Mandibular prognathism (Class III malocclusion) is a craniofacial anomaly characterized by an anteriorly positioned mandible, a concave facial profile and impaired mastication, and appears unusually frequently in Dolang sheep (Ovis aries). We combined clinical phenotyping and three-dimensional (3D) genome profiling to investigate this trait in a Dolang sheep flock. We examined 959 animals using standardized criteria, estimated a local prevalence of 10.3%, and assembled a 200 affected/200 unaffected case–control cohort for genomic analyses. As an exploratory pilot study of 3D genome architecture, we generated in situ Hi-C datasets from mandibular bone of two affected and two control sheep. At 40 kb resolution, global topologically associating domain (TAD) organization and boundary strength were broadly conserved between groups, but sliding-window analyses identified a small number of 1 Mb hotspots where affected animals showed increased TAD-boundary density and strengthened insulation. These UNDER-enriched windows lay near genes with plausible roles in craniofacial development, including ROBO2, COL27A1, VRK2 and a cytokine cluster (IL22/IL26/IFNG with MDM1). Together, our data indicate that mandibular prognathism in Dolang sheep is associated with localized remodeling of chromatin insulation at a restricted set of gene-proximal loci and highlight candidate regions and mechanisms for integration with whole-genome sequencing, association and transcriptomic data.

Turpan Black (TBL) and Altay (ALT) sheep are indigenous breeds adapted to extreme heat and severe cold in their respective native environments. However, the mechanisms underlying their divergent meat quality remain unclear. Using longissimus dorsi muscle from 15 TBL and 15 ALT sheep, we integrated phenotypic evaluation with non-targeted metabolomics and proteomics to elucidate the impact of environmental adaptation on ovine meat quality. Compared to the cold-adapted ALT sheep, the heat-tolerant TBL sheep exhibited lower post-mortem pH, reduced cooking loss, smaller muscle fiber cross-sectional area, and elevated selenium and magnesium levels. Multi-omics identified 99 differentially expressed proteins and 364 differentially expressed metabolites. Core divergence was enriched in lipid and amino acid metabolism and stress response networks, particularly the Apelin signaling, glycerophospholipid metabolism, and ferroptosis pathways. Lipid remodeling driven by glycerophospholipid metabolism emerged as a critical bridge linking adaptation to meat quality. Notably, glycero-3-phosphocholine, regulated by GPCPD1 and related enzymes, maintained cell membrane homeostasis and osmotic pressure, thereby enhancing water-holding capacity and tenderness. These findings reveal the multi-omics basis of climate-driven divergence in ovine meat quality, offering theoretical support for breeding stress-resilient, high-quality indigenous sheep breeds in extreme environments.

H3K4me3, a well-established histone modification associated with active promoters, plays a critical role in orchestrating gene expression programs that govern mammary gland development and lactation. In this study, we present the first comprehensive epigenomic profiling of H3K4me3 modifications during mammary gland development in Yili horses using Cleavage Under Targets and Tagmentation (CUT&Tag) and RNA sequencing. Mammary gland tissues were collected from two developmental stages—early lactation and peak lactation. A total of 393 differentially expressed genes (DEGs) were identified between two groups, among which 72 DEGs (54 upregulated H3K4me3 targets and 18 downregulated targets) were directly regulated by H3K4me3. KEGG enrichment analyses revealed that these DEGs were involved in ECM–receptor interaction, focal adhesion, the PI3K-Akt signaling pathway, and the calcium signaling pathway. In these pathways, five genes were identified as potential regulators of mammary gland development. Among these, PTGES, COL1A1, PDGFRB, and RYR1 exhibited consistent upregulation at both the transcriptomic and chromatin levels, whereas PRKAG3 showed significant downregulation. These findings offer novel insights into the epigenetic regulation of lactation in horses and lay a theoretical foundation for improving milk production traits through targeted molecular breeding strategies.

Excessive tail fat deposition in sheep limits feed conversion efficiency and carcass quality, making the genetic improvement of this trait a priority. This study aimed to elucidate the molecular mechanisms regulating ovine fat metabolism. We analyzed the tissue specific expression of two candidate microRNAs, miR-320d and miR-151b, alongside their target genes SCD and ACACA, across tissues from fat-tailed and thin-tailed sheep using quantitative real-time PCR. The regulatory function of the tail fat specific miR-320d was further validated in vitro using isolated ovine tail preadipocytes. Results indicated that miR-320d and miR-151b are specifically highly expressed in tail and subcutaneous adipose tissues, respectively, and correlate negatively with their target genes. Dual-luciferase reporter assays confirmed that miR-320d directly targets the 3′UTR of SCD and suppresses its transcription. Overexpression of miR-320d significantly inhibited the proliferation of tail preadipocytes and downregulated downstream genes in the fatty acid metabolism pathway, including ACACA, ELOVL6, ELOVL5, and FASN. In conclusion, miR-320d exerts a negative regulatory effect on sheep tail fat deposition by suppressing preadipocyte proliferation and fatty acid synthesis, while miR-151b emerges as a potential candidate for subcutaneous fat regulation.

This study elucidates the biochemical mechanisms by which extreme high-altitude environments are associated with the remodeling of the skeletal muscle flavor profile in sheep. Using Bayinbuluke (high-altitude) and Turpan Black (low-altitude) sheep, we integrated volatilomics, metabolomics, transcriptomics, and proteomics to map flavor precursor networks. Odor activity value analysis revealed that high-altitude meat exhibited sub-threshold suppression of animal off-flavors, such as p-cresol, while significantly amplifying premium fruity esters. Targeted metabolomics attributed this sensory inversion to a structural shift in the precursor pool, specifically the enrichment of highly reactive polyunsaturated fatty acids, L-cysteine, and rhamnose. Multi-omics integration demonstrated that cold and hypoxic stresses are associated with metabolic reprogramming. The synergistic downregulation of the GPAT3 gene and APOC3 protein was associated with redirected lipid flux, suggesting a mechanism for functional fatty acid accumulation. Simultaneously, the pronounced upregulation of the CTH gene, potentially driven by antioxidant defense needs, coincided with substantial L-cysteine accumulation. Correlation networks suggested that this precursor shift is negatively correlated with off-flavor generation, possibly via competitive thermal degradation. In conclusion, extreme ecological stress is associated with convergent metabolic reprogramming, contributing to the reconstruction of the flavor precursor pool to alter the characteristic lipid aroma of plateau meat. While these findings provide a comprehensive structural blueprint of plateau meat characteristics, the proposed mechanisms remain hypothetical and warrant future functional and sensory validation.