Biology subjects

Xu, N.

Publications and source records attributed to Xu, N..

At least 19 recordsLinked to original sources

bioRxiv2026

Towards a complete diploid chicken genome

The repetitive and heterochromatic parts of microchromosomes and dot chromosomes have impeded the creation of a complete, haplotype-resolved chicken genome. To overcome these challenges, we employed a trio-sequencing approach, utilizing long reads from a female chick, supplemented by parental long-read data for accurate haplotype phasing. This strategy produced nearly complete, haplotype-resolved paternal and maternal assemblies, with 14 residual gaps. Telomeric sequences remain missing in two paternal and four maternal chromosomes, suggesting a still incomplete assembly. GGswu2 resolved more than 50 Mb of previously unresolved regions, predominantly within dot chromosomes. The dot chromosomes exhibit low nucleotide diversity but a high density of structural variants between haplotypes. We found that the centromere sizes and relative positions of centromere cores sometimes differ between the two haplotype genomes. These findings suggest that comparative genomics must incorporate the high-resolution of these dynamic complex regions to fully understand avian genome evolution and genetic complexity.

genomics↗

bioRxiv2026

Loss of TDP-43 function drives cryptic circular RNAs in neurodegenerative diseases

TAR DNA-binding protein 43 (TDP-43) is a key pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and a critical regulator of RNA splicing. While loss of TDP-43 induces aberrant splicing in linear transcripts, its impact on circular RNA (circRNA) biogenesis remains unexplored. Here, we show that TDP-43 depletion in human neurons induces widespread circRNA changes, especially upregulation of a distinct class of cryptic circRNAs that arise specifically upon loss of TDP-43. Some of these cryptic circRNAs incorporate cryptic exons derived from intronic sequences. Notably, these cryptic circRNAs exhibit greater stability than their corresponding linear RNA isoforms and accumulate progressively in neurons. Moreover, cryptic circRNAs are elevated in postmortem brain tissues from ALS, FTD and Alzheimer's disease (AD) patients. These findings reveal a previously unrecognized role for TDP-43 in repressing cryptic circRNA formation and establish these circRNAs as stable molecular signatures of TDP-43 dysfunction.

neuroscience↗

bioRxiv2026

Pto evolved from malectin-like RLKs phosphorylates AvrPtoB to promote Prf-mediated immunity in Solanum pimpinellifolium

Bacterial speck, caused by Pseudomonas syringae pv. tomato (Pst), is a devastating disease of tomato that severely limits global tomato productivity. Understanding the molecular mechanisms underlying Pst and tomato is essential for developing disease resistant varieties. Here, we demonstrate that Pto, the first disease-resistance gene conferring recognition of a specific pathogen, phosphorylates Pst type III effector AvrPtoB at serine 335 site. This post-translational modification triggers the dissociation of the Prf immune complex, enhancing immune signaling and reducing bacterial pathogenicity. Furthermore, evolutionary analyses indicate that Pto-associated proteins originated from malectin-like receptor kinases (MLRs) through loss of the extracellular domain. Crucially, we identified two key amino acid substitutions, Arg158 and Glu258 in Pto, which replace the ancestral lysine residues in MLRs (SpHREK1-1, SpHERK1-2 and SpHERK1-3). These substitutions stabilize Pto by preventing degradation mediated by AvrPtoB's E3 ubiquitin ligase activity. Our findings reveal a novel mechanism, by which Pto phosphorylates a bacterial effector to trigger enhanced immunity and elucidate the key evolutionary adaptations that have shaped Pto into a stable resistance protein.

plant biology↗

bioRxiv2026

Lineage recording reveals hijacked hepatic progenitor states as a common origin of HCC and ICC

HighlightsCERAMIC enables continuous and high-capacity lineage tracing of liver tumor initiation Fatty liver-associated hepatocytes acquire regenerative and premalignant cell states before malignant transformation Lineage reconstruction identifies Hep_Bi-zonal cells as the cellular origin of liver tumor initiation Transcriptional and regulatory programs distinguish tumor-fated hepatocytes from failed-to-transform lineages Peroxisomal metabolism is required for progenitor-state formation and liver tumor initiation Spatial remodeling identifies a macrophage niche associated with tumor-fated hepatocytes Dual ontogenies and functional specialization of lipid-associated macrophages shape the tumor-fated hepatocyte niche Fatty liver disease predisposes to primary liver cancer, yet the lineage routes and niche mechanisms that select rare tumor-fated hepatocytes remain unclear. Here we developed CERAMIC, a high-capacity CRISPR-Cas9 lineage recorder that co-recovers editing scars and transcriptomes from single cells, and applied it to an AKT/NRAS-driven model of MASLD-associated liver tumor initiation. Longitudinal lineage, single-cell and spatial analyses revealed a hierarchical trajectory in which bipotential bi-zonal hepatocytes (Hep_Bi-zonal), rather than pericentral-like hepatocytes (Hep_CVlike), generated regenerative and neoplastic hepatocyte progenitor states that progressed toward both hepatocellular carcinoma and intrahepatic cholangiocarcinoma lineages. Tumor-fated cells preferentially expanded along a remodeled midlobular-periportal axis and depended on ACOX1-mediated peroxisomal beta-oxidation to withstand lipotoxic and oxidative stress. Spatial and lineage analyses further identified a sequential lipid-associated macrophage niche, in which monocyte-derived LAMs engaged tumor-fated hepatocytes through an LGALS9-P4HB axis, and P4HB inhibition suppressed tumor expansion. These findings define liver tumor initiation as a lineage-restricted process licensed by peroxisomal metabolic adaptation and macrophage-derived niche signals.

cancer biology↗

bioRxiv2026

Long-read genome sequencing reveals complex variability in lentiviral provirus insertions in deeply characterized Clonal CD19 CAR-T vector copy number reference cell lines

Chimeric antigen receptor (CAR)-T cell therapy is an important therapy involving provirus insertions in the genome. Characterizing these insertions is important for understanding the safety and efficacy of cell products, but the sequence of these insertions is not fully characterized. We generate clonal CD19 CAR-T cell lines with one to five copies of the lentiviral provirus insertions. Vector copy number (VCN) was determined by droplet digital PCR (ddPCR), which revealed that most of the elements (LTR, Psi, RRE, CD19, and WPRE) were 1 to 5 or 6 copies per cell. DdPCR data also revealed that there was an additional copy of eGFP gene in VCN4 and VCN5 cell lines. To fully characterize the sequences and locations of these insertions, we use short- and long-read whole genome sequencing as well as digital PCR and flow cytometry. Long-reads enable full resolution of each insertion, and we find that of 10 insertion events, 3 have the expected insertion sequence, 2 differ from the expected only in small variants, 3 have structural abnormalities, and 2 are small partial insertions missed by most other approaches. One particularly important structural abnormality resolved only by long-reads is a 724 bp deletion of the EF1 promoter disrupting expression of the CD19 CAR. Standard short-read and ddPCR approaches miss this deletion due to this commonly used promoter being in the unengineered human genome. These results demonstrated that these cell lines are suitable VCN reference standards for 1 to 5 or 6 copies and highlight the utility of long-read sequencing in characterizing both quantity and quality of insertions in lentiviral-engineered cells.

genomics↗

bioRxiv2026

Helminth-remodeled microbial indole-3-lactic acid drives AhR-dependent disease tolerance

Helminths systemically suppress host immunity, yet whether they impose immune tolerance by rewiring host-associated microbial metabolism remains unclear. Here we show that Trichinella spiralis infection remodels intestinal tryptophan metabolism to generate an AhR-dependent regulatory immune state. T. spiralis infection enriched the commensal bacterium Ligilactobacillus murinus, which converted tryptophan into indole-3-lactic acid (ILA), a microbial metabolite that directly engaged the aryl hydrocarbon receptor. Antibiotic-mediated microbiota depletion abolished infection-induced ILA accumulation, AhR activation and Treg/Th17 rebalancing, whereas fecal microbiota transplantation from infected donors or supplementation with L. murinus or ILA restored these effects. Pharmacological blockade or genetic deletion of AhR eliminated the ability of T. spiralis, L. murinus and ILA to restrain LPS-induced cytokine-storm-like lung inflammation, establishing AhR as an essential host node in this circuit. Extending these findings to viral inflammatory disease, oral ILA improved survival and reduced pulmonary immunopathology in SARS-CoV-2-infected K18-hACE2 mice. Re-analysis of human COVID-19 metabolomic data further revealed reduced circulating ILA in severe disease. These findings define a helminth-remodeled microbial tryptophan metabolic pathway that promotes disease tolerance and identify the ILA-AhR axis as a candidate postbiotic strategy for limiting hyperinflammatory tissue injury.

immunology↗

bioRxiv2026

A dataset of simultaneous two-photon calcium imaging and auditory discrimination behavior

The emerging field of artificial intelligence for neuroscience relies heavily on high-quality, standardized datasets. Data linking high-dimensional neural population dynamics with complex behavior is crucial for advancing the field of brain-computer interfaces. However, few existing datasets provide these paired modalities in a standardized, AI-ready format, limiting their immediate utility for computational modeling. Here, we present a large-scale dataset comprising simultaneous two-photon calcium imaging of the primary auditory cortex (A1) and detailed behavioral records in mice. The animals performed an auditory two-alternative forced-choice (2AFC) categorization task, classifying tones as low or high frequency by licking left or right water ports. The raw neural and behavioral data were preprocessed, synchronized, and formatted into trial-aligned multi-dimensional tensors. Comprehensive validation confirms that the recorded populations exhibit consistent, high-fidelity temporal dynamics and distinct frequency tuning across all experimental conditions. To evaluate the datasets capacity for neural decoding, we benchmarked it across diverse machine learning architectures and deep learning networks. By bridging biological recordings and behavior, this open-access dataset serves as a valuable benchmark for developing novel decoding algorithms and testing brain-inspired computational models.

neuroscience↗

bioRxiv2026

Channel Capacity for Time-Resolved Effective Connectivity in Functional Neuroimaging

Understanding how brain regions influence one another over time is a central goal of neuroscience. However, existing approaches to effective connectivity often involve tradeoffs among mechanistic interpretability, computational scalability, and time-resolved estimation. Here, we introduce information channel capacity, a model-based measure of directed information transfer between brain regions, and combine it with a sliding-window framework to estimate time-varying directional interactions. We validate channel capacity across multimodal neuroimaging datasets in humans and rodents because this breadth is needed to test three complementary properties that no single dataset can establish alone: sensitivity to evoked information transfer, specificity against false-positive directional effects, and the ability to capture meaningful temporal variability in directed brain-network interactions. Human motor-task fMRI tests sensitivity, showing that channel capacity detects task-related increases in directed interactions and stronger directional effects during task than during rest in motor-related regions. Concurrent rat local field potential (LFP)-fMRI tests specificity, showing minimal spurious directional asymmetry relative to scan-to-scan variability and consistent temporal dynamics across neural and BOLD signals. Mouse Ca2+-fMRI tests temporal variability, showing that channel-capacity patterns identify reproducible connectivity states and transitions over time. Together, these results establish channel capacity as a physiologically grounded framework for measuring dynamic directional interactions across species and neuroimaging modalities.

neuroscience↗

bioRxiv2026

Harmonizing brain rhythms: cortex-wide neuronal dynamics underpin quasi-periodic patterns in resting-state fMRI

Functional magnetic resonance imaging (fMRI) captures whole-brain activity fluctuations non-invasively in humans and animals. Beyond task/stimuli-locked responses, fMRI measures large-scale patterned activity during rest. Among these, quasi-periodic patterns (QPPs) represent recurring waves of activity that unfold over seconds and exhibit consistent spatiotemporal characteristics. Notably, certain fMRI-QPPs are well-preserved across species and altered in various neuropsychiatric and neurodegenerative diseases. Yet, our collective understanding of their neural underpinnings is limited given the indirect nature of blood-oxygen-level dependent (BOLD) fMRI signals. Simultaneous measures of local field potentials have provided some affirmation that fMRI-QPPs have neural origins, but these point-measurements are limited to a handful of sites. Here, we use a unique multimodal implementation of simultaneous wide-field calcium (WF-Ca2+) imaging and fMRI to investigate the neural origins of fMRI-based QPPs. We uncover a robust time-locked correlation between QPPs detected by cortex-wide fluorescent WF-Ca2+ imaging of neural activity and QPPs of BOLD-fMRI. These data validate the hypothesis that BOLD-fMRI QPPs derive from preceding slow waves of neural activity with regional and temporal precision.

neuroscience↗

bioRxiv2026

Coronavirus envelope protein drives iron sensing disorder by hijacking the TAp73-FDXR axis

Iron overload is increasingly recognized as a critical contributor to coronavirus pathogenesis1, yet the underlying induction mechanisms remain unclear. Here, we uncover a fundamental pathway by which coronavirus drives IRP1 RNA-binding activity to induce iron accumulation2 via targeting the TAp73-FDXR axis. Specifically, coronavirus infection represses transcription of FDXR (encoding the key rate-limiting enzyme in host iron-sulfur cluster synthesis3), thereby impairing host iron-sulfur cluster generation to trigger the functional conversion of the cytosolic aconitase 1 (ACO1) into iron-regulatory protein 1 (IRP1)4, ultimately leading to the hosts persistently false perception of iron deficiency. We identify TAp73 as the primary transcription factor governing FDXR expression, and demonstrate that the coronavirus envelope protein (CoV-E) orchestrates TAp73 nuclear export. Subsequently, CoV-E binds TAp73 through a critical valine residue within its C-terminal PBM domain, inducing the K48-linked ubiquitination and proteasomal degradation of TAp73. Furthermore, we developed a CoV-E-targeting molecule, DPTP-FC, which blocks CoV-E-TAp73 interaction via forming steric hindrance and effectively alleviates iron accumulation and tissue damage caused by PEDV, PDCoV, and SARS-CoV-2 infection. Our study reveals the central role of the TAp73-FDXR axis in CoV-induced iron accumulation, highlighting CoV-E as an attractive antiviral target and DPTP-FC as a promising therapeutic candidate.

microbiology↗

bioRxiv2026

Time-Varying Directed Interactions in Functional Brain Networks: Modeling and Validation

Brain function depends on time-resolved directional organization: influence is continuously redistributed across regions, shaping who drives whom, when, and for how long. Yet dynamic neuroimaging has largely emphasized undirected fluctuations in functional connectivity, limiting biological interpretation of asymmetric interactions. Here we show that directed influence can be resolved into two biologically distinct signatures: strength, reflecting the efficacy of influence, and duration, reflecting its temporal extent. To test this principle, we developed sliding-window prediction correlation (SWpC), a framework for estimating these signatures in fMRI and related signals. Across simultaneous rat local field potential (LFP)-fMRI and human motor-task fMRI, strength more closely tracks neural-BOLD coupling and task-evoked reconfiguration, whereas duration captures temporally extended BOLD patterns more susceptible to hemodynamic timing. In post-concussion vestibular dysfunction, altered strength-duration profiles define reproducible vestibular-multisensory states and improve patient-control discrimination. Together, these findings support a general principle of dynamic brain organization spanning neurophysiology, behavior, and disease.

bioengineering↗

bioRxiv2026

Site-specific integration of transposon via engineered piggyBac transposase

The precise integration of large DNA fragments into the human genome holds significant therapeutic potential. Here, we demonstrate that combining engineered piggyBac (PB) transposase with CRISPR/Cas9 enables targeted integration of PB transposons into specified genomic loci. Our engineered PB transposase (PBase) retains high excision activity while substantially reducing endogenous integration activity. In the developed Cas9-PBase fusion system, PBase excises the transposon to generate linear DNA fragments, while Cas9 introduces site-specific double-strand breaks (DSBs), facilitating insertion of the excised fragment at the target locus. The optimized tool achieves 6.1-7.3 kb transposon integration at multiple genomic sites with 10-15% efficiency, demonstrating 60-80% targeted integration specificity. As a proof of concept, we inserted a 7.1 kb transposon encoding three genes into the {beta}2M locus of human induced pluripotent stem cells (iPSCs), conferring protection against allogeneic natural killer (NK) cell-mediated cytotoxicity in derived iNK cells. These results establish Cas9-PBase as a precise and programmable platform for large DNA sequence insertion with potential clinical applications.

genetics↗

bioRxiv2025

Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms

RNA splicing shapes neuronal identity and disease risk, yet current maps lack the developmental resolution and depth to resolve this complexity. Here, we integrate deep long-read RNA sequencing and proteomics in iPSC-derived cortical neurons to generate a high-resolution proteogenomic atlas of human neuron development. We identify 182,371 mRNA isoforms (over half previously unknown) and provide direct peptide evidence for the translation of hundreds of novel protein-coding sequences. Population genetics demonstrates that variants affecting novel exons and splice sites are under negative selection, underscoring the potential significance of these isoforms. During neuronal maturation, we observe that ASD risk genes undergo dynamic isoform switching, including microexon inclusion and intron retention, that remodel key protein domains and regulatory regions. Furthermore, we uncover widespread, long-range coordination between splicing and polyadenylation. Finally, our atlas enables variant reinterpretation in ASD, highlighting the value of an isoform-centric view for interpreting pathogenic variation in neurodevelopment.

bioinformatics↗

bioRxiv2025

Restoration of Spermatogenesis is Dependent on Activation of a SPRY4-ERK Checkpoint Following Germline Stem Cell Damage

Mammalian spermatogonial stem cells (SSCs) sustain male fertility through continuous self-renewal and differentiation, leading to the production of haploid spermatozoa throughout adulthood. However, SSCs are vulnerable to genotoxic drugs, and patients receiving chemotherapy face a high risk of germline instability and infertility. The molecular mechanisms and cellular pathways that choreograph SSC recovery after chemotherapeutic insult remain unknown. Previously, we identified SPRY4 as an ERK-dependent negative feedback regulator of growth factor signaling that is critical for preservation of stem cell activity in cultured mouse SSCs. Here, we demonstrate that following alkylating agent busulfan (BU)-induced injury in adult mice, germline-specific Spry4 gene deletion (Spry4G-KO) reduces stem cell regeneration with an enhanced genotoxic stress response and differentiation with rapidly enhanced nuclear ERK1/2 activity in undifferentiated (Aundiff) spermatogonia (including SSCs). Genes essential for stem cell maintenance, including Id1 and Cxcl12, were dysregulated by loss of Spry4. Furthermore, the MEK1/2 inhibitor PD0325901, but not mTORC1 inhibitor Rapamycin, was sufficient to promote spermatogonial proliferation in Spry4G-KO testis 10 days post-BU treatment. Notably, the restoration of both spermatogonia pool and fertility was delayed in adult Spry4G-KO males long-term after injury. In summary, germline-specific deletion of Spry4 results in hyper-activation of the MAPK/ERK pathway in Aundiff spermatogonia, reducing spermatogonial genome integrity, unleashing excessive spermatogenesis after germline damage, and ultimately impairing germline regeneration in adult males. Our study indicates an essential role for SPRY4-ERK signaling as a molecular checkpoint in securing SSC recovery upon chemotherapy drug-induced germline damage, revealing how stem cells normally withstand environmental stress.

cell biology↗

bioRxiv2025

IGP receptors act as redox sensors to mediate broad-spectrum disease resistance induced by cellooligomers

Cys-oxidation is a well-established post-translational regulator of intracellular protein function, yet its role in extracellular receptor-mediated signaling remains poorly understood. Here, we investigate the LRR-Malectin receptor-like kinase IGP1, a key receptor for plant cell wall damage-associated molecular patterns (DAMPs). We demonstrate that IGP1 directly recognizes cellooligomers with a degree of polymerization [≥] 3 via a conserved binding groove in its LRR domain, not the malectin domain as anticipated. Strikingly, a pair of cysteines within the malectin domain functions as a redox sensor, undergoing hydrogen peroxide-induced oxidation that sterically reduces ligand binding affinity and attenuates immune signaling. Phylogenetic analyses reveal that IGP originated after the terrestrialization of plants, and is an evolutionarily conserved redox sensor in land plants. Functional studies in Arabidopsis (Arabidopsis thaliana), wheat (Triticum aestivum), and soybean (Glycine max) confirm that the IGP-cellooligomer module confers broad-spectrum disease resistance. Our work uncovers a unique mechanism where ligand perception and redox sensing are integrated into a single receptor to regulate DAMP-triggered immunity.

plant biology↗

bioRxiv2025

A complete and near-perfect rhesus macaque reference genome: lessons from subtelomeric repeats and sequencing bias

A truly complete, telomere-to-telomere (T2T), and error-free reference genome remains a foundational resource--and long-standing goal--for unbiased comparative and functional genomics. While recent T2T assemblies of humans and other primates have made substantial progress, most still contain thousands of base-level errors, particularly within highly repetitive regions. Here, we present T2T-MMU8v2.0, a near-perfect T2T assembly of the rhesus macaque (Macaca mulatta), representing the highest base-level accuracy reported in a primate genome to date. By employing an optimized ONT-only assembly strategy, we identify subtelomeric satellite-rich regions as the principal bottleneck to improving assembly quality, owing to technological biases in long-read platforms and limitations in current hybrid assembly frameworks. We discover 268 previously unannotated repeat families and resolve [~]8 Mbp of SATR satellite arrays, with over 99-fold enrichment in historically misassembled subtelomeric regions. These satellites form four distinct genomic architectures, each with unique SATR satellite composition, segmental duplication organization, and epigenetic signatures, distinct from the subtelomeric architectures observed in hominid genomes. Notably, in contrast to the largely gene-poor subtelomeric regions in African hominids, the SATR architectures in macaques harbor 58 actively transcribed genes, supported by open chromatin and expression data, suggesting gene innovation within these repetitive regions. Functionally, T2T-MMU8v2.0 improves read mappability and accuracy across sequencing platforms, and results in a 19% improvement of transcription start site enrichment scores and 5,821 additional chromatin accessibility peaks on average, thereby enhancing variant detection, regulatory annotation, and transcriptomic resolution in population genetics or single-nucleus studies. Together, this work establishes a new benchmark for genomics, offers a roadmap for resolving complex repetitive regions, and reveals previously unrecognized features of subtelomeric genome structure and evolution.

genomics↗

bioRxiv2025

Male-Biased Cyp17a2 Governs Antiviral Sexual Dimorphism in Fish via STING Stabilization and Viral Protein Degradation

Differences in immunity between males and females in living organisms are generally thought to be due to sex hormones and sex chromosomes, and it is often assumed that males have a weaker immune response. Here we report that in fish, males exhibit stronger antiviral immune responses, the male-biased gene cyp17a2 as a critical mediator of this enhanced response. First, we observed that male zebrafish exhibit enhanced antiviral resistance compared to females, and notably, zebrafish lack sex chromosomes. Through transcriptomic screening, we found that cyp17a2 was specifically highly expressed in male fish. Cyp17a2 knockout males were equivalent to wild-type males in terms of sex organs and androgen secretion, but the ability to upregulate IFN as well as antiviral resistance was greatly reduced. Then, Cyp17a2 is identified as a positive IFN regulator which located at endoplasmic reticulum, and specifically interacts with and enhances STING mediated antiviral responses. Mechanistically, Cyp17a2 stabiles STING expression by recruiting the E3 ubiquitin ligase bloodthirsty-related gene family member 32 (btr32), which facilitates K33-linked polyubiquitination. The capacity of IFN induction of Cyp17a2 was abolished when STING is knockdown. Meanwhile, Cyp17a2 also attenuates viral infection directly to strengthen the antiviral capacity as an antiviral protein, Cyp17a2 degrades the spring viremia of carp virus (SVCV) P protein by utilizing USP8 to reduce its K33-linked polyubiquitination. These findings reveal a sex-based regulatory mechanism in teleost antiviral immunity, broadening our understanding of sexual dimorphism in immune responses beyond the conventional roles of sex chromosomes and hormones.

immunology↗

bioRxiv2025

Genome-wide association studies reveal novel loci associated with carcass and body measures in goats (Capra hircus)

Elucidating the genetic architecture of local goat populations is crucial for improving breeding strategies and conservation efforts. In southwestern China, there are numerous local goat resources, featuring rich phenotypic and genetic variations. Nevertheless, in-depth research on their production performance is scarce. Therefore, in this study, whole-genome 7x resequencing was performed on 776 individuals of six goat breeds (Dazu Black Goat, Yudong Black Goat, Banjiao Goat, Hechuan White Goat, Chuandong White Goat, and Youzhou Black Goat) in Chongqing to deeply investigate their population structure, genetic relationships, and heritability, and to identify significant genes related to growth traits and carcass traits. The mapping of significant genes for growth and carcass traits identified novel genetic loci, including a significant association at position 63,248,396 within ASIP on chromosome 13, which was linked to both traits, indicating a potential pleiotropic effect. Additional candidate genes for growth traits included CXCL14, PTGFR, and DPYD (body weight); CCSER1, HMCN1, and MYOM1 (body length); MALRD1 and ASIP (withers height); and MEIS2 and NLRC5 (chest circumference). For carcass traits, key candidate genes included ASIP, ATP5G1, COX3 and BCAR3. Functional enrichment analysis highlighted the calcium signaling pathway, glycan biosynthesis, and cytokine receptor interactions as key biological pathways influencing these traits. These findings provide novel insights into the genetic mechanisms underlying economically important traits in Chongqing local goats. The identification of ASIP as a pleiotropic gene, along with other newly discovered loci, offers valuable targets for genetic improvement and selective breeding programs, enhancing the productivity and sustainability of local goat populations.

genomics↗