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.

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.

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.

Bidirectional causality between the levels of blood lipids and endometriosis: a two-sample mendelian randomization study.

BACKGROUND: Observational studies have found a correlation between the levels of blood lipids and the development and progression of endometriosis (EM). However, the causality and direction of this correlation is unclear. This study aimed to examine the bidirectional connection between lipid profiles and the risk of EM using publicly available genome-wide association study (GWAS) summary statistics. METHODS: Eligible exposure variables such as levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were selected using a two-sample Mendelian randomization (MR) analysis method following a series of quality control procedures. Data on EM were obtained from the publicly available Finnish database of European patients. Inverse variance weighted (IVW), MR Egger, weighted median, and weighted mode methods were used to analyze the causal relationship between lipid exposure and EM, exclude confounders, perform sensitivity analyses, and assess the stability of the results. Reverse MR analyses were performed with EM as exposure and lipid results as study outcomes. RESULTS: IVW analysis results identified HDL as a protective factor for EM, while TG was shown to be a risk factor for EM. Subgroup analyses based on the site of the EM lesion identified HDL as a protective factor for EM of the uterus, while TG was identified a risk factor for the EM of the fallopian tube, ovary, and pelvic peritoneum. Reverse analysis did not reveal any effect of EM on the levels of lipids. CONCLUSION: Blood lipids, such as HDL and TG, may play an important role in the development and progression of EM. However, EM does not lead to dyslipidemia.

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.

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.

Large-Sample Genomic Data Mining for Quantitative Traits in U.S. Holstein Cows.

The U.S. Holstein cattle have unprecedentedly large samples for genomic evaluation with genotypes of Single Nucleotide Polymorphism (SNP) markers and phenotypic observations of dairy quantitative traits. Such large samples provided unprecedented opportunities for the discovery of genetic variants and mechanisms affecting quantitative traits in Holstein cattle. Recent studies using the Holstein large samples on finding genetic variants affecting quantitative traits included a fat percentage study and two studies on reproductive traits. The fat percentage study confirmed that a chromosome region interacted with all chromosomes and the reproductive studies detected sharply negative homozygous recessive genotypes that were recommended for heifer culling. These novel findings provided examples showing the power of large-sample genomic mining for quantitative traits.

Interaction between RNF4 and SART3 is associated with the risk of schizophrenia.

The pathogenesis of schizophrenia (SCZ) is heavily influenced by genetic factors. Ring finger protein 4 (RNF4) and squamous cell carcinoma antigen recognized by T cells 3 (SART3) are thought to be involved in nervous system growth and development via oxidative stress pathways. Moreover, they have previously been linked to SCZ. Yet the role of RNF4 and SART3 in SCZ remains unclear. Here, we investigated how these two genes are involved in SCZ by studying their variants observed in patients. We first observed significantly elevated mRNA levels of RNF4 and SART3 in the peripheral blood in both first-episode (n = 30) and chronic (n = 30) SCZ patients compared to controls (n = 60). Next, we targeted-sequenced three single nucleotide polymorphisms (SNPs) in SART3 and six SNPs in RNF4 for association with SCZ using the genomic DNA extracted from peripheral blood leukocytes from SCZ participants (n = 392) and controls (n = 572). We observed a combination of SNPs that included rs1203860, rs2282765 (both in RNF4), and rs2287550 (in SART3) was associated with increased risk of SCZ, suggesting common pathogenic mechanisms between these two genes. We then conducted experiments in HEK293T cells to better understand the interaction between RNF4 and SART3. We observed that SART3 lowered the expression of RNF4 through ubiquitination and downregulated the expression of nuclear factor E2-related factor 2 (NRF2), a downstream factor of RNF4, implicating the existence of a possible shared regulatory mechanism for RNF4 and SART3. In conclusion, our study provides evidence that the interaction between RNF4 and SART3 contributes to the risk of SCZ. The findings shed light on the underlying molecular mechanisms of SCZ and may lead to the development of new therapies and interventions for this disorder.

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.

Caffeine consumption outcomes on amyotrophic lateral sclerosis disease progression and cognition.

Caffeine consumption outcomes on Amyotrophic Lateral Sclerosis (ALS) including progression, survival and cognition remain poorly defined and may depend on its metabolization influenced by genetic variants. 378 ALS patients with a precise evaluation of their regular caffeine consumption were monitored as part of a prospective multicenter study. Demographic, clinical characteristics, functional disability as measured with revised ALS Functional Rating Scale (ALSFRS-R), cognitive deficits measured using Edinburgh Cognitive and Behavioural ALS Screen (ECAS), survival and riluzole treatment were recorded. 282 patients were genotyped for six single nucleotide polymorphisms tagging different genes involved in caffeine intake and/or metabolism: CYP1A1 (rs2472297), CYP1A2 (rs762551), AHR (rs4410790), POR (rs17685), XDH (rs206860) and ADORA2A (rs5751876) genes. Association between caffeine consumption and ALSFRS-R, ALSFRS-R rate, ECAS and survival were statistically analyzed to determine the outcome of regular caffeine consumption on ALS disease progression and cognition. No association was observed between caffeine consumption and survival (p = 0.25), functional disability (ALSFRS-R; p = 0.27) or progression of ALS (p = 0.076). However, a significant association was found with higher caffeine consumption and better cognitive performance on ECAS scores in patients carrying the C/T and T/T genotypes at rs2472297 (p-het = 0.004). Our results support the safety of regular caffeine consumption on ALS disease progression and survival and also show its beneficial impact on cognitive performance in patients carrying the minor allele T of rs2472297, considered as fast metabolizers, that would set the ground for a new pharmacogenetic therapeutic strategy.

Genetic Variations in TrkB.T1 Isoform and Their Association with Somatic and Psychological Symptoms in Individuals with IBS.

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is often comorbid with somatic pain and psychological disorders. Dysregulated signaling of brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), has been implicated in somatic-psychological symptoms in individuals with IBS. We investigated the association of 10 single nucleotide polymorphisms (SNPs) in the regulatory 3' untranslated region (UTR) of NTRK2 (TrkB) kinase domain-deficient truncated isoform (TrkB.T1) and BDNF Val66Met SNP with somatic and psychological symptoms and quality of life in a cohort from the United States (U.S.) (IBS n=464; healthy controls n=156). We found that the homozygous recessive genotype (G/G) of rs2013566 in individuals with IBS is associated with worsened somatic symptoms, including headache, back pain, joint pain, muscle pain, and somatization as well as diminished sleep quality, energy level and overall quality of life. Validation using United Kingdom BioBank (UKBB) data confirmed the association of rs2013566 with increased likelihood of headache. Several SNPs (rs1627784, rs1624327, rs1147198) showed significant associations with muscle pain in our U.S. cohort. These 4 SNPs are predominantly located in H3K4Me1-enriched regions, suggesting their enhancer and/or transcription regulation potential. Our findings suggest that genetic variation within the 3'UTR region of the TrkB.T1 isoform may contribute to comorbid conditions in individuals with IBS, resulting in a spectrum of somatic and psychological symptoms impacting their quality of life. These findings advance our understanding of the genetic interaction between BDNF/TrkB pathways and somatic-psychological symptoms in IBS, highlighting the importance of further exploring this interaction for potential clinical applications. PERSPECTIVE: This study aims to understand the genetic effects on IBS-related symptoms across somatic, psychological, and quality of life domains, validated by UKBB data. The rs2013566 homozygous recessive genotype correlates with worsened somatic symptoms and reduced quality of life, emphasizing its clinical significance.

Studies on the Relationships between Growth and Gonad Development during First Sexual Maturation of Macrobrachium nipponense and Associated SNPs Screening.

In this study, we used full-sib families to investigate the association between growth and gonad development during first sexual maturation of M. nipponense. We found that male GSI was significantly negatively correlated with growth traits (p < 0.01) and there were no significant correlations between female GSI (Gonadosomatic index) and growth traits (p > 0.05). HSI (Hepatopancreas index) in both males and females showed no significant correlations with growth traits (p > 0.05). We furthermore investigated the association between the specific allele of Mn-CTS L1 polymorphism and gonad development and growth traits. In total, 35 mutation loci were screened and 16 high-quality single-nucleotide polymorphisms (SNPs) loci were obtained after validation. Four and two SNPs proved to be strongly associated with all growth traits in female and male M. nipponense separately, among which A+118T might be a candidate SNP positively associated with large growth traits. Two and one SNPs were screened, respectively, in males and females to associate with GSI, while three SNPs were detected to associate with female HSI, among which A+1379C may be applied as a potential molecular marker for gene-assisted selection to improve both reproduction speed and growth traits in M. nipponense.

Multi-modal deep learning from imaging genomic data for schizophrenia classification.

Background: Schizophrenia (SZ) is a psychiatric condition that adversely affects an individual's cognitive, emotional, and behavioral aspects. The etiology of SZ, although extensively studied, remains unclear, as multiple factors come together to contribute toward its development. There is a consistent body of evidence documenting the presence of structural and functional deviations in the brains of individuals with SZ. Moreover, the hereditary aspect of SZ is supported by the significant involvement of genomics markers. Therefore, the need to investigate SZ from a multi-modal perspective and develop approaches for improved detection arises. Methods: Our proposed method employed a deep learning framework combining features from structural magnetic resonance imaging (sMRI), functional magnetic resonance imaging (fMRI), and genetic markers such as single nucleotide polymorphism (SNP). For sMRI, we used a pre-trained DenseNet to extract the morphological features. To identify the most relevant functional connections in fMRI and SNPs linked to SZ, we applied a 1-dimensional convolutional neural network (CNN) followed by layerwise relevance propagation (LRP). Finally, we concatenated these obtained features across modalities and fed them to the extreme gradient boosting (XGBoost) tree-based classifier to classify SZ from healthy control (HC). Results: Experimental evaluation on clinical dataset demonstrated that, compared to the outcomes obtained from each modality individually, our proposed multi-modal approach performed classification of SZ individuals from HC with an improved accuracy of 79.01%. Conclusion: We proposed a deep learning based framework that selects multi-modal (sMRI, fMRI and genetic) features efficiently and fuse them to obtain improved classification scores. Additionally, by using Explainable AI (XAI), we were able to pinpoint and validate significant functional network connections and SNPs that contributed the most toward SZ classification, providing necessary interpretation behind our findings.

Genetic diversity and population structure of Uganda cassava germplasm.

Cassava (Manihot esculenta Crantz) holds significant economic importance globally. Evaluating a diverse range of germplasm based on molecular characteristics not only enhances its preservation but also supports its utilization in breeding programs. In this study, we assessed genetic diversity and population structure among 155 cassava genotypes from Uganda using 5247 single nucleotide polymorphism (SNP) markers. Genotyping by sequencing (GBS) was employed for SNP discovery and to evaluate genetic diversity and population structure using the ADMIXTURE software. The cassava accessions comprised two populations: 49 accessions from Ugandan lines and 106 accessions resulting from crosses between South American and Ugandan lines. The average call rate of 96% was utilized to assess marker polymorphism. Polymorphic information content values of the markers ranged from 0.1 to 0.5 with an average of 0.4 which was moderately high. The principal component analysis (PCA) showed that the first two components captured ~ 24.2% of the genetic variation. The average genetic diversity was 0.3. The analysis of molecular variance (AMOVA) indicated that 66.02% and 33.98% of the total genetic variation occurred within accessions and between sub-populations, respectively. Five sub-populations were identified based on ADMIXTURE structure analysis (K = 5). Neighbor-joining tree and hierarchical clustering tree revealed the presence of three different groups which were primarily based on the source of the genotypes. The results suggested that there was considerable genetic variation among the cassava genotypes which is useful in cassava improvement and conservation efforts.

Association between primary biliary cholangitis with diabetes and cardiovascular diseases: A bidirectional multivariable Mendelian randomization study.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is an autoimmune disease often accompanied by multisystem damage. This study aimed to explore the causal association between genetically predicted PBC and diabetes, as well as multiple cardiovascular diseases (CVDs). METHODS: Genome-wide association studies (GWAS) summary data of PBC in 24,510 individuals of European ancestry from the European Association for the Study of the Liver was used to identify genetically predicted PBC. We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to estimate the impacts of PBC on diabetes (N = 17,685 to 318,014) and 20 CVDs from the genetic consortium (N = 171,875 to 1,030,836). RESULTS: SVMR provided evidence that genetically predicted PBC is associated with an increased risk of type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), heart failure (HF), hypertension, atrial fibrillation (AF), stroke, ischemic stroke, and small-vessel ischemic stroke. Additionally, there was no evidence of a causal association between PBC and coronary atherosclerosis. In the MVMR analysis, PBC maintained independent effects on T1D, HF, MI, and small-vessel ischemic stroke in most models. CONCLUSION: Our findings revealed the causal effects of PBC on diabetes and 7 CVDs, and no causal relationship was detected between PBC and coronary atherosclerosis.

Genetic Diversity and Population Structure of a Large USDA Sesame Collection.

Sesame, Sesamum indicum L., is one of the oldest domesticated crops used for its oil and protein in many parts of the world. To build genomic resources for sesame that could be used to improve sesame productivity and responses to stresses, a USDA sesame germplasm collection of 501 accessions originating from 36 countries was used in this study. The panel was genotyped using genotyping-by-sequencing (GBS) technology to explore its genetic diversity and population structure and the relatedness among its accessions. A total of 24,735 high-quality single-nucleotide polymorphism (SNP) markers were identified over the 13 chromosomes. The marker density was 1900 SNP per chromosome, with an average polymorphism information content (PIC) value of 0.267. The marker polymorphisms and heterozygosity estimators indicated the usefulness of the identified SNPs to be used in future genetic studies and breeding activities. The population structure, principal components analysis (PCA), and unrooted neighbor-joining phylogenetic tree analyses classified two distinct subpopulations, indicating a wide genetic diversity within the USDA sesame collection. Analysis of molecular variance (AMOVA) revealed that 29.5% of the variation in this population was due to subpopulations, while 57.5% of the variation was due to variation among the accessions within the subpopulations. These results showed the degree of differentiation between the two subpopulations as well as within each subpopulation. The high fixation index (FST) between the distinguished subpopulations indicates a wide genetic diversity and high genetic differentiation among and within the identified subpopulations. The linkage disequilibrium (LD) pattern averaged 161 Kbp for the whole sesame genome, while the LD decay ranged from 168 Kbp at chromosome LG09 to 123 Kbp in chromosome LG05. These findings could explain the complications of linkage drag among the traits during selections. The selected accessions and genotyped SNPs provide tools to enhance genetic gain in sesame breeding programs through molecular approaches.

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.