SNP Genotyping Research Articles (Page 1)

Single-nucleotide polymorphisms (SNPs) play a crucial role in determining an individual’s susceptibility to diseases and influencing their response to drugs. Among the various techniques available for SNP genotyping, hydrolysis probe-based real-time polymerase chain reaction (PCR) has emerged as a highly sensitive and cost-effective method, offering both accuracy and specificity. This method has proven particularly valuable in lung cancer research, where its potential to advance pharmacogenetics holds immense promise. Lung cancer remains the leading cause of cancer-related mortality worldwide, with genetic variations serving as critical markers for both screening and treatment. This review examines the principles, mechanisms, and applications of probes in SNP genotyping, with a focus on method validation and quality control. Hydrolysis probes are distinguished by their high sensitivity and specificity but face challenges such as inconsistent quality control and limitations in multiplex assays. This review underscores the importance of robust validation processes in ensuring the reliability of research findings and facilitating the translation of basic studies into clinical applications. By addressing these challenges, hydrolysis probe-based SNP genotyping can significantly contribute to advancing personalized medicine, particularly in the context of lung cancer research.

Background: Individuals of African ancestry typically express a null variant in the Duffy antigen receptor for chemokines (DARC), encoded by the ACKR1 gene, which is associated with protection against malaria but enhanced inflammation, a common risk factor for both cardiovascular disease (CVD) and cancer. CVD rates are higher in individuals of African ancestry. We assessed the hypothesis that DARC-null African Americans had higher cancer risk and examined the potential modification by CVD. Methods: We included 3,192 African Americans from the Atherosclerosis Risk in Communities (ARIC) study without prior cancer and followed them from visit 1 (1987-1989) until end of 2015, for cancer diagnosis, death, or loss to follow-up. DARC status (Duffy-null [GG] or positive [AG/AA]) was imputed from rs2814778 SNP genotyping. We used Cox proportional hazards models to estimate hazard ratios (HR) for cancer incidence, adjusted for age, sex, and study center. We tested for interaction with demographic, social and CVD risk factors. We also stratified by baseline CVD status. Results: Participants (median age 53.6 years, 61% females, 69% DARC-null) were followed for a median of 22.4 years (62,120 person-years), during which 966 (30%) were diagnosed with cancer. DARC-positive status was not significantly associated with total cancer (aHR 0.95, 95%CI 0.83-1.09, P=0.49). Similar null associations were observed for smoking-related cancer and obesity-related cancers. However, a significant interaction (P=0.002) between DARC and sex was observed, where DARC-positive males, but not DARC-positive females, had a lower risk of smoking-related cancers (aHR 0.65, 95%CI 0.47-0.90, p=0.009). Among participants who developed incident CVD during follow-up, sensitivity analysis indicated that DARC-positive status was significantly associated with a lower risk of smoking-related cancers (aHR 0.44, 95%CI 0.27-0.71), solid cancers (aHR 0.73, 95%CI 0.55-0.97), and lung cancer (aHR 0.39, 95%CI 0.17-0.88). Conclusion: Among African Americans in the ARIC study, Duffy genotype was not associated with overall cancer risk, irrespective of baseline CVD status. A significant association was observed in men and in those with incident CVD. Together, these data suggest that specific factors might modify the association between DARC and the risk for specific cancers, which warrants further investigation with a larger sample size. Funding: NHLBI, NCI, NPCR, AHA

Single-tube Lambda exonuclease-mediated LbuCas13a detect of ssDNA for single-nucleotide polymorphisms genotyping.

Pathogen purification and genetic characterization of SPF BWEL chicken population.

Preservation of proteomic and genomic genotypes in skeletal material from forensically treated cadavers.

The accuracy of single-nucleotide polymorphism (SNP) detection in long sequences is fundamentally constrained by the minuscule thermodynamic differences arising from single-base mismatches, wherein the overall probe binding energy frequently masks single-base-discrimination signals. Here, we develop a plug-and-play competitive hairpin conversion module (CHCM) based on strand-competitive hybridization and toehold-mediated strand displacement. CHCM incorporates two structured hairpin probes (H1 and H2) that specifically recognize wild-type and mutant alleles, respectively. Through thermodynamic competition triggered by single-base variations, the system precisely modulates probe-target binding stability, directing the formation of differential DNA assemblies that convert single-nucleotide information into detectable sequence signals. Critically, CHCM discriminates heterozygous samples with 0.1% mutation abundance in long-sequence backgrounds using only conventional fluorescent probes without enzymatic assistance. Furthermore, CHCM exhibits exceptional technical compatibility: it seamlessly integrates with upstream PCR amplification or downstream catalytic hairpin assembly (CHA) signal amplification while sustaining robust performance. Successful SNP genotyping in soybean leaf genomic DNA validates its practical utility. This work delivers a high-resolution, cost-effective solution for SNP detection in complex matrices and establishes a scalable modular framework for dynamic nucleic acid probe design.

Calving interval (CI) is a multifactorial reproductive trait regulated by both genetic and environmental influences. Although its heritability is relatively low, the genetic basis of CI is highly relevant as it reflects the inherent reproductive efficiency of cattle. The underlying genetic mechanisms affecting CI, however, remain to be clarified. In this study, a whole-genome comparative analysis of five Bos indicus breeds from the Indian subcontinent—Kangayam, Tharparkar, Sahiwal, Red Sindhi, and Hariana, was performed. The NCBI public database was used in this study. The Mark Duplicates tool of Picard tools was used to remove potential PCR duplicates from the aligned reads, and then the uniquely mapped reads were used for the variant calling step. The free bayes output was filtered to include high-quality variants in the candidate genes, that is, quality (QUAL > 1). Furthermore, the identified SNP/InDels were classified as high, moderate, low, and modifier using the SnpEff tool. Across these breeds, 17,252 genes carrying single-nucleotide polymorphisms (SNPs) or InDels predicted to have high or moderate impact on protein function were identified. From these, 57 potential candidate genes associated with CI were detected, including LTF, SELP, GC, LENG8, LEPR, GHR, GH1, RPS9, TLR4, GNRHR, ARHGAP29, SEC24D, METTL14, SLC36A2, SLC36A3, APBA3, TCF12, and ZFR2. Functional annotation revealed enrichment of biological processes such as cellular response to hormonal stimuli, regulation of insulin-like growth factor receptor signalling, glucose metabolism, peptide and lipid responses, and ovulation cycle processes. Pathway enrichment highlighted neuroactive ligand-receptor interactions along with growth hormone and prolactin receptor signalling pathways. Network analysis further identified ESR1, IGF1, LEP, MSTN, TNF, FGF2, TLR4, and LTF as central hub genes with potential regulatory influence on CI in indicine cattle. Overall, this study uncovers genomic variants and key molecular pathways that provide novel insights into the genetic regulation of CI in indigenous Bos indicus breeds adapted to tropical conditions. The discovered genetic variants hold potential applications in the development of customised SNP genotyping chips, as well as in marker-assisted and genomic selection programs for cattle breeding in the future.

Genomic studies on Central Asian populations are still limited, and this study presents the first comprehensive, high-quality genotyping dataset for 224 healthy individuals of Kazakh origin. The data were generated using the Illumina Infinium SNP Genotyping Array GSA MG v2, covering 665,608 SNPs, with 523,630 SNPs retained after quality control. This dataset serves as a valuable reference for comparative studies focused on human genomics, supporting research in population clustering, ethnicity validation, and diverse biomedical investigations on Kazakh individuals. This resource marks a significant contribution to genomic research on individuals from underrepresented region of Central Asia.

Genome-wide single nucleotide polymorphism (SNP) genotyping using microarrays and karyomapping (parental haplotyping) is a universal linkage-based method for preimplantation genetic testing of monogenic disease (PGT-M) and identification of chromosome aneuploidies, including meiotic trisomies, monosomies and deletions. Following IVF, embryos are biopsied at the blastocyst stage and several trophectoderm cells removed. Both parents, a close relative of known disease status and the biopsy samples are genotyped and parental haplotypes analysed. Here we extended the method by combining parental haplotyping with parental intensity ratio analysis. This enables identification of meiotic and mitotic, whole and segmental aneuploidies at high resolution. In 342 cycles of PGT-M in couples with a mean maternal age of 32.9 ± 4.2 (SD), 37% (471/1270) of the biopsy samples were identified as aneuploid with an almost equal number of meiotic and mitotic aneuploidies. Meiotic aneuploidies were predominantly whole chromosome aneuploidies of maternal origin and increased with maternal age. Mitotic aneuploidies (with normal biparental haplotype patterns) were mainly segmental imbalances. For PGT of aneuploidy (PGT-A) in infertile couples, identifying meiotic aneuploidies, which are almost all non-viable, provides a valuable option to minimise the discard of embryos with only mitotic aneuploidies of unknown clinical outcome.

Disclosure: A. Dymova: None. T. Shkeleva: None. S. Kalinchenko: None.Background: Previous studies have investigated the association between genetic variability in the progesterone receptor gene and various hormonally-related conditions, such as breast cancer (BC), endometrial and ovarian cancers. Vitamin D deficiency can also lead to oncological conditions, including BC. Progesterone and Vitamin D induce their hormonal effects on target cells by binding the active form of the hormone to its receptors. Therefore, any genetic variations that may cause the dissociation of progesterone and vitamin D receptors, as well as a reduction in the synthesis of the active hormone form, may lead to increased susceptibility to BC.Notably, earlier studies did not take into account the morphological characteristics of tumors and the influence of molecular-genetic features on the age of disease manifestation.Objective: This study aimed to assess the association between functional-reducing variants in the PGR, VDR, and CYP27B1 genes with the risk of hormone-dependent breast cancer (HBC) and the age of disease manifestation. Methods: A retrospective case-control study was conducted, involving 87 women aged 40 to 72 years. Of these, 42 women had a diagnosis of HBC, and 45 women had no history of HBC in their personal or familial medical records. Genotyping was performed using SNP genotyping methods through direct sequencing. Functional-reducing variants in the progesterone receptor gene PGR c.1486G>T; p.Val660Leu, vitamin D receptor BsmI Polymorphism IVS10+283G>A, and 1α-hydroxylase enzyme g.57764205A>G; c.1137-29T>C were investigated. Results: A significantly higher frequency of the minor allele of PGR (45% vs. 16%), VDR (29% vs. 17%), and the functional-reducing allele of the CYP27B1 enzyme (43% vs. 12%) was observed among patients with HBC compared to the control group, confirming the association of these genetic variants with the risk of developing HBC. A significant association of PGR and VDR genotypes with HBC was observed in younger patients up to 55 years old. In older patients, the frequency of PGR and VDR variants decreased and approached the control group, indicating the contribution of other factors to the pathogenesis of the disease after the age of 55. Conclusions: This report confirms the contribution of PGR, VDR, and CYP27B1 gene variants to the etiology of BC. The low sensitivity of PGR and VDR receptors is associated with earlier forms of HBC. Genotyping of vitamin D receptors (VDR), the activity of the 1α-hydroxylase enzyme (CYP27B1), and progesterone receptors (PGR) in the future will enable the development of a screening strategy for identifying women at risk of developing HBC.Presentation: Monday, July 14, 2025

This study reveals a pleiotropic QTL QPh/Sl/Sn.cau-2D.1 coordinating plant architecture and spike morphology in wheat, and identifies REGULATOR OF GRAIN NUMBER1 (TaRGN-D1) as a key regulator of spikelet number, providing molecular targets and diagnostic markers for yield improvement. Spike architecture traits, particularly spike length (SL) and spikelet number per spike (SN), are crucial determinants of grain yield in wheat (Triticum aestivum L.), while plant height (PH) independently affects lodging resistance, harvest index and final yield potential. Through comprehensive genetic analysis of a recombinant inbred line population derived from AS420 (large-spike line) × Lunxuan987 (LX987, modern cultivar), we identified 36 spike-specific QTLs (22 for SL and 14 for SN) with 22 showing environments stability,and 12 additional PH QTLs with 13 showing environmental stability, using 55K SNP genotyping across six environments. A pleiotropic locus (QPh/Sl/Sn.cau-2D.1) on chromosome 2DS co-regulated PH, SL and SN (8.4-19.75% phenotypic variance (PVE)), and a 2,089-bp deletion on Ppd-D1 promoter was identified as the causal variant. In addition, we characterized REGULATOR OF GRAIN NUMBER1 (TaRGN-D1, TraesCS3D02G265100), encoding R2R3-MYB transcription factor, as the candidate gene for a major SN QTL QSn.cau-3D (6.5% PVE). Functional studies revealed a stronger transcriptional activation by the AS420-derived TaRGN-D1 promoter compared to LX987, correlating with elevated expression during spike development. Field validation confirmed the positive effect of TaRGN-D1 on SN without altering PH. Our findings not only identify new QTLs for wheat molecular breeding of high-yielding purpose, but also deepen our genetic comprehension on PH, SL, and SN regulation in this crop, thereby laying a valuable foundation for future wheat improvement strategies.

Methods for detecting microRNA (miRNA) are well-established, yet strategies for identifying miRNA-related single-nucleotide polymorphisms (miR-SNPs) remain limited. Despite their strong association with cancer development, the clinical application of miR-SNPs has been hindered by the lack of practical detection methods. To bridge this gap, we developed a method termed ligation-triggered hybridization chain reaction for miR-SNP testing (LIGHT). LIGHT utilizes SplintR-triggered ligation for SNP discrimination in miR-196a2, combined with hybridization chain reaction for signal amplification. This approach enables precise allele discrimination with a detection limit of 0.75 aM, offering specificity by distinguishing mutations in miR-196a2 when they constitute only 0.0002% of the wild-type population. LIGHT-based miR-SNP genotyping revealed significantly elevated miR-196a2T expression in non-small cell lung cancer (NSCLC) samples, highlighting the potential of LIGHT for NSCLC diagnostics. Furthermore, by leveraging the isothermal workflow of LIGHT, we developed a 3D-printed visualizer for portable miR-SNP genotyping and demonstrated its potential to facilitate cancer diagnosis in resource-limited settings.

Abstract Background and Aims Anderson–Fabry disease (AFD) is a genetic disorder due to mutations in the GLA gene that result in a deficiency of the enzymatic activity of a-galactosidase A and in a consequent accumulation of glycosphingolipids in various tissues and organs. Historically, AFD was primarily regarded as a disorder driven by substrate accumulation. However, more recent insights into its pathophysiology have highlighted the contribution of secondary mechanisms, including inflammatory responses. Among these, the Nod-like receptor protein 3 (NLRP3) inflammasome has emerged as a key player in regulating inflammatory pathways. Activation of the NLRP3 inflammasome can lead to the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), contributing to tissue damage and fibrosis. Aberrant activation of the NLRP3 inflammasome has been implicated in exacerbating inflammation and triggering the production of inflammatory cytokines. Genetic polymorphisms of NLRP3 are associated with susceptibility to a variety of autoimmune and inflammatory diseases, including CKD. NLRP3-rs10754558 is associated with regulation of inflammasome activity, with specific alleles being associated with increased inflammatory reaction. Similarly, the NLRP3-rs4612666 polymorphism has been implicated in the modulation of NLRP3 expression and inflammasome activation, with an influence on susceptibility to inflammatory conditions. The aim of this study is to investigate whether these genetic variants of the NLRP3 gene can act as genetic modifier of inflammation in AFD and influence the progression and severity of the disease. Method Study Population A total of 33 patients were recruited from Anderson-Fabry Reference Nephrology Centres. Patients included carried both classical and non-classical mutations. The control subjects (n = 20) were recruited after a detailed visit. All control subjects had an eGFR >60 mL/min/1.73 m2 and were negative for GLA gene mutations. SNP Genotyping Genomic DNA was extracted from whole blood (QIAmp DNA Blood kit, QIAGEN) and quantified by a Nanodrop Spectrophotometer. Genotyping was carried out by Polymerase Chain Reaction followed by digestion reaction using restriction enzymes (PCR-RFLP). PCR was performed to amplify fragments overlapping rs10754558 and rs4612666 in the NLRP3 gene. 100 ng of DNA was used in a PCR reaction containing 1× PCR buffer, 2.5 mM MgSO4, 0.25 mM dNTP, 0.5 mM of each primer and 0.5 U Taq-polymerase. After PCR amplification, 10 μl of PCR product was digested by restriction enzyme for 3 h at 37°C and subsequently evaluated by gel electrophoresis on a 3% agarose gel. Statistical Analysis Statistical analyses were performed using the R programming environment (v 4.3.3, https://cran.r-project.org). Genotype and allele frequency distributions were calculated using four different models of inheritance (codominant, dominant, recessive, and overdominant) and the SNPassoc package was used for fitting the relevant regression models. A p-values of 0.05 was used as a cut-off for statistical significance. Results Association analysis revealed that rs4612666-C allele was significantly associated with AFD risk (P < 0.005). Specifically, the frequency of the CT + CC genotypes (dominant model) was higher in AFD patients (60.7%) compared to controls (9.1%) with a corresponding odd ratio of 20.0 (95% CI 2.26–176.75). The genetic variability of rs10754558 was not significantly associated with AFD risk. Conclusion This study shows that the NLRP3-rs4612666 polymorphism is associated with AFD risk and contribute to the high phenotypic heterogeneity observed in patients within the same families. This suggests that the variability of NLRP3 rs4612666 should be taken into account in genetic screening of AFD patients. These preliminary results may contribute to the understanding of the pathophysiology of the disease and to explore the mechanistic links between these polymorphisms and AFD-related inflammation, potentially opening new avenues for targeted therapies.

Abstract Exogenous glucocorticoids (GC) like prednisone are used to treat inflammatory diseases in nearly ten percent of older patients. This increases osteoporosis and the risk of fractures. Until now the negative effect on bone is thought to be a direct effect mediated exclusively by the GC receptor. However, GC effects are also locally regulated at a pre-receptor level by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Here we investigated the role of 11β-HSD1 in the metabolism of exogenous GC in both human mesenchymal-progenitor-cell models and in patients undergoing GC treatment. We performed experiments focusing on regulation, activity, and effects of 11β-HSD1 on the conversion of prednisone to prednisolone and back. Subsequently, GC metabolites were analyzed in combination with adipogenic and osteogenic differentiation. We also analysed 216 patients treated with prednisolone or methylprednisolone for different inflammatory diseases. Bone mineral density, fractures, and history of falls were investigated in combination with genotyping for single nucleotide polymorphisms of HSD11B1 as parameter of 11β-HSD1 activity. Our in vitro experiments prove that not only the activation of prednisone to prednisolone but also the reverse step of inactivation is catalyzed by 11β-HSD1 with corresponding influence on cell differentiation. In fact, in patients the inactivation of prednisolone seems to be the dominant effect influencing bone mineral density. Our results change the understanding of GC responsiveness in patient treatment and further highlight the significance of pre-receptor GC regulation by 11β-HSD1.

BackgroundThe analysis of single nucleotide polymorphism (SNP) genotypes which capture genome-wide polymorphic variation can be used to improve the accuracy of selection in breeding programs and reveal the genetic architecture of quantitative traits. Mid-density SNP genotyping arrays containing > 60 K SNP markers have been developed for numerous production species and have been used to enable enhanced breeding progress. Despite recent genomic advances, Atlantic halibut lacks mid-density genotyping tools, limiting the application of genomic selection and high-resolution association studies in this species. The evolving Atlantic halibut (Hippoglossus hippoglossus) industry is also interested in genetically informed selection of breeding candidates to facilitate genetic improvement. The present study reports the development of the first mid-density SNP-array for use in Atlantic halibut and describes its performance in samples from different breeding populations.ResultsVariant discovery was performed using whole genome sequencing (WGS) data from 40 individuals and resulted in the detection of more than 8 million small genetic variants including 6,224,375 SNPs and 2,131,436 insertion-deletion variants (INDELS). An Affymetrix Axiom custom array containing 70,824 assays (including 697 for determining genetic gender) was created and used to genotype 1152 Atlantic halibut samples. Assays for 59,491 SNP loci (84% of the array total) performed well and generated reliable genotypes, with an average SNP call rate of 99.64% and genotype concordance of 99.0% with whole-genome sequencing data. Of the gender-specific loci, 133 SNP assays could be used to assign genetic gender.ConclusionsThis article describes the first mid-density SNP genotyping array for Atlantic halibut. It contains nearly 60 K robust assays for genome-wide dispersed SNP loci, along with those suitable for determining genetic gender. The array is amenable for use as a platform for high-resolution genetics research into traits of evolutionary and economic importance and the results have practical relevance for genomic selection in Atlantic halibut.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12864-025-12128-1.

Hybridization is a widespread evolutionary process and a key source of evolutionary novelty. Despite intensive study, the extent to which hybridization is deterministic and repeatable, particularly in recurrent contact events involving the same species under varying ecological conditions, remains unclear. Here, we investigated three replicated contact zones between Scots pine (Pinus sylvestris) and dwarf mountain pine (Pinus mugo) in Central Europe: two occurring in peatland habitats and one in a contrasting sandstone outcrop. Using genome-wide SNP genotyping of over 1300 individuals, we analysed genomic structure, diversity, and ancestry patterns across these zones. All sites revealed pervasive hybridization, dominated by later-generation hybrids and a notable scarcity of pure P. mugo. Across environments, hybrid populations exhibited strikingly consistent genomic compositions, with asymmetric introgression strongly biased toward P. mugo ancestry, suggesting that hybrid genome structure may follow predictable patterns under similar ecological conditions and could be shaped by cytonuclear incompatibilities. Nonetheless, we also detected site-specific differences in hybrid diversity and phenotype, highlighting the influence of local environmental selection on shared hybrid genomic backgrounds. We provide genomic evidence that Pinus uliginosa, a morphologically distinct peat bog pine traditionally regarded as a relict and endangered species is instead a partially stabilised hybrid lineage. Its genome reflects incomplete hybridization and ecological filtering, yet it lacks sufficient genetic divergence to be recognised as a distinct species. Together, these results provide evidence for the repeatability of hybridization processes, which result in the formation of phenotypes reflecting a species continuum subjected to strong environmental pressures. The findings support the simplification of taxonomic nomenclature within the Pinus mugo complex, informing adaptive conservation strategies and the genetic management of hybrid lineages.

We compared plasma adiponectin levels between patients with preeclampsia (PE) classified as responsive and nonresponsive to antihypertensive therapy; Moreover, we examined whether ADIPOQ SNPs rs17300539, rs266729,rs2241766, and rs1501299 and their haplotypes are associated with responsiveness to antihypertensive therapy, and whether they affect plasma adiponectin levels in 215 pregnant women with PE. Genotypes for ADIPOQ SNPs were determined using TaqMan allelic discrimination assays, and circulating adiponectin concentrations were measured by ELISA. Patients with PE classified as nonresponsive to antihypertensive therapy showed higher plasma adiponectin levels than responsive patients. The TG genotype of the rs2241766 SNP was more frequent in responsive patients with PE when compared to nonresponsive patients. Nonresponsive patients with PE carrying specific genotypes of the ADIPOQ SNPs rs17300539 (GG or GA+AA), rs266729 (CC), rs2241766(TT), and rs1501299 (GT+TT), respectively, as well as the 'G,C,T,G' and 'G,C,T,T' haplotypes showed higher plasma adiponectin levels than responsive patients with PE carrying the same genotypes/haplotypes. Nonresponsive patients with PE showed higher plasma adiponectin levels than responsive patients, the TG genotype of the rs2241766 SNP was more frequent in the responsive patients with PE when compared to nonresponsive patients. Genotypes of rs17300539, rs266729, rs2241766, and rs1501299 SNPs and haplotypes may affect adiponectin levels in patients with PE classified as nonresponsive to antihypertensive therapy.

Novel variants in ARID1B, SPSB1, and RAET1-AS shape genetic susceptibility and protection in systemic lupus erythematosus and lupus nephritis

IntroductionStem rust (SR), caused by Puccinia graminis f. sp. tritici (Pgt), remains a major threat to global barley production, particularly in regions with conducive environments and evolving pathogen populations. Despite progress in understanding seedling resistance, adult plant resistance (APR) to SR remains underexplored in diverse barley germplasm. This study aimed to dissect the genetic architecture of APR to SR in a panel of diverse origins of two-row spring barley using a genome-wide association study (GWAS).MethodsA total of 273 barley accessions were evaluated for APR to SR in two distinct environments in Kazakhstan. Phenotypic data were combined with high-density SNP genotyping to perform GWAS using five statistical models (GLM, MLM, MLMM, FarmCPU, and BLINK). Population structure and kinship were accounted for to identify robust marker-trait associations (MTAs), followed by haplotype-based QTL delineation. Transcriptomic data from 16 barley tissues were used to identify candidate genes within major QTL regions. Substantial phenotypic variation in SR severity was observed across environments.ResultsA total of 204 MTAs were identified, among which 96 were stable across models, resulting in 19 model-stable QTLs spanning all seven barley chromosomes. Six QTLs co-localized with known SR-resistance QTLs and genes, including Rpg1 and Rpg6. Q_rpg_7H.1 (coinciding with Rpg1) was one of the strongest and most consistent QTL, harboring 42 highly expressed candidate genes. A novel major-effect QTL on chromosome 5H, Q_rpg_5H.1 (3.5 – 9.9 Mb), not previously associated with known resistance loci, contained 10 highly expressed genes grouped into three co-expression clusters, including WRKY transcription factors and PR-5 proteins.ConclusionThis study provides new insights into the complex, multilayered genetic control of SR resistance in barley. The discovery of both known and novel QTLs offers valuable targets for marker-assisted selection and lays the foundation for breeding durable SR-resistant barley adapted to diverse agroecological conditions.

The coagulation cascade is thought to contribute to cancer progression. Although in vitro studies suggest that anticoagulants, such as warfarin, might reduce cancer progression, epidemiological data indicate that warfarin users may have a higher risk of cancer mortality. However, single nucleotide polymorphisms (SNPs) that influence warfarin dosing might affect this association. We investigated the risk associations between warfarin use and prostate cancer (PCa) survival, considering the SNP genotypes of CYP2C9 and VKORC1, which are known to impact both warfarin pharmacokinetics and pharmacodynamics, resulting in lower warfarin dose requirement. We genotyped 2,246 Finnish men with PCa from two different cohorts for SNPs rs1057910, rs1799853, and rs9923231. Genotyping was done using a custom Illumina iSelect genotyping array (iCOGs). Using Cox regression models, we calculated hazard ratios (HRs) and 95% confidence intervals (CI) for the risk of overall death, cancer deaths overall, and PCa-specific death after PCa diagnosis based on SNP genotypes. Data on warfarin purchases was obtained from a national registry. Our findings revealed that the SNPs did not alter the risk of cancer or PCa death in either cohort, nor did they modify the risk among warfarin users. However, overall mortality was higher among warfarin users compared to non-users, particularly in carriers of all three SNPs. Even though the increased mortality is likely due to confounding by indication, warfarin use may increase overall mortality especially in men with lower warfarin dose requirements due to SNP carrier status. However, we need further studies with larger populations to confirm these findings.