Advances in reparative materials for infectious bone defects and their applications in maxillofacial regions.

Infectious bone defects are characterized by the partial loss or destruction of bone tissue resulting from bacterial contaminations subsequent to diseases or external injuries. Traditional bone transplantation and clinical methods are insufficient in meeting the treatment demands for such diseases. As a result, researchers have increasingly focused on the development of more sophisticated biomaterials for improved therapeutic outcomes in recent years. This review endeavors to investigate specific reparative materials utilized for the treatment of infectious bone defects, particularly those present in the maxillofacial region, with a focus on biomaterials capable of releasing therapeutic substances, functional contact biomaterials, and novel physical therapy materials. These biomaterials operate via heightened antibacterial or osteogenic properties in order to eliminate bacteria and/or stimulate bone cells regeneration in the defect, ultimately fostering the reconstitution of maxillofacial bone tissue. Based upon some successful applications of new concept materials in bone repair of other parts, we also explore their future prospects and potential uses in maxillofacial bone repair later in this review. We highlight that the exploration of advanced biomaterials holds promise in establishing a solid foundation for the development of more biocompatible, effective, and personalized treatments for reconstructing infectious maxillofacial defects.

Metagenomic analysis of oral and intestinal microbiome of patients during the initial stage of orthodontic treatment.

INTRODUCTION: This prospective study analyzed changes in the oral and intestinal microbiomes in patients before and after fixed orthodontic treatment, elucidating the impacts of fixed orthodontic treatment on patient health and metabolism. METHODS: Metagenomic analysis was conducted on stool, dental plaque, and saliva samples from 10 fixed orthodontic patients. All the samples were sequenced with Illumina NovaSeq 6000 with a paired-end sequencing length of 150 bp. Identification of taxa in metagenomes and functional annotation of genes of the microbiota were performed using the data after quality control. Clinical periodontal parameters, including the gingiva index, plaque index, and pocket probing depth, were examined at each time point in triplicates. Patients also received a table to record their oral hygiene habits of brushing, flossing, and dessert consumption frequency over 1 month. RESULTS: The brushing and flossing times per day of patients were significantly increased after treatment compared with baseline. The number of times a patient ate dessert daily was also fewer after treatment than at baseline. In addition, the plaque index decreased significantly, whereas the pH value of saliva, gingiva index, and pocket probing depth did not change. No significant differences were observed between the participants before and after orthodontic treatment regarding alpha-diversity analysis of the gut, dental plaque, or saliva microbiota. However, on closer analysis, periodontal disease-associated bacteria levels in the oral cavity remain elevated. Alterations in gut microbiota were also observed after orthodontic treatment. CONCLUSIONS: The richness and diversity of the microbiome did not change significantly during the initial stage of fixed orthodontic treatment. However, the levels of periodontal disease-associated bacteria increased.

A multifunctional polymeric coating with self-adsorbed, antifouling and in situ remineralization properties for caries management.

Dental caries is a biofilm-induced bacterial infectious oral disease, where the early attachment of proteins and pathogenic bacteria to tooth surfaces has been known as the main cause of biofilm formation. Typically, dental caries is commonly accompanied by mineral depletion of enamels, thus causing dental demineralization. Multifunctional materials are highly attractive candidates for treating dental caries. Herein, we successfully synthesized diblock copolymers poly(ethylene glycol)-b-poly(aspartic acid) (PEG-PAsp) and modified them with alendronate sodium (ALN) to serve as bioactive bifunctional coatings (PEG-PAsp-ALN) on teeth. The PEG segments are employed for inhibiting proteins and bacterial adhesion. In addition, due to the presence of both PAsp and ALN, a synergistically strong binding capacity could be achieved with the tooth surface, thus promoting rapid and thorough remineralization in situ, while maintaining excellent safety. The combination treatment can significantly suppress the biofilm formation, which is beneficial for alleviating the demineralization of enamels caused by bacteria, and further, facilitate remineralization in situ. This approach thus demonstrates the potential of the copolymer PEG-PAsp-ALN coating as a multifunctional protecting layer on the tooth surface for high-efficiency prevention and treatment of dental caries.

Multifunctional epoxy resin-based composites with excellent flexural strength and X-ray imaging capacity using micro/nano structured QF-Bi2SiO5 fillers.

Composites have been widely applied in various industries and are beneficial in attaining complicated functionalities. Particularly, for dental fiber posts or orthopedic implants, the composites should have excellent mechanical properties and good imaging effects for visualization in vivo. The traditional method to improve mechanical strength and visibility by adding reinforcing fillers and radiopacifiers is complicated and has poor distributions and long production times. Hence, fabricating an integrated reinforced filler with radiopacity is of considerable economic and social significance. After ball-milling and sintering quartz fiber (QF) and bismuth trioxide (Bi2O3), a multifunctional filler (QF-Bi2SiO5) is fabricated to impart excellent flexural strengths and high X-ray imaging qualities to the composites. A composite made of epoxy resin (EP) and QF-Bi2SiO5 has a high bending strength (126.87 ± 6.78 MPa) and bending modulus (3649.31 ± 343.87 MPa), which are attributed to the tight mechanical interlock between EP and micro/nano structures of QF-Bi2SiO5. The QF-Bi2SiO5/EP composite shows good X-ray imaging quality owing to the Bi2SiO5 crystal. Furthermore, the mechanical and imaging performances of various composites with commercial fillers were compared with that of the QF-Bi2SiO5/EP composite. No filler was found that can perform both functions as well as QF-Bi2SiO5. Hence, the fabricated composites containing micro/nano structured QF-Bi2SiO5 fillers have the potential to be used in a variety of fields requiring mechanical strength and X-ray imaging capability.

Application of a Caries Treatment Difficulty Assessment System in Dental Caries Management.

Dental caries is one of the most common chronic diseases caused by progressive bacteria, affecting all age groups. Today, restorative fillings are widely used for dental caries treatment, but the restorative treatment has a high failure rate. Meanwhile, many researchers have discovered the differences of caries risk among populations by using the caries risk assessment and put forward a new standpoint that caries should be treated individually. Therefore, our research group established a Dental Caries Treatment Difficulty Assessment system in a previous study. This time, we combined the caries risk assessment with the caries treatment difficulty assessment, then used Python to design a Dental Caries Management Software. The purpose of this case report is to present a case applying this software in dental caries management and other data collected in Chengdu, China, with this software on the assessment of caries treatment difficulty. Patients with personalized assessment and management can achieve good treatment results, including reducing the risk and treatment difficulty of dental caries. At the same time, other cases show that the software has good application potential in individual management and group information collection. These cases indicate that the software enables dentists to carry out both the risk assessments and the treatment difficulty assessment of patients, and it has the potential as a tool for epidemiological investigation. It also enables dentists and patients to have a basic understanding of the dental health status of patients and create personalized dental caries treatment, so as to achieve the goal of controlling the progression of dental caries and rebuilding the structure and restoring the function of teeth.

Dental Materials for Oral Microbiota Dysbiosis: An Update.

The balance or dysbiosis of the microbial community is a major factor in maintaining human health or causing disease. The unique microenvironment of the oral cavity provides optimal conditions for colonization and proliferation of microbiota, regulated through complex biological signaling systems and interactions with the host. Once the oral microbiota is out of balance, microorganisms produce virulence factors and metabolites, which will cause dental caries, periodontal disease, etc. Microbial metabolism and host immune response change the local microenvironment in turn and further promote the excessive proliferation of dominant microbes in dysbiosis. As the product of interdisciplinary development of materials science, stomatology, and biomedical engineering, oral biomaterials are playing an increasingly important role in regulating the balance of the oral microbiome and treating oral diseases. In this perspective, we discuss the mechanisms underlying the pathogenesis of oral microbiota dysbiosis and introduce emerging materials focusing on oral microbiota dysbiosis in recent years, including inorganic materials, organic materials, and some biomolecules. In addition, the limitations of the current study and possible research trends are also summarized. It is hoped that this review can provide reference and enlightenment for subsequent research on effective treatment strategies for diseases related to oral microbiota dysbiosis.

Niacin Limitation Promotes Candida glabrata Adhesion to Abiotic Surfaces.

Candida glabrata is a prevalent fungal pathogen in humans, which is able to adhere to host cells and abiotic surfaces. Nicotinic acid (NA) limitation has been shown to promote the adherence of C. glabrata to human epithelial cells. Clinically, the elderly and hospitalized patients who are prone to C. glabrata-related denture stomatitis often suffer from vitamin deficiency. This study aimed to investigate C. glabrata adhesion to abiotic surfaces, including acrylic resin (a denture material) surfaces, cell surface hydrophobicity and adhesion gene expression. C. glabrata CBS138 was grown in media containing decreasing NA concentrations (40, 0.4, 0.04 and 0.004 µM). Adherence of C. glabrata to glass coverslips and acrylic resin was analyzed. C. glabrata adhesion to both surfaces generally increased with decreasing NA concentrations. The highest adhesion was found for the cells grown with 0.004 µM NA. The cell surface hydrophobicity test indicated that NA limitation enhanced hydrophobicity of C. glabrata cells. Quantitative PCR showed that of all adhesion genes tested, EPA1, EPA3 and EPA7 were significantly up-regulated in both 0.004 µM NA and 0.04 µM NA groups compared to those in the 40 µM NA group. No significant up- or down-regulation under NA limitation was observed for the other tested adhesion genes, namely AWP3, AWP4, AWP6 and EPA6. NA limitation resulted in increased expression of some adhesion genes, higher surface hydrophobicity of C. glabrata and enhanced adhesion to abiotic surfaces. NA deficiency is likely a risk factor for C. glabrata-related denture stomatitis in the elderly.

Effect of indel variants within the sorting nexin 29 (SNX29) gene on growth traits of goats.

The sorting nexin 29 gene (SNX29) is a well-known regulator of myocyte differentiation and proliferation. In this work, two indels (17-bp and 21-bp) were identified in the goat SNX29 gene, and their effects on the growth traits of 1,759 Shaanbei white cashmere (SBWC) goats were analyzed. Both indels had three genotypes [homozygote wild type (II), heterozygote (ID), and homozygote mutation (DD)] and displayed medium genetic diversity (0.25 < polymorphism information content (PIC) < 0.50) in the population. The 17-bp indel was significantly associated with chest width (p = 0.009), body weight (p = 0.021), and chest depth (p = 0.032), with the II genotype dominant. The 21-bp indel was significantly associated with chest width (p = 0.001), chest depth (p = 4.8E-5), heart girth (p = 0.007), and hip width (p = 0.002). Because the two indels were in the upstream (17-bp) and intron (21-bp) regions of the SNX29 gene, transcription factor binding sites were predicted. The IRF5 and MYC could bind with the 17-bp indel and 21-bp indel sequences, respectively. This study indicates that SNX29 is a promising candidate gene that can be used to improve meat production in goat breeding.

The prognostic role of radiotherapy and radiotherapy target in cervical lymph node metastatic squamous cell carcinoma with unknown primary: a retrospective study.

OBJECTIVES: Aim to analyze the effect of radiotherapy for cervical lymph node metastatic carcinoma with unknown primary (CCUP) and compare the survival benefits between Comprehensive radiotherapy and Involved Field radiotherapy. MATERIALS AND METHODS: The patients diagnosed with CCUP between 2009 and 2019 in our institution were analyzed retrospectively. The categorical variables were tested by χ2 test. Kaplan-Meier method was used for survival analysis. Log-rank test and Cox proportional hazards regression were performed with overall survival (OS) and disease-free survival (DFS) as the primary outcome variables. RESULTS: Of 139 patients, 64.7% (90/139) of them received radiotherapy. Of the 90 patients who underwent radiotherapy, 45.6% (41/90) received Involved Field radiotherapy and the rest 49 patients received Comprehensive radiotherapy. The median follow-up of 139 patients is 69 months. The 1-year, 3-year, and 5-year OS rates are 87%, 62%, and 39%, respectively, and the DFS rates are 73%, 45%, and 29%, respectively. Multivariate analysis of 139 patients with CCUP shows that differentiation grade, N stage, radiotherapy, and the length of the largest lymph node (DmaxLN) are the independent prognostic factors for both OS and DFS. Subgroup analysis of 90 patients who received radiotherapy shows that the Comprehensive radiotherapy group has a better OS (P < 0.001) and DFS (P < 0.001) compared with Involved Field radiotherapy. CONCLUSION: Radiotherapy is the independent prognostic factor for CCUP. Comprehensive radiotherapy may be superior to Involved Field radiotherapy in survival benefits.

Engineered red blood cell membrane for sensitive and precise electrochemical detection of salivary exosomes.

As a kind of promising non-invasive biomarker, exosomes naturally occurring in saliva have recently attracted considerable attention in view of their potential use in the diagnosis of oral diseases. Herein, we propose a new electrochemical method for the sensitive and precise detection of salivary exosomes. A red blood cell membrane (RBCM) engineered with CD63 aptamer is the core element of the method and is used to camouflage a gold electrode, thus giving the electrode superior antifouling and targeting ability. Target exosomes presented in saliva are recognized and captured by the highly specific interaction between the exosomal CD63 and the aptamers engineered in RBCM. Then, silver nanoparticles modified with CD63 aptamers are recruited onto the electrode surface to generate significant electrochemical signals, which enables the sensitive detection of target exosomes. By using human oral squamous cell carcinoma CAL27 cell-derived exosomes as a model, the method allows target salivary exosome detection in a wide linear range from 5 × 102 to 1 × 106 particles per mL and a low detection limit of 2.07 × 102 particles per mL. Moreover, the method displays good reproducibility and is feasible for detecting target exosomes with high precision in saliva samples. Overall, the method may provide a useful tool for salivary exosome detection and may have great potential for practical use in the clinical diagnosis of oral diseases.

Fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage.

Unrestrained inflammation is harmful to tissue repair and regeneration. Immune cell membrane-camouflaged nanoparticles have been proven to show promise as inflammation targets and multitargeted inflammation controls in the treatment of severe inflammation. Prevention and early intervention of inflammation can reduce the risk of irreversible tissue damage and loss of function, but no cell membrane-camouflaged nanotechnology has been reported to achieve stage-specific treatment in these conditions. In this study, we investigated the prophylactic and therapeutic efficacy of fibroblast membrane-camouflaged nanoparticles for topical treatment of early inflammation (early pulpitis as the model) with the help of in-depth bioinformatics and molecular biology investigations in vitro and in vivo. Nanoparticles have been proven to act as sentinels to detect and competitively neutralize invasive Escherichia coli lipopolysaccharide (E. coli LPS) with resident fibroblasts to effectively inhibit the activation of intricate signaling pathways. Moreover, nanoparticles can alleviate the secretion of multiple inflammatory cytokines to achieve multitargeted anti-inflammatory effects, attenuating inflammatory conditions in the early stage. Our work verified the feasibility of fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage, which widens the potential cell types for inflammation regulation.

Insertion/deletion variants within the IGF2BP2 gene identified in reported genome-wide selective sweep analysis reveal a correlation with goat litter size.

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2, also called IMP2) plays an essential role in the development and maturation of germ cells and embryos and is a candidate gene for goat litter size, based on a previous genome-wide selective sweep analysis. In this study, the mRNA expression level of IGF2BP2 was found to be significantly higher in a single-lamb group than in a multi-lamb group. Insertions/deletions (indels) within the goat IGF2BP2 gene, including P4-Ins-13bp and P5-Del-12bp, were verified in 918 Shaanbei White Cashmere (SBWC) female goats. The minor allelic frequencies (MAFs) of P4-Ins-13bp and P5-Del-12bp loci were 0.349 and 0.295, respectively. Analysis using the Chi-square (χ2) test showed that the genotype (χ2=14.479, P=0.006) distribution of P4-Ins-13bp was significantly different between the single-lamb and multi-lamb groups. Correlation analysis demonstrated that P4-Ins-13bp was significantly associated with goat litter size (P=0.022), and individual goats with the homozygous deletion/deletion (DD) genotype produced more litters than other goats. Therefore, considered as a potential molecular marker significantly related to lambing traits, the P4-Ins-13bp mutation of the goat IGF2BP2 gene can be used in goat breeding with practical molecular marker-assisted selection (MAS) to optimize female reproduction and improve economic efficiency in the goat industry.

The mRNA expression profile of the goat prion protein testis-specific (PRNT) gene and its associations with litter size.

The goat PRNT gene was initially identified as a testis-specific gene with a role in spermatogenesis. In this study, we used quantitative real-time PCR (qPCR) to first determine the mRNA expression profile of this gene in different goat tissues. Surprisingly, we found that PRNT was expressed not only in the testis but also in nine other tissues in goats. Moreover, PRNT was weakly expressed in the testis, while its expression was strongest in the ovary. These results, combined with those of other studies, led us to hypothesize that the goat PRNT gene has a role in both male and female reproduction. We further used direct DNA sequencing to detect potential SNPs within this gene in Shaanbei whit cashmere (SBWC) rams and ewes, and identified three SNPs within the PRNT gene, namely, c.-58C > T, c.71A > G (p.Alanine24Valine), and c.102C > T (synonymous). In rams, c.-58C > T and c.102C > T were strongly linked with each other (D' = 1.000, r2 = 0.504), whereas no significant association (P > 0.05) was found between the three SNPs and semen quality, which was consistent with the low expression of the PRNT gene in the testis. Interestingly, in ewes (n = 502), c.-58C > T and c.71A > G were also strongly linked with each other (D' = 0.973, r2 = 0.537). Additionally, the c.71A > G locus, especially the AA genotype, had a significant influence on litter size (P = 0.006), consistent with the high PRNT expression in the ovary. Combined, the results of the expression profiling and analysis of the association between the SNPs and reproductive traits showed that two strongly linked nucleotide sequence variants within PRNT were significantly associated with goat litter size. These findings provide potential DNA markers for use in the marker-assisted selection (MAS) of goats with high-fertility traits.

Adhesion of Streptococcus mutans on remineralized enamel surface induced by poly(amido amine) dendrimers.

The aim of this study was to investigate the surface topography of remineralized enamel induced by poly(amido amine) (PAMAM) dendrimers and evaluate Streptococcus mutans (S. mutans) adhesion on regenerated enamel for the first time. PAMAM-COOH and PAMAM-NH2 were used as organic templates to induce enamel surface remineralization. The mineral deposits after remineralization were characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and X-ray diffraction (XRD). The surface topography of the remineralized enamel was analyzed by atomic force microscopy (AFM). An AFM tipless cantilever was functionalized with S. mutans and acted as a force probe to measure the adhesion force between bacteria and the remineralized enamel surface. Colony-forming unit (CFU) counts of biofilm on remineralized enamel surface were performed after 24 h incubation in S. mutans suspension. Both PAMAM-COOH and PAMAM-NH2 achieved effective remineralization on demineralized enamel surfaces, which smoothed the enamel surface and reduced S. mutans adhesion. PAMAM dendrimers are promising materials for early caries treatment because of their excellent remineralization ability. The remineralization induced by PAMAM dendrimers smoothed the surface and reduced S. mutans adhesion, which could prevent secondary caries.

A 5-bp mutation within MSTN/GDF8 gene was significantly associated with growth traits in Inner Mongolia White Cashmere goats.

Myostatin (MSTN) gene, also known as growth and differentiation factor 8 (GDF8) gene, is a negative regulator of skeletal muscle growth and development, especially the number, size and type of muscle fibers. Its mutations contribute to the double-muscling (DBM) phenomenon which significantly increases the muscle mass. Hence, variations within MSTN/GDF8 gene receive so much attention in several kinds of species such as bovines, poultries, goats, sheep, horses. A 5-base pairs (bp) indel in the 5' untranslated region (5'UTR) of goat MSTN/GDF8 was verified to be significantly associated with growth traits except Inner Mongolia White Cashmere (IMWC) goats. Given that almost all sample sizes were below 150, we enlarged sample sizes to more than 500 to uncover the association between the 5-bp indel and growth traits in IMWC goats. Only two genotypes (deletion/deletion (DD) and insertion/deletion (ID)) were found, and DD genotypes were dominant genotypes. The detected locus displayed low genetic diversity (PIC = 0.090). Interestingly, the association analyses revealed that the 5-bp indel had a significant effect on the chest depth (p = 0.003), and DD genotypes were dominant genotypes. Hinted that the 5-bp indel could act as an effective marker in molecular marker-assisted selection (MAS) processes for selection of excellent goat individuals.

Application of poly(lactic-co-glycolic acid) in the treatment of pulp diseases / 口腔疾病防治

@#The development of materials science is of great significance to the treatment of dental pulp diseases. Poly lactic acid glycolic acid (PLGA) copolymer is an organic macromolecule compound that is widely used in the preparation of biomedical materials. In recent years, PLGA, as a drug/molecular loaded system and tissue regeneration scaffold, has shown prospects for application in the treatment of dental pulp diseases. This paper will review the application of PLGA in the treatment of dental pulp diseases and provide a basis for its further development and utilization. The results of the literature review show that PLGA is a drug/molecular delivery system that is mainly used in the improvement of pulp capping materials, root canal disinfectant and apexification materials. PLGA-improved pulp capping agents can prolong the action time of the drug and reduce toxicity. The modified root canal disinfectant can realize the sustained release of drug, make the drug penetrate deeper into the subtle structure, and contact more widely with the pathogenic bacteria. The modified apexification materials can provide more convenient administration methods for apexifixment. As a scaffold for tissue engineering, PLGA is mainly used in the study of pulp regeneration. The optimization of PLGA physical properties and action environment can provide a more suitable microenvironment for seed cells to proliferate and differentiate. How to utilize the advantages of PLGA to develop a more suitable material for endodontic application needs further study.

Two Novel Rare Strongly Linked Missense SNPs (P27R and A85G) Within the GDF9 Gene Were Significantly Associated With Litter Size in Shaanbei White Cashmere (SBWC) Goats.

Growth differentiation factor 9 (GDF9) is a high-fertility candidate gene that plays a crucial role in early folliculogenesis in female mammals. In this study, direct sequencing was used to screen possible SNP loci in the goat GDF9 gene. Three SNP loci, p.proline27alanine (P27R), p.leucine61leucine (L61L), and p.alanine85glycine (A85G), were identified in Shaanbei white cashmere (SBWC) goats. Among the three SNPs, two rare missense SNP loci (P27R and A85G) were discovered to be strongly linked with each other (D' value = 0.926, r 2 value = 0.703). Both P27R and A85G loci had two genotypes: wild type and heterozygous type. A85G exerted a significant effect on litter size (P = 0.029) in SBWC goats, and the heterozygous genotype was superior in comparison with the wild type. The heterozygous genotype was also superior in P27R but no significant association was found. However, the combination genotypes of P27R and A85G were identified to have superior effects on litter size (P = 3.8E-15). This information suggested that these two SNPs influenced litter size in goats synergistically. Combining this information with our previous studies, we propose that the GDF9 gene is the principal high-fertility candidate gene and that the A85G locus is a promising SNP that affects litter size in goats. These results may fill a research gap regarding rare mutations as well as provide crucial molecular markers that could be useful in marker-assisted selection (MAS) goat rearing when selecting superior individuals.

Borate bioactive glass prevents zoledronate-induced osteonecrosis of the jaw by restoring osteogenesis and angiogenesis.

OBJECTIVES: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of systemic nitrogen-containing bisphosphonate (N-BP) administration, which leads to osteonecrosis, pain, and infection. Despite much effort, effective remedies are yet to be established. This study aimed to investigate potential recovery effect of borate bioactive glass (BBG) in vitro and in vivo. METHODS: The effect of BBG on zoledronate-treated bone marrow mesenchymal cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) was explored by cell counting kit-8, EdU assay, flow cytometry, alkaline phosphatase staining, alizarin red staining, angiogenesis experiment, and real-time quantitative polymerase chain reaction. The preventive effect of BBG on zoledronate-induced osteonecrosis of the jaw in rat model was examined by micro-CT, HE staining, and immunohistochemistry. RESULTS: Exposure of BBG to BMSCs and HUVECs increased cell proliferation and restored their osteogenesis and angiogenesis potential in vitro. The BRONJ lesions were satisfactorily repaired and bone mineral density, bone volume/tissue volume, trabecula number, OCN-positive cells, and CD31-positive cells were increased in the BBG-treated groups compared with saline-treated groups. CONCLUSIONS: Exposure of BMSCs and HUVECs to BBG restores osteogenesis and angiogenesis inhibited by zoledronate. BBG successfully restores extraction socket healing of BRONJ in rat model.

Multiple morphological abnormalities of the sperm flagella (MMAF)-associated genes: The relationships between genetic variation and litter size in goats.

Several genes are associated with the multiple morphological abnormalities of the sperm flagella (MMAF) syndrome, including QRICH2, CFAP43, CFAP44, CFAP69, CCDC39, and AKAP4 genes. Although previous work has shown that these genes are significantly associated with male reproductive traits in certain species, it is not yet known whether they are associated with reproductive traits in the goat. In this study, we investigated the correlations between 47 putative indel mutations in MMAF- associated genes, and first-born litter sizes in 1479 Shaanbei white cashmere (SBWC) goats. Our analysis showed that five of these indel mutations were polymorphic: QRICH2-P4, CFAP43-P20, CFAP69-P4, CFAP69-P6, and CFAP69-P7. Association analysis revealed that only a 6-bp indel variation within CFAP43 (CFAP43-P20) was strongly significantly associated with litter sizes in SBWC goats (P = 0.000). We also identified a significant difference in the genotypic distribution between the mothers of single lambs and the mothers of multiple lambs (P = 0.001); carriers of the DD genotype had greater litter sizes than carriers of the II or ID genotype. Our analysis also revealed 8-bp and 6-bp indels in CFAP69 (CFAP69-P4 and CFAP69-P6, respectively) that were in complete linkage disequilibrium with each other (D' = 0.99, r2 = 1.00). These findings indicate that the 6-bp indel mutation in the CFAP43 gene can be used as an effective molecular marker for selecting reproductive traits in goat breeding operations.

Detection of a 4 bp Mutation in the 3'UTR Region of Goat Sox9 Gene and Its Effect on the Growth Traits.

The SRY-type HMG box 9 (Sox9) gene plays an important role in chondrocyte development as well as changes in hypertrophic chondrocytes, indicating that Sox9 can regulate growth in animals. However, no studies to date have examined the correlation between variations in Sox9 and growth traits in goats. Here, we found a 4 bp indel in the 3'UTR of Sox9 and verified its association with growth traits in Shaanbei white cashmere goats (n = 1109). The frequencies of two genotypes (ID and II) were 0.397 and 0.603, respectively, and polymorphic information content (PIC) values showed that the indel had a medium PIC (PIC > 0.25). The 4 bp indel was significantly correlated with body length (p = 0.006), heart girth (p = 0.001), and hip width (p = 4.37 × 10 -4). Notably, individuals with the ID genotype had significantly superior phenotypic traits compared with individuals bearing the II genotype. Hence, we speculated that the 4 bp indel is an important mutation affecting growth traits in goat, and may serve as an effective DNA molecular marker for marker-assisted selection in goat breeding programs.