed based on gender and anatomic locations of idiopathic scleritis.The frequencies of CC genotype (p = 6.18 × 10−4, Pc = 0.04, OR = 0.67,95%CI = 0.53–0.84) and C allele (p = 7.08 × 10−4, Pc = 0.04, OR = 0.71,95%CI = 0.58–0.87) for HIF-1α/rs2057482 were found significantly lower in idiopathic scleritis patients when compared to healthy controls. Stratified analysis depending on gender showed significant decreased frequencies of CC genotype (CC: p = 4.04 × 10−4, Pc = 0.02, OR = 0.54, 95%CI = 0.39–0.76) and C allele (C: p = 1.62 × 10−4, Pc = 0.01, OR = 0.58, 95%CI = 0.44–0.77) in male patients. Stratification analysis of rs2057482 according to location of scleritis did not show any significant difference between three subgroups and healthy controls.This study showed association between polymorphism of HIF-1α/rs2057482 and susceptibility to idiopathic scleritis in Han Chinese male patients. [ABSTRACT FROM AUTHOR]

To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P < 0.05; C vs A: OR = 1.558, P < 0.001), and this locus increased the risk of SLE in the dominant model and the recessive model (AC + CC vs AA: OR = 1.542, P < 0.05; CC vs AA + AC: OR = 1.707, P < 0.001), while the risk of SLE was reduced in the overdominant model (AC vs AA + CC: OR = 0.628, P < 0.001). The GT genotype and T allele at locus rs1799983 may be a protective factor for SLE (GT vs GG: OR = 0.328, P < 0.001; T vs G: OR = 0.438, P < 0.001) and this locus reduced the risk of SLE in the overdominant model (GT vs GG + TT: OR = 0.385, P < 0.001). There is a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene. Among them, the formed haplotype AG increased the risk of SLE compared to GG. AT and GT decreased the risk of SLE compared to GG. In this study, the eNOS gene rs3918188 and rs1799983 loci were found to be associated with susceptibility to SLE. This helps to deeply explore the mechanism of eNOS gene and genetic susceptibility to SLE. It provides a certain research basis for the subsequent exploration of the molecular mechanism of these loci and SLE, as well as the early diagnosis, treatment and prognosis of SLE. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between the single nucleotide polymorphism (SNP) of preg‑ nane X receptor (PXR) gene and the risk of type 2 diabetes mellitus (T2DM) . Methods Totally 285 T2DM patients (observation group) and 230 healthy volunteers (control group) were selected. Fasting peripheral venous blood of all sub‑ jects was collected, genomic DNA was extracted, and PXR gene sites rs1523127, rs3814055 and rs6785049 were sequenced and genotyping was performed. Serum PXR, glucose transporter 2 (GLUT2) and glucokinase (GCK) were detected by enzyme ELISA. The genotypes and allele frequencies of rs1523127, rs3814055, rs6785049 and serum levels of PXR, GLUT2 and GCK were compared between the two groups. We analyze the relationship between SNP of PXR gene and the risk of T2DM. Results Through Hardy-Weinberg genetic balance test, the genotypes and allele frequencies of PXR genes at different loci were consistent with the law of genetic balance in the two groups. There were no significant dif‑ ferences in genotypes or allele frequencies of rs1523127 and rs6785049 of PXR gene between two groups (all P>0. 05) . The frequencies of CT/TT genotype and T allele at rs3814055 of PXR gene in the observation group were higher than those in the control group (both P<0. 05), and the odds ratio (OR) of T2DM patients with CT and TT genotype was 1. 591 and 2. 398 times higher than that of patients with CC genotype. The OR of T allele carriers for T2DM was 1. 638 times higher than that of C allele carriers. Serum PXR level in the observation group was higher than that in the control group, and serum GLUT2 and GCK levels were lower than those in the control group (both P<0. 05) . The level of serum PXR in CT/TT genotype at rs3814055 of PXR gene in T2DM patients was higher than that in patients with CC genotype, and the levels of serum GLUT2 and GCK were lower than those in patients with CC genotype (both P<0. 05) . Conclusion The mutation of C allele at rs3814055 of PXR gene to T allele can increase its transcriptional activity, inhibit serum GLUT2 and GCK levels, impair glucose tolerance, and increase the risk of T2DM. [ABSTRACT FROM AUTHOR]

To explore whether rs2073244 at PAX9 increased susceptibility for full-term low birth weight infants and whether indoors passive smoking exposure has a combined effect with rs2073244 on newborn low birth weight (LBW), a 1:2 paired case–control study of LBW newborns was conducted at Xiamen University Affiliated Women and Children’s Hospital from March 2010 to October 2013. The rate of indoor passive smoking exposure in the LBW group was higher than it in the NBW group (p = 0.019). GG of PAX9 rs2073244 decreased the risk of LBW [OR = 0.38, 95% CI: (0.15-0.98)] and smaller HC [OR = 0.44, 95% CI:(0.20-0.98)]. The relative excess risk for LBW contributed by the additive interaction between the rs2073244 risk genotypes AG/AA and mother pregnancy passive smoking exposure was 10.679 (95%CI 1.728–65.975). Our study suggested that the AG/AA genotype of PAX9 rs2073244 might be a risk factor for LBW of full-term newborns, especially in maternal passive smoking. [ABSTRACT FROM AUTHOR]

Genetic and epigenetic alterations occur in many physiological and pathological processes. The existing knowledge regarding the association of PIWI‐interacting RNAs (piRNAs) and their genetic variants on risk and progression of prostate cancer (PCa) is limited. In this study, three genome‐wide association study datasets are combined, including 85,707 PCa cases and 166,247 controls, to uncover genetic variants in piRNAs. Functional investigations involved manipulating piRNA expression in cellular and mouse models to study its oncogenetic role in PCa. A specific genetic variant, rs17201241 is identified, associated with increased expression of PROPER (piRNA overexpressed in prostate cancer) in tumors and are located within the gene, conferring an increased risk and malignant progression of PCa. Mechanistically, PROPER coupled with YTHDF2 to recognize N6‐methyladenosine (m6A) and facilitated RNA‐binding protein interactions between EIF2S3 at 5′‐untranslated region (UTR) and YTHDF2/YBX3 at 3′‐UTR to promote DUSP1 circularization. This m6A‐dependent mRNA‐looping pattern enhanced DUSP1 degradation and inhibited DUSP1 translation, ultimately reducing DUSP1 expression and promoting PCa metastasis via the p38 mitogen‐activated protein kinase (MAPK) signaling pathway. Inhibition of PROPER expression using antagoPROPER effectively suppressed xenograft growth, suggesting its potential as a therapeutic target. Thus, targeting piRNA PROPER‐mediated genetic and epigenetic fine control is a promising strategy for the concurrent prevention and treatment of PCa. [ABSTRACT FROM AUTHOR]

Background: The foodborne bacterium Listeria monocytogenes (Lm) causes a range of diseases, from mild gastroenteritis to invasive infections that have high fatality rate in vulnerable individuals. Understanding the population genomic structure of invasive Lm is critical to informing public health interventions and infection control policies that will be most effective especially in local and regional communities. Methods: We sequenced the whole draft genomes of 936 Lm isolates from human clinical samples obtained in a two-decade active surveillance program across 58 counties in New York State, USA. Samples came mostly from blood and cerebrospinal fluid. We characterized the phylogenetic relationships, population structure, antimicrobial resistance genes, virulence genes, and mobile genetic elements. Results: The population is genetically heterogenous, consisting of lineages I–IV, 89 clonal complexes, 200 sequence types, and six known serogroups. In addition to intrinsic antimicrobial resistance genes (fosX, lin, norB, and sul), other resistance genes tetM, tetS, ermG, msrD, and mefA were sparsely distributed in the population. Within each lineage, we identified clusters of isolates with ≤ 20 single nucleotide polymorphisms in the core genome alignment. These clusters may represent isolates that share a most recent common ancestor, e.g., they are derived from the same contamination source or demonstrate evidence of transmission or outbreak. We identified 38 epidemiologically linked clusters of isolates, confirming eight previously reported disease outbreaks and the discovery of cryptic outbreaks and undetected chains of transmission, even in the rarely reported Lm lineage III (ST3171). The presence of animal-associated lineages III and IV may suggest a possible spillover of animal-restricted strains to humans. Many transmissible clones persisted over several years and traversed distant sites across the state. Conclusions: Our findings revealed the bacterial determinants of invasive listeriosis, driven mainly by the diversity of locally circulating lineages, intrinsic and mobile antimicrobial resistance and virulence genes, and persistence across geographical and temporal scales. Our findings will inform public health efforts to reduce the burden of invasive listeriosis, including the design of food safety measures, source traceback, and outbreak detection. [ABSTRACT FROM AUTHOR]

The grasshopper Trimerotropis pallidipennis species complex is distributed across arid and semi-arid environments from North to South America, reaching high altitudes along the Andes Mountain range. Currently, there are four valid species of Trimerotropis in South America. However, some species were found to comprise several genetic lineages. Here, we describe the genetic structure, lineage diversification, and environmental requirements within the Trimerotropis species complex in South America based on sequences from the mitochondrial COI gene, 4048 single nucleotide polymorphisms, and ecological niche modelling. The analyses revealed the existence of at least five lineages: two with a restricted geographical distribution and three with a very wide one. The results provide evidence that glacial cycles promoted not only the presence of refuge areas but also the isolation of widely distributed lineages on the eastern and western sides of the southern Andes, potentially driving the emergence of the Trimerotropis sp. lineage, which can tolerate more temperate habitats. Our results provide evidence for the effects of Pleistocene climatic changes on the diversification history of a South American grasshopper species complex. [ABSTRACT FROM AUTHOR]

Objective To investigate whether there is a causal relationship between gut microbiota and autism in children using the Mendelian randomization (MR) analysis method. Methods Genetic data from 18 340 individuals collected by the MiBioGen consortium across 24 cohorts were utilized. Reliable instrumental variables were constructed by selecting genetic variations associated with 33 microbial taxa. Using results from a genome-wide association study (GWAS) on susceptibility genes for autism in children conducted in Europe, we comprehensively assessed the causal link between gut microbiota and autism using inverse variance weighting (IVW), MR-Egger regression, and weighted median estimation (WME). Results Among the three selected single nucleotide polymorphisms (SNPs), the abundance of Bacteroidetes was significantly associated with autism (OR=0.508, 95%CI: 0.267-0.966, P=0.039). The IVW results indicated that for every one standard deviation increase in Bacteroidetes abundance, the average risk of developing autism decreased by 49.2%. Conclusion This study suggests a negative causal effect of Bacteroidetes abundance on the risk of developing autism in children. [ABSTRACT FROM AUTHOR]

Cleft lip and/or palate (CL/P) are the most common congenital anomalies in the craniofacial region, leading to morphological and functional disruptions in the facial region. Their etiology involves genetic and environmental factors, with genetics playing a crucial role. This study aimed to investigate the association of four single nucleotide polymorphisms (SNPs)—rs987525, rs590223, rs522616, and rs4714384—with CL/P in the Polish population. We analyzed DNA samples from 209 individuals with CL/P and 418 healthy controls. The impact of SNPs on the presence of CL/P was assessed using multivariate logistic regression. Significant associations were found with rs987525. Specifically, the AC genotype was linked to an increased CL/P risk (odds ratio [OR] = 1.95, 95% confidence interval [CI]: 1.34–2.83, p < 0.001), while the CC genotype was associated with a decreased risk (OR = 0.46, 95% CI: 0.32–0.67, p < 0.001). Rs4714384 was also significant, with the CT genotype correlated with a reduced risk of CL/P (OR = 0.66, 95% CI: 0.46–0.94, p = 0.011). SNPs rs590223 and rs522616 did not show statistically significant associations. These results underscore the role of rs987525 and rs4714384 in influencing CL/P risk and suggest the utility of genetic screening in understanding CL/P etiology. [ABSTRACT FROM AUTHOR]

Objective: In the hypothalamic-pituitary-gonadotrophin axis, estrogen plays a key role in the regulation of bone maturation and growth plate closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in a North Indian population. Methods: Four SNPs of ESR1 (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in ISS patients and controls. Linkage disequilibrium (LD) and haplotyping were done by SNPStat and SHEsisPlus software. The extent of LD was determined by calculating D' and R2 values in SNP paired combinations. Results: Fifty-two ISS patients were compared with 68 controls. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility. The frequencies of the rs6557177 CC genotype [p=0.030; odds ratio (OR)=0.13; 95% confidence interval (CI): 0.01-1.10] and rs543650 genotype TT (p=0.043; OR=0.29; 95% CI: 0.09-0.92) were increased in the ISS group compared with controls. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 showed strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. Conclusion: Our study showed that the CC genotype at rs6557177 and TT genotype at rs543650 of ESR1 constituted a risk factor for developing ISS in North Indian children. These findings may lead to a better understanding of the SNPs associated with ISS susceptibility. [ABSTRACT FROM AUTHOR]

The inhibin alpha (INHA) serves as a marker for the number of fully developed ovarian follicles and plays a crucial role in regulating the secretion of pituitary FSH (follicle-stimulating hormone) and the frequency of ovulation. This study aims to examine the effect of INHA gene polymorphisms on the litter size of thin-tailed sheep. Detection of single nucleotide polymorphisms (SNPs) in the INHA gene was performed using PCR and DNA sequencing techniques. A total of 45 ewes were included in the study. Three SNPs were identified: g.236311141G>C, g.236311367G>A, and g.236311368G>A. Further investigation of the g.236311367G > A variant revealed that individuals with the GA genotype had a significantly higher litter size than those with the AA or GG genotype (p<0.05). SNPs at positions g.236311141G/C and g.236311368G/A were non-synonymous mutations resulting in amino acid changes p.A225P and V301I, respectively. Our results suggest that g.236311367G>A loci may serve as a potential molecular marker for improving the litter size trait in thin-tailed sheep. [ABSTRACT FROM AUTHOR]

Aneuploidy is a genetic condition characterized by the loss or gain of one or more chromosomes. Aneuploidy affecting the sex chromosomes can lead to infertility in otherwise externally phenotypically normal cattle. Early identification of cattle with sex chromosomal aneuploidy is important to minimize the costs associated with rearing infertile cattle and futile breeding attempts. As most livestock breeding programs routinely genotype their breeding populations using single nucleotide polymorphism (SNP) arrays, this study aimed to assess the feasibility of integrating an aneuploidy screening tool into the existing pipelines that handle dense SNP genotype data. A further objective was to estimate the prevalence of sex chromosome aneuploidy in a population of 146,431 juvenile cattle using available genotype intensity data. Three genotype intensity statistics were used: the LogR Ratio (LRR), R‐value (the sum of X and Y SNP probe intensities), and B‐allele frequency (BAF) measurements. Within the female‐verified population of 124,958 individuals, the estimated prevalence rate was 0.0048% for XO, 0.0350% for XXX, and 0.0004% for XXY. The prevalence of XXY in the male‐verified population was 0.0870% (i.e., 18 out of 20,670 males). Cytogenetic testing was used to verify 2 of the XXX females who were still alive. The proposed approach can be readily integrated into existing genomic pipelines, serving as an efficient, large‐scale screening tool for aneuploidy. Its implementation could enable the early identification of infertile animals with sex‐chromosome aneuploidy. [ABSTRACT FROM AUTHOR]

Aim - to analyze the current literature on the role of single nucleotide polymorphism (SNP) of human genes in shaping the clinical course of the new coronavirus disease (COVID-19). Results. Based on the results of the analysis and synthesis of the current literature on the role of SNP in shaping the clinical course and outcome of COVID-19, the clinical and prognostic significance of SNP of genes encoding receptors responsible for the penetration of SARS-CoV-2 into target cells has been demonstrated. The presence of the D-allele of the ACE gene (DD and ID genotypes) is associated with the highest risk of severe COVID-19, which makes it possible to offer it as an informative prognostic marker of COVID-19 severity. SNP of the TMPRSS2 co-receptor gene, known as the androgen responsive gene, at certain loci is prognostically important, as it leads to an increase in TMPRSS2 expression in men, which promotes virus fusion with the target cell membrane and has an unfavorable effect on the course of COVID-19 in men. The data accumulated in the current literature on the clinical and prognostic value of SNP host genes encoding the immune response has also been analyzed. The role of HLA SNP genes, genes encoding innate immunity factors (TLR), as well as genes encoding pro-inflammatory cytokines (IL-6, TNF-α, etc.) and acute-phase inflammatory components (CRP) in the development of severe COVID-19 and the risk of death has been demonstrated. Attention has been paid to the determined role of SNP in the ACE gene in the development of pulmonary embolism in patients with severe COVID-19. The article has analyzed publications on the SNP role of host genes in the development of clinical events that are currently interpreted as long COVID. The prognostic role of the IL-10 gene SNP and its receptor gene in the formation of long-term consequences of the new coronavirus infection has been demonstrated. Conclusions. SNP of host genes encoding receptors responsible for the entry of SARS-CoV-2 into target cells and SNP of genes encoding immune response have some prognostic value in assessing the risk of severe course and adverse effects of COVID-19. The accumulation of data on genetic risk factors for adverse outcomes of the new coronavirus disease will allow us to enhance the understanding of this infection pathogenesis, improve patient stratification and individualize therapeutic interventions. [ABSTRACT FROM AUTHOR]

Introduction: According to the conducted studies, breast cancer is one of the most common malignant tumors, and its incidence rate is increasing yearly. One of the measures to reduce the mentalities from breast cancer is early diagnosis of biomarkers, such as Leptin polymorphisms (rs7799039 and rs2167270), and timely treatment. Leptin is an adipocytokine made by fat cells, playing a crucial role in cell proliferation, survival, migration, and immune response. The present study aimed to assess the association between polymorphisms in the Leptin gene and breast cancer risk in Arak, Iran. Materials & Methods: Two SNPs of the Leptin gene (rs7799039 and rs2167270) were genotyped by PCR-RFLP method (polymerase chain reaction-restriction fragment length polymorphism) in a case-control study, including 80 breast cancer patients and 80 healthy controls. In this study, all statistical analyses were performed in SPSS software (version 26) using the Chi-Squared test at P˂ 0.05 significant level. Results: Based on the results, rs7799039 and rs2167270 showed no significant association with breast cancer risk (P=0.183 and P=0.86, respectively). In this study, the mean age in the patient group was 47 ( an age range of 28-79 years). Conclusion: As evidenced by the obtained results, Leptin gene polymorphisms (rs7799039 and rs2167270) did not increase the risk of breast cancer in the Arak population in Iran. Although based on the present study results, there was no significant association between Leptin gene polymorphisms and breast cancer risk, according to the prominent role of the Leptin gene, the polymorphisms of this gene could be used as biomarkers to predict breast cancer in other populations. [ABSTRACT FROM AUTHOR]

In adult mammals, the inability to digest lactose due to lactase non-persistence or adult-type hypolactasia, is relatively common after the weaning stage. However, there is a fraction of the adult population who continue to exhibit lactase persistence, sparking the interest of many scientists. The epigenetics of lactase persistence and non-persistence differ greatly, as well as the factors affecting the genotype and phenotype. Other studies used genome editing technology, genomic DNA isolation, genomic DNA methylation analysis and more to investigate the factors determining the LCT gene expression. Here, analyzed field data highlighted these significant findings together to discuss the epigenetics of lactase non-persistence. This paper will review the epigenetics of lactase non-persistence and lactase persistence and the factors influencing expression and modification on a molecular level. Findings regarding nutritional and environmental factors, as well as differences in frequencies in various continents will also be displayed. The aim of this article is to deepen the understanding of the epigenetic mechanisms revolving around lactase non-persistence, factors like mutations in the -13910 allele, and analyze past and recent articles to inform on epigenetic targets and implications as future treatments. [ABSTRACT FROM AUTHOR]

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Copyright of Osmangazi Journal of Medicine / Osmangazi Tip Dergisi is the property of Eskisehir Osmangazi University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)