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1.
J Dairy Sci ; 107(3): 1535-1548, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37690717

RESUMEN

Disease-related milk losses directly affect dairy herds' profitability and the production efficiency of the dairy industry. Therefore, this study aimed to quantify phenotypic variability in milk fluctuation periods related to diseases and to explore milk fluctuation traits as indicators of disease resilience. By combining high-frequency daily milk yield data with disease records of cows that were treated and recovered from the disease, we estimated milk variability trends within a fixed period around the treatment day of each record for 5 diseases: udder health, reproductive disorders, metabolic disorders, digestive disorders, and hoof health. The average milk yield decreased rapidly from 6 to 8 d before the treatment day for all diseases, with the largest milk reduction observed on the treatment day. Additionally, we assessed the significance of milk fluctuation periods highly related to diseases by defining milk fluctuations as a period of at least 10 consecutive days in which milk yield fell below 90% of the expected milk production values at least once. We defined the development and recovery phases of milk fluctuations using 3,847 milk fluctuation periods related to disease incidences, and estimated genetic parameters of milk fluctuation traits, including milk losses, duration of the fluctuation, variation rate in daily milk yield, and standard deviation of milk deviations for each phase and their genetic correlation with several important traits. In general, the disease-related milk fluctuation periods lasted 21.19 ± 10.36 d with a milk loss of 115.54 ± 92.49 kg per lactation. Compared with the development phase, the recovery phase lasted an average of 3.3 d longer, in which cows produced 11.04 kg less milk and exhibited a slower variation rate in daily milk yield of 0.35 kg/d. There were notable differences in milk fluctuation traits depending on the disease, and greater milk losses were observed when multiple diseases occurred simultaneously. All milk fluctuation traits evaluated were heritable with heritability estimates ranging from 0.01 to 0.10, and moderate to high genetic correlations with milk yield (0.34 to 0.64), milk loss throughout the lactation (0.22 to 0.97), and resilience indicator (0.39 to 0.95). These results indicate that cows with lower milk losses and higher resilience tend to have more stable milk fluctuations, which supports the potential for breeding for more disease-resilient cows based on milk fluctuation traits. Overall, this study confirms the high effect of diseases on milk yield variability and provides insightful information about their relationship with relevant traits in Holstein cattle. Furthermore, this study shows the potential of using high-frequency automatic monitoring of milk yield to assist on breeding practices and health management in dairy cows.


Asunto(s)
Leche , Resiliencia Psicológica , Femenino , Bovinos , Animales , Lactancia , Glándulas Mamarias Animales , Fenotipo
2.
BMC Genomics ; 24(1): 733, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38049711

RESUMEN

BACKGROUND: Eurasian pigs have undergone lineage admixture throughout history. It has been confirmed that the genes of indigenous pig breeds in China have been introduced into Western commercial pigs, providing genetic materials for breeding Western pigs. Pigs in Taihu Lake region (TL), such as the Meishan pig and Erhualian pig, serve as typical representatives of indigenous pig breeds in China due to their high reproductive performances. These pigs have also been imported into European countries in 1970 and 1980 s. They have played a positive role in improving the reproductive performances in European commercial pigs such as French Large White pigs (FLW). However, it is currently unclear if the lineage of TL pigs have been introgressed into the Danish Large White pigs (DLW), which are also known for their high reproductive performances in European pigs. To systematically identify genomic regions in which TL pigs have introgressed into DLW pigs and their physiological functions, we collected the re-sequencing data from 304 Eurasian pigs, to identify shared haplotypes between DLW and TL pigs. RESULTS: The findings revealed the presence of introgressed genomic regions from TL pigs in the genome of DLW pigs indeed. The genes annotated within these regions were found to be mainly enriched in neurodevelopmental pathways. Furthermore, we found that the 115 kb region located in SSC16 exhibited highly shared haplotypes between TL and DLW pigs. The major haplotype of TL pigs in this region could significantly improve reproductive performances in various pig populations. Around this genomic region, NDUFS4 gene was highly expressed and showed differential expression in multiple reproductive tissues between extremely high and low farrowing Erhualian pigs. This suggested that NDUFS4 gene could be an important candidate causal gene responsible for affecting the reproductive performances of DLW pigs. CONCLUSIONS: Our study has furthered our knowledge of the pattern of introgression from TL into DLW pigs and the potential effects on the fertility of DLW pigs.


Asunto(s)
Lagos , Sus scrofa , Porcinos/genética , Animales , Sus scrofa/genética , Genoma , Fertilidad/genética , Polimorfismo de Nucleótido Simple , Dinamarca
3.
Mol Cell Biochem ; 478(1): 1-11, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35708865

RESUMEN

This study aimed to explore the role of IL-10 in the pathogenesis of HIV/AIDS patients with cryptococcal meningitis (CM).Patients were assigned into 4 groups (n = 40/group): group A (HIV/AIDS with CM), group B (HIV/AIDS with tuberculosis), group C (HIV/AIDS), and group D (CM). The levels of IL-10 and associated indicators were measured and the correlations were analyzed by Pearson correlation and partial correlation method. In plasma and cerebrospinal fluid (CSF), no significant difference was observed on IL-10 level between group A and other groups (P > 0.050). R values for IL-10 and relevant indicators in blood were as follows (P < 0.050): group A, IFN-γ (-0.377), IL-12 (0.743), IL-4 (0.881), and IL-6 (0.843); group B, IL-12 (0.740), IL-4 (0.573), and IL-6 (0.900); group C, IL-12 (0.402) and IL-4 (0.896); group D, IL-12 (0.575), IL-4 (0.852), and CD8 (0.325). R values for IL-10 and related indicators in CSF were as follows (P < 0.050): group A, TNF-α (0.664), IL-4 (0.852), white blood cells (WBCs, 0.321) and total protein (TP, 0.330); group B, TNF-α (0.566), IL-4 (0.702), and lactate dehydrogenase (LDH, 0.382); group D, IFN-γ (0.807) and IL-4 (0.441). IL-10 level was positively correlated with IL-4, IL-6, IL-12, TNF-α, WBC, and TP in blood or CSF, and negatively correlated with IFN-γ in blood, suggesting that IL-10 affected both pro-inflammatory and anti-inflammatory activities in the pathogenesis of HIV/AIDS with CM.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Meningitis Criptocócica , Humanos , Infecciones por VIH/complicaciones , Interleucina-10 , Interleucina-12 , Interleucina-4 , Interleucina-6 , Meningitis Criptocócica/líquido cefalorraquídeo , Factor de Necrosis Tumoral alfa
4.
Genet Sel Evol ; 55(1): 45, 2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37407936

RESUMEN

BACKGROUND: The breeding value of a crossbred individual can be expressed as the sum of the contributions from each of the contributing pure breeds. In theory, the breeding value should account for segregation between breeds, which results from the difference in the mean contribution of loci between breeds, which in turn is caused by differences in allele frequencies between breeds. However, with multiple generations of crossbreeding, how to account for breed segregation in genomic models that split the breeding value of crossbreds based on breed origin of alleles (BOA) is not known. Furthermore, local breed proportions (LBP) have been modelled based on BOA and is a concept related to breed segregation. The objectives of this study were to explore the theoretical background of the effect of LBP and how it relates to breed segregation and to investigate how to incorporate breed segregation (co)variance in genomic BOA models. RESULTS: We showed that LBP effects result from the difference in the mean contribution of loci between breeds in an additive genetic model, i.e. breed segregation effects. We found that the (co)variance structure for BS effects in genomic BOA models does not lead to relationship matrices that are positive semi-definite in all cases. However, by setting one breed as a reference breed, a valid (co)variance structure can be constructed by including LBP effects for all other breeds and assuming them to be correlated. We successfully estimated variance components for a genomic BOA model with LBP effects in a simulated example. CONCLUSIONS: Breed segregation effects and LBP effects are two alternative ways to account for the contribution of differences in the mean effects of loci between breeds. When the covariance between LBP effects across breeds is included in the model, a valid (co)variance structure for LBP effects can be constructed by setting one breed as reference breed and fitting an LBP effect for each of the other breeds.


Asunto(s)
Genómica , Modelos Genéticos , Genómica/métodos , Hibridación Genética , Frecuencia de los Genes , Alelos
5.
J Anim Breed Genet ; 140(4): 355-365, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36843354

RESUMEN

Reproductive traits of dairy cattle are bound to the actual efficiency of farm operation, which therefore show great economic importance. Among them, some traits were deemed to be simultaneously affected by service sire and mating cow. Service sires are proved to play an important role in reproduction process of cows. However, limited study explored the genetic effect of service sire (GESS), let alone the genomic prediction of this effect. In the present study, 2244 genotyped bulls together with phenotypic records were used to predict the GESS on conception rate, 56-day non-return rate, calving ease, stillbirth and gestation length. The feasibilities of multi-step genomic best linear unbiased predictor (msGBLUP) and single-step genomic best linear unbiased predictor (ssGBLUP) were investigated under different scenarios, that is, different marker densities and validation population. The predictive accuracies and unbiasedness for GESS ranged from 0.159 to 0.647 and from 0.202 to 2.018, respectively, when validated on young bulls, while the accuracies and unbiasedness ranged from 0.409 to 0.802 and 0.333 to 1.146 when validated on random split data sets. It is feasible to predict GESS on reproductive traits by using a linear mixed model and genomic data, and high-density marker panel had limited contribution to the prediction. This research investigated the potential factors that influence the genomic prediction of GESS on reproductive traits and indicated the possibility of genomic selection on GESS, both in ideal and practical circumstances.


Asunto(s)
Genoma , Reproducción , Bovinos/genética , Animales , Femenino , Masculino , Reproducción/genética , Genoma/genética , Genotipo , Genómica/métodos , Fenotipo
6.
Heredity (Edinb) ; 128(3): 154-158, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35132207

RESUMEN

The dominance effect is considered to be a key factor affecting complex traits. However, previous studies have shown that the improvement of the model, including the dominance effect, is usually less than 1%. This study proposes a novel genomic prediction method called CADM, which combines additive and dominance genetic effects through locus-specific weights on heterozygous genotypes. To the best of our knowledge, this is the first study of weighting dominance effects for genomic prediction. This method was applied to the analysis of chicken (511 birds) and pig (3534 animals) datasets. A 5-fold cross-validation method was used to evaluate the genomic predictive ability. The CADM model was compared with typical models considering additive and dominance genetic effects (ADM) and the model considering only additive genetic effects (AM). Based on the chicken data, using the CADM model, the genomic predictive abilities were improved for all three traits (body weight at 12th week, eviscerating percentage, and breast muscle percentage), and the average improvement in prediction accuracy was 27.1% compared with the AM model, while the ADM model was not better than the AM model. Based on the pig data, the CADM model increased the genomic predictive ability for all the three pig traits (trait names are masked, here designated as T1, T2, and T3), with an average increase of 26.3%, and the ADM model did not improve, or even slightly decreased, compared with the AM model. The results indicate that dominant genetic variation is one of the important sources of phenotypic variation, and the novel prediction model significantly improves the accuracy of genomic prediction.


Asunto(s)
Modelos Genéticos , Polimorfismo de Nucleótido Simple , Animales , Genoma , Genómica/métodos , Genotipo , Heterocigoto , Fenotipo , Porcinos/genética
7.
J Dairy Sci ; 105(6): 5178-5191, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35465992

RESUMEN

Genomic predictions have been applied for dairy cattle for more than a decade with great success, but genomic estimated breeding values (GEBV) are not widely available for crossbred dairy cows. The large reference populations already in place for genomic evaluations of many pure breeds makes it interesting to use the accurate solutions, in particular the estimated marker effects, from these evaluations for calculation of GEBV for crossbred heifers and cows. Effects of marker alleles in crossbred animals can depend on breed origin of the alleles (BOA). Therefore, our aim was to investigate if reliable GEBV for crossbred dairy cows can be obtained by combining estimated marker effects from purebred evaluations based on BOA. We used data on 5,467 Danish crossbred dairy cows with contributions from Holstein, Jersey, and Red Dairy Cattle breeds. We assessed BOA assignment on their genotypes and found that we could assign 99.3% of the alleles to a definite breed of origin. We compared GEBV for 2 traits, protein yield and interval between first and last insemination of cows, with 2 models that both combine estimated marker effects from the genomic evaluations of the pure breeds: a breed of origin model that accounts for BOA and a breed proportion model that only accounts for genomic breed proportions in the crossbred animals. We accounted for the difference in level between the purebred evaluations by including intercepts in the models based on phenotypic averages. The predictive ability for protein yield was significantly higher from the breed of origin model, 0.45 compared with 0.43 from the breed proportion model. Furthermore, for the breed proportion model, the GEBVs had level bias, which made comparison across groups with different breed composition skewed. We therefore concluded that reliable genomic predictions for crossbred dairy cows can be obtained by combining estimated marker effects from the genomic evaluations of purebreds using a model that accounts for BOA.


Asunto(s)
Genómica , Alelos , Animales , Bovinos/genética , Femenino , Genotipo , Fenotipo
8.
J Dairy Sci ; 105(3): 2426-2438, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35033341

RESUMEN

This study investigated the reliability of genomic prediction (GP) using breed origin of alleles (BOA) approach in the Nordic Red (RDC) population, which has an admixed population structure. The RDC population consists of animals with varying degrees of genetic materials from the Danish Red (RDM), Swedish Red (SRB), Finnish Ayrshire (FAY), and Holstein (HOL) because bulls have been used across the breeds. The BOA approach was tested using 39,550 RDC animals in the reference population and 11,786 in the validation population. Deregressed proofs (DRP) of milk, fat and protein were used as response variable for GP. Direct genomic breeding values (DGV) for animals in the validation population were calculated with (BOA model) or without (joint model) considering breed origin of alleles. The joint model assumed homogeneous marker effects and a single set of marker effects were estimated, whereas BOA model assumed heterogeneous marker effects, and different sets of marker effects were estimated across the breeds. For the BOA approach, we tested scenarios assuming both correlated (BOA_cor) and uncorrelated (BOA_uncor) marker effects between the breeds. Additionally, we investigated GP using a standard Illumina 50K chip and including SNP selected from imputed whole-genome sequencing (50K+WGS). We also studied the effect of estimating (co)variances for genome regions of different sizes to exploit the information of the genome regions contributing to the (co)variance between the breeds. Region sizes were set as 1 SNP, a group of 30 or 100 adjacent SNP, or the whole genome. Reliability of DGV was measured as squared correlations between DGV and DRP divided by the reliability of DRP. Across the 3 traits, in general, RS30 and RS100 SNP yielded the highest reliabilities. Including WGS SNP improved reliabilities in almost all scenarios (0.297 on average for 50K and 0.307 on average for 50K+WGS). The BOA_uncor (0.233 on average) was inferior to the joint model (0.339 on average), but the reliabilities obtained using BOA_cor (0.334 on average) in most cases were not significantly different from those obtained using the joint model. The results indicate that both including additional whole-genome sequencing SNP and dividing the genome into fixed regions improve GP in the RDC. The BOA models have the potential to increase the reliability of GP, but the benefit is limited in populations with a high exchange of genetic material for a long time, as is the case for RDC.


Asunto(s)
Bovinos , Genómica , Polimorfismo de Nucleótido Simple , Alelos , Animales , Cruzamiento , Bovinos/genética , Genómica/métodos , Genotipo , Masculino , Fenotipo , Reproducibilidad de los Resultados
9.
J Dairy Sci ; 105(12): 9822-9836, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36307242

RESUMEN

For genomic prediction of crossbred animals, models that account for the breed origin of alleles (BOA) in marker genotypes can allow the effects of marker alleles to differ depending on their ancestral breed. Previous studies have shown that genomic estimated breeding values for crossbred cows can be calculated using the marker effects that are estimated in the contributing pure breeds and combined based on estimated BOA in the genotypes of the crossbred cows. In the presented study, we further exploit the BOA information for improving the prediction of genomic breeding values of crossbred dairy cows. We investigated 2 types of BOA-derived breed proportions: global breed proportions, defined as the proportion of marker alleles assigned to each breed across the whole genome; and local breed proportions (LBP), defined as the proportions of alleles on chromosome segments which were assigned to each breed. Further, we investigated 2 BOA-derived measures of heterozygosity for the prediction of total genetic value. First, global breed heterozygosity, defined as the proportion of marker loci that have alleles originating in 2 different breeds over the whole genome. Second, local breed heterozygosity (LBH), defined as proportions of marker loci on chromosome segments that had alleles originating in 2 different breeds. We estimated variance related to LBP and LBH on the remaining variation after accounting for prediction with solutions from the genomic evaluations of the pure breeds and validated alternative models for production traits in 5,214 Danish crossbred dairy cows. The estimated LBP variances were 0.9, 1.2, and 1.0% of phenotypic variance for milk, fat, and protein yield, respectively. We observed no clear LBH effect. Cross-validation showed that models with LBP effects had a numerically small but statistically significantly higher predictive ability than models only including global breed proportions. We observed similar improvement in accuracy by the model having an across crossbred residual additive genetic effect, accounting for the additive genetic variation that was not accounted for by the solutions from purebred. For genomic predictions of crossbred animals, estimated BOA can give useful information on breed proportions, both globally in the genome and locally in genome regions, and on breed heterozygosity.


Asunto(s)
Modelos Genéticos , Polimorfismo de Nucleótido Simple , Femenino , Bovinos/genética , Animales , Genómica , Alelos , Genotipo , Fenotipo
10.
J Dairy Sci ; 105(8): 6749-6759, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35840408

RESUMEN

High mortality and involuntary culling rates cause great economic losses to the worldwide dairy cattle industry. However, there is low emphasis on wellness traits in replacement animals (dairy calves and replacement heifers) during their development stages in modern dairy cattle breeding programs. Therefore, the main objectives of this study were to estimate genetic parameters of wellness traits in replacement cattle (replacement wellness traits) and obtain their genetic correlations with 12 cow health and longevity traits in the Chinese Holstein population. Seven replacement wellness traits were analyzed, including birth weight, survival from 3 to 60 d (Sur1), survival from 61 to 365 d (Sur2), survival from 366 d to the first calving (Sur3), calf diarrhea, calf pneumonia, and calf serum total protein (STP). Single and bivariate animal models were employed to estimate (co)variance components using the data from 189,980 Holstein cattle. The genetic correlations between replacement wellness traits and cow longevity, health traits were calculated by employing bivariate models, including 6 longevity traits and 6 health traits (clinical mastitis, metritis, ketosis, displaced abomasum, milk fever, and hoof health or hoof disease). The estimated heritabilities (± SE) were 0.335 (± 0.008), 0.088 (± 0.005), 0.166 (± 0.006), 0.102 (±0 .006), 0.048 (± 0.003), 0.063 (± 0.004), and 0.170 (± 0.019) for birth weight, Sur1, Sur2, Sur3, pneumonia, diarrhea, and STP, respectively. The majority of the genetic correlations among the 7 replacement wellness traits were negligible. The genetic correlations among Sur1, Sur2, and Sur3 ranged from 0.112 (Sur1 and Sur3) to 0.445 (Sur1 and Sur2) when fitting a linear model (estimates in the observed scale), and from 0.560 (Sur1 and Sur3) to 0.773 (Sur1 and Sur2) when fitting a threshold model (estimates in the liability scale). The genetic correlations between replacement wellness and cow longevity were low (absolute value lower than 0.30), but some of them were significantly different from zero. Compared with other replacement wellness traits, Sur3 and STP had relatively high genetic correlations with cow longevity. Replacement wellness traits are heritable and can be improved through direct genetic and genomic selection. The results from the current study will contribute for better balancing dairy cattle breeding goals to genetically improve dairy cattle wellness in the period from birth to first calving.


Asunto(s)
Enfermedades de los Bovinos , Longevidad , Animales , Peso al Nacer , Bovinos/genética , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/genética , Diarrea/veterinaria , Femenino , Lactancia/genética , Longevidad/genética , Leche
11.
Heredity (Edinb) ; 127(6): 546-553, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34750534

RESUMEN

There are rich and vast genetic resources of indigenous pig breeds in the world. Currently, great attention is paid to either crossbreeding or conservation of these indigenous pig breeds, and insufficient attention is paid to the combination of conservation and breeding along with their long-term effects on genetic diversity. Therefore, the objective of this study is to compare the long-term effects of using conventional conservation and optimal contribution selection methods on genetic diversity and genetic gain. A total of 11 different methods including conventional conservation and optimal contribution selection methods were investigated using stochastic simulations. The long-term effects of using these methods were evaluated in terms of genetic diversity metrices such as expected heterozygosity (He) and the rate of genetic gain. The results indicated that the rates of true inbreeding in these conventional conservation methods were maintained at around 0.01. The optimal contribution selection methods based either on the pedigree (POCS) or genome (GOCS) information showed more genetic gain than conventional methods, and POCS achieved the largest genetic gain. Furthermore, the effect of using GOCS methods on most of the genetic diversity metrics was slightly better than the conventional conservation methods when the rate of true inbreeding was the same, but this also required more sires used in OCS methods. According to the rate of true inbreeding, there was no significant difference among these conventional methods. In conclusion, there is no significant difference in different ways of selecting sows on inbreeding when we use different conventional conservation methods. Compared with conventional methods, POCS method could achieve the most genetic gain. However, GOCS methods can not only achieve higher genetic gain, but also maintain a relatively high level of genetic diversity. Therefore, GOCS is a better choice if we want to combine conservation and breeding in actual production in the conservation farms.


Asunto(s)
Genoma , Endogamia , Animales , Femenino , Variación Genética , Heterocigoto , Linaje , Porcinos
12.
Heredity (Edinb) ; 126(1): 206-217, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32665691

RESUMEN

Records on groups of individuals could be valuable for predicting breeding values when a trait is difficult or costly to measure on single individuals, such as feed intake and egg production. Adding genomic information has shown improvement in the accuracy of genetic evaluation of quantitative traits with individual records. Here, we investigated the value of genomic information for traits with group records. Besides, we investigated the improvement in accuracy of genetic evaluation for group-recorded traits when including information on a correlated trait with individual records. The study was based on a simulated pig population, including three scenarios of group structure and size. The results showed that both the genomic information and a correlated trait increased the accuracy of estimated breeding values (EBVs) for traits with group records. The accuracies of EBV obtained from group records with a size 24 were much lower than those with a size 12. Random assignment of animals to pens led to lower accuracy due to the weaker relationship between individuals within each group. It suggests that group records are valuable for genetic evaluation of a trait that is difficult to record on individuals, and the accuracy of genetic evaluation can be considerably increased using genomic information. Moreover, the genetic evaluation for a trait with group records can be greatly improved using a bivariate model, including correlated traits that are recorded individually. For efficient use of group records in genetic evaluation, relatively small group size and close relationships between individuals within one group are recommended.


Asunto(s)
Cruzamiento , Genómica , Animales , Porcinos
13.
Rapid Commun Mass Spectrom ; 35(22): e9195, 2021 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-34491599

RESUMEN

RATIONALE: Pyrotinib is an irreversible EGFR/HER2 inhibitor that has shown antitumor activity and tolerance in the treatment of breast cancer. Studies focused on its metabolic pathways and major metabolites are insufficient. In the evaluation of drug safety and therapeutic use, metabolite characterization is critical. The metabolism of pyrotinib in vitro was studied utilizing rat, dog and human hepatocytes in this study. METHODS: Pyrotinib (10 µM) was incubated with hepatocytes in Williams' E medium. The metabolites were examined and profiled using ultrahigh-performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry. The metabolite structures were deduced by comparing their precise molecular weights, fragment ions and retention times with those of the parent drug. RESULTS: A total of 16 metabolites, including 6 novel ones, were discovered and structurally described under the present conditions. Oxidation, demethylation, dehydrogenation, O-dealkylation and glutathione (GSH) conjugation were all involved in the metabolism of pyrotinib in hepatocytes. The most predominant metabolic route was identified as GSH conjugation (M5). CONCLUSIONS: This study generated valuable metabolite profiles of pyrotinib in several species, which will aid in the understanding of the drug's disposition in various species and in evaluating the contribution of metabolites to overall effectiveness and toxicity of pyrotinib.


Asunto(s)
Acrilamidas/química , Acrilamidas/metabolismo , Aminoquinolinas/química , Aminoquinolinas/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Hepatocitos/metabolismo , Animales , Cromatografía Líquida de Alta Presión/métodos , Perros , Hepatocitos/química , Humanos , Ratas , Espectrometría de Masas en Tándem/métodos
14.
Analyst ; 146(18): 5474-5495, 2021 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-34515706

RESUMEN

Acute myocardial infarction (AMI) is the main cause of death from cardiovascular diseases. Thus, early diagnosis of AMI is essential for the treatment of irreversible damage from myocardial infarction. Traditional electrocardiograms (ECG) cannot meet the specific detection of AMI. Cardiac troponin I (cTnI) is the main biomarker for the diagnosis of myocardial infarction, and the detection of cTnI content has become particularly important. In this review, we introduced and compared the advantages and disadvantages of various cTnI detection methods. We focused on the analysis and comparison of the main indicators and limitations of various cTnI biosensors, including the detection range, detection limit, specificity, repeatability, and stability. In particular, we pay more attention to the application and development of electrochemical biosensors in the diagnosis of cardiovascular diseases based on different biological components. The application of electrochemical microfluidic chips for cTnI was also briefly introduced in this review. Finally, this review also briefly discusses the unresolved challenges of electrochemical detection and the expectations for improvement in the detection of cTnI biosensing in the future.


Asunto(s)
Técnicas Biosensibles , Infarto del Miocardio , Biomarcadores , Diagnóstico Precoz , Humanos , Infarto del Miocardio/diagnóstico , Troponina I
15.
Genet Sel Evol ; 53(1): 84, 2021 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-34742238

RESUMEN

BACKGROUND: In dairy cattle, genomic selection has been implemented successfully for purebred populations, but, to date, genomic estimated breeding values (GEBV) for crossbred cows are rarely available, although they are valuable for rotational crossbreeding schemes that are promoted as efficient strategies. An attractive approach to provide GEBV for crossbreds is to use estimated marker effects from the genetic evaluation of purebreds. The effects of each marker allele in crossbreds can depend on the breed of origin of the allele (BOA), thus applying marker effects based on BOA could result in more accurate GEBV than applying only proportional contribution of the purebreds. Application of BOA models in rotational crossbreeding requires methods for detecting BOA, but the existing methods have not been developed for rotational crossbreeding. Therefore, the aims of this study were to develop and test methods for detecting BOA in a rotational crossbreeding system, and to investigate methods for calculating GEBV for crossbred cows using estimated marker effects from purebreds. RESULTS: For detecting BOA in crossbred cows from rotational crossbreeding for which pedigree is recorded, we developed the AllOr method based on the comparison of haplotypes in overlapping windows. To calculate the GEBV of crossbred cows, two models were compared: a BOA model where marker effects estimated from purebreds are combined based on the detected BOA; and a breed proportion model where marker effects are combined based on estimated breed proportions. The methods were tested on simulated data that mimic the first four generations of rotational crossbreeding between Holstein, Jersey and Red Dairy Cattle. The AllOr method detected BOA correctly for 99.6% of the marker alleles across the four crossbred generations. The reliability of GEBV was higher with the BOA model than with the breed proportion model for the four generations of crossbreeding, with the largest difference observed in the first generation. CONCLUSIONS: In rotational crossbreeding for which pedigree is recorded, BOA can be accurately detected using the AllOr method. Combining marker effects estimated from purebreds to predict the breeding value of crossbreds based on BOA is a promising approach to provide GEBV for crossbred dairy cows.


Asunto(s)
Genómica , Hibridación Genética , Alelos , Animales , Bovinos/genética , Femenino , Linaje , Reproducibilidad de los Resultados
16.
Genet Sel Evol ; 53(1): 46, 2021 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-34058971

RESUMEN

BACKGROUND: In dairy cattle populations in which crossbreeding has been used, animals show some level of diversity in their origins. In rotational crossbreeding, for instance, crossbred dams are mated with purebred sires from different pure breeds, and the genetic composition of crossbred animals is an admixture of the breeds included in the rotation. How to use the data of such individuals in genomic evaluations is still an open question. In this study, we aimed at providing methodologies for the use of data from crossbred individuals with an admixed genetic background together with data from multiple pure breeds, for the purpose of genomic evaluations for both purebred and crossbred animals. A three-breed rotational crossbreeding system was mimicked using simulations based on animals genotyped with the 50 K single nucleotide polymorphism (SNP) chip. RESULTS: For purebred populations, within-breed genomic predictions generally led to higher accuracies than those from multi-breed predictions using combined data of pure breeds. Adding admixed population's (MIX) data to the combined pure breed data considering MIX as a different breed led to higher accuracies. When prediction models were able to account for breed origin of alleles, accuracies were generally higher than those from combining all available data, depending on the correlation of quantitative trait loci (QTL) effects between the breeds. Accuracies varied when using SNP effects from any of the pure breeds to predict the breeding values of MIX. Using those breed-specific SNP effects that were estimated separately in each pure breed, while accounting for breed origin of alleles for the selection candidates of MIX, generally improved the accuracies. Models that are able to accommodate MIX data with the breed origin of alleles approach generally led to higher accuracies than models without breed origin of alleles, depending on the correlation of QTL effects between the breeds. CONCLUSIONS: Combining all available data, pure breeds' and admixed population's data, in a multi-breed reference population is beneficial for the estimation of breeding values for pure breeds with a small reference population. For MIX, such an approach can lead to higher accuracies than considering breed origin of alleles for the selection candidates, and using breed-specific SNP effects estimated separately in each pure breed. Including MIX data in the reference population of multiple breeds by considering the breed origin of alleles, accuracies can be further improved. Our findings are relevant for breeding programs in which crossbreeding is systematically applied, and also for populations that involve different subpopulations and between which exchange of genetic material is routine practice.


Asunto(s)
Bovinos/genética , Hibridación Genética , Polimorfismo de Nucleótido Simple , Animales , Estudio de Asociación del Genoma Completo/métodos , Estudio de Asociación del Genoma Completo/normas , Endogamia , Modelos Genéticos , Sitios de Carácter Cuantitativo , Estándares de Referencia , Selección Artificial
17.
Genet Sel Evol ; 53(1): 33, 2021 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-33832423

RESUMEN

BACKGROUND: In breeding programs, recording large-scale feed intake (FI) data routinely at the individual level is costly and difficult compared with other production traits. An alternative approach could be to record FI at the group level since animals such as pigs are normally housed in groups and fed by a shared feeder. However, to date there have been few investigations about the difference between group- and individual-level FI recorded in different environments. We hypothesized that group- and individual-level FI are genetically correlated but different traits. This study, based on the experiment undertaken in purebred DanBred Landrace (L) boars, was set out to estimate the genetic variances and correlations between group- and individual-level FI using a bivariate random regression model, and to examine to what extent prediction accuracy can be improved by adding information of individual-level FI to group-level FI for animals recorded in groups. For both bivariate and univariate models, single-step genomic best linear unbiased prediction (ssGBLUP) and pedigree-based BLUP (PBLUP) were implemented and compared. RESULTS: The variance components from group-level records and from individual-level records were similar. Heritabilities estimated from group-level FI were lower than those from individual-level FI over the test period. The estimated genetic correlations between group- and individual-level FI based on each test day were on average equal to 0.32 (SD = 0.07), and the estimated genetic correlation for the whole test period was equal to 0.23. Our results demonstrate that by adding information from individual-level FI records to group-level FI records, prediction accuracy increased by 0.018 and 0.032 compared with using group-level FI records only (bivariate vs. univariate model) for PBLUP and ssGBLUP, respectively. CONCLUSIONS: Based on the current dataset, our findings support the hypothesis that group- and individual-level FI are different traits. Thus, the differences in FI traits under these two feeding systems need to be taken into consideration in pig breeding programs. Overall, adding information from individual records can improve prediction accuracy for animals with group records.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales/genética , Peso Corporal , Cruzamiento/métodos , Carácter Cuantitativo Heredable , Porcinos/genética , Animales , Ingestión de Alimentos , Linaje , Porcinos/fisiología
18.
J Dairy Sci ; 104(9): 10010-10019, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34099302

RESUMEN

Despite the importance of the quality of semen used in artificial insemination to the reproductive success of dairy herds, few studies have estimated the extent of genetic variability in semen quality traits. Even fewer studies have quantified the correlation between semen quality traits and male fertility. In this study, records of 100,058 ejaculates collected from 2,885 Nordic Holstein bulls were used to estimate genetic parameters for semen quality traits, including pre- and postcryopreservation semen concentration, sperm motility and viability, ejaculate volume, and number of doses per ejaculate. Additionally, summary data on nonreturn rate (NRR) obtained from insemination of some of the bulls (n = 2,142) to cows in different parities (heifers and parities 1-3 or more) were used to estimate correlations between the semen quality traits and service sire NRR. In the study, low to moderate heritability (0.06-0.45) was estimated for semen quality traits, indicating the possibility of improving these traits through selective breeding. The study also showed moderate to high genetic and phenotypic correlations between service sire NRR and some of the semen quality traits, including sperm viability pre- and postcryopreservation, motility postcryopreservation, and sperm concentration precryopreservation, indicating the predictive values of these traits for service sire NRR. The positive moderate to high genetic correlations between semen quality and service sire NRR traits also indicated that selection for semen quality traits might be favorable for improving service sire NRR.


Asunto(s)
Fertilidad , Análisis de Semen , Animales , Bovinos/genética , Femenino , Fertilidad/genética , Inseminación Artificial/veterinaria , Masculino , Semen , Análisis de Semen/veterinaria , Motilidad Espermática/genética
19.
Heredity (Edinb) ; 124(2): 274-287, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31641237

RESUMEN

Widely used genomic prediction models may not properly account for heterogeneous (co)variance structure across the genome. Models such as BayesA and BayesB assume locus-specific variance, which are highly influenced by the prior for (co)variance of single nucleotide polymorphism (SNP) effect, regardless of the size of data. Models such as BayesC or GBLUP assume a common (co)variance for a proportion (BayesC) or all (GBLUP) of the SNP effects. In this study, we propose a multi-trait Bayesian whole genome regression method (BayesN0), which is based on grouping a number of predefined SNPs to account for heterogeneous (co)variance structure across the genome. This model was also implemented in single-step Bayesian regression (ssBayesN0). For practical implementation, we considered multi-trait single-step SNPBLUP models, using (co)variance estimates from BayesN0 or ssBayesN0. Genotype data were simulated using haplotypes on first five chromosomes of 2200 Danish Holstein cattle, and phenotypes were simulated for two traits with heritabilities 0.1 or 0.4, assuming 200 quantitative trait loci (QTL). We compared prediction accuracy from different prediction models and different region sizes (one SNP, 100 SNPs, one chromosome or whole genome). In general, highest accuracies were obtained when 100 adjacent SNPs were grouped together. The ssBayesN0 improved accuracies over BayesN0, and using (co)variance estimates from ssBayesN0 generally yielded higher accuracies than using (co)variance estimates from BayesN0, for the 100 SNPs region size. Our results suggest that it could be a good strategy to estimate (co)variance components from ssBayesN0, and then to use those estimates in genomic prediction using multi-trait single-step SNPBLUP, in routine genomic evaluations.


Asunto(s)
Bovinos/genética , Genoma , Modelos Genéticos , Fenotipo , Sitios de Carácter Cuantitativo , Animales , Teorema de Bayes , Genómica , Polimorfismo de Nucleótido Simple
20.
Heredity (Edinb) ; 124(4): 618, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32086444

RESUMEN

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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