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1.
Medicine (Baltimore) ; 98(39): e17198, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574828

RESUMO

BACKGROUND: The aim of our study was to assess the value of serum human epididymis protein 4 (HE4) to diagnose lung cancer and provide reliable scientific conclusions to guide clinical practice. METHODS: A systematic search of the PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature, and WANFANG databases was conducted to identify all studies examining serum HE4 in the diagnosis of lung cancer published up to June, 2017. The Quality Assessment of Diagnostic Accuracy Studies tool was used to evaluate the methodological quality of each trial. The meta-analysis was performed using STATA software and Review Manager 5.3. RESULTS: There were 21 studies involving 1883 cases and 1696 controls included in our meta-analysis. The pooled sensitivity and specificity of HE4 for diagnosing lung cancer were 0.73 (95% confidence interval [CI] 0.68-0.78) and 0.86 (95% CI 0.81-0.91), respectively. The positive likelihood ratio and negative likelihood ratio were 5.4 (95% CI 3.8-7.5) and 0.31 (95% CI 0.26-0.37), respectively. The diagnostic odds ratio was 17 (95% CI 12-26). The area under the curve of the summary receiver-operating characteristic curve was 0.86 (95% CI 0.83-0.89). Race, assay method, type of cancer, sample size, and publication date might be sources of heterogeneity in our meta-analysis. Subgroup analyses showed that the sensitivity in Caucasians was higher than that in Asians (0.81, 95% CI 0.71-0.91; and 0.71, 95% CI 0.66-0.77, respectively), but the specificity in Asians was better than that in Caucasians (0.87, 95% CI 0.81-0.92; and 0.85, 95% CI 0.73-0.97, respectively). The chemiluminescent microparticle immunoassay had the highest sensitivity, with 0.79 (95% CI 0.73-0.97), and the enzyme-linked immunosorbent assay had the highest specificity, with 0.87 (95% CI 0.79-0.94). HE4 had high diagnostic efficacy when screening for small cell lung cancer with the highest specificity (0.90, 95% CI 0.77-1.00). CONCLUSIONS: HE4 is a relatively promising and effective biomarker for the diagnosis of lung cancer. Furthermore, given the limitations of our study, additional large-scale and well-designed studies are needed in the future.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Proteínas/análise , Biomarcadores Tumorais/sangue , Humanos , Razão de Chances , Sensibilidade e Especificidade
2.
An Bras Dermatol ; 94(4): 434-441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644616

RESUMO

BACKGROUND: In-vitro studies showed that Leucine-rich glioma inactivated 3 (LGI3) is a keratinocyte-derived cytokine that stimulates melanin synthesis and is increased after ultra violet B (UVB) irradiation. So, we postulated that LGI3 may be involved in vitiligo aetiopathogenesis and may participate in narrow band ultra violet B (NB-UVB) induced pigmentation in vitiligo. OBJECTIVES: To assess this hypothesis, lesional LGI3 immunohistochemical expression of vitiligo patients before and after NB-UVB phototherapy was studied, and its correlation with repigmentation was evaluated. METHODS: Forty vitiligo patients and 20 age, sex, and skin phenotype-matched controls were enrolled. Patients were treated with NB-UVB thrice weekly for 12 weeks. VASI score was evaluated before and after NB-UVB sessions. For vitiligo patients, baseline LGI3 immunohistochemical staining was estimated, and compared to that of controls and to its post-treatment data in those patients. Results: Baseline LGI3 immunohistochemical studied parameters (expression, intensity, percentage and H score) were significantly lower in vitiligo cases than controls (p=0.003, 0.013, 0.001 and 0.001 respectively). After 12 weeks of NB-UVB phototherapy, these LGI3 immunohistochemical parameters were up-regulated and became comparable to that of controls (p >0.05 for all). There was a significant positive correlation between the improvement of both VASI score and LGI3 H score mean values (r=-0.349 , p=0.027). STUDY LIMITATIONS: Small number of investigated subjects. CONCLUSIONS: Decreased LGI3 protein may play an active role in vitiligo pathogenesis and its up-regulation after NB-UVB phototherapy, may actively participate in NB-UVB photo-induced melanogenesis.


Assuntos
Citocinas/análise , Proteínas/análise , Terapia Ultravioleta/métodos , Vitiligo/patologia , Vitiligo/radioterapia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , Imuno-Histoquímica , Queratinócitos/efeitos da radiação , Masculino , Melanócitos/efeitos da radiação , Pessoa de Meia-Idade , Valores de Referência , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
3.
Adv Clin Chem ; 92: 217-243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31472755

RESUMO

In recent years, proteomics has been used widely in reproductive research in order to understand the molecular mechanisms related to gametes at the cellular level and the role of proteins involved in fertilization. Network and pathway analysis using bioinformatic tools have paved way to obtain a wider picture on the possible pathways associated with the key differentially expressed proteins (DEPs) and its implication in various infertility scenarios. A brief overview of advanced techniques and bioinformatic tools used for reproductive proteomics is presented. Key findings of proteomic-based studies on male and female reproduction are also presented. Furthermore, the chapter sheds light on the cellular pathways and potential biomarkers associated with male and female infertility. Proteomics coupled with bioinformatic analysis provides an ideal platform for non-invasive management of infertility in couples.


Assuntos
Proteínas/metabolismo , Proteômica , Reprodução , Feminino , Humanos , Masculino , Proteínas/análise
4.
Chem Commun (Camb) ; 55(67): 9979-9982, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31367719

RESUMO

A chemical tag enhances peptide detection by multiple orders in mass spectrometry. The substantial improvement in the peptide mapping along with simplified and enhanced fragmentation pattern enables the unambiguous sequencing of a protein and antibody. The chemoselective sensitivity booster provides a tool for remarkably improved analysis of protein bioconjugates.


Assuntos
Peptídeos/análise , Proteínas/análise , Citocromos c/análise , Lisina/química , Mapeamento de Peptídeos , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem
5.
Chem Asian J ; 14(18): 3145-3148, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31359597

RESUMO

The N-acylsulfonamide group, known as a safety-catch linker, has been applied to photoaffinity labeling (PAL) using a cinnamate-type photocrosslinker to improve the efficiency of PAL-based target identification. A bioorthogonal sulfo-click reaction was used to stably link a photocrosslinker unit with N-acylsulfonamide linkage to produce a photoactivatable probe without any protection. In addition, the crosslinked protein was selectively isolated with a small cinnamate tag via linkage disruption upon N-alkylation. Furthermore, the tag moiety was photochemically converted to a stable coumarin derivative by losing a water molecule, which is a useful property in MS-based identification.


Assuntos
Cinamatos/química , Reagentes para Ligações Cruzadas/química , Marcadores de Fotoafinidade/química , Proteínas/análise , Sulfonamidas/química , Estrutura Molecular , Processos Fotoquímicos
6.
Chem Commun (Camb) ; 55(62): 9188-9191, 2019 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-31305808

RESUMO

The metal salts ubiquitously present in biological samples cause serious ion suppression, capillary clogging and signal fluctuation in ESI/nESI. Herein, a current-limited high voltage polarity reversing approach was applied for the online separation of intrinsic metal ions in biological samples, resulting in the generation of protonated analytes at the nESI tip for mass analysis without interference from salt cations. Stable and durable signals (∼30-60 s) were observed for protonated proteins, peptides and metabolites in complex biological samples, including liquids, solids and viscous samples, even with very high salt concentration (100 mM NaCl), allowing comprehensive tandem MS analysis with on average ca. 5-times higher analyte signal intensities compared to the conventional nESI analysis. Therefore this approach offers improved performance of nESI/ESI for the sensitive molecular analysis of untreated biological samples, opening new possibilities in various disciplines, including biology, medicine, chemistry, life sciences, etc.


Assuntos
Peptídeos/análise , Proteínas/análise , Cloreto de Sódio/química , Íons/análise , Peptídeos/metabolismo , Proteínas/metabolismo , Prótons , Espectrometria de Massas por Ionização por Electrospray/instrumentação
7.
Adv Exp Med Biol ; 1140: 27-43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347040

RESUMO

Matrix assisted laser desorption ionization (MALDI) mass spectrometry allows for the rapid profiling of different biomolecular species from both biofluids and tissues. Whilst originally focused upon the analysis of intact proteins and peptides, MALDI mass spectrometry has found further applications in lipidomic analysis, genotyping, microorganism identification, biomarker discovery and metabolomics. The combining of multiple profiles data from differing locations across a sample furthermore, allows for spatial distribution of biomolecules to be established utilizing imaging MALDI analysis. This chapter discusses the MALDI process, its usual applications in the field of protein identification via peptide mass fingerprinting before focusing upon advances in the application of the profiling potential of MALDI mass spectrometry and its' various applications in biomedicine.


Assuntos
Peptídeos/análise , Proteínas/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Humanos , Mapeamento de Peptídeos
8.
Adv Exp Med Biol ; 1140: 121-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347045

RESUMO

Of the 25,000-30,000 human genes, about 2 % code for proteins. However, there are about 1-2 million protein entities. This is primarily due to alternative splicing, post-translational modifications (PTMs) or protein-protein interactions. Proteomics sets out to identify proteins, their sequence and known modifications as well as their quantitation in a biological sample for the purpose of understanding biological processes, protein cellular functions, and their physiological and pathological involvement in diseases.Proteins interact at the molecular level with other proteins, nucleic acids, lipids, carbohydrates and metabolites to perform numerous cellular activities. Protein complexes can consist of sets of more stably (stable PPIs) and less stably (transient PPIs) interacting proteins or combination of both. Here, we discuss the proteomics and non-proteomics approaches to study stable and transient PPIs.


Assuntos
Processamento de Proteína Pós-Traducional , Proteínas/análise , Proteômica , Humanos
9.
Adv Exp Med Biol ; 1140: 265-287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347053

RESUMO

Recent developments of mass spectrometry (MS) allow us to identify, estimate, and characterize proteins and protein complexes. At the same time, structural biology helps to determine the protein structure and its structure-function relationship. Together, they aid to understand the protein structure, property, function, protein-complex assembly, protein-protein interaction, and dynamics. The present chapter is organized with illustrative results to demonstrate how experimental mass spectrometry can be combined with computational structural biology for detailed studies of protein's structures. We have used tumor differentiation factor protein/peptide as ligand and Hsp70/Hsp90 as receptor protein as examples to study ligand-protein interaction. To investigate possible protein conformation, we will describe two proteins-lysozyme and myoglobin. As an application of MS-based assignment of disulfide bridges, the case of the spider venom polypeptide Phα1ß will also be discussed.


Assuntos
Biologia Computacional , Espectrometria de Massas , Peptídeos/análise , Proteínas/análise , Conformação Proteica
10.
Adv Exp Med Biol ; 1140: 575-583, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347072

RESUMO

The global measurement of assembly and turnover of protein containing complexes within cells has advanced with the development of pulse stable isotope labelled amino acid approaches. Stable isotope labeling with amino acids in cell culture (SILAC) allows the incorporation of "light" 12-carbon amino acids or "heavy" 13-carbon amino acids into cells or organisms and the quantitation of proteins and peptides containing these amino acid tags using mass spectrometry. The use of these labels in pulse or pulse-chase scenarios has enabled measurements of macromolecular dynamics in cells, on time scales of several hours. Here we review advances with this approach and alternative or parallel strategies. We also examine the statistical considerations impacting datasets detailing mitochondrial assembly, to highlight key parameters in establishing significance and reproducibility.


Assuntos
Aminoácidos/química , Técnicas de Cultura de Células , Marcação por Isótopo , Espectrometria de Massas , Proteínas/análise , Reprodutibilidade dos Testes
11.
Adv Exp Med Biol ; 1140: 753-769, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347083

RESUMO

Mass spectrometry (MS) is the core for advanced methods in proteomic experiments. When effectively used, proteomics may provide extensive information about proteins and their post-translational modifications, as well as their interaction partners. However, there are also many problems that one can encounter during a proteomic experiment, including, but not limited to sample preparation, sample fractionation, sample analysis, data analysis & interpretation and biological significance. Here we discuss some of the problems that researchers should be aware of when performing a proteomic experiment.


Assuntos
Espectrometria de Massas , Proteínas/análise , Proteômica/métodos , Processamento de Proteína Pós-Traducional
12.
Mol Biol (Mosk) ; 53(3): 524-528, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31184618

RESUMO

Proteins with homo-repeats of more than 4 amino acid residues in length were examined to understand whether some splicing sites in pre-mRNA may be attributed to homo-repeats in human proteins. The human proteome was found to contain a total of 404 proteins with homo-repeats that account for at least one splicing site in pre-mRNA. Pre-mRNA splicing sites were more often found in the C-terminal part (67%) than in the middle orN-terminal part of a homo-repeat. Ten homo-repeats were identified to have two splicing sites per repeat. The repeats were lysine homo-repeats in all but one case.


Assuntos
Proteínas/análise , Proteínas/química , Precursores de RNA/genética , Sítios de Splice de RNA/genética , Sequências Repetitivas de Aminoácidos/genética , Humanos , Lisina/genética , Lisina/metabolismo , Proteínas/genética , Proteoma/análise , Proteoma/química , Proteoma/genética , Processamento de RNA/genética
13.
Adv Exp Med Biol ; 1073: 125-135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236841

RESUMO

Urine is a biological fluid that can be collected noninvasively in relatively large quantities which can be used for the search of biomarkers of disease, both diseases of the urological tract and systemic diseases. One of the most important aspects in proteomic studies is sample treatment before further analysis. Methods of preparation of a urine sample depend on the techniques that will be used later for separation and identification of the proteins. Also, urine preparation should be as simple as possible to increase reproducibility. Normal urine has a much diluted protein concentration with a high-salt content, which interferes with proteomic analysis. Thus, an initial step in the handling of urine sample should be to concentrate and eliminate salts. As range of protein concentrations in urine spans several orders of magnitude, effective proteomic analyses require either removal of most abundant protein or enrichment of the less abundant ones. In this chapter, we discuss the aspects related to the collection and treatment of urine for proteomic studies.


Assuntos
Proteômica , Manejo de Espécimes/métodos , Urinálise/métodos , Biomarcadores/urina , Humanos , Proteínas/análise , Reprodutibilidade dos Testes
14.
J Immunoassay Immunochem ; 40(4): 439-447, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31204576

RESUMO

The beneficial effects promoted from the use of biomolecular substances into the formulations of personal care products are considered useful ingredients in cosmetic and therapeutic applications. Innovations in cosmetics are based on new bioactive formulations such as vitamins, oils, peptides, and protein hydrolysates. In skin care, the monomeric amino acids such as serine, threonine, alanine are common ingredients in cosmetics as they function as natural moisturizing factors which act as water-binding molecules. Amino acids and their salts e.g., arginine, glycine, etc. are also used as hair- and skin-conditioning agents in cosmetic formulations. The peptides are composed of short chain of amino acids and are used in cosmetics due to their numerous pathophysiological properties including anti-aging. There is growing interest in bioactive peptides in products for stimulating collagen and elastin synthesis in skin and improve surface healing. The main benefit of using proteins in cosmeceuticals is to improve the hydration of skin. Proteins increase the dehydration in the skin which helps to reduce wrinkles and improves the functions of the skin barrier. This review article describes the peptides, proteins that are most frequently used in cosmeceuticals and their potential benefits and practical use in cosmetic science and skincare.


Assuntos
Cosmecêuticos/química , Cosmecêuticos/farmacologia , Peptídeos/análise , Proteínas/análise , Rejuvenescimento/fisiologia , Higiene da Pele/métodos , Pele/efeitos dos fármacos , Animais , Cosmecêuticos/uso terapêutico , Técnicas Cosméticas , Humanos , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Proteínas/farmacologia , Proteínas/uso terapêutico , Pele/imunologia , Pele/patologia
15.
J Mass Spectrom ; 54(8): 716-727, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31254303

RESUMO

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a molecular imaging technology uniquely capable of untargeted measurement of proteins, lipids, and metabolites while retaining spatial information about their location in situ. This powerful combination of capabilities has the potential to bring a wealth of knowledge to the field of molecular histology. Translation of this innovative research tool into clinical laboratories requires the development of reliable sample preparation protocols for the analysis of proteins from formalin-fixed paraffin-embedded (FFPE) tissues, the standard preservation process in clinical pathology. Although ideal for stained tissue analysis by microscopy, the FFPE process cross-links, disrupts, or can remove proteins from the tissue, making analysis of the protein content challenging. To date, reported approaches differ widely in process and efficacy. This tutorial presents a strategy derived from systematic testing and optimization of key parameters, for reproducible in situ tryptic digestion of proteins in FFPE tissue and subsequent MALDI IMS analysis. The approach describes a generalized method for FFPE tissues originating from virtually any source.


Assuntos
Proteínas/análise , Manejo de Espécimes/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Análise Serial de Tecidos/métodos , Formaldeído/química , Humanos , Inclusão em Parafina , Proteólise , Fixação de Tecidos , Tripsina/química
16.
Anal Bioanal Chem ; 411(19): 4523-4540, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31161324

RESUMO

Fluctuation correlation spectroscopy (FCS) is a single-molecule/particle detection technique based on measuring signal fluctuations in a highly focused detection volume. Multiple-parameter information can be obtained from the FCS measurement including the amplitude, characteristic diffusion time of correlation curve, and brightness of the adopted probes. The multiple-parameter change is related with physical or chemical change occurring in the probes. Meanwhile, the detection method has advantages such as short sample time in seconds, sample volume with low limit in femtoliters, and mixing to detection without any separations. These advantages make the FCS technique suitable for homogeneous analysis. In this review, we summarized recent novel applications of FCS and its variants in homogeneous analysis including nucleic acid analysis, protein analysis, enzyme activity assay, direct characterization of nanoparticles in solution, and others. Graphical abstract.


Assuntos
Espectrometria de Fluorescência/métodos , Nanopartículas/química , Ácidos Nucleicos/análise , Proteínas/análise , Espectrometria de Fluorescência/instrumentação
17.
Food Chem ; 297: 125012, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253295

RESUMO

To obtain better understanding of the formation mechanisms of bitterness and adhesiveness, protease activities, proteolysis index and protein degradation were investigated among raw, normal and defective hams. Normal and defective hams both showed a decrease in cathepsin B and B + L activities compared with raw ham, while higher residual activities were observed in defective ham. Approximate 1.2-fold values of proteolysis index were observed in defective ham than in normal ham, indicating that cathepsin B and B + L activities were key contributors in degrading muscle proteins of dry-cured ham. 322 proteins were identified by label-free proteomics, and 49 down-regulated proteins were found in the comparison between normal and defective hams. Creatine kinase, myosin, α-actinin and troponin-T showed the most intense response to bitterness and adhesiveness of dry-cured ham, confirmed by partial least squares regression analysis. Myosin could be a suitable biomarker to monitor bitterness and adhesiveness of dry-cured ham.


Assuntos
Produtos da Carne/análise , Proteômica/métodos , Paladar/fisiologia , Adesividade , Animais , Catepsina B/metabolismo , Catepsina L/metabolismo , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Regulação para Baixo , Análise dos Mínimos Quadrados , Proteínas/análise , Proteólise , Suínos , Espectrometria de Massas em Tandem , Troponina T/análise
19.
Int. j. morphol ; 37(2): 773-779, June 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1002292

RESUMO

La información disponible referente a las características proteómicas del E. granulosus es escasa (no supera los 50 estudios publicados); y nos parece que la identificación proteómica, podría mejorar la comprensión de algunas características bioquímicas e inmunológicas de la Equinococosis Quística (EQ). De tal modo que el proteoma de E. granulosus aún no está bien descrito. Sólo existen reportes de algunas secuencias de proteínas. El objetivo de este manuscrito fue comentar algunos aspectos de la evidencia existente respecto de los estudios del perfil proteómico del E. granulosus. Se recomienda el estudio de al menos el quiste y su pared, el líquido hidatídico y la víscera del hospedero. Para ello, existen metodologías que han sido empleadas para estudiar las características proteómicas de la EQ. Entre ellas, destacan SDS-PAGE, electroforesis bidimensional combinada con Western Blot, inmunoanálisis, y espectrometría de masas mediante técnicas MALDI-TOF. Se han identificado una serie de proteínas en muestras de EQ. Algunas de ellas, asociadas a procesos inmunológicos, de gluconeogénesis, glucogenolisis y glucogénesis. Por otra parte, se ha documentado la liberación de exosomas al líquido hidatídico por parte de los protoescólex y la capa germinativa; estructuras en las que se han identificado factores de virulencia asociados con la supervivencia del quiste. No obstante lo anteriormente señalado, se requiere de múltiples estudios exhaustivos en la materia para comprender mejor la caracterización perfil proteómico del E. granulosus.


The information available regarding the proteomic characteristics of E. granulosus is scarce; and it seems that the proteomic identification could improve the understanding of some biochemical and immunological characteristics of cystic echinococcosis (CE). So, the proteome of E. granulosus is still not well described yet. There are only reports of some protein sequences. The objective of this manuscript was to comment on some aspects of the existing evidence regarding studies of the proteomic profile of E. granulosus. The study of at least the cyst and its wall, the hydatid fluid and the viscera of the host are recommended. There are a series of methodologies that have been used to study the proteomic characteristics of EQ. These include SDS-PAGE, bidimensional electrophoresis combined with Western Blot, immunoassay, and mass spectrometry using MALDI-TOF techniques. A series of proteins have been identified in CE samples. Some of them, associated with immune response, gluconeogenesis, glycogenolysis and glycogenesis. On the other hand, release of exosomes to the hydatid fluid by protoescolex and germinative layer has been documented (associated virulence factors have been identified in these structures). Notwithstanding the foregoing, it requires multiple exhaustive studies in the field to better understand the characterization of the proteomic profile of E. granulosus.


Assuntos
Proteínas/análise , Proteômica/métodos , Echinococcus granulosus/química , Echinococcus granulosus/genética , Echinococcus granulosus/metabolismo , Eletroforese em Gel de Poliacrilamida
20.
J Dairy Sci ; 102(7): 6276-6287, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31056336

RESUMO

Energy demand for milk production in early lactation exceeds energy intake, especially in high-yielding Holstein cows. Energy deficiency causes increasing susceptibility to metabolic disorders. In addition to several blood parameters, the fat-to-protein ratio (FPR) is suggested as an indicator for ketosis, because a FPR >1.5 refers to high lipolysis. The aim of this study was to analyze phenotypic, quantitative genetic, and genomic associations between FPR and ketosis. In this regard, 8,912 first-lactation Holstein cows were phenotyped for ketosis according to a veterinarian diagnosis key. Ketosis was diagnosed if the cow showed an abnormal carbohydrate metabolism with increased content of ketone bodies in the blood or urine. At least one entry for ketosis in the first 6 wk after calving implied a score = 1 (diseased); otherwise, a score = 0 (healthy) was assigned. The FPR from the first test-day was defined as a Gaussian distributed trait (FPRgauss), and also as a binary response trait (FPRbin), considering a threshold of FPR = 1.5. After imputation and quality controls, 45,613 SNP markers from the 8,912 genotyped cows were used for genomic studies. Phenotypically, an increasing ketosis incidence was associated with significantly higher FPR, and vice versa. Hence, from a practical trait recording perspective, first test-day FPR is suggested as an indicator for ketosis. The ketosis heritability was slightly larger when modeling the pedigree-based relationship matrix (pedigree-based: 0.17; SNP-based: 0.11). For FPRbin, heritabilities were larger when modeling the genomic relationship matrix (pedigree-based: 0.09; SNP-based: 0.15). For FPRgauss, heritabilities were almost identical for both pedigree and genomic relationship matrices (pedigree-based: 0.14; SNP-based: 0.15). Genetic correlations between ketosis with FPRbin and FPRgauss using either pedigree- or genomic-based relationship matrices were in a moderate range from 0.39 to 0.71. Applying genome-wide association studies, we identified the specific SNP rs109896020 (BTA 5, position: 115,456,438 bp) significantly contributing to ketosis. The identified potential candidate gene PARVB in close chromosomal distance is associated with nonalcoholic fatty liver disease in humans. The most important SNP contributing to FPRbin was located within the DGAT1 gene. Different SNP significantly contributed to ketosis and FPRbin, indicating different mechanisms for both traits genomically.


Assuntos
Doenças dos Bovinos/genética , Gorduras/análise , Estudo de Associação Genômica Ampla/veterinária , Cetose/genética , Proteínas/análise , Animais , Bovinos , Doenças dos Bovinos/metabolismo , Gorduras/metabolismo , Feminino , Genoma , Genômica , Genótipo , Cetose/metabolismo , Cetose/veterinária , Lactação/genética , Masculino , Leite/metabolismo , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas/metabolismo
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