Search Results (62)

The unique ecological gradients of Xinjiang have fostered a rich reservoir of genetic resources in local sheep populations. However, the population genetic structure, adaptive mechanisms to extreme environments, and the genetic basis underlying key economic traits of these breeds remain poorly understood. To address this gap, we performed whole-genome resequencing of 140 individuals from seven indigenous sheep populations—Altay, Bayinbuluke, Kazakh, Kirgiz, Bashibai, Turpan Black, and Yemule White—identifying 18,700,507 high-quality SNPs. Genetic diversity analyses revealed that all populations exhibited comparable levels of genetic diversity, with modest variation across breeds, with Turpan Black sheep exhibiting the highest observed heterozygosity (Ho = 0.3110) and proportion of polymorphic sites, whereas Kirgiz sheep showed comparatively lower values. Population structure analyses consistently indicated that geographic isolation is the primary driver of genetic differentiation, with Kirgiz sheep from the Pamir Plateau in southern Xinjiang displaying the greatest genetic distance relative to northern Xinjiang populations. By integrating multiple selection signature detection methods—including F_ST, π ratio, and XP-CLR—we found that genes under selection in Kirgiz sheep were significantly enriched in biological pathways related to stem cell pluripotency regulation (e.g., BMPR1B), DNA repair (e.g., DDB2), and neural development, thereby elucidating their unique genetic adaptations to high-altitude environments. In contrast, Turpan Black sheep appear to cope with heat stress through mechanisms involving basal transcriptional regulation (e.g., GTF2I), maintenance of protein homeostasis (e.g., DNAJB14), and melanin biosynthesis (e.g., MC1R). Furthermore, comparative analysis of body size identified a suite of candidate genes associated with growth and development (e.g., CUX1, KIT), which are primarily involved in transcriptional regulation, protein kinase activity, and the ubiquitin-mediated proteolytic system, thereby revealing a multi-layered genetic regulatory network governing body conformation. Collectively, this study provides a comprehensive genomic framework for understanding the genetic structure, adaptive evolution, and molecular basis of economically important traits in indigenous sheep breeds from Xinjiang, offering valuable candidate targets for future functional validation and precision breeding programs. Full article

The greater amberjack (Seriola dumerili) is a globally important aquaculture fish species belonging to the family Carangidae. However, current research on the ovarian development and regulation of the greater amberjack is limited, particularly with regard to early ovarian development in artificially bred individuals. Therefore, this study aims to analyze the ovarian transcriptomes at the primary growth stage in one-year-old fish at the chromatin nucleolar stage and two-year-old fish at the perinucleolar stage to suggest how early ovarian development takes place in artificially bred greater amberjacks. To do this, the study constructed ovarian mRNA expression profiles of different stages of artificially bred fish and identified differentially expressed genes (DEGs), Gene Ontology terms, and Kyoto Encyclopedia of Genes and Genomes pathways important for various physiological processes. A functional analysis revealed that the DEGs closely related to ovarian development were involved in cell growth and death (e.g., ccnd1, cdk1, cdc6, cdc25b, fbxo43, cdkn1a and cdkn1d), the TGF-beta signaling pathway (e.g., gdf6, bmpr1b, gsdf, amh, tgfb3, and smad6), steroid hormone biosynthesis (e.g., hsd3b1, hsd11b2, hsd17b12 and hsd20b2), and the endocrine system (e.g., mapk8a, mapk11, mapk12a, mapk13 and adcy9). These findings suggest that ovarian development is the result of the coordinated regulation of various genes responsible for various functions. This study provides a theoretical basis for exploring the underlying molecular mechanisms of early ovarian development in artificially bred greater amberjacks. Full article

Understanding the functional mechanisms of genes influencing economically important traits in the domestic pig is essential for optimizing marker-assisted selection (MAS). This study aimed to characterize the biological functions, molecular mechanisms, and metabolic pathways of genes associated with morphological, productive, reproductive, and carcass quality traits through a functional bioinformatics approach. Genes were compiled from 116 peer-reviewed studies published between 2000 and 2024, and subsequently grouped according to trait. A de novo functional bioinformatics analysis was performed on this dataset. Functional enrichment analysis was conducted using DAVID and the clusterProfiler package in R, applying FDR correction (≤0.05). Protein-protein interaction (PPI) networks were explored using STRING. No individual gene was consistently reported with high frequency. Among the most frequently reported genes were VRTN (17 studies) for teat number, HOMER1 (3 studies) for leg strength, and BMPR1B (3 studies) for litter size. Enriched GO terms included processes such as positive regulation of transcription (GO:0045944), chondrocyte differentiation (GO:0032331), and SMAD signaling (GO:0060391; an FDR = 7.34 × 10⁻⁷). The PPI networks revealed key genes involved in signaling and immune regulation. In conclusion, this bioinformatics analysis provides an integrated functional overview of the genes underlying key economic traits in pigs, identifying pleiotropic pathways such as SMAD/TGF-β signaling, which supports the development of more effective MAS strategies in pig breeding programs. Full article

Background/Objectives: Targeted gene sequencing (TGS) for Comprehensive Genomic Profiling (CGP) use in sarcomas has recently increased in clinical practice. We report on TGS real-world data over a period of 3 years (2022–2025) at the IRCCS Istituto Ortopedico Rizzoli, with the aim of identifying potential actionable targets and providing therapeutic indications for advanced sarcoma patients. Methods: We analyzed 22 advanced sarcoma patients by using the VariantPlex Pan Solid Tumor kit panel, including 185 genes. In nine cases, saliva samples for germinal DNA analysis were available. Sequencing was performed on the NextSeq-500 Platform and analyzed with Archer Analysis software. The Cancer Genome Interpreter and OncoKB Database tools were used to find potential actionable targets. Results: We found the most frequent genetic variants, including missense, deletion, duplication, and delins, in the NOTCH4, AR, BARD1, MUC16, and ROS1 genes. Copy Number alterations affected the CDKN2A, CDKN2B, TP53, RHOA, MYC, CCND3, and DDR2 genes mainly in osteosarcoma samples. In four patients, longitudinal analyses of subsequent lesions showed the maintenance of most genomic alterations and enrichment in missense or splice variants in PMS2, SMARCA4, ARID1A, AKT1, BMPR1A, and PTEN, indicating the occurrence of tumor evolution. Germline variants subtraction identified the specific somatic tumor mutations. Advantages and disadvantages of our approach were considered in order to refine the analysis setting and better select possible actionable targets. Conclusions: Early access to genomic analyses, routine germline assessment, and broad gene panels would help in identifying possible targeted drugs with sufficient evidence of activity beneficial to each patient. In the clinical management of advanced sarcoma patients, when analyzing cost-effectiveness and sustainability, the role of the Molecular Tumor Board in the governance of the complexity introduced by mutational oncology should be considered. Full article

Duolang sheep, a meat–fat dual-purpose breed indigenous to Xinjiang, China, has been cultivated traditionally by the local Uyghur people for its prolificacy and precocious sexual maturity, while little research on the population structure and trait inheritance characteristics of Duolang sheep is available. This study employed whole-genome resequencing data from a cohort of 60 Duolang sheep to dissect their genetic population structure and genes related to reproductive traits. A total of 1565 Gb of high-quality data with an average depth of 14.06× was generated. After SNP calling and quality control, 31,300,060 SNPs were identified. Following linkage disequilibrium (LD)-based pruning, a total of 4,479,177 high-quality SNPs were retained for subsequent analyses. Based on these SNPs, the internal genetic structure of the Duolang sheep population was elucidated, with 14 kinship outliers detected through principal component analysis (PCA). Furthermore, LD decay analysis revealed that the r² declined below 0.1 at approximately 10 kb, indicating a relatively low level of selection pressure in the population. Within the population, Tajima’s D and iHS methods detected 517,218 and 82,534 candidate SNPs under selection, respectively, with 24,453 SNPs overlapping between the two methods. By splitting Duolang sheep into single-lamb (n = 29) and multiple-lamb (n = 12) subgroups according to litter size, 267,654 SNPs were identified by XP-CLR, while 184,179 SNPs suffering from selection were detected by F_ST and 62,150 by XP-EHH. Functional enrichment analysis of selected genes reveals the selection directions (domestication, growth, and reproduction) and related candidate genes in the Duolang sheep population, including ESRRA, ESRRB, OXT, FSHR, ESR2, GNRHR, and BMPR1B. This study provides the first comprehensive genomic landscape of Duolang sheep, elucidating genetic signatures of its adaptive traits. Full article

Background/Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease, in which multiple genetic and environmental factors may contribute. This study aimed to identify potential genetic determinants in patients with CTEPH and to compare their occurrence to a control group, which included patients with pulmonary embolism who had not developed CTEPH. Methods: Tier 1 and 2 genes related to coagulation, fibrinolysis and platelet disorders—as recommended by the International Society on Thrombosis and Haemostasis—and genes associated with vascular conditions were analyzed in n = 15 patients with CTEPH and n = 17 controls using next-generation sequencing. Non-synonymous, rare variants were collected and interpreted. Results: As expected, no single gene or variant was consistently present among CTEPH patients. Instead, individuals carried different mutations and combinations of variants. We identified several variants that were not found in the control group. Candidate variants were detected in F12, F13A1, F13B, F5, KNG1, SERPIND1, THBD, ADAMTS13, VWF, STIM1, ETV6, THPO, MPL, SERPINA1, ENG, RASA1, ACVRL1, GDF2, NFE2, SOX17 and RNF213. We did not detect exclusive variants in FGA, CPB2, and BMPR2 although they were suggested as candidates in previous studies. Elevated factor VIII and von Willebrand factor in CTEPH could not be explained by mutations in VWF and F8. Conclusions: Our study supports the hypothesis of heterogeneous genetic background in CTEPH, involving multiple pathways such as coagulation, altered fibrinolysis and impaired angiogenesis. These results provide a basis for more detailed investigations into specific genes and variants potentially associated with CTEPH in larger cohorts. Full article

Background: Tibetan sheep (Ovis aries) have evolved remarkable adaptations to the extreme high-altitude environment of the Qinghai–Tibet Plateau. While previous studies have identified some genetic features underlying these adaptations, a comprehensive understanding of their population genetics and selection signatures remains incomplete. We hypothesized that Tibetan sheep harbor unique genetic diversity and population structure distinct from low-altitude sheep (Hu sheep and Small Tail Han sheep), and that whole-genome resequencing could identify key positively selected genes driving their high-altitude adaptation and economic trait variation. Thus, this study aimed to characterize the population structure and genetic diversity of Tibetan sheep via whole-genome resequencing and identify genomic regions and candidate genes under positive selection related to high-altitude adaptation and important economic traits (growth, meat quality, wool, reproduction). Results: Using whole-genome resequencing of 90 Tibetan sheep (ZY) compared to 90 Hu sheep (HY) and 90 Small Tail Han sheep (XWHY), we identified significantly higher genetic diversity in Tibetan sheep (Pn = 0.6399, PIC = 0.1731). Population structure analyses revealed distinct clustering of Tibetan sheep, with principal components explaining 20.69% (PCA1), 12.26% (PCA2), and 14.18% (PCA3) of genetic variation. Selective sweep analysis identified 713 genomic regions (containing 207 genes) under positive selection, including key hypoxia adaptation genes (HDAC5, BMP2/BMPR1B, DUOX2) and economic trait genes (FGF9 for growth; SLC27A2 for meat quality; KRTAP for wool; IZUMO1R for reproduction). Functional enrichment highlighted pathways in oxygen transport (EPO regulation), energy metabolism (fatty acid β-oxidation), and vascular remodeling (TGF-β signaling). Conclusions: Our study provides the most comprehensive genomic characterization of Tibetan sheep to date, revealing both their unique genetic diversity and molecular mechanisms of high-altitude adaptation. The identified candidate genes offer valuable targets for marker-assisted breeding to improve productivity while maintaining adaptive traits, supporting sustainable development of plateau animal husbandry. Full article

Corneal fibrosis, a significant source of visual impairment, can result from keratocyte-to-myofibroblast transdifferentiation during wound healing. This study investigated the antifibrotic role of 1,25-dihydroxyvitamin D₃ (1,25 Vit D) and the lesser-known vitamin D, 24,25-dihydroxyvitamin D₃ (24,25 Vit D), in human and mouse corneal stromal cells (HSCs and MSCs) and in a Vit D receptor knockout (VDR KO) mouse model. Cells were treated with TGF-β1 ± Vit D metabolites and the expression of fibrotic and antifibrotic genes and proteins was evaluated. Both metabolites significantly reduced α-smooth muscle actin levels in HSCs, MSCs and organ-cultured mouse corneas (p < 0.05). They also upregulated the mRNA expression of BMP2, BMP6, BMPR2, and TGF-β3, as well as the protein expression of BMP6 and TGF-β3. VDR KO corneas subjected to alkali injury exhibited increased fibrotic responses and reduced CD45+ immune cell infiltration compared to wild-type controls. Notably, 24,25 Vit D exerted antifibrotic effects even in VDR KO cells, and the alternative 24,25 Vit D receptor FAM57B was expressed in all corneal cell layers. These results reveal consistent antifibrotic effects of both 1,25 and 24,25 Vit D across species, support the existence of VDR-independent mechanisms in the cornea, and offer new insights into potential therapeutic strategies for preventing corneal fibrosis. Full article

The Indonesian Local Ettawah Goat (ILEG) exhibits substantial genetic variation, suggesting its potential for high productivity and promote sustainable practices in farm animal breeding. This study aimed to investigate the molecular characteristics of prolific ILEG by identifying potential candidate genes through polymerase chain reaction (PCR) analysis of the bone morphogenetic protein receptor type 1B (BMPR1B) gene with two variants: alleles G and A. The research involved PCR amplification and sequencing of the BMPR1B A allele, followed by a combined PCR approach integrating both A and G alleles for genotyping. Blood samples were collected from 73 does with documented prolificacy history and 358 does without prolificacy histories, sourced from seven village breeding operations in East Java. PCR amplification yielded fragments of 556–1181 base pairs in all samples. Haplotype analysis revealed 15 unique haplotypes with a diversity of 0.94 and a mutation frequency of 27.15%. Integration of the BMPR1B alleles G and A revealed polymorphic prolific traits. Polymorphism analysis of 385 ILEGs demonstrated allele frequencies of 0.55 for allele A and 0.45 for the allele G. Average fecundity rates associated with the BMPR1B polymorphism were 1.49 offspring for the homozygous AA, 1.60 for the heterozygous GA, and 1.89 for the homozygous GG. While overall differences among genetic groups were approached statistically significantly (Kruskal–Wallis, p = 0.056), pairwise comparison (Mann–Whitney test) revealed that homozygous GG was significantly associated with higher prolificacy compare to the heterozygous GA (p = 0.029) and homozygous AA (p = 0.040). Similar results were also obtained from data without documented history. These findings suggest that the GG polymorphism of BMPR1B may increase prolificacy in ILEG. Furthermore, the higher frequency of allele G highlights the importance of considering prolificacy traits in breeding selection strategies to enhance sustainable genetic improvement and increase litter size in ILEG. It is recommended to apply dual-primer specific amplification and fragment size differentiation as key molecular approaches for polymorphism of the BMPR1B gene and prolificacy, since these methods can highlight genetic variation and provide valuable markers for breeding programs of the Indonesian Local Etawah Goat. Full article

Appendage autotomy frequently occurs during the cultivation of Exopalaemon carinicauda, which severely impacts its survival and economic benefits. To investigate the molecular mechanism underlying appendage regeneration in E. carinicauda, this study presents a comparative transcriptome analysis on samples from different stages of appendage regeneration in individuals of the same family of E. carinicauda. A total of 6460 differentially expressed genes (DEGs) were identified between the samples collected at 0 h post-autotomy (D0) and those collected at 18 h post-autotomy (D18h). Additionally, 7740 DEGs were identified between D0 and 14 d post-autotomy (D14d), with 3382 DEGs identified between D18h and D14d. Among them, differentially expressed genes such as EcR, RXR, BMP1, and Smad4 are related to muscle growth or molting and may be involved in the regeneration process. qRT-PCR results revealed that EcBMPR2 was expressed at relatively high levels in the gonad and ventral nerve cord tissues and that the highest level of expression was detected in the regenerative basal tissue at 24 h post-autotomy. In situ hybridization results indicated strong signals of this gene in the cells at the wound site at 72 h post-autotomy. Following knockdown of EcBMPR2, the expression levels of both EcBMPR1B and EcSmad1 were significantly downregulated, and long-term interference with the EcBMPR2 gene resulted in a significantly slower appendage regeneration process compared to the control group. When the downstream transcription factor EcSmad1 was knocked down, the two receptor genes EcBMPR2 and EcBMPR1B were downregulated, whereas EcBMP7 was upregulated. After inhibiting the BMP signaling pathway, the degree of cell aggregation at the autotomy site in the experimental group was significantly lower than that in the control group, the wound healing rate was delayed, and the blastema regeneration time was prolonged from 5 d to 7 d. Collectively, these results indicate that the BMP signaling pathway plays a critical role in the early stages of appendage regeneration in E. carinicauda. This study provides important theoretical insights for understanding limb regeneration in crustaceans. Full article

Background: The bone morphogenetic protein (BMP) signaling pathway is essential for lung development. BMP4, a key regulator, binds to type I (BMPR1) and type II (BMPR2) receptors to initiate downstream signaling. While the inactivation of Bmpr1a and Bmpr1b leads to tracheoesophageal fistulae, the role of BMPR2 mutations in lung epithelial development remains unclear. Methods: We generated induced pluripotent stem cells (iPSCs) from a patient carrying a BMPR2 mutation (c.631C>T), and gene-corrected isogenic controls were created using CRISPR/Cas9. These iPSCs were differentiated into lung progenitor cells and subsequently cultured to generate alveolar and airway organoids. The differentiation efficiency and epithelial lineage specification were assessed using immunofluorescence, flow cytometry, and qRT-PCR. Results: BMPR2-mutant iPSCs showed no impairment in forming a definitive or anterior foregut endoderm. However, a significant reduction in lung progenitor cell differentiation was observed. Further, while alveolar epithelial differentiation remained largely unaffected, airway organoids derived from BMPR2-mutant cells exhibited impaired goblet and ciliated cell development, with an increase in basal and club cell markers, indicating skewing toward undifferentiated airway cell populations. Conclusions: BMPR2 dysfunction selectively impairs late-stage lung progenitor specification and disrupts airway epithelial maturation, providing new insights into the developmental impacts of BMPR2 mutations. Full article

The transforming growth factor-beta (TGF-β) superfamily plays a crucial role in regulating female reproductive traits, particularly litter size, in small ruminants, such as sheep and goats. This review comprehensively examines the molecular mechanisms through which TGF-β superfamily members—including bone morphogenetic proteins (BMPs), growth differentiation factor 9 (GDF9), inhibin (INHA and INHB), and associated signaling genes—influence ovarian follicular development, ovulation rate, and ultimately, litter size. We synthesize recent findings on polymorphisms in key genes, such as BMPR1B, BMP15, GDF9, inhibins and SMADs family genes, across diverse sheep and goat breeds worldwide. The manuscript highlights how specific mutations in these genes create an intricate signaling network that modulates granulosa cell proliferation, follicular sensitivity to FSH, and the prevention of dominant follicle selection. These molecular interactions result in increased ovulation rates and larger litter sizes in prolific breeds. The gene dosage effects observed in heterozygous versus homozygous mutation carriers further illuminate the complex nature of these reproductive regulations. This improved the understanding of the genetic basis for prolificacy provides valuable insights for marker-assisted selection strategies aimed at enhancing reproductive efficiency in small ruminant breeding programs, with significant implications for improving livestock productivity and economic outcomes. Full article

Background: Colonic diverticulosis is a common condition, particularly in the elderly population. While dietary habits, obesity, smoking, and physical inactivity contribute to its pathogenesis, emerging evidence highlights a genetic predisposition affecting extracellular matrix (ECM) remodeling, inflammation, and connective tissue integrity. The aim of this systematic review was to summarize genetic determinants of colonic diverticulosis. Methods: The PubMed^® database was searched for original studies in humans. The inclusion criteria were named genetic factor and confirmed diverticulosis. Patients with diverticulitis and diverticular diseases were excluded from this review. Results: Out of 137 publications, 10 articles met the inclusion criteria: six large association studies (GWAS) and four cross-sectional studies. The genes regulating ECM turnover, including TIMP1, MMP3, and MMP9, are involved in diverticulosis development. The TIMP1 (rs4898) T allele has been associated with increased susceptibility, potentially due to its role in ECM remodeling. Similarly, MMP3 (rs3025058) and MMP9 (rs3918242) polymorphisms contribute to altered collagen degradation. The COL3A1 (rs3134646) variant coding modified collagen type III may promote diverticular formation. Other genes, such as ARHGAP15 (rs4662344, rs6736741), affect cytoskeletal dynamics. Identified in GWAS studies, gene candidates may be grouped into blood group and immune system-related genes (ABO, HLA-DQA1, HLA-H, OAS1, TNFSF13, FADD), extracellular matrix and connective tissue genes (COL6A1, COLQ, EFEMP1, ELN, HAS2, TIMP2), signaling and cell communication (BMPR1B, WNT4, RHOU, PHGR1, PCSK5), nervous system and neurodevelopment (BDNF, CACNB2, GPR158, SIRT1, SCAPER, TRPS1), metabolism and transporters (SLC25A28, SLC35F3, RBKS, PPP1R14A, PPP1R16B), lipids and cholesterol (LDAH, LYPLAL1, STARD13), transcription and gene regulation (ZBTB4, UBTF, TNRC6B), apoptosis (FADD, PIAS1), and poorly characterized genes (C1TNF7, ENSG00000224849, ENSG00000251283, LINC01082, DISP2, SNX24, THEM4, UBL4B, UNC50, WDR70, SREK1IP1). Conclusions: There are a number of gene variants that probably predispose to colonic diverticulosis. Detailed characterization of the multigene background of diverticulosis will enable appropriate therapeutic or preventive interventions in the future. Full article

The A-to-G mutation (FecB) in the BMPR1B gene is strongly linked to fertility in sheep, significantly increasing ovulation rates and litter sizes compared to wild-type populations. The rapid and reliable screening of the FecB gene is therefore critical for advancing sheep breeding programs. This study aimed to develop a fast and accurate method for detecting the FecB mutation and genotyping the gene to enhance sheep reproduction and productivity. To achieve this, we integrated the CRISPR-Cas12a system with an optimized amplification refractory mutation system (ARMS). A similar DNA origami technique-based fluorescence reporter nanotree structure was synthesized using gold nanomagnetic beads as carriers to amplify the fluorescence signal further. The resulting biosensing platform, termed CRISPR-ARMS, demonstrated excellent sensitivity for detecting FecB mutations, with a detection limit as low as 0.02 pmol. Therefore, this innovative approach shows great promise for single-base mutation detection and represents a pioneering tool for high-yield genetic screening. Full article

The shape of the skull plays a crucial role in the evolution and adaptation of species to their environments. In the case of aquaculture fish, the size of the head is also an important economic trait, as it is linked to fillet yield and ornamental value. This study applies our GRAMMAR-Lambda method to perform a genome-wide association study analysis on loci related to head size in catfish. Compared with traditional GWAS methods, the GRAMMAR-Lambda method offers higher computational efficiency, statistical power, and stability, especially in complex population structures. This research identifies many candidate genes closely related to cranial morphology in terms of head length, width, and depth in catfish, including bmpr1bb, fgfrl1b, nipbl, foxp2, and pax5, etc. Based on the results of gene–gene interaction analysis, we speculate that there may be frequent genetic interactions between chromosome 19 and chromosome 29 in bone development. Additionally, many candidate genes, gene families, and mechanisms (such as SOCE mechanisms) affecting skeletal development and morphology have been identified. These findings contribute to our understanding of the genetic architecture of head size and will support marker-assisted breeding in aquaculture, also reflecting the potential application of the GRAMMAR-Lambda method in genetic studies of complex traits. Full article