RESUMO
BACKGROUND: Teat number is a vital reproductive trait in sows, crucial for providing immunity and nutrition to piglets during lactation. However, "missing heritability" in Single Nucleotide Polymorphism (SNP)-based Genome-Wide Association Studies (GWAS) has led to an increasing focus on structural variations in the genetic analysis of complex biological traits. RESULTS: In this study, we generated a comprehensive CNV map in a population of French Yorkshire pigs (n = 644) and identified 429 CNVRs. Notably, 44% (189 CNVRs) of these were detected for the first time. Subsequently, we conducted GWAS for teat number in the French Yorkshire pig population using both 80K chip and its imputed data, as well as a GWAS analysis based on CNV regions (CNVR). Interestingly, 80K chip GWAS identified two SNPs located on Sus scrofa chromosome 5 (SSC5) that were simultaneously associated with Total Teat Number (TTN), Left Teat Number (LTN), and Right Teat Number (RTN). The leading SNP (WU_10.2_5_76130558) explained 3.33%, 2.69%, and 2.67% of the phenotypic variance for TTN, LTN, and RTN, respectively. Moreover, through imputed GWAS, we successfully identified 30 genetic variants associated with TTN located within the 73.22 -73.30 Mb region on SSC5. The two SNPs identified in the 80K chip GWAS were also located in this region. In addition, CNVR-based GWAS revealed three significant CNVRs associated with TTN. Finally, through gene annotation, we pinpointed two candidate genes, TRIM66 and PRICKLE1, which are related to diverse processes such as breast cancer and abnormal vertebral development. CONCLUSIONS: Our research provides an in-depth analysis of the complex genetic structure underlying teat number, contributing to the genetic enhancement of sows with improved reproductive performance and, ultimately, bolstering the economic benefits of swine production enterprises.
Assuntos
Estudo de Associação Genômica Ampla , Glândulas Mamárias Animais , Polimorfismo de Nucleotídeo Único , Animais , Feminino , Suínos/genética , Variações do Número de Cópias de DNA , Fenótipo , Locos de Características Quantitativas , Sus scrofa/genéticaRESUMO
PURPOSE: Optimal extended adjuvant endocrine therapy (ET) duration and strategy for hormone receptor-positive (HR +) early breast cancer remain unclear. In this network meta-analysis (NMA), the efficacy and safety of all available extended adjuvant ETs were compared and ranked. METHODS: PubMed, Embase, and Cochrane Library and abstracts presented at ASCO, SABCS, and ESMO were searched on March 5, 2022. Fourteen randomized controlled trials (RCTs) comprising eight extended adjuvant ETs for HR + breast cancer and 38,070 patients were analyzed. Main outcomes were disease-free survival (DFS), overall survival (OS), grade ≥ 3 adverse events (AEs), and contralateral breast cancer (CBC). Direct and indirect comparisons were integrated via Bayesian NMA. Hierarchical cluster analysis was performed to jointly rank efficacy and safety outcomes. RESULTS: Compared with that of 5 year ET, extended 10 year aromatase inhibitor (AI) treatment provided the greatest DFS benefit (HR = 0.45, 95%CrI 0.23-0.83), whereas no strategy differed significantly in terms of the other main outcomes. Extended 10 year AI treatment was the preferred strategy for DFS improvement and CBC prevention (surface under the cumulative ranking curve: 93.51% and 91.29% probability, respectively). All strategies had comparable safeties (grade ≥ 3 AEs). Compared with that of 5 year ET, 10 year extended AI significantly increased arthralgia (OR = 1.65, 95%CrI 1.02-2.93) and osteoporosis (OR = 3.33, 95%CrI 1.19-9.68). CONCLUSION: Extended 10 year AI therapy may be optimal for HR + early breast cancer given its relatively high efficacy and safety.
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Neoplasias da Mama , Humanos , Feminino , Metanálise em Rede , Quimioterapia Adjuvante , Inibidores da Aromatase/efeitos adversos , Intervalo Livre de Doença , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
This study aimed at identifying genes associated with loin muscle area (LMA), loin muscle depth (LMD) and backfat thickness (BFT). We performed single-trait and multi-trait genome-wide association studies (GWASs) after genotyping 685 Duroc × (Landrace × Yorkshire) (DLY) pigs using the Geneseek Porcine 50K SNP chip. In the single-trait GWASs, we identified two, eight and two significant SNPs associated with LMA, LMD and BFT, respectively, and searched genes within the 1 Mb region near the significant SNPs with relevant functions as candidate genes. Consequently, we identified one (DOCK5), three (PID1, PITX2, ELOVL6) and three (CCR1, PARP14, CASR) promising candidate genes for LMA, LMD and BFT, respectively. Moreover, the multi-trait GWAS identified four significant SNPs associated with the three traits. In conclusion, the GWAS analysis of LMA, LMD and BFT in a DLY pig population identified several associated SNPs and candidate genes, further deepening our understanding of the genetic basis of these traits, and they may be useful for marker-assisted selection to improve the three traits in DLY pigs.
Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Suínos , Animais , Músculos , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Compelling evidence has indicated a significant association between leukocyte mitochondrial DNA copy number (mtDNAcn) and prognosis of several malignancies in a cancer-specific manner. However, whether leukocyte mtDNAcn can predict the clinical outcome of breast cancer (BC) patients has not been well investigated. METHODS: The mtDNA copy number of peripheral blood leukocytes from 661 BC patients was measured using a Multiplex AccuCopy™Kit based on a multiplex fluorescence competitive PCR principle. Kaplan-Meier curves and Cox proportional hazards regression model were applied to investigate the association of mtDNAcn with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer special survival (BCSS), and overall survival (OS) of patients. The possible mtDNAcn-environment interactions were also evaluated by the Cox proportional hazard regression models. RESULTS: BC patients with higher leukocyte mtDNA-CN exhibited a significantly worse iDFS than those with lower leukocyte mtDNAcn (5-year iDFS: fully-adjusted model: HR = 1.433[95%CI 1.038-1.978], P = 0.028). Interaction analyses showed that mtDNAcn was significantly associated with hormone receptor status (adjusted p for interaction: 5-year BCSS: 0.028, 5-year OS: 0.022), so further analysis was mainly in the HR subgroup. Multivariate Cox regression analysis demonstrated that mtDNAcn was an independent prognostic factor for both BCSS and OS in HR-positive patients (HR+: 5-year BCSS: adjusted HR (aHR) = 2.340[95% CI 1.163-4.708], P = 0.017 and 5-year OS: aHR = 2.446 [95% CI 1.218-4.913], P = 0.011). CONCLUSIONS: For the first time, our study demonstrated that leukocyte mtDNA copy number might influence the outcome of early-stage breast cancer patients depending on intrinsic tumor subtypes in Chinese women.
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Neoplasias da Mama , DNA Mitocondrial , Humanos , Feminino , DNA Mitocondrial/genética , Variações do Número de Cópias de DNA , Neoplasias da Mama/genética , Prognóstico , LeucócitosRESUMO
BACKGROUND: Carcass traits are important in pig breeding programs for improving pork production. Understanding the genetic variants underlies complex phenotypes can help explain trait variation in pigs. In this study, we integrated a weighted single-step genome-wide association study (wssGWAS) and copy number variation (CNV) analyses to map genetic variations and genes associated with loin muscle area (LMA), loin muscle depth (LMD) and lean meat percentage (LMP) in Duroc pigs. RESULTS: Firstly, we performed a genome-wide analysis for CNV detection using GeneSeek Porcine SNP50 Bead chip data of 3770 pigs. A total of 11,100 CNVs were detected, which were aggregated by overlapping 695 CNV regions (CNVRs). Next, we investigated CNVs of pigs from the same population by whole-genome resequencing. A genome-wide analysis of 21 pigs revealed 23,856 CNVRs that were further divided into three categories (851 gain, 22,279 loss, and 726 mixed), which covered 190.8 Mb (~ 8.42%) of the pig autosomal genome. Further, the identified CNVRs were used to determine an overall validation rate of 68.5% for the CNV detection accuracy of chip data. CNVR association analyses identified one CNVR associated with LMA, one with LMD and eight with LMP after applying stringent Bonferroni correction. The wssGWAS identified eight, six and five regions explaining more than 1% of the additive genetic variance for LMA, LMD and LMP, respectively. The CNVR analyses and wssGWAS identified five common regions, of which three regions were associated with LMA and two with LMP. Four genes (DOK7, ARAP1, ELMO2 and SLC13A3) were highlighted as promising candidates according to their function. CONCLUSIONS: We determined an overall validation rate for the CNV detection accuracy of low-density chip data and constructed a genomic CNV map for Duroc pigs using resequencing, thereby proving a value genetic variation resource for pig genome research. Furthermore, our study utilized a composite genetic strategy for complex traits in pigs, which will contribute to the study for elucidating the genetic architecture that may be influenced and regulated by multiple forms of variations.
Assuntos
Variações do Número de Cópias de DNA , Estudo de Associação Genômica Ampla , Animais , Genótipo , Fenótipo , Polimorfismo de Nucleotídeo Único , Suínos/genéticaRESUMO
BACKGROUND: In the process of pig breeding, the average daily gain (ADG), days to 100 kg (AGE), and backfat thickness (BFT) are directly related to growth rate and fatness. However, the genetic mechanisms involved are not well understood. Copy number variation (CNV), an important source of genetic diversity, can affect a variety of complex traits and diseases and has gradually been thrust into the limelight. In this study, we reported the genome-wide CNVs of Duroc pigs using SNP genotyping data from 6627 animals. We also performed a copy number variation region (CNVR)-based genome-wide association studies (GWAS) for growth and fatness traits in two Duroc populations. RESULTS: Our study identified 953 nonredundant CNVRs in U.S. and Canadian Duroc pigs, covering 246.89 Mb (~ 10.90%) of the pig autosomal genome. Of these, 802 CNVRs were in U.S. Duroc pigs with 499 CNVRs were in Canadian Duroc pigs, indicating 348 CNVRs were shared by the two populations. Experimentally, 77.8% of nine randomly selected CNVRs were validated through quantitative PCR (qPCR). We also identified 35 CNVRs with significant association with growth and fatness traits using CNVR-based GWAS. Ten of these CNVRs were associated with both ADG and AGE traits in U.S. Duroc pigs. Notably, four CNVRs showed significant associations with ADG, AGE, and BFT, indicating that these CNVRs may play a pleiotropic role in regulating pig growth and fat deposition. In Canadian Duroc pigs, nine CNVRs were significantly associated with both ADG and AGE traits. Further bioinformatic analysis identified a subset of potential candidate genes, including PDGFA, GPER1, PNPLA2 and BSCL2. CONCLUSIONS: The present study provides a necessary supplement to the CNV map of the Duroc genome through large-scale population genotyping. In addition, the CNVR-based GWAS results provide a meaningful way to elucidate the genetic mechanisms underlying complex traits. The identified CNVRs can be used as molecular markers for genetic improvement in the molecular-guided breeding of modern commercial pigs.
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Variações do Número de Cópias de DNA , Estudo de Associação Genômica Ampla , Animais , Canadá , Genoma , Polimorfismo de Nucleotídeo Único , Sus scrofa/genética , Suínos/genéticaRESUMO
To excavate the application of Jerusalem artichoke on poly(γ-glutamic acid) (γ-PGA) production, a γ-PGA producing strain Bacillus amyloliquefaciens NX-2S154 was obtained through atmospheric and room temperature plasma mutagenesis, which produced 14.83 ± 0.31 g/L of γ-PGA in batch fermentation with raw inulin extract. Simultaneous saccharification and fermentation (SSF) by adding commercial inulinase were further investigated for γ-PGA fermentation. Results showed SSF could eliminate the ineffective utilization of inulin while avoiding inhibition effect of high concentration substrate, which made γ-PGA concentration reach 18.54 ± 0.39 g/L with the process being shortened by 17%. Finally, an immobilized column for reducing inulinase cost was introduced to γ-PGA production. Repeated batch cultures showed the novel bioreactor exhibited higher stability and simplicity and gave average γ-PGA concentration and productivity of 19.40 ± 0.37 g/L and 0.27 ± 0.008 g/L/h, respectively. This work proposes a productive method for efficient γ-PGA production using Jerusalem artichoke feedstock.
Assuntos
Bacillus amyloliquefaciens/crescimento & desenvolvimento , Inulina/metabolismo , Ácido Poliglutâmico/biossíntese , Bacillus amyloliquefaciens/genética , Mutagênese , Gases em Plasma , Ácido Poliglutâmico/genéticaRESUMO
Homopolymeric amino acids (HPAs) are a class of microbial polymers that can be classified into two categories: anionic and cationic HPAs. Notable examples include γ-poly-glutamic acid (γ-PGA) and ε-poly-L-lysine (ε-PL) that have wide-ranging applications in medicine, food, and agriculture. The primary method of manufacture is through microbial synthesis. In recent decades significant efforts have been made to enhance the production of HPAs, specifically focusing on γ-PGA and ε-PL. We comprehensively review current advances in understanding the synthetic mechanisms as well as metabolic engineering and fermentation process techniques to improve the production of HPAs. In addition, we discuss the major challenges and solutions associated with desired structure regulation of HPAs and the development of novel structures.
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Aminoácidos , Engenharia Metabólica , Fermentação , Engenharia Metabólica/métodosRESUMO
Tremella fuciformis polysaccharide (TFPS) is a natural mushroom mucopolysaccharide widely used in health foods, medical care, cosmetic and surgical materials. In this study, we developed an efficient strategy for the repeated batch production of highly bioactive TFPS from the agro-industrial residue cane molasses. Cane molasses contained 39.92 % sucrose (w/w), 6.36 % fructose and 3.53 % glucose, all of which could be utilized by T. fuciformis spores, whereas, the TFPS production efficiency only reached 0.74 g/L/d. Corn cobs proved to be the best immobilized carrier that could tightly absorb spores and significantly shorten the fermentation lag period. The average yield of TFPS in eight repeated batch culture was 5.52 g/L with a production efficiency of 2.04 g/L/d. The average fermentation cycle after optimization was reduced by 61.61 % compared with the initial conditions. Compared to glucose as a carbon source, cane molasses significantly increased the proportion of low-molecular-weight TFPS (TFPS-2) in total polysaccharides from 3.54 % to 17.25 % (w/w). Moreover, TFPS-2 exhibited potent antioxidant capacity against four free radicals (O2-, ABTS+, OH, and DPPH). In conclusion, this study lays the foundation for the efficient conversion of cane molasses and production of TFPS with high bioactivity.
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Basidiomycota , Técnicas de Cultura Celular por Lotes , Melaço , Bengala , Polissacarídeos/farmacologia , Polissacarídeos/química , Fermentação , GlucoseRESUMO
Liquid fermentation could revolutionize mushroom polysaccharide production, but the low temperature constraint hampers the process. This study implemented adaptive laboratory evolution (ALE) to enhance the thermotolerance of Naematelia aurantialba strains and increase expolysaccharide production. After 75 ALE cycles at 30 °C, the adaptive strain surpassed the wild-type strain by 5 °C. In a 7.5 L fermentor at 30 °C, the ALE strain yielded 17 % more exopolysaccharide than the wild type strain at 25 °C. Although the exopolysaccharide synthesized by both strains shares a consistent monosaccharide composition, infrared spectrum, and glycosidic bond composition, the ALE strain's exopolysaccharide has a larger molecular weight. Furthermore, the ALE strain's exopolysaccharide exhibits superior cryoprotection performance compared to that produced by the original strain. The adapted strain demonstrated lower ROS levels and increased activity of antioxidant enzymes, indicating improved performance. Fatty acid profiling and transcriptomics revealed reconfiguration of carbohydrate metabolism, amino acid metabolism, and membrane lipid synthesis in thermophilic strains, maintaining cellular homeostasis and productivity. This study provides efficient strains and fermentation methods for high-temperature mushroom polysaccharide production, reducing energy consumption and costs.
Assuntos
Basidiomycota , Reatores Biológicos , Polissacarídeos , Temperatura , FermentaçãoRESUMO
Adequate dietary L-tryptophan (Trp) governs intestinal homeostasis in piglets. However, the defensive role of Trp in the diet against enterotoxigenic Escherichia coli F4 (K88) in pigs is still poorly understood. Here, sixty (6.15 ± 1.52 kg, 24-day-old, Duroc × Landrace × Yorkshire) weaned piglets were used for an E. coli F4 attack test in a 2 × 2 factorial design. The growth (ADG, ADFI, GH), immune factors (IL-10, IgA, IgG, IgM), Trp metabolite 5-HT, intestinal morphology (jejunal and colonic VH), mRNA expression of ß-defensins (jejunal BD-127, BD-119, ileal BD-1, BD-127), and abundance of beneficial microorganisms in the colon (Prevotella 9, Lactobacillus, Phascolarctobacterium, Faecalibacterium) were higher in the piglets in the HT (High Trp) and HTK (High Trp, K88) groups than in the LT (Low Trp) and LTK (Low Trp, K88) groups (P<.05), while FCR, diarrhea rate, diarrhea index, serum Trp, Kyn, IDO, D-LA, ET, and abundance of harmful microorganisms in the colon (Spirochaetes, Fusobacteria, Prevotella, Christensenellaceae R7) were lower in the HT and HTK groups than in the LT and LTK groups (P<.05). High Trp reduced the expression of virulence genes (K88 and LT) after E. coli F4 attack (P<.05). The IL-6, TNF-α was lower in the HTK group than in the LT, LTK group (P<.05). In short, a diet containing 0.35% Trp protected piglets from enterotoxigenic E. coli F4 (K88) via Trp metabolism promoting BD expression in the intestinal mucosa, which improved growth and intestinal health.
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Escherichia coli Enterotoxigênica , Triptofano , Desmame , beta-Defensinas , Animais , Triptofano/metabolismo , Suínos , beta-Defensinas/metabolismo , Infecções por Escherichia coli/veterinária , Doenças dos Suínos/microbiologia , Doenças dos Suínos/prevenção & controle , Intestinos/microbiologia , Ração Animal , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Dieta/veterináriaRESUMO
This study investigated the effects of citrus flavonoids (CF) and compared to antibiotics on piglet growth and gut health. Weaned piglets were fed either a basal diet (CON) or a basal diet supplemented with 75 mg/kg chlortetracycline (CTC), 20 mg/kg CF (CF1), 40 mg/kg CF (CF2), or 80 mg/kg CF (CF3). The CF group, especially CF3, exhibited improved growth performance; reduced diarrhea; significantly higher levels of serum growth factors, immunoglobulins, and anti-inflammatory cytokines; and significantly lower levels of pro-inflammatory factors and markers of intestinal barrier damage (P < 0.05). The intestinal mucosa proteins ZO-1 and occludin increased, while NF-κB and TLR2 decreased, correlating with CF dosage (P < 0.05). Furthermore, CF promoted a favorable balance in the gut microbiota, with an increased relative abundance of Bacteroidetes and Prevotella and decreased taxa Tenericutes and Clostridiales. Overall, CF enhanced piglet growth and gut health by modulating the TLR2/NF-κB pathway, offering a natural antibiotic alternative. The optimal dose of CF was 80 mg/kg.
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Bactérias , Citrus , Flavonoides , Microbioma Gastrointestinal , NF-kappa B , Transdução de Sinais , Receptor 2 Toll-Like , Desmame , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Suínos/crescimento & desenvolvimento , Suínos/imunologia , NF-kappa B/metabolismo , NF-kappa B/imunologia , NF-kappa B/genética , Receptor 2 Toll-Like/metabolismo , Citrus/química , Flavonoides/administração & dosagem , Flavonoides/farmacologia , Transdução de Sinais/efeitos dos fármacos , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/metabolismo , Bactérias/crescimento & desenvolvimento , Suplementos Nutricionais/análise , Ração Animal/análise , MasculinoRESUMO
Mushroom polysaccharides exhibit numerous health-enhancing attributes that are intricately linked to the breakdown, assimilation, and exploitation of polysaccharides within the organism. Naematelia aurantialba polysaccharides (NAPS-A), highly prized polysaccharides derived from mushrooms, remain shrouded in uncertainty regarding their characteristics pertaining to gastrointestinal digestion and gut microbial fermentation. The study aimed to understand the digestion and fecal fermentation patterns of NAPS-A. After simulated digestion, NAPS-A's physicochemical properties remained unchanged. However, during in vitro fecal fermentation, indigestible NAPS-A underwent significant changes in various properties, such as reducing sugar, chemical composition, constituent monosaccharides, Molecular weight, apparent viscosity, FT-IR spectra, and microscopic morphology. Notably, NAPS-A was effectively utilized by the gut microbiota, with unchanged properties after digestion but altered after fermentation. It influenced gut microbe composition by increasing beneficial bacteria (Lactobacillus, Faecalibacterium, and Roseburia), lowering pH, and producing short-chain fatty acids. NAPS-A fermentation enriches carbohydrate, fatty acid, and amino acid metabolic pathways through PICRUSt prediction analysis. Overall, these findings emphasize NAPS-A's role in regulating gut bacteria and their metabolic functions, despite its challenging digestibility.
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Agaricales , Basidiomycota , Digestão , Fermentação , Espectroscopia de Infravermelho com Transformada de Fourier , Ácidos Graxos Voláteis/metabolismo , Polissacarídeos/metabolismo , Agaricales/metabolismo , Bactérias/metabolismoRESUMO
PURPOSE: Limited data are available regarding the partner and localizer of BRCA2 (PALB2) in Chinese patients with early breast cancer. This study aimed to assess the spectrum and characteristics of germline PALB2 pathogenic variants in this population. METHODS: Peripheral blood samples were collected from 1556 patients diagnosed with BRCA1/2-negative early-onset breast cancer. All coding regions and exonâintron boundaries of the PALB2 genes were screened through next-generation sequencing. RESULTS: The prevalence of PALB2 pathogenic variants was approximately 0.77% in the cohort. Eleven PALB2 pathogenic variants were identified in twelve participants, including five frameshift mutations and six nonsense mutations. All other variants were detected once, except for PALB2 c.1056_1057del (detected twice). Two PALB2 carriers (2/12, 16.7%) have documented family history of breast cancer and/or ovarian cancer. Patients with a positive family history exhibited a threefold higher possibility of being identified as PALB2 carriers than those without a family history (2% vs. 0.69%), although the difference was not statistically significant (p = 0.178). Compared to non-carriers, PALB2 carriers has a tendency to appear in younger age (≤ 30 years) (25% vs 14.4%), human epidermal growth factor receptor-2 (HER2)-negative status (83.3% vs. 70.2%), and diagnosed with invasive micropapillary carcinoma (16.7% vs 3.1%). CONCLUSION: The prevalence of the germline PALB2 pathogenic variants was approximately 0.77% in Chinese patients with BRCA1/2-negative early-onset breast cancer. Our findings is crucial for understanding population-specific genetic risks and offering insights that can enhance genetic counseling and genetic testing strategies in this population.
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Idade de Início , Neoplasias da Mama , Proteína do Grupo de Complementação N da Anemia de Fanconi , Mutação em Linhagem Germinativa , Humanos , Feminino , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/epidemiologia , Adulto , Pessoa de Meia-Idade , China/epidemiologia , Predisposição Genética para Doença , Adulto Jovem , Proteína BRCA2/genéticaRESUMO
Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.
Assuntos
Alelos , Metilação de DNA , Animais , Suínos/genética , Feminino , Cromatina/genética , Cromatina/metabolismo , Especificidade de Órgãos/genética , Fígado/metabolismo , Placenta/metabolismo , Masculino , Encéfalo/metabolismo , Sus scrofa/genética , Sequenciamento Completo do Genoma , Gravidez , MultiômicaRESUMO
As the two most widely used Kluyveromyces yeast, Kluyveromyces marxianus and K. lactis have gained increasing attention as microbial chassis in biocatalysts, biomanufacturing and the utilization of low-cost raw materials owing to their high suitability to these applications. However, due to slow progress in the development of molecular genetic manipulation tools and synthetic biology strategies, Kluyveromyces yeast cell factories as biological manufacturing platforms have not been fully developed. In this review, we provide a comprehensive overview of the attractive characteristics and applications of Kluyveromyces cell factories, with special emphasis on the development of molecular genetic manipulation tools and systems engineering strategies for synthetic biology. In addition, future avenues in the development of Kluyveromyces cell factories for the utilization of simple carbon compounds as substrates, the dynamic regulation of metabolic pathways, and for rapid directed evolution of robust strains are proposed. We expect that more synthetic systems, synthetic biology tools and metabolic engineering strategies will adapt to and optimize for Kluyveromyces cell factories to achieve green biofabrication of multiple products with higher efficiency.
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Kluyveromyces , Kluyveromyces/genética , Kluyveromyces/metabolismo , Engenharia Metabólica , Biologia SintéticaRESUMO
Ammonia and nitrite are nitrogenous pollutants in aquaculture effluents, which pose a major threat to the health of aquatic animals. In this study, we developed a nitrogen conversion strategy based on synthesis of poly-γ-glutamic acid (γ-PGA) by Bacillus subtilis NX-2. The nitrogen removal efficiency of NX-2 was closely related to synthesizing γ-PGA, and was positively correlated with the inoculum level. The degradation rates of ammonia nitrogen and nitrite at 104 CFU/mL were 84.42 % and 62.56 %, respectively. Through adaptive laboratory evolution (ALE) experiment, we obtained a strain named ALE 5 M with ammonia degradation rate of 98.03 % and nitrite of 93.62 % at the inoculum level of 104 CFU/mL. Transcriptome analysis showed that the strain was more likely to produce γ-PGA after ALE. By enzyme activity and qPCR analysis, we confirmed that ALE 5 M degraded ammonia nitrogen through γ-PGA synthesis, which provided a new way for nitrogen removal in aquaculture water.
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Amônia , Ácido Glutâmico , Ácido Glutâmico/metabolismo , Amônia/metabolismo , Nitrogênio/metabolismo , Nitritos/metabolismo , Bacillus subtilis/metabolismo , Ácido Poliglutâmico/metabolismo , AquiculturaRESUMO
Internal organ weight is an essential indicator of growth status as it reflects the level of growth and development in pigs. However, the associated genetic architecture has not been well explored because phenotypes are difficult to obtain. Herein, we performed single-trait and multi-trait genome-wide association studies (GWASs) to map the genetic markers and genes associated with six internal organ weight traits (including heart weight, liver weight, spleen weight, lung weight, kidney weight, and stomach weight) in 1518 three-way crossbred commercial pigs. In summation, single-trait GWASs identified a total of 24 significant single- nucleotide polymorphisms (SNPs) and 5 promising candidate genes, namely, TPK1, POU6F2, PBX3, UNC5C, and BMPR1B, as being associated with the six internal organ weight traits analyzed. Multi-trait GWAS identified four SNPs with polymorphisms localized on the APK1, ANO6, and UNC5C genes and improved the statistical efficacy of single-trait GWASs. Furthermore, our study was the first to use GWASs to identify SNPs associated with stomach weight in pigs. In conclusion, our exploration of the genetic architecture of internal organ weights helps us better understand growth traits, and the key SNPs identified could play a potential role in animal breeding programs.
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Early weaning of piglets was prone to increase reactive oxygen species, disrupt the redox balance, decrease antioxidant capacity, cause oxidative stress and intestinal oxidative damage, and lead to diarrhea in piglets. This research aimed to study dietary taurine (Tau) supplementation at a level relieving intestinal oxidative damage in early-weaned piglets. A total of 48 piglets were assigned to four groups of 12 individuals and fed a basal diet with 0.0% Tau (CON), 0.2% Tau (L-Tau), 0.3% Tau (M-Tau), or 0.4% Tau (H-Tau), respectively. The animal experiment lasted 30 days. The final weight, weight gain, average daily gain, and feed conversion rate increased with the increase in dietary Tau (Linear, p < 0.05; Quadratic p < 0.05), while the diarrhea index of piglets decreased with the increase in dietary Tau (Linear, p < 0.05). Serum malondialdehyde, nitric oxide (NO), D-lactose, and oxidized glutathione (GSSG) concentrations decreased with the increase in dietary Tau (Linear, p < 0.05). The O2â¢- and â¢OH clearance rate in serum, liver, and jejunum mucosa increased with the increase in dietary Tau (Linear, p < 0.05). Serum superoxide dismutase (SOD) activity, glutathione peroxidase (GPX) activity, catalase (CAT) activity, and peroxidase (POD) activity and total antioxidant capacity increased with the increase in dietary Tau (Linear, p < 0.05). The serum glutathione (GSH) concentration and the ratio of GSH to GSSG increased with the increase in dietary Tau (Linear, p < 0.05). The POD and glutathione synthase activity in the liver and jejunum mucosa increased with the increase in dietary Tau (Linear, p < 0.05). The mRNA abundances of HO-1 and GPX1 in the H-Tau group were higher than that in the L-Tau, M-Tau, and CON groups (p < 0.05). The mRNA abundances of SOD1 and Nrf2 in the M-Tau and H-Tau groups were higher than in the L-Tau and CON groups (p < 0.05). The mRNA abundance of SOD2 in the L-Tau, M-Tau, and H-Tau groups was higher than in the CON group (p < 0.05). The VH and the ratio of VH to CD of jejunum and ileum increased with the increase in dietary Tau (Linear, p < 0.05). The mRNA abundances of occludens 1 and claudin 1 in the H-Tau group were higher than that in the CON, L-Tau, and M-Tau (p < 0.05). The mRNA abundance of occludin in the L-Tau, M-Tau, and H-Tau groups was higher than that in CON (p < 0.05). The abundance of Firmicutes increased with the increase in dietary Tau (Linear, p < 0.05), while Proteobacteria and Spirochaetota decreased with the increase in dietary Tau (Linear, p < 0.05). Collectively, dietary supplementation of 0.3% and 0.4% Tau in feed could significantly improve the growth performance and enhance the antioxidant capacity of piglets.
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OBJECTIVE: Loin muscle area (LMA) is an important target trait of pig breeding. This study aimed to identify single nucleotide polymorphisms (SNPs) and genes associated with LMA in the Duroc×(Landrace×Yorkshire) crossbred pigs (DLY). METHODS: A genome-wide association study was performed using the Illumina 50K chip to map the genetic marker and genes associated with LMA in 511 DLY pigs (255 boars and 256 sows). RESULTS: After quality control, we detected 35,426 SNPs, including six SNPs significantly associated with LMA in pigs, with MARC0094338 and ASGA0072817 being the two key SNPs responsible for 1.77% and 2.48% of the phenotypic variance of LMA, respectively. Based on previous research, we determined two candidate genes (growth hormone receptor [GHR] and 3-oxoacid Co A-transferase 1 [OXCT1]) that are associated with fat deposition and muscle growth and found further additional genes (MYOCD, ARHGAP44, ELAC2, MAP2K4, FBXO4, FBLL1, RARS1, SLIT3, and RANK3) that are presumed to have an effect on LMA. CONCLUSION: This study contributes to the identification of the mutation that underlies quantitative trait loci associated with LMA and to future pig breeding programs based on marker-assisted selection. Further studies are needed to elucidate the role of the identified candidate genes in the physiological processes involved in LMA regulation.