Biomedical subjects

Yang Zhang

Publications and source records attributed to Yang Zhang.

17 recordsLinked to original sources

PubMed2026

Enhancing phytosterol tolerance and Repeated-Batch androstenedione production in Mycolicibacterium by modulating global acylation levels.

Global protein lysine acylation, driven by intracellular acyl-coenzyme A (acyl-CoA) accumulation during phytosterol catabolism, has emerged as a potential regulatory mechanism in steroid biotransformation, yet its role in androstenedione (AD) production by Mycolicibacterium remains unexplored. Here, we identified and functionally characterized two antagonistic enzymes in Mycobacterium sp. LZ2 (Msp): MpKat, a GNAT-family acyltransferase catalyzing lysine succinylation, and MpSir, an NAD+-dependent Sirtuin-family deacylase. Genome-wide prediction indicated that 21.56% of lysine residues in the Msp proteome are potential acylation sites, underscoring the broad regulatory impact of this modification. Targeted genetic manipulation revealed that MpSir overexpression increased AD yield by 13.28% (to 83.24%), and MpKat knockout improved yield by 8.86%, while MpKat overexpression decreased yield by 8.69%. Reducing global acylation levels alleviated oxidative stress, elevated NAD+/NADH ratios, enhanced phytosterol tolerance, and improved cell viability. In repeated-batch fermentation, the MpSir-overexpressing strain achieved an average AD yield of 76.5% with a 51% reduction in fermentation time compared to the wild type. This work demonstrates for the first time that modulation of protein acylation via the MpKat/MpSir regulatory axis is a viable and effective strategy to enhance steroid bioconversion in mycobacteria, offering a new dimension for metabolic engineering beyond conventional pathway optimization.

Androstenedione↗

PubMed2026

First Isolation and Genomic Characterization of BVDV-1c in Przewalski's Gazelle (Procapra przewalskii) from the Qinghai-Tibet Plateau, China.

Przewalski's gazelle (Procapra przewalskii) is an endangered ungulate endemic to the Qinghai-Tibet Plateau of China. Increasing habitat alteration and close contact with domestic livestock have raised concerns about cross-species pathogen transmission, yet infectious disease studies in this species remain limited. To determine the etiology of illness in two deceased gazelles from a conservation facility in Qinghai Province, we screened samples for a panel of pathogens, including Mycoplasma ovipneumoniae, Clostridium perfringens toxin genes, Mannheimia haemolytica, Klebsiella pneumoniae, Mycoplasma capricolum subsp. capripneumoniae, Pasteurella multocida, Peste des petits ruminants virus (PPRV), Bovine viral diarrhea virus (BVDV), and Infectious bovine rhinotracheitis virus (IBRV), using PCR and RT-PCR. BVDV-specific nucleic acids were detected in tissue samples from both individuals, whereas all other targeted pathogens tested negative. The virus was successfully isolated in Madin-Darby Bovine Kidney (MDBK) cells and confirmed by RT-PCR, followed by whole-genome sequencing of the isolate, which was designated QH PSYL 2026. Phylogenetic analysis based on the full-length genome and 5'UTR sequences assigned the isolate to the BVDV-1c subgenotype. Notably, its 5'UTR sequence shared 100% identity with those of local cattle-derived BVDV strains, providing molecular evidence suggestive of an epidemiological linkage between wildlife and livestock. Integrating clinical signs, gross pathology, and laboratory results, the cases were consistent with BVDV infection as the primary presumptive etiology. To our knowledge, this is the first report of BVDV infection, virus isolation, and genomic characterization in Przewalski's gazelle. The detection of a BVDV-1c strain in this endangered species highlights the potential threat that livestock-associated pathogens pose to wildlife on the Qinghai-Tibet Plateau. These findings furnish crucial baseline data for disease surveillance, molecular epidemiology, and conservation management of Przewalski's gazelle and provide valuable scientific evidence for wildlife disease prevention and control in plateau ecosystems.

BVDV-1c↗

PubMed2026

SHMT2: a Metabolic and Immune Biomarker of Aggressive Lung Adenocarcinoma.

Serine/glycine-one-carbon (SGOC) metabolism is frequently altered in lung adenocarcinoma (LUAD), but its relationship to tumor behavior and predicted immunotherapy responsiveness remains incompletely defined. Metabolomic profiling of 23 paired LUAD and adjacent normal lung tissues was performed using internal extractive electrospray ionization mass spectrometry. Transcriptomic and clinical data from The Cancer Genome Atlas LUAD cohort (TCGA-LUAD) were analyzed to assess SHMT2 expression, prognosis, differentially expressed genes, and immune-related features. Predicted response to immune checkpoint blockade was evaluated using Tumor Immune Dysfunction and Exclusion (TIDE) and The Cancer Immunome Atlas (TCIA), and drug sensitivity was inferred using oncoPredict. Single-cell RNA-seq data were used to examine the cellular distribution of SHMT2. Experimental validation included quantitative reverse-transcription PCR (RT-qPCR), western blotting, Human Protein Atlas (HPA) immunohistochemistry, and short hairpin RNA (shRNA)-mediated SHMT2 knockdown followed by proliferation, wound-healing and colony formation assays. Metabolomic analysis identified glycine, serine, and threonine metabolism as a prominently altered pathway in LUAD. SHMT2 was upregulated in LUAD and associated with worse overall survival and adverse clinicopathological features. SHMT2-high tumors displayed enrichment of cell-cycle and SGOC-related transcriptional programs, lower immune and stromal scores, and reduced predicted responsiveness to immunotherapy. Single-cell analysis showed relative enrichment of SHMT2 expression in B cell populations. In vitro, SHMT2 was overexpressed in LUAD cells, and its knockdown suppressed proliferation, migration, and clonogenic growth. Collectively, SHMT2 is associated with SGOC metabolic reprogramming, aggressive tumor phenotypes, and an immune-disadvantaged state in LUAD, supporting its potential relevance as a biomarker; therapeutic targeting requires additional pharmacologic and in vivo validation.

Humans↗

PubMed2026

Tissue-based genomic instability markers for predicting malignant transformation in oral leukoplakia and proliferative verrucous leukoplakia: a systematic review.

OBJECTIVES: Although several biomarkers have been described for predicting malignant transformation in oral leukoplakias (OLs) and proliferative verrucous leukoplakias (PVLs), no systematic review has comprehensively evaluated tissue-based genomic instability markers. This review aimed to evaluate the evidence for these markers and their potential role in biomarker panel development. METHODS: A systematic review across PubMed, Embase and Cochrane Library was performed to identify studies evaluating the differences in tissue-based genomic markers between OL and PVL patients with and without malignant transformation. RESULTS: 34 observational studies comprising 3,237 patients were included, and genomic aberrations were categorised into DNA-level, chromosomal, and gene-specific alterations. For studies on OLs, DNA-level and chromosomal markers for which individual studies reported associations with malignant transformation included aneuploidy, impaired DNA repair capacity, loss of heterozygosity, chromosomal instability, and copy number alterations. Multiple gene-specific alterations also showed associations (e.g., TP53, MKI67, FGFR1), but findings varied across studies. The genomic markers of PVLs differed substantially, with fewer consistent predictors found. No meta-analysis was performed as all included studies were observational. CONCLUSIONS: Genomic instability across multiple levels contributes to malignant transformation, and represents a promising biological framework for predicting malignant transformation for OLs. While no single marker reliably demonstrates sufficient predictive performance, the integration of complementary genomic alterations with clinical and histopathological risk factors may provide a basis for the development of robust multi-marker panels. Future prospective studies using standardised detection methods and multivariable prediction models are required before clinical implementation. SYSTEMATIC REVIEW REGISTRATION: identifier CRD42024585830.

carcinoma↗

PubMed2026

Decreased H3K79 acetylation and dysregulation of neurodevelopmental genes in fetal down syndrome.

BACKGROUND: Down syndrome (DS), the most prevalent chromosomal disorder caused by trisomy 21, manifests intellectual disability and cognitive dysfunction. Cumulative studies confirm epigenetic pathways including DNA methylation and non-coding RNAs drive DS pathological progression. Histone post-translational modifications (PTMs) are core epigenetic regulators of fetal brain development. However, genome-wide PTM alterations and their downstream functions in fetal DS brains remain poorly characterized, leaving a key gap in revealing epigenetic mechanisms underlying DS neurodevelopmental defects. To address this, we aimed to establish the first comprehensive landscape of histone PTMs in fetal DS cortex and investigate whether specific PTM changes contribute to aberrant neurodevelopmental gene expression. METHODS: Fetal cortexs from control and DS groups were subjected to global histone modification profiling via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). We detected mono-, di-, and tri-methylation, acetylation, homocysteinylation and malonylation on all four core histones (H2A, H2B, H3, H4). Chromatin immunoprecipitation sequencing (ChIP-seq) was used to map genomic binding profiles of H3 lysine 79 acetylation (H3K79ac). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to quantify mRNA levels of candidate neurodevelopmental genes. RESULTS: HPLC-MS/MS analysis identified 172 distinct histone PTMs in control fetal cortices and 168 PTMs in DS fetal cortical samples. Quantitative comparison of 22 quantifiable histone PTMs revealed that H3K79ac showed the most prominent reduction in DS samples, with a 34% decrease (P<0.05). Chromatin immunoprecipitation (ChIP)-seq verified specific H3K79ac occupancy at the genomic loci of three vital neurodevelopmental genes: TNFSF13B, NXPH1 and CAMK4. Correspondingly, qRT-PCR revealed aberrant transcription levels of these three genes in DS fetal cortices. CONCLUSIONS: This study establishes the first quantitative landscape of histone PTMs in in DS fetal cortical tissues. We demonstrate that depleted H3K79ac acts as a candidate epigenetic driver of DS neuropathology by disrupting the transcription of critical neurodevelopmental genes. This work reveals a novel epigenetic mechanism and a promising therapeutic target for DS-related neurodevelopmental disorders.

Down syndrome (DS)↗

PubMed2026

CREAT: A CRISPR-Based Genome Trimming Strategy for Systematic Identification of Dispensable Regions and Rapid Genome Reduction.

The construction of minimal-genome microbes offers an ideal platform for understanding fundamental biological processes and synthetic biology, yet the research is hindered by incomplete lists of essential genes in microbes and by multiple rounds of genome trimming with a trial-and-error nature. To address this, we introduce CREAT (CRISPR-based genome trimming with a multi-homology-arm template)-a streamlined approach that integrates CRISPR-targeted genome cleavage and homology arm walking to classify essential from non-essential genomic subregions, thus providing the basis for predicting essential genes in a given organism. These essential genes were then assembled into synthetic gene cassettes for one-step replacement of the targeted non-deletable genomic regions for further genome trimming. Eight consecutive rounds of CREAT genome trimming achieved a 20.8% reduction in genome size in Saccharolobus islandicus. Furthermore, Cas9-based CREAT genome trimming was developed for Bacillus subtilis and Escherichia coli, with efficiency greatly enhanced by the λ-Red recombinase in the latter. Together, this iterative application of CREAT provides a scalable and generally applicable strategy for rapidly constructing minimal genomes across diverse microorganisms.

CRISPR-Cas Systems↗

PubMed2026

Advances in the diagnosis and classification of B-ALL: comparative insights from updated guidelines.

Accurate molecular classification is essential for diagnosis, risk stratification, and treatment selection in B-cell lymphoblastic leukemia (B-ALL). In this study, we performed a comprehensive, real-world reclassification of 1015 consecutively diagnosed B-ALL patients using the fifth edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) and the International Consensus Classification (ICC). An integrative genomic strategy that combined whole transcriptome sequencing, fusion detection, mutational analysis, and cytogenetics enabled reclassification according to both the WHO-HAEM5 and ICC frameworks, thereby substantially reducing the proportion of unclassifiable B-ALL from 41.9% (2016 WHO revision [WHO-HAEM4R]) to 15.9% (WHO-HAEM5) and 11.9% (ICC). Distinct clinical and prognostic features were identified across newly defined subtypes. Multivariable analysis confirmed that this genomic classification is a robust, independent predictor of survival after adjusting for age, minimal residual disease status, and transplant intervention. Specifically, HLF-rearranged and MEF2D-rearranged B-ALL conferred a persistently poor prognosis across all age groups despite allogeneic hematopoietic stem cell transplantation, highlighting an urgent need for novel therapeutic strategies. Gene expression profiling resolved cryptic subtypes, including ETV6::RUNX1-like, ZNF384-rearranged-like, and BCR::ABL1-like B-ALL, and uncovered diagnostic ambiguity in patients with concurrent lesions. In addition, we report emerging high-risk groups, including IDH1/2- and ZEB2 Q1072-mutated B-ALL, that may warrant recognition as distinct molecular entities. Our findings demonstrate the clinical use of integrative transcriptomic profiling in refining B-ALL taxonomy in guiding risk-adapted therapies and informing future revisions of diagnostic standards. This study supports the incorporation of high-throughput molecular diagnostics into routine leukemia classification and precision treatment planning.

Humans↗

PubMed2026

A duplicated female pathway gene figla-like evolves as the male sex-determining gene in tilapia.

As the largest group of vertebrates, fish exhibit frequent turnover of sex-determining (SD) genes. Here, we assemble a chromosome-level YY red tilapia genome and identify figla-like (figlal) as the SD gene on tilapia linkage group (LG) 1. Integrative phylogenetic and genomic evidence suggests that figlal originated from a tilapia-specific duplication and transposition of the ancestral bHLH family gene figla from LG12 to LG1. Fluorescence in situ hybridization reveals expression divergence between figla and figlal, with figla expressed in female oocytes and figlal expressed in male gonadal somatic cells during early gonadal differentiation. The shift in expression after duplication might be driven by the insertion of cis-regulatory elements mediated by transposable elements. Knockout of figlal in XY fish results in male-to-female sex reversal as indicated by ovarian morphology, down-regulation of the male pathway gene dmrt1, and up-regulation of the female pathway gene cyp19a1a in the gonads. In contrast, overexpression of figlal in XX fish induces female-to-male sex reversal. These findings implicate figlal as an SD gene on tilapia LG1 and reveal the history of a unique evolutionary innovation in which a female oocyte gene evolved into a male SD gene via duplication, transposition, and cis-regulatory rewiring.

Animals↗

PubMed2025

Lamin A/C loss promotes R-loop-mediated genomic instability and poor survival in small-cell lung cancer.

Lamin A/C (LMNA), a key component of the nuclear envelope, is essential for maintaining nuclear integrity and genome organization [W. Xie et al., Curr. Biol. 26, 2651-2658 (2016)]. While LMNA dysregulation has been implicated in genomic instability across cancer and aging, the underlying mechanisms remain poorly understood [S. Graziano et al., Nucleus 9, 258-275 (2018)]. Here, we define a mechanistic role for LMNA in preserving genome stability in small-cell lung cancer (SCLC), a malignancy marked by extreme genomic instability [N. Takahashi et al., Cancer Res. Commun. 2, 503-517 (2022)]. LMNA depletion promotes R-loop accumulation, transcription-replication conflicts, replication stress, DNA breaks, and micronuclei formation. Mechanistically, LMNA deficiency disrupts nuclear pore complex organization, specifically reducing phenylalanine-glycine (FG)-nucleoporin incorporation, resulting in impaired RNA export and nuclear retention of RNA. LMNA expression is repressed by EZH2 and reexpressed during SCLC differentiation from neuroendocrine (NE) to non-NE states, and low LMNA levels correlate with poor clinical outcomes. These findings establish LMNA as a key regulator of nuclear transport and genome integrity, linking nuclear architecture to SCLC progression and therapeutic vulnerability.

Lamin Type A↗

PubMed2025

Lamin A/C Deficiency Drives Genomic Instability and Poor Survival in Small-Cell Lung Cancer through Increased R-loop Accumulation.

Lamin A/C (LMNA), a key component of the nuclear envelope, is essential for maintaining nuclear integrity and genome organization [1]. While LMNA dysregulation has been implicated in genomic instability across cancer and aging, the underlying mechanisms remain poorly understood [2]. Here, we investigate LMNA's role in small-cell lung cancer (SCLC), a highly aggressive malignancy characterized by extreme genomic instability [3, 4]. We demonstrate that LMNA depletion promotes R-loop accumulation, transcription-replication conflicts, replication stress, DNA breaks, and micronuclei formation. Mechanistically, LMNA loss disrupts nuclear pore complex distribution, reducing phenylalanine-glycine (FG)-nucleoporin incorporation and impairing RNA export efficiency. Furthermore, we show that LMNA expression is epigenetically repressed by EZH2 during SCLC differentiation from neuroendocrine (NE) to non-NE states. Clinically, low LMNA levels correlate with significantly worse survival in SCLC patients. These findings uncover a novel role for LMNA in safeguarding genome integrity and shaping tumor heterogeneity, with broad implications for cancer and aging.

Biological Sciences↗

PubMed2025

The causal relationship between steroid hormones and risk of stroke: evidence from a two-sample Mendelian randomization study.

It is unclear how steroid hormones contribute to stroke, and conducting randomized controlled trials to obtain related evidence is challenging. Therefore, Mendelian randomization (MR) technique was employed in this study to examine this association. Through genome-wide association meta-analysis, the genetic variants of steroid hormones, including testosterone/17β-estradiol (T/E2) ratio, aldosterone, androstenedione, progesterone, and hydroxyprogesterone, were acquired as instrumental variables. Analysis was done on the impact of these steroid hormones on the risk of stroke subtypes. The T/E2 ratio was associated to an elevated risk of small vessel stroke (SVS) according to the inverse variance weighted approach which was the main MR analytic technique (OR, 1.23, 95% CI: 1.05-1.44, p = 0.009). These findings were solid since no heterogeneity nor horizontal pleiotropy were found. The causal association between T/E2 and SVS was also confirmed in the replication study (p = 0.009). Nevertheless, there was no proof that other steroid hormones increased the risk of stroke. According to this study, T/E2 ratio and SVS are causally related. However, strong evidence for the impact of other steroid hormones on stroke subtypes is still lacking. These findings may be beneficial for developing stroke prevention strategies from steroid hormones levels.

Mendelian Randomization Analysis↗

PubMed2025

Integrated genomic, transcriptomic, and metabolomic analyses of Chrysanthemum aromaticum provide insights into the volatile terpene biosynthesis.

Chrysanthemum aromaticum is renowned for its uniformly emitted strong and attractive scent, primarily attributed to volatile terpenes. Despite its commercial and horticultural significance, the molecular mechanisms underlying volatile terpene production in C. aromaticum remain largely unexplored. Here, we present the haplotype-resolved genome assembly of C. aromaticum, with a total size of 3.10 Gb, comprising nine anchored chromosomes with a contig N50 of 30.66 Mb and a scaffold N50 of 350.58 Mb. Phylogenetic analyses revealed a distant relationship between C. aromaticum and C. indicum, suggesting that C. aromaticum likely represents a distinct species rather than a variety of C. indicum. Through integrated genomic, transcriptomic, metabolomic, and biochemical analyses, we identified seven TPS involved in monoterpene biosynthesis and six TPS for sesquiterpene biosynthesis. Notably, comparative genomic analysis revealed a gene cluster for α-bisabolol biosynthesis in C. aromaticum, which has specifically expanded in Chrysanthemum species through tandem gene duplications, contributing to the elevated accumulation of α-bisabolol in the leaves of C. aromaticum. Our study provides important insights into the biosynthesis of volatile terpenes, highlighting the genetic basis for C. aromaticum's unique aromatic profile.

Chrysanthemum↗

PubMed2025

Multi-omics analysis of ubiquitin E2 genes in Setaria: evidence for the roles of E2 genes in various aspects of plant development, stress tolerance, and domestication.

Ubiquitin E2 enzymes (E2s) are critical mediators in the ubiquitination cascade, a post-translational modification process that regulates protein stability, activity, localization, and degradation. Here, we analyzed the E2 gene family in foxtail millet (Setaria italica), integrating comparative genomics, transcriptomics, and functional studies. A total of 52 E2 genes were identified and classified into four subfamilies (UBC, UEV, SCE, and RCE) based on phylogenetic analysis across 49 species. Notably, foxtail millet exhibited significant gene expansion. Tissue-specific expression profiling revealed distinct roles of E2 genes in growth and development. Haplotype and quantitative trait loci analyses demonstrated that several E2 genes, including SiUBC39, are associated with key agronomic traits, such as plant height, flowering time, and stress tolerance. Using CRISPR/Cas9, we validated the functional role of SiUBC39, finding that its disruption led to phenotypes resembling wild species (Setaria viridis), such as early flowering and reduced plant height and grain yield. IP-MS and transcriptome analysis revealed SiUBC39's involvement in growth and development regulation, drought stress response, and immune response. SiPIP2;1 and SiEhd2 were identified as interactors of SiUBC39, explaining its roles in blast resistance and flowering time control. Furthermore, domestication analysis identified an A/G mutation in the SiUBC39 promoter TATA box, distinguishing domesticated and wild haplotypes and highlighting its role in domestication selection. This study underscores the essential roles of E2 genes in regulating crop agronomic traits and stress responses, providing valuable insights for genetic improvement in foxtail millet and other cereals.

Setaria Plant↗

PubMed2024

Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAK.

Pseudorabies virus (PRV) is an ideal model for mechanistic investigations into α-herpesvirus. The neurotropism and latent infection of PRV have been extensively studied. Apart from neurological symptoms, diarrhea caused by PRV infection is also an essential cause of mortality in newborn and weaned piglets. However, little research has been done on PRV invasion of the gut. To fill this gap, a nasal drip PRV-infection mouse model was developed, consisting of three groups: the challenged group (Group A), the immunization-challenged group (Group B), and a mock group (Group C). The results showed that immunization with PRV XJ delgE/gI/TK successfully prevented intestinal damage caused by PRV drop-nose infection. Subsequently, intestines were collected for transcriptional analysis. Differentially expressed genes analysis revealed that PRV XJ delgE/gI/TK was effective in reducing the organismal intestinal transcriptional activity caused by PRV. The Group A vs Group C and Group A vs Group B had similar Kyoto Encyclopedia of Genes and Genomes (KEGG)-enriched signaling pathways and the differentially expressed genes were primarily enriched in pathways, such as cell adhesion molecules, focal adhesion kinase, and actin cytoskeleton regulation. Notably, transcriptome analysis indicated that genes associated with the focal adhesion kinase (FAK) signaling pathway (ECM-ITGA/ITGB-p-FAK) were significantly more highly expressed in Group A than in Group B and Group C. The results of quantitative real-time PCR (RT-qPCR) and western blotting were consistent with KEGG analysis. Therefore, we hypothesized that PRV promotes self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway and that PRV XJ delgE/gI/TK immunization could attenuate the intestinal damage caused by PRV by inhibiting the activation of this pathway.IMPORTANCEPseudorabies virus (PRV) poses a significant threat to the swine industry and public health due to its ability to infect multiple species, including humans, leading to substantial economic losses and potential health risks. This study addresses a critical gap in understanding the impact of PRV infection on the gut, which has been less explored compared to its neurological effects. By developing a drip-nose PRV-infection mouse model, the research indicated that PRV might promote self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway, and PRV XJ delgE/gI/TK immunization effectively prevents intestinal damage by significantly reducing the expression of genes in the ECM-ITGA/ITGB-p-FAK signaling pathway. The research has important implications for the swine industry and public health by contributing to the development of better vaccines and treatments, ultimately helping to control PRV and prevent its cross-species transmission.

Animals↗

PubMed2024

Identification of a novel EYA4 likely pathogenic variant in a Chinese family with postlingual non-syndromic hearing loss and analysis of molecular epidemiology of EYA4 variants.

BACKGROUND: EYA4 variants are responsible for DFNA10 deafness. Due to its insidious onset and slow progression, hearing loss in autosomal dominant non-syndromic hearing loss (ADNSHL) is usually challenging to detect early in clinical settings, with limited intervention options. Genetic testing can aid in early detection of hearing loss, enabling timely intervention to reduce disability rates and improve the quality of life. METHODS: In this study, we report the case of a Chinese family with postlingual and progressive hearing loss that was passed down for four generations. Whole-exome sequencing (WES) was performed on DNA samples from the proband. Candidate variants identified in the proband and family members were confirmed via Sanger sequencing. In silico prediction tools and co-segregation analyses were used to assess the pathogenicity of identified variants. A literature review of known EYA4 variants was performed, analysing variant frequency, distribution characteristics across different populations, and genotype-phenotype correlations. RESULTS: We identified a novel EYA4 variant, c.1745_1748del (p.Glu582ValfsTer6), in a Chinese family with ADNSHL, and co-segregation with the family's phenotype was confirmed. The audiometry showed mid-to-high frequency downsloping hearing loss. To date, 52 pathogenic variants of EYA4 have been reported, with majority identified in Asian populations. Most observed are the missense and frameshift variants. CONCLUSIONS: A novel variant of EYA4 was identified in a Chinese family with postlingual hearing loss, contributing to the expanding spectrum of EYA4 variants. The audiological features of EYA4 variants are highly heterogeneous and often challenging to detect early in clinical settings. Our findings highlight the significance of genetic testing in patients presenting with postlingual hearing loss.

Humans↗

PubMed2024

Networks of human milk microbiota are associated with host genomics, childhood asthma, and allergic sensitization.

The human milk microbiota (HMM) is thought to influence the long-term health of offspring. However, its role in asthma and atopy and the impact of host genomics on HMM composition remain unclear. Through the CHILD Cohort Study, we followed 885 pregnant mothers and their offspring from birth to 5 years and determined that HMM was associated with maternal genomics and prevalence of childhood asthma and allergic sensitization (atopy) among human milk-fed infants. Network analysis identified modules of correlated microbes in human milk that were associated with subsequent asthma and atopy in preschool-aged children. Moreover, reduced alpha-diversity and increased Lawsonella abundance in HMM were associated with increased prevalence of childhood atopy. Genome-wide association studies (GWASs) identified maternal genetic loci (e.g., ADAMTS8, NPR1, and COTL1) associated with HMM implicated with asthma and atopy, notably Lawsonella and alpha-diversity. Thus, our study elucidates the role of host genomics on the HMM and its potential impact on childhood asthma and atopy.

Humans↗

PubMed2024

Haplotype-resolved genome assembly and implementation of VitExpress, an open interactive transcriptomic platform for grapevine.

Haplotype-resolved genome assemblies were produced for Chasselas and Ugni Blanc, two heterozygous Vitis vinifera cultivars by combining high-fidelity long-read sequencing and high-throughput chromosome conformation capture (Hi-C). The telomere-to-telomere full coverage of the chromosomes allowed us to assemble separately the two haplo-genomes of both cultivars and revealed structural variations between the two haplotypes of a given cultivar. The deletions/insertions, inversions, translocations, and duplications provide insight into the evolutionary history and parental relationship among grape varieties. Integration of de novo single long-read sequencing of full-length transcript isoforms (Iso-Seq) yielded a highly improved genome annotation. Given its higher contiguity, and the robustness of the IsoSeq-based annotation, the Chasselas assembly meets the standard to become the annotated reference genome for V. vinifera. Building on these resources, we developed VitExpress, an open interactive transcriptomic platform, that provides a genome browser and integrated web tools for expression profiling, and a set of statistical tools (StatTools) for the identification of highly correlated genes. Implementation of the correlation finder tool for MybA1, a major regulator of the anthocyanin pathway, identified candidate genes associated with anthocyanin metabolism, whose expression patterns were experimentally validated as discriminating between black and white grapes. These resources and innovative tools for mining genome-related data are anticipated to foster advances in several areas of grapevine research.

Vitis↗