Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore

Detalhes bibliográficos
Autor(a) principal: Lima, Andressa Oliveira de
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: eng
Título da fonte: Repositório Institucional da UFSCAR
Texto Completo: https://repositorio.ufscar.br/handle/ufscar/11650
Resumo: Feeding accounts for most of the costs in beef cattle production. To reduce it, as well as the environmental impact, greenhouse gas emission, and land occupation have been mandatory to improve the animal feed efficiency. Multifactorial, feed efficiency (FE) has been evaluated by different indexes and approaches. Among them, genomic studies from animals genetically divergent for FE pointed out candidate genes and pathways such as energy metabolism, inflammatory and oxidative stress. However, these studies did not take into account the continuous variation of the gene expression within the population. Thereby, from a previous differential approach carried out in divergent Nelore steers for FE, we selected six hepatic candidate genes (COL1A1, CTGF, CYP2B6, EGR1, PRUNE2, and the PRUNE2_isoform) based on their biological role on pathways related to feed efficiency. We carried out a realtime quantitative PCR (RT-qPCR) assay in 52 Nelore steers to evaluate the hepatic expression profile of the overmentioned genes and their association with FE related-traits such as average daily gain (ADG), body weight (BW), dry matter intake (DMI), feed conversion ratio (FCR), feed efficiency ratio (FE), Kleiber index (KI), metabolic body weight (MBW), residual feed intake (RFI), and relative growth rate (RGR). Based on a linear mixed model, we identified that the total expression of PRUNE2 has an unfavorable effect on feed efficiency related-traits, likely related to mitochondrial dysfunction. However, when taking only the PRUNE2_isoform, we observed a favorable effect on the evaluated trait. Still, to shed light on the genetic mechanisms affecting feed efficiency in Nelore, we applied a coexpression approach using muscle RNAseq data from 180 animals. Based on the weighted gene co-expression network analysis (WGCNA) software, we identified 391 potential biomarkers (hub genes) related to feed efficiency variation. These hub genes partook in protein synthesis, muscle growth, and immune response pathways. Among the hub genes, we highlighted CCDC80, FBLN5, SERPINF1, and OGN genes, which were associated to ADG, FCR, FE, KI, and RGR traits, and were related to glucose homeostasis, oxidative stress, and osteogenesis. Furthermore, we found 13 transcription factors among the hub genes described for bovine and six of them are putative regulators for the others hub genes identified in this study. Among them, the TCF4 may have a role in muscle growth metabolism and regulator of DE genes for divergent RFI in muscle previously identified by our research group. Finally, we identified potential regulatory regions and functional variants related to the potential biomarkers identified in this study.
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spelling Lima, Andressa Oliveira deRegitano, Luciana Correia de Almeidahttp://lattes.cnpq.br/9595338480545794Tizioto, Polyana Cristinehttp://lattes.cnpq.br/4754030540306395http://lattes.cnpq.br/8264911787257919b398457b-504c-4946-8282-d09c778cd8082019-08-08T18:15:49Z2019-08-08T18:15:49Z2019-05-08LIMA, Andressa Oliveira de. Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore. 2019. Tese (Doutorado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11650.https://repositorio.ufscar.br/handle/ufscar/11650Feeding accounts for most of the costs in beef cattle production. To reduce it, as well as the environmental impact, greenhouse gas emission, and land occupation have been mandatory to improve the animal feed efficiency. Multifactorial, feed efficiency (FE) has been evaluated by different indexes and approaches. Among them, genomic studies from animals genetically divergent for FE pointed out candidate genes and pathways such as energy metabolism, inflammatory and oxidative stress. However, these studies did not take into account the continuous variation of the gene expression within the population. Thereby, from a previous differential approach carried out in divergent Nelore steers for FE, we selected six hepatic candidate genes (COL1A1, CTGF, CYP2B6, EGR1, PRUNE2, and the PRUNE2_isoform) based on their biological role on pathways related to feed efficiency. We carried out a realtime quantitative PCR (RT-qPCR) assay in 52 Nelore steers to evaluate the hepatic expression profile of the overmentioned genes and their association with FE related-traits such as average daily gain (ADG), body weight (BW), dry matter intake (DMI), feed conversion ratio (FCR), feed efficiency ratio (FE), Kleiber index (KI), metabolic body weight (MBW), residual feed intake (RFI), and relative growth rate (RGR). Based on a linear mixed model, we identified that the total expression of PRUNE2 has an unfavorable effect on feed efficiency related-traits, likely related to mitochondrial dysfunction. However, when taking only the PRUNE2_isoform, we observed a favorable effect on the evaluated trait. Still, to shed light on the genetic mechanisms affecting feed efficiency in Nelore, we applied a coexpression approach using muscle RNAseq data from 180 animals. Based on the weighted gene co-expression network analysis (WGCNA) software, we identified 391 potential biomarkers (hub genes) related to feed efficiency variation. These hub genes partook in protein synthesis, muscle growth, and immune response pathways. Among the hub genes, we highlighted CCDC80, FBLN5, SERPINF1, and OGN genes, which were associated to ADG, FCR, FE, KI, and RGR traits, and were related to glucose homeostasis, oxidative stress, and osteogenesis. Furthermore, we found 13 transcription factors among the hub genes described for bovine and six of them are putative regulators for the others hub genes identified in this study. Among them, the TCF4 may have a role in muscle growth metabolism and regulator of DE genes for divergent RFI in muscle previously identified by our research group. Finally, we identified potential regulatory regions and functional variants related to the potential biomarkers identified in this study.Os custos com alimentação podem representar mais da metade do custo total de produção. A eficiência alimentar é uma característica complexa, que pode contribuir com a redução de gastos com alimentação dos animais, podendo ainda estar associada à redução dos impactos ambientais relacionados com a ocupação territorial e com a emissão de gases poluentes, como o metano. Apesar do perfil de expressão em grupos contrastantes para eficiência alimentar ter sido investigado em diferentes tecidos, resultando na identificação de vias e processos biológicos relacionados a esse fenótipo, a relação da expressão gênica com a variação contínua de características de eficiência alimentar é pouco explorada na literatura. Assim, dentre os genes previamente identificados como sendo diferencialmente expressos (DE) em tecido hepático de grupos extremos de consumo alimentar residual (CAR) de bovinos da raça Nelore, selecionou-se genes em vias biológicas importantes para eficiência alimentar. Com base nessa seleção, verificou-se a influência da expressão dos genes COL1A1, CTGF, CYP2B6, EGR1, PRUNE2 e de uma isoforma deste último (PRUNE2_isoform) na variação de características relacionadas à eficiência alimentar, a saber: consumo de matéria seca (CMS), consumo alimentar residual (CAR), conversão alimentar (CA), eficiência alimentar (EA), ganho de peso diário (GPD), índice de Kleiber (IK), peso médio (PM), peso médio metabólico (PMM) e taxa relativa de crescimento (TRC). Para isso, realizou-se ensaios de PCR quantitativa em tempo real (RT-qPCR) dos genes e isoforma selecionados em 52 amostras do tecido hepático de bovinos Nelore, seguido pela análise de associação por meio de um modelo linear misto. Esse estudou revelou que o padrão de expressão do gene PRUNE2 desfavorece a eficiência alimentar, e esse fato pode estar relacionado indiretamente à disfunção mitocondrial. No entanto, o padrão de expressão da sua isoforma (PRUNE2_isoform) aparentemente atua de forma contrária à expressão total do gene, favorecendo a eficiência alimentar. Além disso, para melhor entendimento dos mecanismos genéticos envolvidos com a eficiência alimentar, nós realizamos análise de rede de coexpressão gênica, construída pela metodologia weighted gene co-expression network analysis (WGCNA) a partir de 180 amostras de tecido muscular (Longissimus thoracis) de bovinos Nelore, identificou-se 391 potenciais biomarcadores (hub genes) relacionados com a variação da eficiência alimentar. Tais hub genes participam de vias relacionadas com síntese de proteínas, crescimento muscular e resposta imune. Entre esses hub genes nós destacamos os CCDC80, FBLN5, SERPINF1 e OGN associados com as características CA, EA, GPD, IK e TRC. Esses genes estão relacionados com a homeostase da glicose, estresse oxidativo e formação óssea. Entre os hubs genes, identificou-se que 13 fatores de transcrição descritos para bovinos, e seis desses revelaram potenciais reguladores de outros hub genes identificados nesse estudo. Entre eles, o fator de transcrição TCF4 pode desempenhar uma função importante no crescimento muscular e é um potencial regulador de genes previamente identificados por nosso grupo de pesquisa como DE no tecido muscular em grupos extremos de consumo alimentar residual (CAR). Finalmente, identificou-se potenciais regiões regulatórias e variantes funcionais relacionadas aos potenciais biomarcadores identificados nesse estudo.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CAPES: Código de Financiamento 001engUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEvUFSCarBos indicusEficiência alimentarElementos regulatóriosRedes gênicas de co-expressãoRT-qPCRSNPsWGCNAFeed efficiencyRegulatory elementsCo-expression networkCIENCIAS BIOLOGICAS::GENETICAGenes e variantes genéticas na regulação da eficiência alimentar de gado NeloreGenes and genetic variants in the regulation of feed efficiency in Nelore cattleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisOnlined01ccf4a-eded-40d0-baa1-67970b99caebinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALLIMA_Thesis_final.pdfLIMA_Thesis_final.pdfapplication/pdf2969436https://repositorio.ufscar.br/bitstream/ufscar/11650/2/LIMA_Thesis_final.pdf29b79dc28d9b05ea2e14236bd261b2bcMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81957https://repositorio.ufscar.br/bitstream/ufscar/11650/5/license.txtae0398b6f8b235e40ad82cba6c50031dMD55TEXTLIMA_Thesis_final.pdf.txtLIMA_Thesis_final.pdf.txtExtracted texttext/plain162858https://repositorio.ufscar.br/bitstream/ufscar/11650/6/LIMA_Thesis_final.pdf.txtda46a591d7b96b76dea9e12718bd0f78MD56THUMBNAILLIMA_Thesis_final.pdf.jpgLIMA_Thesis_final.pdf.jpgIM Thumbnailimage/jpeg6350https://repositorio.ufscar.br/bitstream/ufscar/11650/7/LIMA_Thesis_final.pdf.jpg0d66e56c1cf9622a6b6681af4f08dcfdMD57ufscar/116502023-09-18 18:31:23.057oai:repositorio.ufscar.br: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Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:31:23Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore
dc.title.alternative.eng.fl_str_mv Genes and genetic variants in the regulation of feed efficiency in Nelore cattle
title Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore
spellingShingle Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore
Lima, Andressa Oliveira de
Bos indicus
Eficiência alimentar
Elementos regulatórios
Redes gênicas de co-expressão
RT-qPCR
SNPs
WGCNA
Feed efficiency
Regulatory elements
Co-expression network
CIENCIAS BIOLOGICAS::GENETICA
title_short Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore
title_full Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore
title_fullStr Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore
title_full_unstemmed Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore
title_sort Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore
author Lima, Andressa Oliveira de
author_facet Lima, Andressa Oliveira de
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/8264911787257919
dc.contributor.author.fl_str_mv Lima, Andressa Oliveira de
dc.contributor.advisor1.fl_str_mv Regitano, Luciana Correia de Almeida
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/9595338480545794
dc.contributor.advisor-co1.fl_str_mv Tizioto, Polyana Cristine
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/4754030540306395
dc.contributor.authorID.fl_str_mv b398457b-504c-4946-8282-d09c778cd808
contributor_str_mv Regitano, Luciana Correia de Almeida
Tizioto, Polyana Cristine
dc.subject.por.fl_str_mv Bos indicus
Eficiência alimentar
Elementos regulatórios
Redes gênicas de co-expressão
RT-qPCR
SNPs
WGCNA
topic Bos indicus
Eficiência alimentar
Elementos regulatórios
Redes gênicas de co-expressão
RT-qPCR
SNPs
WGCNA
Feed efficiency
Regulatory elements
Co-expression network
CIENCIAS BIOLOGICAS::GENETICA
dc.subject.eng.fl_str_mv Feed efficiency
Regulatory elements
Co-expression network
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::GENETICA
description Feeding accounts for most of the costs in beef cattle production. To reduce it, as well as the environmental impact, greenhouse gas emission, and land occupation have been mandatory to improve the animal feed efficiency. Multifactorial, feed efficiency (FE) has been evaluated by different indexes and approaches. Among them, genomic studies from animals genetically divergent for FE pointed out candidate genes and pathways such as energy metabolism, inflammatory and oxidative stress. However, these studies did not take into account the continuous variation of the gene expression within the population. Thereby, from a previous differential approach carried out in divergent Nelore steers for FE, we selected six hepatic candidate genes (COL1A1, CTGF, CYP2B6, EGR1, PRUNE2, and the PRUNE2_isoform) based on their biological role on pathways related to feed efficiency. We carried out a realtime quantitative PCR (RT-qPCR) assay in 52 Nelore steers to evaluate the hepatic expression profile of the overmentioned genes and their association with FE related-traits such as average daily gain (ADG), body weight (BW), dry matter intake (DMI), feed conversion ratio (FCR), feed efficiency ratio (FE), Kleiber index (KI), metabolic body weight (MBW), residual feed intake (RFI), and relative growth rate (RGR). Based on a linear mixed model, we identified that the total expression of PRUNE2 has an unfavorable effect on feed efficiency related-traits, likely related to mitochondrial dysfunction. However, when taking only the PRUNE2_isoform, we observed a favorable effect on the evaluated trait. Still, to shed light on the genetic mechanisms affecting feed efficiency in Nelore, we applied a coexpression approach using muscle RNAseq data from 180 animals. Based on the weighted gene co-expression network analysis (WGCNA) software, we identified 391 potential biomarkers (hub genes) related to feed efficiency variation. These hub genes partook in protein synthesis, muscle growth, and immune response pathways. Among the hub genes, we highlighted CCDC80, FBLN5, SERPINF1, and OGN genes, which were associated to ADG, FCR, FE, KI, and RGR traits, and were related to glucose homeostasis, oxidative stress, and osteogenesis. Furthermore, we found 13 transcription factors among the hub genes described for bovine and six of them are putative regulators for the others hub genes identified in this study. Among them, the TCF4 may have a role in muscle growth metabolism and regulator of DE genes for divergent RFI in muscle previously identified by our research group. Finally, we identified potential regulatory regions and functional variants related to the potential biomarkers identified in this study.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-08-08T18:15:49Z
dc.date.available.fl_str_mv 2019-08-08T18:15:49Z
dc.date.issued.fl_str_mv 2019-05-08
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv LIMA, Andressa Oliveira de. Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore. 2019. Tese (Doutorado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11650.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/11650
identifier_str_mv LIMA, Andressa Oliveira de. Genes e variantes genéticas na regulação da eficiência alimentar de gado Nelore. 2019. Tese (Doutorado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11650.
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language eng
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Universidade Federal de São Carlos
Câmpus São Carlos
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEv
dc.publisher.initials.fl_str_mv UFSCar
publisher.none.fl_str_mv Universidade Federal de São Carlos
Câmpus São Carlos
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFSCAR
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institution UFSCAR
reponame_str Repositório Institucional da UFSCAR
collection Repositório Institucional da UFSCAR
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