Genome-wide association study reveals marker-trait associations for major agronomic traits in proso millet (Panicum miliaceum L.).

MAIN CONCLUSION: The pilot-scale genome-wide association study in the US proso millet identified twenty marker-trait associations for five morpho-agronomic traits identifying genomic regions for future studies (e.g. molecular breeding and map-based cloning). Proso millet (Panicum miliaceum L.) is an ancient grain recognized for its excellent water-use efficiency and short growing season. It is an indispensable part of the winter wheat-based dryland cropping system in the High Plains of the USA. Its grains are endowed with high nutritional and health-promoting properties, making it increasingly popular in the global market for healthy grains. There is a dearth of genomic resources in proso millet for developing molecular tools to complement conventional breeding for developing high-yielding varieties. Genome-wide association study (GWAS) is a widely used method to dissect the genetics of complex traits. In this pilot study of the first-ever GWAS in the US proso millet, 71 globally diverse genotypes of 109 the US proso millet core collection were evaluated for five major morpho-agronomic traits at two locations in western Nebraska, and GWAS was conducted to identify single nucleotide polymorphisms (SNPs) associated with these traits. Analysis of variance showed that there was a significant difference among the genotypes, and all five traits were also found to be highly correlated with each other. Sequence reads from genotyping-by-sequencing (GBS) were used to identify 11,147 high-quality bi-allelic SNPs. Population structure analysis with those SNPs showed stratification within the core collection. The GWAS identified twenty marker-trait associations (MTAs) for the five traits. Twenty-nine putative candidate genes associated with the five traits were also identified. These genomic regions can be used to develop genetic markers for marker-assisted selection in proso millet breeding.

Development of DNA-Based Lateral Flow Assay for Detection of LDLR Gene Mutation for Familial Hypercholesterolemia.

Background: The techniques for detecting single nucleotide polymorphisms (SNP) require lengthy and complex experimental procedures and expensive instruments that may only be available in some laboratories. Thus, a deoxyribonucleic acid (DNA)-based lateral flow assay (LFA) was developed as a point-of-care test (POCT) diagnostic tool for genotyping. In this study, single nucleotide variation (E101K) in the low-density lipoprotein receptor (LDLR) gene leading to familial hypercholesterolemia (FH) was chosen as a model. Methods: Hypercholesterolemic individuals (n = 103) were selected from the Malaysian Cohort project (UKM Medical Molecular Biology Institute) while the control samples were selected from the Biobank (UKM Medical Molecular Biology Institute). The DNA samples were isolated from whole blood. Polymerase chain reaction (PCR) amplification process was performed using bifunctional labelled primers specifically designed to correspond to the variant that differentiates wild-type and mutant DNA for visual detection on LFA. The variant was confirmed using Sanger sequencing, and the sensitivity and specificity of the LFA detection method were validated using the Agena MassARRAY® technique. Results: Out of 103 hypercholesterolemic individuals, 5 individuals (4.8%) tested positive for E101K, LDLR mutation and the rest, including healthy control individuals, tested negative. This result was concordant with Sanger sequencing and Agena MassARRAY®. These five individuals could be classified as Definite FH, as the DNA diagnosis was confirmed. The sensitivity and specificity of the variant detection by LFA is 100% compared to results using the genotyping method using Agena MassARRAY®. Conclusion: The developed LFA can potentially be used in the POC setting for detecting the E101K variant in the LDLR gene. This LFA can also be used to screen family members with E101K variant in the LDLR gene and is applicable for other SNP's detection.

Immunomodulatory gene polymorphisms in non-small cell lung carcinoma susceptibility and survival.

Lung cancer is the leading cause of cancer-associated mortality and non-small cell lung carcinoma (NSCLC) constitutes 85 % of all lung cancer cases. This malignancy is characterized by multifactorial risk factors, poor prognosis, and deplorable clinical outcome. Considerable evidence indicates that there is inter-individual variability in the lung cancer predisposition and survival due to genetic variations introduced by genetic polymorphisms between individuals, indirectly affecting the lung cancer susceptibility and the patient survival. In the past decades, immune landscape in the tumour environment and host immune response are constantly implicated as determining factor in NSCLC development and patients' survival. With the change of paradigm in NSCLC treatment to immunotherapy and increasing recognition of the role of the immune system in cancer development and survival, the inspection of single nucleotide polymorphisms (SNPs) in immunomodulated markers associated with the risk and prognosis for NSCLC is crucial. Despite extensive studies reported the implication of SNPs in predicting the risk and survival of NSCLC. SNPs in the genes that modulate immune response in NSCLC have not been reviewed before. Hence, this review uncovers the evidence on the genetic polymorphisms of immunomodulatory markers which include immune checkpoints, immune checkpoint inhibitors, chemokines, interleukins, human leukocyte antigen and its receptors, and antigen presenting machinery genes, and their significance in the susceptibility, prognosis and survival in NSCLC. The identification of genetic factors associated with NSCLC risk and survival provides invaluable information for a greater comprehension of the pathogenesis and progression of the disease, also to refine prognosis and personalize clinical care in early and advanced-stages disease.

Association between rs1799724 of TNF- α gene and early onset preeclampsia in Chinese: A pilot study.

Objective: To investigate the association between polymorphisms of TNF- α (rs1799724, rs1800629), VEGF (rs3025039) and VEGFR1 (rs 722503) and early onset preeclampsia (EOPE) in Chinese. Methods: A total of 132 EOPE patients from January 2016 to December 2018 at the Second Hospital of Tianjin Medical University were selected as the EOPE group, and 156 normal pregnant patients as the Control group. In both groups, 5 ml of peripheral venous blood was obtained after admission. The characteristics of genotype and allele distribution at the four SNPs in the study subjects were examined by matrix-assisted laser desorption ionization time-of-flight mass spectrometric genotyping. Results: The genotype frequency distribution and allele frequency distribution of rs1799724 were significantly different between the EOPE group and the Control group (P = 0.002，P = 0.003). The T allele was statistically associated with the development of EOPE under a dominant genetic model (P = 0.001). The genotype and allele frequency distributions of rs1800629, rs3025039, and rs 722503 did not differ significantly between the EOPE group and the Control group (P > 0.05). There was no linkage disequilibrium among rs1799724, rs1800629 and rs3025039 loci, the corresponding haploid cannot be formed. Conclusions: The rs1799724 of TNF- α gene is a genetic susceptibility locus for EOPE and may be a potential predictors of preeclampsia.

Danzhou chicken: a unique genetic resource revealed by genome-wide resequencing data.

Danzhou chicken (DZ) is a local breed in China noted for its strong adaptability, roughage resistance, strong wildness, and delicious taste, thus containing important genetic resources. In this study, genome re-sequencing data was generated from 200 DZ chickens. Combined with previously generated data from 72 additional chickens across six other exotic and local breeds, these data were used to systematically evaluate the germplasm characteristics of DZ chickens from a genomic perspective. Unlike exotic breeds, both DZ and southern local chicken varieties exhibited high genetic diversity, and the genetic distance between DZ and southern local chickens was smaller than the genetic distance between DZ and exotic chickens. A reconstructed Neighbor-Joining phylogenetic tree indicated that all sampled populations clustered into single independent populations, with DZ chickens showing clear evidence of intra-population differentiation, forming 2 subpopulations. Principal component analysis and ADMIXTURE analysis showed that DZ was significantly different from other breeds. These results indicate that DZ is a unique genetic resource that is different from other southern native and exotic chickens. The results of the study will improve our understanding of the genetic structure and current status of the DZ breed, which is of great significance in promoting the conservation of genetic resources of DZ chickens and fostering breed innovations and genetic improvement.

Evaluation of the associations of interlukin-7 genetic variants with toxicity and efficacy of immune checkpoint inhibitors: A replication study of a Japanese population, based on the findings of a European genome-wide association study.

AIM: Recent genome-wide association studies of European populations have identified rs16906115, a single-nucleotide polymorphism in the interleukin-7 gene, as a predictor of immune-related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single-nucleotide polymorphism in a Japanese population. METHODS: From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow-up ≥12 weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non-responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non-responders. RESULTS: In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non-responders (p = 0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p = 0.015) in the univariate analysis and 0.315 (p = 0.023) in the multivariate analysis. CONCLUSIONS: In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry with the number UMIN000043798.

Unravelling the potential of TIM-3 gene polymorphism in allogeneic hematopoietic stem cell transplantation - a preliminary study.

BACKGROUND: T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) molecule is a key regulator of the immune response by exerting an inhibitory effect on various types of immune cells. Understanding the role of TIM-3 in hematopoietic stem cell transplantation (HSCT) may improve transplant outcomes. Our study evaluated the potential association between TIM-3 polymorphisms, namely rs1036199 (A > C) or rs10515746 (C > A), changes which are located in exon 3 and the promoter region of the TIM-3 gene, and post-HSCT outcomes. METHODS: One-hundred and twenty allogeneic HSCT patients and their respective donors were enrolled and genotyped for TIM-3 single nucleotide polymorphisms (SNPs) using real-time PCR with TaqMan assays. RESULTS: We found that the presence of the rare alleles and heterozygous genotypes of studied SNP in recipients tended to protect against or increase the risk for acute graft-versus-host disease (aGvHD). For the rs1036199 polymorphism, recipients with the AC heterozygous genotype (p = 0.0287) or carrying the rarer C allele (p = 0.0334) showed a lower frequency of aGvHD development along all I-IV grades. A similar association was detected for the rs10515746 polymorphism as recipients with the CA genotype (p = 0.0095) or the recessive A allele (p = 0.0117) less frequently developed aGvHD. Furthermore, the rarer A allele of rs10515746 SNP was also associated with a prolonged aGvHD-free survival (p = 0.0424). Cytomegalovirus (CMV) infection was more common in patients transplanted with TIM-3 rs10515746 mismatched donors (p = 0.0229) and this association was also found to be independent of HLA incompatibility and pre-transplant CMV-IgG status. Multivariate analyses confirmed the role of these recessive alleles and donor-recipient TIM-3 incompatibility as an independent factor in aGvHD and CMV development. CONCLUSIONS: Polymorphism of TIM-3 molecule may affect the immune response in HSCT patients. The recessive alleles of rs1036199 and rs10515746 SNPs decreased the risk of developing aGvHD. TIM-3 donor-recipient genetic matching may also affect the risk of post-transplant CMV infection, indicating the potential value of genetic profiling in optimizing transplant strategies.

Genetic evidence for a causal link between gut microbiota and arterial embolism and thrombosis: a two-sample Mendelian randomization study.

Background: Previous research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study. Methods: Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Results: We identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08-2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42-0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25-3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P<0.05). Conclusion: Our systematic analyses provided evidence to support a potential causal relationship between several gut microbiota taxa and the risk of arterial embolism and thrombosis. More studies are required to show how the gut microbiota affects the development of arterial embolism and thrombosis.

Functional Impact of the FADS1 rs174546 Single Nucleotide Polymorphism on Serum Lipid Levels: Insights from Molecular Mechanisms and Therapeutic Perspectives in Korean Population.

SCOPE: Single nucleotide polymorphisms (SNP) in the fatty acid desaturase 1 (FADS1) gene is suggested as risk factor of metabolic diseases in genome-wide association studies (GWAS). This study hypothesized that FADS1_rs174546T associates with serum triglycerides (TG) in Korean Genome and Epidemiology Study (KoGES). In addition, functional study of SNP genotypes in cultured cells is performed. METHODS AND RESULTS: FADS1_rs174546T is associated with high level of serum TG (effect size of variant: 6.48 ± 1.84 mg dL-1) in Korean individuals (normotriglyceridemia, n = 5128; hypertriglyceridemia, n = 3714). Functional study in cells with FADS1_rs174546T, shows reduced transcriptional activity, when compared with rs174546C. MiR-6728-3p, which is predicted to bind with rs174546T, decreases transcriptional activity of rs174546T but not in rs174546C, and it is reversed by miR-6728-3p inhibitor. Formononetin is selected as binding molecule to 3'-UTR of FADS1 and increases luciferase activity in both rs174546 (C/T). Moreover, formononetin compensates for the reduced luciferase activity by rs174546T and miR-6728-3p. Formononetin also increases endogenous FADS1 expression and long-chain polyunsaturated fatty acid (LC-PUFA) ratio. CONCLUSION: FADS1_rs174546T is a crucial risk factor for hypertriglyceridemia in the Koreans potentially through the interaction with miR-6728-3p. Formononetin can be a potent dietary intervention to prevent and improve hypertriglyceridemia in both rs174546 (C/T) populations.

piRNA PROPER Suppresses DUSP1 Translation by Targeting N6-Methyladenosine-Mediated RNA Circularization to Promote Oncogenesis of Prostate Cancer.

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.

A Novel Detection Method for High-Order SNP Epistatic Interactions Based on Explicit-Encoding-Based Multitasking Harmony Search.

To elucidate the genetic basis of complex diseases, it is crucial to discover the single-nucleotide polymorphisms (SNPs) contributing to disease susceptibility. This is particularly challenging for high-order SNP epistatic interactions (HEIs), which exhibit small individual effects but potentially large joint effects. These interactions are difficult to detect due to the vast search space, encompassing billions of possible combinations, and the computational complexity of evaluating them. This study proposes a novel explicit-encoding-based multitasking harmony search algorithm (MTHS-EE-DHEI) specifically designed to address this challenge. The algorithm operates in three stages. First, a harmony search algorithm is employed, utilizing four lightweight evaluation functions, such as Bayesian network and entropy, to efficiently explore potential SNP combinations related to disease status. Second, a G-test statistical method is applied to filter out insignificant SNP combinations. Finally, two machine learning-based methods, multifactor dimensionality reduction (MDR) as well as random forest (RF), are employed to validate the classification performance of the remaining significant SNP combinations. This research aims to demonstrate the effectiveness of MTHS-EE-DHEI in identifying HEIs compared to existing methods, potentially providing valuable insights into the genetic architecture of complex diseases. The performance of MTHS-EE-DHEI was evaluated on twenty simulated disease datasets and three real-world datasets encompassing age-related macular degeneration (AMD), rheumatoid arthritis (RA), and breast cancer (BC). The results demonstrably indicate that MTHS-EE-DHEI outperforms four state-of-the-art algorithms in terms of both detection power and computational efficiency. The source code is available at https://github.com/shouhengtuo/MTHS-EE-DHEI.git .

CD147 TagSNP is associated with the vulnerability to lung cancer in the Chinese population: a case-control study.

BACKGROUND: Lung cancer, with its high morbidity and mortality, presents a major significant public health challenge. CD147, linked to cancer progression and metastasis, is a promising therapeutic target, including for lung cancer. The genetic variation may influence the expression of the gene and consequently the risk of lung cancer. This study aims to investigate single nucleotide polymorphisms (SNPs) in CD147 to understand their association with the risk of developing lung cancer in the Han Chinese population. METHODS: A hospital-based case-control investigation was conducted, enrolling 700 lung cancer patients and 700 cancer-free controls. TagSNPs were selected using Haploview v4.2, and genotype data from the 1000 Genomes Project database were utilized. The selected SNPs (rs28992491, rs67945626, and rs79361899) within the CD147 gene were evaluated using the improved multiple ligation detection reaction method. Statistical analysis included chi-square tests, logistic regression models, and interaction analyses. RESULTS: Baseline characteristics of the study population showed no significant differences in gender distribution between cases and controls, but there was a notable difference in smoking rates. No significant associations were found between the three TagSNPs and lung cancer susceptibility in the codominant model. However, stratification analyses revealed interesting findings. Among females, the rs79361899 AA/AG genotype was associated with an increased risk of lung cancer. In individuals aged ≥ 65 years old, the rs28992491 GG and rs79361899 AA genotypes were linked to a higher susceptibility. Furthermore, an interaction analysis demonstrated significant genotype × gender interactions in the rs79361899 recessive model, indicating an increased lung cancer risk in female carriers of the heterozygous or homozygous polymorphic genotype. CONCLUSIONS: CD147 polymorphisms play an important role in lung cancer development, particularly in specific subgroup of age and gender. These findings highlight the significance of incorporating genetic variations and their interactions with demographic factors in comprehending the intricate etiology of lung cancer.

Effective population size in field pea.

BACKGROUND: Effective population size (Ne) is a pivotal parameter in population genetics as it can provide information on the rate of inbreeding and the contemporary status of genetic diversity in breeding populations. The population with smaller Ne can lead to faster inbreeding, with little potential for genetic gain making selections ineffective. The importance of Ne has become increasingly recognized in plant breeding, which can help breeders monitor and enhance the genetic variability or redesign their selection protocols. Here, we present the first Ne estimates based on linkage disequilibrium (LD) in the pea genome. RESULTS: We calculated and compared Ne using SNP markers from North Dakota State University (NDSU) modern breeding lines and United States Department of Agriculture (USDA) diversity panel. The extent of LD was highly variable not only between populations but also among different regions and chromosomes of the genome. Overall, NDSU had a higher and longer-range LD than the USDA that could extend up to 500 Kb, with a genome-wide average r2 of 0.57 (vs 0.34), likely due to its lower recombination rates and the selection background. The estimated Ne for the USDA was nearly three-fold higher (Ne = 174) than NDSU (Ne = 64), which can be confounded by a high degree of population structure due to the selfing nature of pea. CONCLUSIONS: Our results provided insights into the genetic diversity of the germplasm studied, which can guide plant breeders to actively monitor Ne in successive cycles of breeding to sustain viability of the breeding efforts in the long term.

Whole genome sequencing and genomic characteristics analysis of carbapenem-resistant Acinetobacter baumannii clinical isolates in two hospitals in China.

Nosocomial outbreaks caused by carbapenem-resistant Acinetobacter baumannii (CRAB) strains are rapidly emerging worldwide and are cause for concern. Herein, we aimed to describe the genomic characteristics of CRAB strains isolated from two hospitals in China in 2023. The A. baumannii isolates were mainly collected from the ICU and isolated from the sputum (71.43%, 15/21), followed by urine (14.29%, 3/21). Twenty-one A. baumannii strains possessed a multidrug-resistant (MDR) profile, and whole-genome sequencing showed that they all carried blaOXA-23. Based on the Pasteur multilocus sequence typing (MLST) scheme, all strains were typed into a sequence type 2 (ST2). Based on the Oxford MLST scheme, six strains belonged to ST540, three of which were ST208, and four strains were assigned to ST784. Kaptive showed most of the strains (38.10%, 8/21) contained KL93. As for the lipoolygosaccharide (OC locus) type, OCL1c and OCL1d were identified, accounting for 33.33% (7/21) and 66.67% (14/21), respectively. Based on the BacWGSTdb server, we found that the strains belonging to ST540 and ST784 were all collected from China. However, the ST938 strains were isolated from Malaysia and Thailand. Comparative genomics analysis showed that the AB10 strain had a closed relationship with SXAB10-SXAB13 strains, suggesting the transmission happened in these two hospitals and other hospital in China. In addition, the 4300STDY7045869 strain, which was collected from Thailand, possessed near genetic relationship with our isolates in this study, suggesting the possible spread among various countries. Additionally, 3-237 single nucleotide polymorphisms were observed among these strains. In conclusion, this study conducted a genome-based study for A. baumannii strains collected from two hospitals in China and revealed their epidemiological and molecular features. Clone spreading occurred in these two hospitals. Hence, there is an urgent need for increased surveillance in hospitals and other clinical settings to prevent and control CRAB spreading.

Genetic Variants in the Fat Mass and Obesity-Associated Gene and Risk of Obesity/Overweight in Children and Adolescents: A Systematic Review and Meta-Analysis.

OBJECTIVE: The variations in the single-nucleotide polymorphisms (SNPs) of the fat mass and obesity (FTO)-associated gene have been linked to being overweight or obese in children. In this research a thorough examination was performed to elucidate the connection between various FTO gene SNPs and overweight or obesity in children and adolescents. METHOD: We searched PubMed, Google scholar, Web of Science and Scopus until January 2024 to find studies that investigate the association between different SNPs of FTO gene and the risk of overweight/obesity in children and adolescents. After filtering the relevant studies, meta-analysis was used to quantify the association of FTO gene SNPs within different genetic inheritance models. RESULTS: We have identified 32 eligible studies with 14,930 obese/overweight cases and 24,765 healthy controls. Our recessive model showed a significant association with rs9939609 (OR: 1.56, 95% CI: 1.20; 2.02, p < 0.01) and rs1421085 (OR: 1.77, 95% CI: 1.14; 2.75, p < 0.01). Besides, in the homozygote model, rs1421085 showed the highest association (OR: 2.32, 95% CI: 1.38; 3.89, p < 0.01) with the risk of obesity in a population of children and adolescents. Moreover, there are other SNPs of FTO genes, such as rs9921255, rs9928094 and rs9930333, which showed a positive association with obesity and overweight. However, their effects were evaluated in very few numbers of studies. CONCLUSION: In this study, we have found that the FTO rs9939609 and rs1421085 are associated to an increased risk of obesity among children and adolescents. Besides, the findings of this study further reaffirmed the established link between rs9939609 and obesity in children and adolescents.

The Benefit of a National Genomic Testing Scheme.

Although a significant cost, genotyping an entire population offers many benefits, many of which can reduce the workload and effort in decision-making on farm. As well as providing more accurate predictions of the genetic merit of individuals (and by extension their expected performance), national genotyping strategies enable complete traceability from the cradle to the grave as well as parentage discovery. The information available per animal aids more informed breeding and management decisions, including mating advice, and determining the optimal role and eventual fate of each animal.

Unveiling novel genetic variants in 370 challenging medically relevant genes using the long read sequencing data of 41 samples from 19 global populations.

BACKGROUND: A large number of challenging medically relevant genes (CMRGs) are situated in complex or highly repetitive regions of the human genome, hindering comprehensive characterization of genetic variants using next-generation sequencing technologies. In this study, we employed long-read sequencing technology, extensively utilized in studying complex genomic regions, to characterize genetic alterations, including short variants (single nucleotide variants and short insertions and deletions) and copy number variations, in 370 CMRGs across 41 individuals from 19 global populations. RESULTS: Our analysis revealed high levels of genetic variants in CMRGs, with 68.73% exhibiting copy number variations and 65.20% containing short variants that may disrupt protein function across individuals. Such variants can influence pharmacogenomics, genetic disease susceptibility, and other clinical outcomes. We observed significant differences in CMRG variation across populations, with individuals of African ancestry harboring the highest number of copy number variants and short variants compared to samples from other continents. Notably, 15.79% to 33.96% of short variants were exclusively detectable through long-read sequencing. While the T2T-CHM13 reference genome significantly improved the assembly of CMRG regions, thereby facilitating variant detection in these regions, some regions still lacked resolution. CONCLUSION: Our results provide an important reference for future clinical and pharmacogenetic studies, highlighting the need for a comprehensive representation of global genetic diversity in the reference genome and improved variant calling techniques to fully resolve medically relevant genes.

Plasma soluble fms-like tyrosine kinase-1, placental growth factor, and vascular endothelial growth factor system gene variants as predictors of survival in heart failure.

AIMS: Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), components of the vascular endothelial growth factor (VEGF) system, play key roles in angiogenesis. Reports of elevated plasma levels of sFlt-1 and PlGF in coronary heart disease and heart failure (HF) led us to investigate their utility, and VEGF system gene single nucleotide polymorphisms (SNPs), as prognostic biomarkers in HF. METHODS AND RESULTS: ELISA assays for sFlt-1, PlGF and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed on baseline plasma samples from the PEOPLE cohort (n = 890), a study of outcomes among patients after an episode of acute decompensated HF. Eight SNPs potentially associated with sFlt-1 or PlGF levels were genotyped. sFlt-1 and PlGF were assayed in 201 subjects from the Canterbury Healthy Volunteers Study (CHVS) matched to PEOPLE participants. All-cause death was the major endpoint for clinical outcome considered. In PEOPLE participants, mean plasma levels for both sFlt-1 (125 ± 2.01 pg/ml) and PlGF (17.5 ± 0.21 pg/ml) were higher (both p < 0.044) than in the CHVS cohort (81.2 ± 1.31 pg/ml and 15.5 ± 0.32 pg/ml, respectively). sFlt-1 was higher in HF with reduced ejection fraction compared to HF with preserved ejection fraction (p = 0.005). The PGF gene SNP rs2268616 was univariately associated with death (p = 0.016), and was also associated with PlGF levels, as was rs2268614 genotype. Cox proportional hazards modelling (n = 695, 246 deaths) showed plasma sFlt-1, but not PlGF, predicted survival (hazard ratio 6.44, 95% confidence interval 2.57-16.1; p < 0.001) in PEOPLE, independent of age, NT-proBNP, ischaemic aetiology, diabetic status and beta-blocker therapy. CONCLUSIONS: Plasma sFlt-1 concentrations have potential as an independent predictor of survival and may be complementary to established prognostic biomarkers in HF.

Survey on Interaction Between Nutrient Status and Selected Polymorphisms in Association with Weight Loss of Patients with Severe Obesity Underwent Bariatric Surgery.

BACKGROUND: There is little information about the effect of single nucleotide polymorphisms (SNP) and nutritional status and weight loss after bariatric surgery. This study investigated the interactive effect of eight obesity-related SNPs and nutritional status on weight loss after Roux-en-Y gastric bypass (RYGB). METHOD: This is a case-control study. After 1-year follow-up, the patients who underwent RYGB were dividing into two groups. The case group consisted of patients who lost more than 50% of their excess body weight (EBW%) 1 year after the surgery. The control group included patients who lost < 50% of EBW at same time frame. Then, the relationship between eight SNPs related to UCP2, FTO, LEPR, GHRL, and NPY genes with weight loss were checked. RESULTS: In this study, 160 patients were recruited. The median of age for case and control group were 43 and 42 respectively. The presence of mutant variant NPYrs16147 had a significant relationship in terms of weight loss between the two groups (P > 0.05). In dominant model, two SNPs, UCP2 rs659366 and UCP2 rs660339, showed protective effect of the vitamin D deficiency. CONCLUSION: In conclusion, the presence mutant variant of NPYrs16147 is directly related to the incidence of weight loss greater than 50% of EBW. However, it is apparent individual behavioral, dietary, and other factors may have more influence on weight loss among patients underwent RYGB.