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PubMed2026

From gut to pancreas: Shared genetic susceptibility and biological convergence in acute pancreatitis and Crohn's disease.

BACKGROUND: Acute pancreatitis (AP) and Crohn's disease (CD) exhibit overlapping clinical presentations and an unexpectedly high rate of comorbidity. Whether this reflects shared genetic susceptibilities remains unclear. METHODS: We performed a cross-trait genome-wide association analysis leveraging European-ancestry summary statistics for AP (Ncases = 8446; Ncontrols = 437,418) and CD (Ncases = 12,194; Ncontrols = 28,072). Firstly, cross-trait genetic correlation was estimated using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL). Secondly, to pinpoint specific pleiotropic loci and prioritize candidate genes, we employed PLACO under a rigorous composite null hypothesis, integrated with Bayesian colocalization and SMR/HEIDI analyses. Finally, we dissected the underlying biological context by mapping tissue-specific regulatory enrichment and pathway convergence using FUMA, MAGMA, and Stratified LD Score Regression (S-LDSC). RESULTS: AP and CD showed significant positive genetic correlation (LDSC: rg = 0.178, SE = 0.079, P = 0.025; HDL: rg = 0.294, SE = 0.096, P = 0.0021). Pleiotropy analyses revealed 86 SNPs and 6 independent genome-wide significant pleiotropic loci (lead variants at 5q33.1, 6q22.33, 7q34, 10q24.2, 15q22.33 and 19q13.11, PPLACO < 5 × 10-8). Colocalization showed suggestive evidence of a shared causal signal at 6q22.33 (PP4 = 0.666). Gene-based tests of the AP-CD cross-trait statistics prioritized eight pleiotropic genes-RSPO3, ATG16L1, SMAD3, FADS1, ZPBP2, FADS2, PRKAA1 and IRGM. Gene-set analyses highlighted IL-23/Th17-related and broader inflammatory response pathways. CONCLUSIONS: AP and CD share polygenic susceptibility and converge on immune and inflammatory processes, with prioritized genes pointing to autophagy, lipid metabolism and TGF-β/SMAD-related biology.

Humans↗

PubMed1975

Immunological interference with fertilization.

Rabbit antisera against mouse and hamster ovaries and sheep antisera against rabbit ovary have been used to demonstrate ovary specific antigens in these three species of mammals. That one or more of the specific antigens are located in the zona pellucida which surrounds the egg was indicated in immunofluorescence studies and by the effects antibodies have on the zona. After exposure to the antibody a precipitate forms on the zonae of preovulatory, unfertilized and fertilized eggs and all embryonic stages up to the time when the zona is shed. The precipitate was always seen near the outer surface of the zona suggesting that the active sites of the antigen(s) are located in this region. Trypsin and pronase which usually dissolve the zona were ineffective on the precipitated outer portion but did dissolve the inner, unprecipitated region. Species- and tissue-specificity and chemical nature of the zona are discussed. Important roles for the zona antigen(s) in a number of early events in reproduction were indicated by the effects of antizona antibodies have on fertilization and implantation. Pretreatment of unfertilized hamster eggs with zona precipitating antibodies was most effective in blocking sperm attachment to the zona. When the antibody was added subsequent to in vitro insemination, but before the sperm had passed through the outer region of the zona, sperm penetration was blocked. Mouse embryos treated with zona precipitating antibody and cultured in vitro failed to escape from the zonae, implying that implantation could be inhibited by antibody. Passive immunization of female mice with antizona antibodies and precipitattion of the zonae of hamster embryos in transfer experiments reduced the number of implantation sites. The identification of zona antigens and the effects of zona precipitating antibodies on early reproductive events encourage further studies on the zona in reference to immunological control of fertility.

Animals↗

PubMed2025

SARS-CoV-2 infection and vaccination elicit distinct pharyngeal mucosal B cell responses in children.

Mucosal immunity is an important correlate of protection against respiratory infections such as SARS-CoV-2. Comparing B cell responses in the upper respiratory tract following vaccination and infection may offer unique insights into mucosal immunity. Here, we characterized antigen-specific B cells in the tonsils, adenoids, and peripheral blood of children who had been infected with SARS-CoV-2 or vaccinated with SARS-CoV-2 mRNA vaccines. SARS-CoV-2-specific switched memory B cells (BSM) and germinal center B cells were found in the blood and pharyngeal lymphoid tissues after vaccination or infection. However, infection generated a higher proportion of IgA+ BSM and CXCR3+CD21+ BSM, which showed distinct spatial localization, greater clonal expansion and increased propensity for plasma cell differentiation compared to their CXCR3- counterparts, accompanied by persistent activation of innate and T follicular helper cells in the tissues. Our data provide evidence for tissue-specific B cell memory after either SARS-CoV-2 vaccination or infection, but with distinct characteristics that can influence the quality, durability, and localization of immunity.

Journal Article↗

PubMed2025

Genomic relationship between polycystic ovary syndrome and bipolar disorder.

Women with bipolar disorder (BIP) have a higher risk of developing polycystic ovary syndrome (PCOS). Shared genetic architecture may underlie this comorbidity. Valproate, a mood-stabilizer commonly used to treat BIP, increases the risk of PCOS. Still, the mechanism underlying PCOS in BIP remains unknown. Here, we aimed to identify genetic variants shared between BIP and PCOS, as well as their interaction with valproate. We used the results of large-scale genome-wide association studies of BIP (41,510 cases and 354,340 controls), and PCOS (3,609 cases and 229,788 controls). Using conditional false discovery rate, we discovered genetic variants jointly associated with BIP and PCOS. Gene mapping of identified variants was performed using the Open Targets platforms. We analyzed the tissue-specific expression, interaction with valproate, and involvement in biological pathways of the mapped genes. We identified two loci shared between BIP and PCOS. Among the 10 genes mapped to the locus on chromosome 8:11455262, GATA4, NEIL2, and FDFT1 showed expression profiles suggesting their role in the observed comorbidity. Mapped to the locus on chromosome 12:2499849, CACNA1C, FKBP4, DCP1B, and ITFG2 are expressed in both the ovaries and the brain. CACNA1C expression is affected by valproate, and CACNA1C plays a role in biological pathways involving other valproate-affected genes. We identified shared genetic underpinnings of BIP and PCOS, and implicated genes which may explain the biological mechanisms of the comorbidity between these disorders and a potential mechanism for the role of valproate.

bipolar disorder↗

PubMed2026

The Potential Link Between Eosinophilic Esophagitis and Food Allergy: Inflammatory Pathogenesis and Management.

Eosinophilic esophagitis (EoE) has transitioned from an isolated gastrointestinal disorder to a recognized type 2 immune-mediated allergic disease, most likely representing a late manifestation of the atopic march. This comprehensive review examines the complex inflammatory pathogenesis linking EoE and food allergy, and critically discusses the mechanisms of disease induction, dietary treatments, and emerging clinical challenges. While genome-wide association studies identify shared susceptibility loci with classic atopy, EoE exhibits distinct tissue-specific pathways, particularly dominated by the local interleukin (IL)-13 axis and highly esophagus-selective proteases like Calpain-14. This unique immunological interplay is clinically epitomized by food oral immunotherapy (OIT)-induced EoE. During OIT, systemic immune reprogramming successfully drives immune tolerance-marked by a robust increase in plasma food-specific IgG4-but fails at the local level, due to the persistence of pathogenic Th2 cells and aberrant mucosal IgG4 immune complex deposition within the esophageal lamina propria. Regarding therapeutic management, conventional skin and serum allergy testing remain highly inaccurate in identifying dietary triggers, rendering test-guided diets ineffective. Conversely, empiric elimination diets achieve robust histological remission, ranging from standardized six-food restrictions to pragmatic single-food approaches targeting cow's milk. Furthermore, novel insights into industrial milk processing (such as UHT sterilization and homogenization) and specific beta-casein genetic variants (A1 vs A2) highlight how altered protein structures generate neoantigens that accelerate esophageal immunogenicity. In conclusion, decoding the divergent immunological mechanisms operating in the refractory esophagus is essential to move beyond trial-and-error dietary interventions towards non-invasive monitoring tools, precision medicine, and optimized biological therapies in EoE management.

Calpain14↗

PubMed2026

Shared Genetic Basis, Biological Function and Causal Relationship Between Sleep Traits and Hypothyroidism: Evidence from a Comprehensive Genetic Analysis.

BACKGROUND: This research attempts to clarify whether there are any genetic similarities between sleep traits and hypothyroidism based on publicly accessible large-scale genomewide association studies. METHODS: The methodology included colocalization analysis, cross-phenotype association analysis, and linkage disequilibrium score regression analysis to find common genetic overlap. Through tissue function specificity and functional mapping, we were able to identify the shared genetic level. Genetic instrumental factors were used for causal inference in two-sample univariate and multivariable Mendelian randomization analyses. RESULTS: A hereditary correlation between hypothyroidism and napping during the day and getting up in the morning (rg= -0.0982, P= 0.0007; rg= -0.101, P= 0.0001). MAGI3, and HLA-DRB1 BX296568.1 may be potential targets for shared treatments. Colocalization and tissue-specific analysis demonstrated that the common genes and SNPs were identified in the thyroid, lung, brain, and lymphatic tissues. Functional analysis emphasized the importance of these common genes in processes like as protein transport, inflammatory response, and MHC class II protein synthesis. Furthermore, an association has been established between hypothyroidism and sleep duration (IVW, OR 1.5208; 95% CI 1.1142-2.0758, P=0.0082) and getting up in the morning (IVW, OR 1.8375; 95%CI: 1.4502-2.3284, P=4.73E-07). Furthermore, the reverse MR analysis revealed no causal connection between aberrant sleep traits and hypothyroidism. The enduring impact of insomnia on hypothyroidism persists despite controlling for alcohol consumption and smoking habits. CONCLUSION: Certain genetic correlations between sleep traits and hypothyroidism have been emphasized. These findings may elucidate the origin of comorbidity and have implications for future clinical trials.

Humans↗

PubMed2026

A horizontally acquired gene mediates insect cocoon pigmentation in the eri silkmoth, Samia ricini.

Holometabolous insects make cocoons during larval-pupal metamorphosis to protect the pupal phase. The materials used for cocoon construction vary widely. Lepidopteran insects typically secrete silk to form cocoons, which display diverse colors. The eri silkworm, Samia cynthia ricini, is an economically important domesticated species that mostly produces white cocoons, with some varieties producing red cocoons. The enzyme kynureninase (KYNU), acquired from bacteria by horizontal gene transfer, has previously been implicated in insect coloration, while the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) has been identified as a red pigment. However, exactly how KYNU is involved in cocoon pigmentation remains unclear. Here, we report that a horizontally transferred bacterial gene encoding KYNU regulates red cocoon formation. Metabolomic analysis revealed a high accumulation of 3-HAA in red cocoons, confirming its role as the primary pigment and associating the coloration with tryptophan metabolism. Quantitative real-time polymerase chain reaction (qPCR) analysis indicated that SrKYNU is highly expressed in the silk glands and significantly downregulated in the red cocoon strain compared to the white cocoon strain. Genomic sequencing identified a 141 bp deletion in the upstream regulatory region of KYNU in the red cocoon strain compared to the white cocoon strain. Dual-luciferase assays confirmed that this deletion significantly reduced promoter activity. CRISPR/Cas9 knockout of SrKYNU in the white-cocoon strain resulted in mutants producing red cocoons with elevated 3-HAA content. These findings reveal that the horizontally transferred gene SrKYNU exhibits tissue-specific expression and regulates cocoon coloration in S. ricini, illustrating that horizontal gene transfer can play an important role in regulating an insect physiological process.

Animals↗

PubMed2026

Genomic insights into local adaptation of indigenous chickens.

Indigenous chickens are an essential part of biodiversity and a vital protein resource to humans, yet global warming and environmental changes pose serious threats to their survival and productivity. Therefore, assessing population adaptive capacity under shifting environments is crucial for breeding resilient animals, and guiding conservation strategies. Here, we integrated ecological and whole-genome resequencing data from 1 022 chickens from 44 Chinese indigenous populations to reveal genomic signatures of local adaptation. From 87 agroclimatic variables, we identified eight dominant environmental factors including solar radiation, precipitation, diurnal temperature range, and five landcover variables (cropland areas, water areas, trees coverage, bare ground and shrubs coverage) that shape ecological niches of indigenous chickens. Landscape and comparative genomics analyses revealed both known and novel candidate genes, such as UNC80, PTPRO, NCOR2, CSF2RB, NXT2 and PALLD for the solar radiation, precipitation, diurnal temperature range, cropland areas, trees coverage and bare ground, respectively. Particularly, adaptive non-coding variants harbored in these genes exhibited spatial allelic changes across populations and acted as regulatory elements via chromatin accessibility and DNA methylation, influencing adaptation in a tissue-specific manner. Our findings underscore the rich genetic diversity of Chinese indigenous chickens and provide new insights into genomic mechanisms of local adaptation, offering valuable references for domestic animal breeding, conservation, and climate resilience.

Animals↗

PubMed2026

Genome-wide identification of the superoxide dismutase gene family in Lycium barbarum and their expression profiles under abiotic stress and phytohormone treatment.

BACKGROUND: Superoxide dismutases (SODs) are crucial metalloenzymes that constitute the first line of defense against reactive oxygen species in plants under abiotic stress. Wolfberry (Lycium barbarum) is an economically important medicinal plant with notable stress tolerance, however, a comprehensive genome-wide analysis of its SOD gene family has not yet been performed. RESULTS: We identified ten wolfberry SOD genes (LbaSODs) and classified them into three subfamilies: iron-SODs (Fe-SODs), manganese-SODs (Mn-SODs), and copper/zinc-SODs (Cu/Zn-SODs). Members within each subfamily shared conserved gene structures and motifs. Segmental duplication was the primary driver of LbaSOD expansion, with three paralogous pairs identified. Analysis of cis-regulatory elements in the promoter region revealed a predominance of stress- and hormone-responsive cis-elements, particularly ABA-responsive elements (ABREs) (22 copies) and LTR (17 copies) motifs. Tissue-specific expression profiling revealed that LbaSOD2 and LbaSOD5 expression peaked during early fruit development, whereas LbaSOD6, LbaSOD9, and LbaSOD10 were progressively upregulated through fruit maturation. Under abiotic conditions, Fe-SOD members were markedly suppressed during prolonged drought, whereas LbaSOD9 and LbaSOD10 were rapidly induced in response to salt stress. Among the phytohormone treatments, methyl jasmonate (MeJA) elicited the most pronounced response, with LbaSOD5 expression increasing by approximately 60-fold after 24 hours. Notably, abscisic acid (ABA) triggered an exceptionally strong transcriptional induction of LbaSOD5 (2.5 × 105-fold), LbaSOD10 (6 × 105-fold), and LbaSOD6 (70-fold). In addition, LbaSOD3 and LbaSOD7 transcripts were undetectable in any of the tested conditions. CONCLUSIONS: This study provides the first comprehensive characterization of the LbaSOD gene family and elucidates its hormone- and stress-responsive regulatory landscape, providing a valuable foundation for future functional investigations of LbaSOD genes in abiotic stress adaptation. The extraordinarily strong ABA-mediated induction of specific LbaSOD members, together with their tissue- and stress-specific expression patterns, highlights their potential as targets for genetic improvement of stress tolerance in wolfberry.

Lycium barbarum↗

PubMed2026

Systematic mining and characterization of metal transporter families regulating zinc homeostasis provide insights into metal homeostasis in Camellia sinensis.

BACKGROUND AND AIMS: Zinc is essential for tea plant growth and quality formation, yet its homeostatic mechanisms remain poorly understood. This study identified metal transporter families regulating zinc homeostasis, analyzed their evolution, structure, and expression, and clarified zinc uptake, transport, detoxification networks, and their links to metabolism. METHODS: This study identified zinc homeostasis-related metal transporter families in the tea plant genome, characterized their structural features and expression profiles across tissues and developmental stages through integrative bioinformatics and transcriptomic analyses, and delineated the molecular mechanisms underlying zinc uptake, translocation, and detoxification by systematically integrating published evidence. RESULTS: This study identified 74 metal transporter genes from six families: 13 CsZIPs, 12 CsNRAMPs, 10 CsHMAs, 10 CsYSLs, 14 CsMTPs, and 15 CsCAXs in the 'Shuchazao2' genome, revealing closer affinity to woody species than to Arabidopsis. These proteins exhibit conserved domains, diverse subcellular localizations (cell membrane, vacuole, chloroplast, and Golgi apparatus), and tissue-specific expression with abundant stress/hormone-responsive cis-elements. At the plant-soil interface, tea plants mobilize rhizospheric zinc via proton and organic acid secretion; CsYSLs, CsNRAMPs, and CsZIPs mediate zinc uptake, aided by arbuscular mycorrhizal fungi (AMF) and plant growth-promoting rhizobacteria (PGPR) that expand root absorption zones. Xylem CsHMAs and phloem CsYSLs coordinate root-to-shoot zinc translocation, and vacuolar transporters (CsMTPs, CsCAXs), cell wall immobilization, and antioxidant systems alleviate high-zinc stress injury. CONCLUSIONS: These findings collectively delineate an integrated zinc "acquisition-distribution-buffering" network in tea plants, offering a repertoire of candidate genes with potential utility in zinc biofortification breeding and improving acid soil adaptation. Further experimental validation, including tea transgenesis, zinc-stress qRT-PCR, and heterologous functional complementation, is essential to substantiate their biological roles.

Camellia sinensis↗

PubMed2025

Shared Genetic Architecture Between Atopic Dermatitis and Autoimmune Diseases.

Atopic dermatitis (AD) and autoimmune diseases exhibit epidemiological comorbidity, yet the shared genetic architecture remains incompletely understood. We investigated the genetic overlap between AD and three autoimmune disorders including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and vitiligo, leveraging genome-wide association data. Despite modest evidence for global genetic correlations, we found 113 independent pleiotropic loci shared among AD and autoimmune diseases, with 11 displaying a concordant effect across all 3 pairwise comparisons. Gene-set and tissue enrichment analyses evidenced the inflammatory background of pleiotropic associations. Multi-trait colocalization analysis prioritized 22 loci, linking the tissue-specific expression of DOK2, GPR132, RERE, RERE-AS1, SUOX, TNFRSF11A, and TRAF1 pleiotropic genes with AD risk. Mendelian randomization revealed no causal effect of genetic liability to AD on autoimmune diseases. Nevertheless, genetic liability to IBD increased AD risk, while vitiligo exhibited a protective effect post outlier correction. Our findings provide mechanistic insights into the multimorbidity of atopic dermatitis (AD) and autoimmune diseases, offering additional evidence for the pleiotropic genetic architecture of AD that contributes to systemic immune dysregulation across multiple organ systems.

Humans↗

PubMed2026

Cucurbitacins in Plant-Insect Interactions: Biosynthesis, Regulation, Ecological Functions, and Prospects for Crop Protection.

Cucurbitacins are highly oxygenated tetracyclic triterpenoids characterized by intense bitterness, substantial structural diversity, and important consequences for plant-herbivore interactions. Although best known from Cucurbitaceae, cucurbitacins and related cucurbitane-type metabolites also occur in phylogenetically distant herbaceous and woody plants. Genetic and biochemical studies have validated several core biosynthetic steps, including cucurbitadienol formation by oxidosqualene cyclases and subsequent modification by cytochrome P450 monooxygenases, acyltransferases, and glycosyltransferases. Tissue-preferential basic helix-loop-helix transcription factors constitute the best-characterized regulatory layer, whereas the evidence supporting accessory regulators, transporters, and environmental responses varies from functional validation to transcriptomic or genomic prediction. From the plant perspective, cucurbitacins deter feeding or impair performance in many generalist and non-adapted herbivores. By contrast, their use as host-recognition cues and feeding stimulants by specialist diabroticite beetles reflects evolved herbivore adaptations involving perception, tolerance, metabolism, or sequestration rather than a second defensive function of the plant trait. Herbivore-induced cucurbitacin accumulation has been demonstrated in particular systems, although its regulatory mechanisms and ecological generality remain unresolved. Unlike previous reviews centered primarily on cucurbitacin chemistry, pharmacological activity, or individual biosynthetic pathways, this review integrates evidence-graded pathway reconstruction and molecular regulation with taxonomic distribution, insect adaptation, domestication, and agroecological consequences. Mechanistically, this review traces how scaffold formation, oxidative tailoring, conjugation, tissue-specific regulation, and transport give rise to contrasting ecological outcomes through herbivore-specific perception, tolerance, metabolism, and sequestration. We conclude that uniformly increasing or eliminating cucurbitacins is unlikely to provide broadly effective crop resistance because either direction may favor a different herbivore group. Future priorities include functional validation of candidate genes, spatially resolved metabolite analysis, comparative investigation of non-cucurbit lineages, and field evaluation involving generalist and specialist herbivores, crop quality, and non-target organisms. These advances will support context-specific fruit-quality improvement, behavioral pest control, and integrated pest management strategies rather than cucurbitacin manipulation as a stand-alone resistance approach.

agroecology↗

PubMed2026

Genome-Wide Identification of the Soybean GH5 Gene Family and Functional Analysis of GmGH5-22 in Salt Tolerance.

Plant GH5 family genes function in both cell wall biosynthesis and stress responses. However, comprehensive studies on GH5 genes in the soybean remain limited. Here, we identified 28 GmGH5 genes from the soybean genome. Phylogenetic analysis assigned these genes to three subfamilies (I-III), with no representatives in subfamily IV. The GmGH5 family harbors 15 conserved motifs, which are largely similar within subfamilies but differ across subfamilies. Additionally, exon-intron structures (2-7 introns) exhibit clade-specific patterns, with members within the same clade sharing similar intron numbers and lengths, whereas distinct clades show some variation. The promoter regions of GmGH5 genes contained various cis-acting regulatory elements associated with stress responses and developmental processes. Transcriptome-based expression profiling revealed distinct tissue-specific expression patterns of GmGH5 genes. RT-qPCR further confirmed their differential expression under salt, alkaline, cold, and drought stresses, especially a significant increase in GmGH5-22 expression under salt stress (approximately 22-fold at 6 h, **** p < 0.0001). Furthermore, GmGH5-22 was highly expressed in roots, and transient expression in tobacco leaves showed its peripheral localization, which aligns with its predicted extracellular localization, suggesting that GmGH5-22 is highly likely localized to the cell wall. Overexpression of GmGH5-22 in soybean hairy roots significantly improved tolerance to salt stress. These findings establish a foundation for functional characterization of GmGH5 genes and provide viable targets for molecular breeding to enhance salt tolerance in soybeans.

GH5 family↗

PubMed2026

The Key Trichoderma-Induced Gene Encoding a DUF568 Domain-Containing Protein Mediates Defense Responses in Wheat.

Genes encoding DUF568 domain-containing proteins participate in plant stress adaptation. To elucidate the functional role of DUF568 domain-containing genes in Trichoderma-induced wheat defense responses against wheat Fusarium crown rot, we performed a genome-wide identification and characterization of the TaDUF568 gene family in hexaploid wheat (Triticum aestivum L.). In this study, a total of 33 TaDUF568 family genes were systematically identified and characterized at the genome-wide level, exhibiting uneven chromosomal distribution and diverse physicochemical properties. Phylogenetic, structural, and collinearity analyses revealed conserved family characteristics among monocot species. Segmental duplication was verified as the primary driver of gene family expansion. Expression profiling revealed divergent tissue-specific expression patterns among TaDUF568 family members, among which TaDUF568.18 was strongly induced by Trichoderma M2. Subcellular localization assays confirmed that TaDUF568.18 is a plasma membrane-localized protein. Functional validation via stable transgenes demonstrated that overexpression of TaDUF568.18 restricted lesion expansion, improved agronomic traits, and enhanced disease resistance. This study is the first to characterize the wheat DUF568 family and confirm that TaDUF568.18 (annotated as TaAIR12) acts as a positive regulator of Trichoderma-mediated wheat defense, providing a valuable gene resource for wheat disease-resistance breeding.

DUF568↗

PubMed2026

Clinical Variant Interpretation with the Integrative Genomics Viewer (IGV) for Molecular Pathologists.

The integrative genomics viewer (IGV) is a pivotal tool in clinical genomics, enabling the visualization and interpretation of complex sequencing data. Bringing clinical knowledge to bear with visual evaluation of sequencing results is the primary means by which molecular pathologists and other professionals assess and finalize cases. A variety of software tools can assist, but their relationship to the underlying data must be understood and applied systematically. This study includes essential background on next-generation sequencing (NGS) data file types (e.g., FASTQ, BAM, VCF) with a discussion of their format and purpose. We then describe features of IGV that derive nuances from these files. We utilize a series of curated practical cases based on clinical vignettes through which the reader will interact with clinical NGS sequencing data using the IGV software to review various types of clinically relevant variants relative to the human reference genome. These clinical vignettes have been curated to describe examples of some of the complexities of interpretation of genomic data, and how utilizing IGV as part of a routine workflow can provide additional interpretive information for variants beyond routine bioinformatic software algorithm variant calls. The visual inspection of genomic variants utilizing the tools within IGV can unmask subtle contextual cues (i.e., variant allele frequency, strand bias, tissue-specific context) that can influence the interpretation of genomic variants. Although this study focuses on using IGV for the detection and interpretation of somatic variants, the provided applications can be extrapolated for use in the germline setting, including analysis of complex variants and detection of mosaicism.

Humans↗

PubMed2026

Genetic evidence prioritizes circulating proteins for heart failure beyond shared BMI-related genetic liability.

BACKGROUND: Heart failure (HF) and body mass index (BMI) share substantial genetic architecture, which may lead genetically informed target discovery to preferentially identify adiposity-related pathways. We sought to identify circulating proteins associated with HF beyond this shared genetic component. METHODS: We applied GWAS-by-subtraction to overall HF, nonischemic HF, and nonischemic HF with reduced or preserved ejection fraction to derive BMI-related and BMI-subtracted HF components. We then performed proteome-wide cis-pQTL Mendelian randomization and colocalization using four independent proteomic cohorts, followed by tissue-specific eQTL colocalization, cardiac transcriptomic annotation, and druggability assessment. RESULTS: Compared with the original HF phenotypes, the BMI-subtracted components showed attenuated genetic correlations with BMI (0.045-0.147) while retaining 28 independent loci for overall HF and nine for nonischemic HF. Across 19,930 protein-HF tests, 11 associations involving nine proteins were prioritized by the Mendelian randomization and colocalization analyses. For example, a 1-SD increase in genetically predicted CELSR2 abundance was associated with lower overall HF risk (odds ratio, 0.96 [95% CI, 0.94-0.98]; P=8.6×10-7), whereas a 1-SD increase in genetically predicted CSF3 abundance was associated with higher nonischemic HF risk (odds ratio, 1.32 [95% CI, 1.18-1.48]; P=2.0×10-6). CELSR2 and TMEM106B colocalized with cis-eQTLs in failing left ventricular myocardium, and DAG1 showed cardiomyocyte enrichment with concordant downregulation in failing hearts. CONCLUSIONS: We identified nine circulating proteins associated with HF beyond the genetic component shared with BMI. These findings extend the range of genetically supported pathways implicated in HF and nominate candidate proteins for further mechanistic and therapeutic investigation.

Genetics↗

PubMed1977

Red blood cell selection in chimeric mice.

Starch gel electrophoresis of a large number of tissues and organs from C3H in equilibrium C57BL aggregation chimeras suggests that the C57BL red blood cell population predominates, whereas for other tissues the proportions of the two components are more nearly equal. A similar predominance of (C57BL X C3H)F1 red blood cells is seen in (C57BL X C3H)F1 in equilibrium Recessive chimeras. Analysis of blood samples taken from the same animals at different times suggests that a temporal shift in the proportions of the two component red cell populations occurs in some adult chimeras and results in an unbalanced chimeric phenotype. It is suggested that differential mitotic activity contributes to strain-dependent, tissue-specific selection pressures in the erythropoietic tissue.

Age Factors↗

PubMed1976

Immunogenetic factors in preeclampsia and eclampsia. Erythrocyte, histocompatibility, and Y-dependent antigens.

Determination of ABO and HL-A antigens and sex ratio of infants born to 46 women with preeclampsia or eclampsia, in comparison with normal controls, disclosed no predominant blood group, HL-A haplotype, or qualitative difference in maternal-fetal incompatibility. These results suggest that a link between immunologic mechanisms and the pathogenesis of toxemia syndromes, if present at all, must be associated with feto-placental tissue-specific antigens.

ABO Blood-Group System↗