Introduction: Identifying genetic markers associated with economically important traits in dairy goats helps enhance breeding efficiency, thereby increasing industry value. However, the potential genetic structure of key economic traits in dairy goats is still largely unknown.Methods: This study used three genome-wide association study (GWAS) models (GLM, MLM, FarmCPU) to analyze dairy goat milk production traits (milk yield, fat percentage, protein percentage, lactose percentage, ash percentage, total dry matter, and somatic cell count). The goal was to identify SNPs and positional and functional candidate genes significantly associated with these traits.Results: The GWAS analysis results identified a total of 242 significant SNPs. Among these, 45 SNPs exhibited genome-wide significance, while 197 SNPs demonstrated suggestive associations, corresponding to 99 positional candidate genes within a 50 kb upstream and downstream range. 15 significant SNP loci were consistently identified across all three models, corresponding to 18 candidate genes.The integrated analysis of three models detected 2, 19, 17, 4, 115, 23, and 62 significant SNPs associated with milk yield, ash percentage, protein percentage, lactose percentage, somatic cell count, fat percentage, and total dry matter percentage, respectively. Correspondingly, 6, 24, 9, 12, 37, 14, and 30 candidate genes were identified for these traits. Additionally, several new candidate genes related to milk production traits were proposed (LCORL, TNFRSF1A, VWF, SPATA6, MAN1C1, MASP1, BRCA2).Discussion: In summary, the results of this study provide an important reference for further exploration of the genetic mechanisms underlying dairy goat milk production traits and the development of molecular breeding markers.

Background: Horn development is a key ruminant trait involving multi-cell type coordination via molecular pathways. This study used scRNA-seq to analyze cellular heterogeneity and fate trajectories during early horn bud niche formation, revealing key gene expression profiles. Combining with hematoxylin–eosin (HE) staining and immunohistochemical analysis, we further verified the asynchronous developmental pathways of key cells in the skin tissue of fetal goat horn bud at induction (embryonic day (E) 50; E50), organogenesis (E60), and cytodifferentiation (E70) stages, and demonstrated the signal transmission routes for the development of early horn buds. Results: We revealed temporal and spatial differences of the main signal transmission of horn bud development combining with existing literatures. We speculated that multiple cell types under the guidance of nerve cells collaborated on horn bud initiation in dairy goats. In detail, neural cells receive initial horn bud signals, stimulating hair follicle cell degeneration and transmitting to dermal cells, which evolve through intermediates, amplify signals to epithelial cells, and differentiate into mesenchymal cells. Nerve cell branches also trigger neural crest cell production/migration, working with chondrocytes to promote keratinocyte differentiation for horn bud formation. In addition, we further identified the early horn bud developmental specific events, including the screening of biological functions, signaling pathways and key candidate genes. Conclusions: This study employed scRNA-seq to characterize cell fate trajectories and gene expression profiles in goat fetal horn buds. Histological comparisons between hornless and horned fetuses revealed cellular heterogeneity in epithelial, dermal, nerve, and hair follicle cells, with pseudo-time analysis identifying distinct differentiation paths. Dermal and epithelial cell transcriptional dynamics were critical for horn bud initiation (branch 1), supported by immunohistochemistry. Keratinocyte and nerve cell state transitions actively regulated horn development, with asynchronous cell development visualized via immunohistochemistry. Functional enrichment analyses (GO/KEGG) highlighted neural crest development and keratinocyte differentiation pathways, identifying candidate genes ( EGR1 , ZEB2 , SFRP2 , KRT10 , FMOD , CENPW , LDB1 , TWIST1 ) involved in horn morphogenesis. These findings advance understanding of goat horn development and genetic determinants.

Polled intersex syndrome in goats impairs productivity and economic benefits, and serves as a valuable model for human reproductive defects, yet its underl

Polled intersex syndrome in goats severely impacts productivity and economic benefits, serving as a potential model for human reproductive defects. However, its specific molecular and cellular regulatory mechanisms remain unclear. This study combined single-cell RNA-sequencing (scRNA-seq) with tissue morphology and immunofluorescence detection to investigate the cellular heterogeneity, pseudo-time differentiation trajectory, differentially expressed genes, and regulatory networks of female, intersex, and male gonads during the 55-65 days embryonic stage of goats. The results indicated significant heterogeneity and cell fate transition in the somatic and germ cells of female, intersex, and male gonads at different developmental stages. Stromal cells may initiate female and intersexual gonad development, and epithelial cells may be the source of gonad cells in male fetuses. The abnormal expression of FOXL2 , SOX9 , AMH , DMRT1 , RSPO1 , INSL3 , TCF21 and CSF1R may cause female-to-male sex reversal. The new candidate genes like PHLDB2 , ZNRF3 and TEAD1 may contribute to the gender differentiation. Additionally, TREM2 ⁺ macrophages analogous to those in humans were identified in male gonads, while genes such as CSF1R and TYROBP potentially regulate macrophage immune privilege mechanisms. Early gonadal development in goats may also be regulated by circadian rhythm mechanisms similar to humans, with genes such as NR1D1 , LGR4 , and ATG5 involved in granulosa cell development, while genes such as ATG5 , NRIP1 , and FBXW11 may affect intersex trait development. In general, this study provided an important reference for exploring molecular and cellular mechanisms of intersex initiation during early embryonic development in goats and also for modelling human reproductive defects. Author summary: In this study, we investigated the cell fate trajectory and key gene expression profile of goat fetus gonads using scRNA-seq. The analysis revealed cellular heterogeneity among normal male, normal female, and intersex gonadal somatic and germ cells, alongside their dynamic fate transitions across various developmental states. Pseudo-time trajectory analysis suggested that stromal cells might act as the initiation signal for female and intersexual gonad development, while epithelial cells could serve as the primary source of gonadal cells in male fetal goats. GO functional enrichment and KEGG analyses confirmed that abnormal expression of FOXL2 , SOX9 , AMH , DMRT1 and RSPO1 was linked to the emergence of intersexual gonads. Newly identified candidate genes including LRP2 , PITX2 , ARX , LHX9 , PHLDB2 , ZNRF3 and TEAD1 may contribute to sex-specific differences, while INSL3 and TCF21 could be linked to intersexual gonads. We identified TREM2 ⁺ macrophages analogous to those in humans, which could regulate immune privilege mechanisms. Circadian rhythmic changes were observed during early goat gonadal development.