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Universidade Federal De Uberlândia Instituto De Biotecnologia Pós-Graduação Em Biotecnologia UNIVERSIDADE FEDERAL DE UBERLÂNDIA INSTITUTO DE BIOTECNOLOGIA PÓS-GRADUAÇÃO EM BIOTECNOLOGIA MONIZE ANGELA DE ANDRADE IDENTIFICAÇÃO DE CNVR ASSOCIADAS À QUALIDADE DE CARCAÇA E CARNE EM BOVINOS DA RAÇA NELORE PATOS DE MINAS - MG ABRIL DE 2019 MONIZE ANGELA DE ANDRADE IDENTIFICAÇÃO DE CNVR ASSOCIADAS À QUALIDADE DE CARCAÇA E CARNE EM BOVINOS DA RAÇA NELORE Dissertação de Mestrado apresentada ao Programa de Pós-graduação em Biotecnologia como requisito parcial para obtenção do título de Mestre em Biotecnologia. Profa. Dra. Fernanda Marcondes de Rezende PATOS DE MINAS – MG ABRIL DE 2019 MONIZE ANGELA DE ANDRADE IDENTIFICAÇÃO DE CNVR ASSOCIADAS À QUALIDADE DE CARCAÇA E CARNE EM BOVINOS DA RAÇA NELORE Dissertação de Mestrado apresentada ao Programa de Pós-graduação em Biotecnologia como requisito parcial para obtenção do título de Mestre em Biotecnologia. Aprovado em 26/04/2019 BANCA EXAMINADORA ______________________________________________________ Profa Dra Fernanda Marcondes de Rezende ______________________________________________________ Profa Dra Tatiane Cristina Seleguim Chud _______________________________________________________ Profa Dra Terezinha Aparecida Teixeira PATOS DE MINAS – MG ABRIL DE 2019 Dados Internacionais de Catalogação na Publicação (CIP) Sistema de Bibliotecas da UFU, MG, Brasil. A553i Andrade, Monize Angela de, 1993- 2019 Identificação de CNVR associadas à qualidade de carcaça e carne em bovinos da raça nelore [recurso eletrônico] / Monize Angela de Andrade. - 2019. Orientadora: Fernanda Marcondes de Rezende. Dissertação (mestrado) - Universidade Federal de Uberlândia, Programa de Pós-Graduação em Biotecnologia. Modo de acesso: Internet. Disponível em: http://dx.doi.org/10.14393/ufu.di.2019.28 Inclui bibliografia. Inclui ilustrações. 1. Biotecnologia. 2. Gado - Carcaças - Qualidade. 3. Nelore (Zebu). 4. Carne bovina - Qualidade. 5. Genomas - Variações. I. Rezende, Fernanda Marcondes de, 1981-, (Orient.). II. Universidade Federal de Uberlândia. Programa de Pós-Graduação em Biotecnologia. III. Título. CDU: 60 Rejâne Maria da Silva – CRB6/1925 i RESUMO O estudo foi conduzido com o objetivo de identificar variações estruturais do genoma do tipo CNV (variações no número de cópias), e investigar a associação de CNVRs (regiões com número de cópias variável) com características de qualidade de carcaça e de carne em 658 tourinhos da raça Nelore com avaliação de peso de carcaça quente (HCW), área de olho de lombo (REA), espessura de gordura subcutânea (SBT), maciez (TD) após 7, 14 e 21 dias de maturação e teores de lipídios (IFC) e colesterol (ICC) intramuscular. Dentre esses, 407 animais foram genotipados pela plataforma Illumina Bovine beadchip HD® (777.962 SNPs). O software PennCNV foi utilizado para a identificação das CNVs, as quais foram concatenadas e associadas com as características de interesse pelo programa CNVRuler. Finalmente, os genes sobrepondo total ou parcialmente as CNVRs significativas (p<0,05) foram identificados por meio do pacote BioMart do R utilizando a versão UMD3.1 do genoma bovino. No total, foram identificadas 2.119 CNVs distintas, representando 1.248 duplicações únicas, 5 duplicações duplas, 794 deleções únicas e 72 deleções dupla. As CNVs foram condensadas em 475 CNVRs, representando 2,29% do genoma bovino. Destas 59 CNVRs foram significativamente associadas com as características analisadas. Alguns genes identificados nas regiões CNVs significativas apresentaram provável efeito pleiotrópico na qualidade da carcaça e da carne, sendo esses envolvidos em processos biológicos relacionados ao sistema imunológico, estrutura das membranas celulares, ligação de ATP e receptores olfativos. A identificação de CNVs ao longo do genoma bovino e a associação de CNVRs com características de qualidade da carcaça e da carne em bovinos da raça Nelore podem auxiliar no entendimento da arquitetura biológica dessas características complexas. Além de possibilitarem o desenvolvimento de novas estratégias de seleção. Palavras chaves: Bos primigenius indicus, copy number variation, CNV, variantes estruturais. ii ABSTRACT The proposal of the study was to identify structural variants in the genome, named as CNVs (copy number variations), and investigate the association of CNVRs (copy number variation regions) with carcass and meat quality traits in 658 Nellore bulls with evaluation of hot carcass weight (HCW), rib-eye area (REA), subcutaneous backfat thickness (SBT), meat tenderness (TD) after 7, 14 and 21 days of aging, intramuscular fat content (IFC) and intramuscular cholesterol content (ICC). Among those, 407 animals were genotyped with the Illumina Bovine beadchip HD® (777,962 SNPs). The PennCNV software was used to identify CNVs, which were concatenated and associated with the traits of interest by the CNVRuler program. Finally, genes overlapping total or partially the significant CNVRs (p<0.05) were identified by the BioMart package from R software using the UMD3.1 version of the bovine genome. In total, 2,119 distinct CNVs, representing 1,248 single duplications, 5 double replications, 794 single deletions and 72 double deletions, were identified. The CNVs were condensed into 475 CNVRs, covering 2.29% of the bovine genome. Of those, 59 CNVRs were significantly associated with the analyzed traits. Some genes identified in the significant CNV regions showed putative pleiotropic effect on carcass and meat quality traits, being involved in biological processes related to the immune system, cellular membrane structure, ATP binding and olfactory receptors. The identification of CNVs along the bovine genome and the association of CNVRs with carcass and meat quality traits in Nellore cattle may improve our knowledge on the biological architecture of these complex traits. In addition to enabling the development of novel selection strategies. Keywords: Bos primigenius indicus, copy number variation, CNV, structural variants. SUMÁRIO 1 INTRODUÇÃO ...................................................................................................................... 1 2 REVISÃO DA LITERATURA .............................................................................................. 3 2.1 Características de qualidade de carcaça e carne....................................................................3 2.2 Variantes estruturais..............................................................................................................5 2.3 Identificação das CNVs.........................................................................................................8 2.4 Associação das CNVs com fenótipo......................................................................................9 GENOME-WIDE CNV DETECTION AND CNVR ASSOCIATION WITH CARCASS AND MEAT QUALITY TRAITS……………………………………………….............................10 Abstract….................................................................................................................................11 Introduction...............................................................................................................................13 Material and methods................................................................................................................14 Population and phenotypes.......................................................................................................14 Genotypic data and CNV calling ….........................................................................................16 CNVR indentification and association analysis…....................................................................16 Probable genes and functional enrichment in CNV regions.....................................................18 Results and discussion…..........................................................................................................18 Genome-wide CNV detection. ............................................................................................... ..19 CNV regions mapping and association analysis…………………...…....................................20 Gene content of significant CNV regions…………………...…………..................................22 Functional annotation of significant CNVRs............................................................................30 Conclusion……………………………………........................................................................33 Acknowledgement…................................................................................................................33 References……………………………………........................................................................33 Supporting infomation…..........................................................................................................44 Funding information….............................................................................................................45 Authors contributions...............................................................................................................45 Data availability statement…...................................................................................................45 Supplementary information…..................................................................................................46 4 CONCLUSÃO….................................................................................................................229 REFERÊNCIAS…..................................................................................................................230 ANEXO……………………...................................................................................................235
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