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This study aimed to investigate genetic parameters for sow pelvic organ prolapse in purebred and crossbred herds. Pelvic organ prolapse was recorded as normal or prolapsed on the individual sow level across 32 purebred and 8 crossbred farms. In total, 75,162 purebred Landrace sows from a single maternal line were recorded between 2018 and 2023, while 18,988 commercial two-way crossbred (Landrace x Large White) sows were available between 2020 and 2023. There were 5,122,005 animals included in the pedigree. The prolapse in purebreds and crossbreds was considered two different traits in the model. Pedigrees of the crossbred sows were determined based on genotypes through parentage assignment. The average incidence rates were 1.81% and 3.93% for purebreds and crossbreds, respectively. The bivariate model incorporated fixed effects of parity group and region with random effects of contemporary group (farm and mating year and month at the first parity), additive genetic, and residual. Genetic parameter estimates were obtained using BLUPF90+ with the AIREML option. The estimated additive variance was larger in crossbreds than in purebreds. Estimates of heritability in the observed scale were 0.09 (0.006) for purebreds and 0.11 (0.014) for crossbreds, with a genetic correlation of 0.83 using a linear model. Results suggested that including data from crossbreds with higher incidence rate is beneficial and selection to reduce the prolapse incidence in purebred sow herds would also benefit commercial crossbred sow herds.
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Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied. Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed. Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [P = .03%] and 1.0% vs 3.8% [P = .05], respectively). Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD.
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Acrilamidas , Compostos de Anilina , Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Receptores ErbB , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Acrilamidas/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Receptores ErbB/genética , Quimiorradioterapia/métodos , Quimiorradioterapia/efeitos adversos , Compostos de Anilina/uso terapêutico , Compostos de Anilina/administração & dosagem , Mutação , Indóis , PirimidinasRESUMO
Sepsis-induced acute kidney injury (AKI) is a common complication in patients with severe illness and leads to increased risks of mortality and chronic kidney disease. We investigated the association between monocyte distribution width (MDW), red-blood-cell volume distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), sepsis-related organ-failure assessment (SOFA) score, mean arterial pressure (MAP), and other risk factors and sepsis-induced AKI in patients presenting to the emergency department (ED). This retrospective study, spanning 1 January 2020, to 30 November 2020, was conducted at a university-affiliated teaching hospital. Patients meeting the Sepsis-2 consensus criteria upon presentation to our ED were categorized into sepsis-induced AKI and non-AKI groups. Clinical parameters (i.e., initial SOFA score and MAP) and laboratory markers (i.e., MDW, RDW, and NLR) were measured upon ED admission. A logistic regression model was developed, with sepsis-induced AKI as the dependent variable and laboratory parameters as independent variables. Three multivariable logistic regression models were constructed. In Model 1, MDW, initial SOFA score, and MAP exhibited significant associations with sepsis-induced AKI (area under the curve [AUC]: 0.728, 95% confidence interval [CI]: 0.668-0.789). In Model 2, RDW, initial SOFA score, and MAP were significantly correlated with sepsis-induced AKI (AUC: 0.712, 95% CI: 0.651-0.774). In Model 3, NLR, initial SOFA score, and MAP were significantly correlated with sepsis-induced AKI (AUC: 0.719, 95% CI: 0.658-0.780). Our novel models, integrating MDW, RDW, and NLR with initial SOFA score and MAP, can assist with the identification of sepsis-induced AKI among patients with sepsis presenting to the ED.
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BACKGROUND: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). METHODS: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. RESULTS: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality. CONCLUSION: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB.
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Bronquiectasia , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , Bronquiectasia/fisiopatologia , Bronquiectasia/diagnóstico por imagem , Taiwan/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Volume Expiratório Forçado , Adulto , Pseudomonas aeruginosa/isolamento & purificaçãoRESUMO
BACKGROUND: With the introduction of digital phenotyping and high-throughput data, traits that were previously difficult or impossible to measure directly have become easily accessible, offering the opportunity to enhance the efficiency and rate of genetic gain in animal production. It is of interest to assess how behavioral traits are indirectly related to the production traits during the performance testing period. The aim of this study was to assess the quality of behavior data extracted from day-wise video recordings and estimate the genetic parameters of behavior traits and their phenotypic and genetic correlations with production traits in pigs. Behavior was recorded for 70 days after on-test at about 10 weeks of age and ended at off-test for 2008 female purebred pigs, totaling 119,812 day-wise records. Behavior traits included time spent eating, drinking, laterally lying, sternally lying, sitting, standing, and meters of distance traveled. A quality control procedure was created for algorithm training and adjustment, standardizing recording hours, removing culled animals, and filtering unrealistic records. RESULTS: Production traits included average daily gain (ADG), back fat thickness (BF), and loin depth (LD). Single-trait linear models were used to estimate heritabilities of the behavior traits and two-trait linear models were used to estimate genetic correlations between behavior and production traits. The results indicated that all behavior traits are heritable, with heritability estimates ranging from 0.19 to 0.57, and showed low-to-moderate phenotypic and genetic correlations with production traits. Two-trait linear models were also used to compare traits at different intervals of the recording period. To analyze the redundancies in behavior data during the recording period, the averages of various recording time intervals for the behavior and production traits were compared. Overall, the average of the 55- to 68-day recording interval had the strongest phenotypic and genetic correlation estimates with the production traits. CONCLUSIONS: Digital phenotyping is a new and low-cost method to record behavior phenotypes, but thorough data cleaning procedures are needed. Evaluating behavioral traits at different time intervals offers a deeper insight into their changes throughout the growth periods and their relationship with production traits, which may be recorded at a less frequent basis.
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Comportamento Alimentar , Suínos/genética , Feminino , Animais , Fenótipo , Modelos LinearesRESUMO
Porcine reproductive and respiratory syndrome (PRRS) is one of the world's most persistent viral pig diseases, with a significant economic impact on the pig industry. PRRS affects pigs of all ages, causing late-term abortions and stillbirths in sows, respiratory disease in piglets, and increased susceptibility to secondary bacterial infection with a high mortality rate. PRRS disease is caused by a positive single-stranded RNA PRRS virus (PRRSV), which has a narrow host-cell tropism limited to monocyte-macrophage lineage cells. Several studies demonstrated that the removal of CD163 protein or, as a minimum, its scavenger receptor cysteine-rich domain 5 (SRCR5) precludes the viral genome release, conferring resistance to PRRSV in live animals. Today, very limited information exists about the impact of such edits on animal performance from birth to maturity in pigs. Using CRISPR-Cas9 with dual-guide RNAs and non-homologous end joining (NHEJ), first-generation (E0) pigs were produced with a deletion of exon 7 in the CD163 gene. The selected pigs were bred to produce the next three generations of pigs to establish multiple lines of pigs homozygous for the edited allele, thereby confirming that the CD163 gene with removed exon 7 was stable during multiple breeding cycles. The pigs were evaluated relative to non-edited pigs from birth to maturity, including any potential changes in meat composition and resistance to PRRSV. This study demonstrates that removing the SRCR5 domain from the CD163 protein confers resistance to PRRSV and, relative to unedited pigs, resulted in no detected differences in meat composition and no changes in the growth rate, health, and ability to farrow. Together, these results support the targeted use of gene editing in livestock animals to address significant diseases without adversely impacting the health and well-being of the animals or the food products derived from them.
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Lung cancer is the third most common cancer with Black/AA men showing higher risk and poorer outcomes than NHW men. Lung cancer disparities are multifactorial, driven by tobacco exposure, inequities in care access, upstream health determinants, and molecular determinants including biological and genetic factors. Elevated expressions of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis have been observed in many cancers. Most importantly, our study shows that PRMT6 displays higher expression in lung cancer tissues of Black/AA men compared to NHW men. In this study, we investigated the underlying mechanism of PRMT6 and its cooperation with PRMT1 to form a heteromer as a driver of lung cancer. Disrupting PRMT1/PRMT6 heteromer by a competitive peptide reduced proliferation in non-small cell lung cancer cell lines and patient-derived organoids, therefore, giving rise to a more strategic approach in the treatment of Black/AA men with lung cancer and to eliminate cancer health disparities.
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Dietary restriction (DR) is a potential intervention for ameliorating ageing-related damages. Mitochondrial quality control is the key mechanism for regulating cellular functions in skeletal muscle. This study aimed to explore the effect of age and DR on the homeostasis of mitochondrial quality control in skeletal muscle. To study the effect of age on mitochondrial homeostasis, young (3 months old) male C57BL/6J mice were fed ad libitum (AL) until 7 (Young), 14 (Middle), and 19 months (Aged) of age. For the DR intervention, 60% of AL intake was given to the mice at 3 months of age until they reached 19 months of age (16 months). The quadriceps femoris muscle was collected for further analysis. Significant changes in the skeletal muscle were noticed during the transition between middle age and the elderly stages. An accumulation of collagen was observed in the muscle after middle age. Compared with the Middle muscle, Aged muscle displayed a greater expression of VDAC, and lower expressions of mitochondrial dynamic proteins and OXPHOS proteins. The DR intervention attenuated collagen content and elongated the sarcomere length in the skeletal muscle during ageing. In addition, DR adjusted the abnormalities in mitochondrial morphology in the Aged muscle. DR downregulated VDAC expression, but upregulated OPA1 and DRP1 expressions. Taken together, greater pathological changes were noticed in the skeletal muscle during ageing, especially in the transition between middle age and the elderly, whereas early-onset DR attenuated the muscular ageing via normalising partial functions of mitochondria.
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Envelhecimento , Restrição Calórica , Camundongos Endogâmicos C57BL , Mitocôndrias Musculares , Músculo Quadríceps , Animais , Masculino , Músculo Quadríceps/metabolismo , Camundongos , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Mitocôndrias Musculares/metabolismo , Colágeno/metabolismoRESUMO
PURPOSE: Weight cycling is a phenomenon characterized by fluctuating body weight that is commonly observed in individuals employing intentional weight loss methods. Despite its prevalence, the impact of weight cycling on health remains equivocal. The current investigation aimed to examine the effects of weight cycling on liver health. METHODS: The weight cycling model was established by switching the feeding method of mice between ad libitum (AL) and restricted intake (DR or 60% of AL) of the breeding diet to cause weight gain and weight loss, respectively. The weight cycling model comprised two and a half cycles, with one group terminating the experience during the weight-gain period (S-AL) and the other during the weight-loss period (S-DR). Liver tissue was collected to investigate morphology alterations, apoptosis, lipid metabolism, and mitochondrial homeostasis. RESULTS: The results demonstrated that the termination point of weight cycling affected body weight and hepatic steatosis. All parameters examined in the S-DR mice exhibited a comparable trend to those observed in the DR mice. Notably, S-AL mice showed a significant increase in lipid metabolism-related proteins in the liver compared to AL-fed mice, along with reduced lipid droplets. Moreover, hepatic apoptosis and fibrosis were exacerbated in the S-AL mice compared to AL mice, whereas mitochondrial fusion, biogenesis, and mitophagy were decreased in the S-AL mice. CONCLUSION: Weight cycling ending in weight gain exacerbated hepatic fibrosis, potentially by inducing apoptosis or disrupting mitochondrial homeostasis. Conversely, weight cycling ending in weight loss demonstrated beneficial effects on hepatic health.
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Fígado , Ciclo de Peso , Camundongos , Masculino , Animais , Fígado/metabolismo , Cirrose Hepática , Aumento de Peso , Redução de Peso , Camundongos Endogâmicos C57BL , Dieta HiperlipídicaRESUMO
The influence of inhaled corticosteroids (ICS) on COVID-19 outcomes remains uncertain. To address this, we conducted a systematic review and meta-analysis, analyzing 30 studies, to investigate the impact of ICS on patients with COVID-19. Our study focused on various outcomes, including mortality risk, hospitalization, admission to the intensive care unit (ICU), mechanical ventilation (MV) utilization, and length of hospital stay. Additionally, we conducted a subgroup analysis to assess the effect of ICS on patients with chronic obstructive pulmonary disease (COPD) and asthma. Our findings suggest that the prior use of ICS did not lead to significant differences in mortality risk, ICU admission, hospitalization, or MV utilization between individuals who had used ICS previously and those who had not. However, in the subgroup analysis of patients with COPD, prior ICS use was associated with a lower risk of mortality compared to non-users (OR, 0.95; 95% CI, 0.90-1.00). Overall, while the use of ICS did not significantly affect COVID-19 outcomes in general, it may have beneficial effects specifically for patients with COPD. Nevertheless, more research is needed to establish a definitive conclusion on the role of ICS in COVID-19 treatment. PROSPERO registration number: CRD42021279429.
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COVID-19 , Doença Pulmonar Obstrutiva Crônica , Humanos , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , COVID-19/complicações , Tratamento Farmacológico da COVID-19 , Doença Pulmonar Obstrutiva Crônica/complicaçõesRESUMO
Nanofibrous mats as a wound dressing have received great attention in recent year. The development of biocompatible dressings with antibiofouling capability and long-lasting antibacterial properties is important but challenging. Antibacterial photodynamic therapy (aPDT) effectively eliminates pathogens via a photodynamic process that can circumvent the emergence of antibiotic-resistant pathogens. In this study, we integrated the zwitterionic materials (2-methacryloyloxyethyl phosphorylcholine (MPC) moiety) and aPDT photosensitizer, methylene blue (MB), to fabricate a long-lasting antibacterial nanofibrous mat using electrospinning technology. The prepared nanofibers possessed an appropriate water absorption and retention ability, superior cytocompatibility, and antibiofouling ability against both proteins and L929 cell adhesion. MB-loaded nanofibrous mats have exhibited superior aPDT against Gram-positive Staphylococcus aureus compared to Gram-negative Escherichia coli under moderate irradiation (100 W m-2) due to the presence of an extra outer membrane of Gram-negative bacteria serving as a protective barrier. In vitro release study demonstrated that the nanofibrous mat had a long-lasting drug release profile, which can efficiently suppress bacterial growth via aPDT. The antibacterial ability of the MB-loaded nanofibrous mat was commensurate or slightly inferior to antibiotics such as tetracycline and kanamycin, suggesting that it has the potential to be used as an antibiotic alternative. Overall, this zwitterionic nanofibrous mat with long-lasting aPDT function and nonadherent properties has potential as a promising antibacterial wound dressing.
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Coronavirus Disease 2019 (COVID-19) has been associated with a high thromboembolic risk among patients in intensive care units. Asian populations may share a similar thromboembolic risk, but with a higher prevalence of arterial thromboembolism than venous thromboembolism. To clarify this risk in Taiwan, this single-center retrospective study collected 27 consecutive intensive care unit patients with COVID-19 confirmed by polymerase chain reaction, with a median age of 67.6 years (male 81.5%). Twenty-three patients received prophylactic anticoagulation (85.2%), and there were four bleeding events (14.8%). Nine patients had thromboembolism (33.3%), including three with deep vein thrombosis, two with peripheral artery thromboembolism, and four with ischemic stroke. There were no significant clinical differences between the patients with or without thromboembolism. Initial serum ferritin [adjusted odds ratio (OR): 13.19, 95% confidence interval (CI): 1.01-172.07] and peak serum procalcitonin (adjusted OR: 18.93, 95% CI: 1.08-330.91) were associated with a higher risk of thromboembolism. Furthermore, prophylactic anticoagulation (adjusted OR: 0.01, 95% CI: < 0.001-0.55) was associated with a lower risk of thromboembolism. All cases of deep vein thrombosis and one peripheral artery thromboembolism occurred at intravascular catheter locations. No association between thromboembolism and survival was found (age-adjusted hazard ratio: 0.55, 95% CI: 0.10-2.95). In conclusion, the prevalence of COVID-19 thromboembolism among Taiwanese patients in intensive care units was high, even with prophylactic anticoagulation. Serum ferritin and procalcitonin may identify high-risk populations. Prophylactic anticoagulation may reduce the risk of thromboembolism with a manageable bleeding risk. Larger prospective studies are needed to clarify the risk of COVID-19 thromboembolism and its risk factors in the post-Omicron era.
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Historical data collection for genetic evaluation purposes is a common practice in animal populations; however, the larger the dataset, the higher the computing power needed to perform the analyses. Also, fitting the same model to historical and recent data may be inappropriate. Data truncation can reduce the number of equations to solve, consequently decreasing computing costs; however, the large volume of genotypes is responsible for most of the increase in computations. This study aimed to assess the impact of removing genotypes along with phenotypes and pedigree on the computing performance, reliability, and inflation of genomic predicted breeding value (GEBV) from single-step genomic best linear unbiased predictor for selection candidates. Data from two pig lines, a terminal sire (L1) and a maternal line (L2), were analyzed in this study. Four analyses were implemented: growth and "weaning to finish" mortality on L1, pre-weaning and reproductive traits on L2. Four genotype removal scenarios were proposed: removing genotyped animals without phenotypes and progeny (noInfo), removing genotyped animals based on birth year (Age), the combination of noInfo and Age scenarios (noInfoâ +â Age), and no genotype removal (AllGen). In all scenarios, phenotypes were removed, based on birth year, and three pedigree depths were tested: two and three generations traced back and using the entire pedigree. The full dataset contained 1,452,257 phenotypes for growth traits, 324,397 for weaning to finish mortality, 517,446 for pre-weaning traits, and 7,853,629 for reproductive traits in pure and crossbred pigs. Pedigree files for lines L1 and L2 comprised 3,601,369 and 11,240,865 animals, of which 168,734 and 170,121 were genotyped, respectively. In each truncation scenario, the linear regression method was used to assess the reliability and dispersion of GEBV for genotyped parents (born after 2019). The number of years of data that could be removed without harming reliability depended on the number of records, type of analyses (multitrait vs. single trait), the heritability of the trait, and data structure. All scenarios had similar reliabilities, except for noInfo, which performed better in the growth analysis. Based on the data used in this study, considering the last ten years of phenotypes, tracing three generations back in the pedigree, and removing genotyped animals not contributing own or progeny phenotypes, increases computing efficiency with no change in the ability to predict breeding values.
Recording data for long years is common in animal breeding and genetics. However, the larger the data, the higher the computing cost of the analysis, especially with genomic information. This study aimed to investigate the impact of removing data, namely, genotypes, phenotypes, and pedigree, on the computing performance and prediction ability of genomic breeding values. We tested four scenarios to remove genotyped individuals in pig populations. For each scenario, phenotypes were removed according to birth year, and the pedigree was either kept complete or traced back from two to three generations. Reliabilities for young, genotyped animals did not differ after removing genotypes for older or less important animals. However, using only two generations of data slightly reduces the reliability for young, genotyped animals. The dispersion did not change across the studied scenarios, and its worst value was observed when using only one generation in the pedigree. Using the last ten years of phenotypes, a pedigree depth of three generations, and removing genotyped animals not contributing own or progeny phenotypes reduces computing cost with no change in the ability to predict breeding values.
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Genômica , Modelos Genéticos , Animais , Suínos/genética , Linhagem , Reprodutibilidade dos Testes , Fenótipo , Genômica/métodosRESUMO
Hypoxic microenvironment and limited penetration of photosensitizers within solid tumors are two crucial factors that restrict photodynamic therapy (PDT) efficacy. Herein, a new fluorinated mixed micelle (M60@PFC-Ce6) is developed as a tumor-penetrating and oxygen-enriching nanoplatform, which consists of chlorin e6 (Ce6) and perfluorocarbons (PFCs) co-loaded into fluorinated micelles to relieve hypoxia conditions as well as folate as targeting ligand that facilitates the selective biodistribution within tumor solids. The incorporation of fluorinated copolymers into mixed micelles exhibits not only a great increase in the oxygen-loading capacity, but also improves the stability of liquid PFCs emulsion within micelles without leakage. M60@PFC-Ce6 shows excellent oxygen delivery capability, good intracellular reactive oxygen species (ROS) generation, and superior phototoxicity in vitro for both 2D monolayer of cells and 3D multicellular spheroid model. These results indicate the enriched oxygen delivery and increased cellular uptake resulting from folate-targeted ability to enhance ROS production and PDT efficacy. The penetration study of M60@PFC-Ce6 into a 3D spheroid confirms that small micellar size and folate-conjugation are beneficial for micelles to penetrate and accumulate within spheroids. Thus, a new nanoplatform with enriched oxygen-carrying amounts, better drug penetration, and stable micellar properties that relieve tumor hypoxia and improve PDT efficacy is provided.
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Nanopartículas , Fotoquimioterapia , Porfirinas , Fotoquimioterapia/métodos , Oxigênio , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Micelas , Distribuição Tecidual , Fármacos Fotossensibilizantes/farmacologia , Ácido Fólico , Nanopartículas/uso terapêuticoRESUMO
BACKGROUND: Most genomic prediction applications in animal breeding use genotypes with tens of thousands of single nucleotide polymorphisms (SNPs). However, modern sequencing technologies and imputation algorithms can generate ultra-high-density genotypes (including millions of SNPs) at an affordable cost. Empirical studies have not produced clear evidence that using ultra-high-density genotypes can significantly improve prediction accuracy. However, (whole-genome) prediction accuracy is not very informative about the ability of a model to capture the genetic signals from specific genomic regions. To address this problem, we propose a simple methodology that detects chromosome regions for which a specific model (e.g., single-step genomic best linear unbiased prediction (ssGBLUP)) may fail to fully capture the genetic signal present in such segments-a phenomenon that we refer to as signal leakage. We propose to detect regions with evidence of signal leakage by testing the association of residuals from a pedigree or a genomic model with SNP genotypes. We discuss how this approach can be used to map regions with signals that are poorly captured by a model and to identify strategies to fix those problems (e.g., using a different prior or increasing marker density). Finally, we explored the proposed approach to scan for signal leakage of different models (pedigree-based, ssGBLUP, and various Bayesian models) applied to growth-related phenotypes (average daily gain and backfat thickness) in pigs. RESULTS: We report widespread evidence of signal leakage for pedigree-based models. Including a percentage of animals with SNP data in ssGBLUP reduced the extent of signal leakage. However, local peaks of missed signals remained in some regions, even when all animals were genotyped. Using variable selection priors solves leakage points that are caused by excessive shrinkage of marker effects. Nevertheless, these models still miss signals in some regions due to low linkage disequilibrium between the SNPs on the array used and causal variants. Thus, we discuss how such problems could be addressed by adding sequence SNPs from those regions to the prediction model. CONCLUSIONS: Residual single-marker regression analysis is a simple approach that can be used to detect regional genomic signals that are poorly captured by a model and to indicate ways to fix such problems.
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Genoma , Genômica , Animais , Suínos , Teorema de Bayes , Genômica/métodos , Genótipo , Fenótipo , Polimorfismo de Nucleotídeo Único , Linhagem , Modelos GenéticosRESUMO
Weaning is a critical period in raising pigs. Novel animal feed additives that promote gut health and regulate immune function of piglets without antibiotics are needed. In this study, we aimed to test the ability of mesobiliverdin IXα-enriched microalgae (MBV IXα-enriched microalgae) to eliminate reliance on antibiotics to promote intestinal health in piglets. Eighty 28-day-old weaned piglets were randomly allocated to four groups each with four replicate pens and five piglets per pen. The dietary treatments were a basal diet as control (NC), basal diet plus 0.05% tylosin (PC), basal diet plus 0.1% or 0.5% MBV IXα-enriched microalgae as low (MBV-SP1) or high (MBV-SP2) dose respectively. All treated animals showed no significant differences in live weight, average daily gain and feed efficiency compared to control animals. Histological examination showed that MBV-SP1 and particularly MBV-SP2 increased the ratio of villus height to crypt depth in the jejunum and ileum compared to NC (p < 0.05). Similarly, tylosin treatment also increased villi lengths and the ratio of villus height to crypt depth in the jejunum and ileum compared to the NC (p < 0.05). MBV-SP1 and particularly MBV-SP2 reduced the levels of inflammatory cytokines interleukin-6 and tumour necrosis factor-alpha in the small intestine. MBV-SP2 and tylosin similarly reduced the lipid peroxidation marker (TBARS value) in the duodenum and ileum. In conclusion, feed supplementation with MBV IXα-enriched microalgae improved gut health by villus height and production of immunomodulators that correlated with down-regulated secretion of inflammatory cytokines.
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Suplementos Nutricionais , Microalgas , Animais , Suínos , Desmame , Tilosina/farmacologia , Antibacterianos/farmacologia , Dieta/veterinária , Citocinas , Ração Animal/análiseRESUMO
BACKGROUND: Whole-genome sequence (WGS) data harbor causative variants that may not be present in standard single nucleotide polymorphism (SNP) chip data. The objective of this study was to investigate the impact of using preselected variants from WGS for single-step genomic predictions in maternal and terminal pig lines with up to 1.8k sequenced and 104k sequence imputed animals per line. METHODS: Two maternal and four terminal lines were investigated for eight and seven traits, respectively. The number of sequenced animals ranged from 1365 to 1491 for the maternal lines and 381 to 1865 for the terminal lines. Imputation to sequence occurred within each line for 66k to 76k animals for the maternal lines and 29k to 104k animals for the terminal lines. Two preselected SNP sets were generated based on a genome-wide association study (GWAS). Top40k included the SNPs with the lowest p-value in each of the 40k genomic windows, and ChipPlusSign included significant variants integrated into the porcine SNP chip used for routine genotyping. We compared the performance of single-step genomic predictions between using preselected SNP sets assuming equal or different variances and the standard porcine SNP chip. RESULTS: In the maternal lines, ChipPlusSign and Top40k showed an average increase in accuracy of 0.6 and 4.9%, respectively, compared to the regular porcine SNP chip. The greatest increase was obtained with Top40k, particularly for fertility traits, for which the initial accuracy based on the standard SNP chip was low. However, in the terminal lines, Top40k resulted in an average loss of accuracy of 1%. ChipPlusSign provided a positive, although small, gain in accuracy (0.9%). Assigning different variances for the SNPs slightly improved accuracies when using variances obtained from BayesR. However, increases were inconsistent across the lines and traits. CONCLUSIONS: The benefit of using sequence data depends on the line, the size of the genotyped population, and how the WGS variants are preselected. When WGS data are available on hundreds of thousands of animals, using sequence data presents an advantage but this remains limited in pigs.