Epistatic interactions associated with fatty acid profile of beef from Nellore cattle
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2020-10-23
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Universidade Estadual Paulista (Unesp)
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A carne é uma fonte importante de aminoácidos, vitaminas, minerais e ácidos graxos. A seleção genômica tem sido sugerida como uma alternativa para lidar com características complexas como o perfil de ácidos graxos da carne. A epistasia é um efeito genético não aditivo e ocorre entre SNPs (polimorfismos de nucleotídeo único), genes ou QTLs (loci de característica quantitativa). Abordagens para modelar efeitos epistáticos já foram desenvolvidas na seleção genômica, no entanto, estudos que consideram a identificação de efeitos epistáticos entre regiões genômicas em animais de produção ainda são raros. A variação na composição dos ácidos graxos pode ser explicada pela caracterização e identificação de interações epistáticas que podem ser úteis para a predição de fenótipos. Assim, o objetivo deste estudo foi identificar interações epistáticas para as características do perfil de ácidos graxos (AG) da carne em animais Nelore. Foram utilizados dados de 963 machos Nelore de fazendas que integram os programas de melhoramento DeltaGen, CRV PAINT e Nelore Qualitas. O perfil de AG foi analisado em amostras de Longissimus thoracis por cromatografia gasosa, com coluna capilar de 100 m. Este estudo teve como objetivo realizar um Estudo de Interação Genômica para identificar interações gene-gene usando o método empírico Critério de Independência de Hilbert-Schmidt (HSIC) para testar epistasia em características do perfil de ácidos graxos. O controle de qualidade dos marcadores SNP consistiu em excluir aqueles com posição genômica desconhecida, localizados nos cromossomos sexuais; monomórficos e marcadores com frequência do alelo menor que 0,10; SNP que estavam fora do equilíbrio de Hardy-Weinberg, e call rate de 90%, marcadores com excesso de heterozigosidade e SNP muito correlacionados. Após o controle de qualidade, 347.393 SNP de 890 amostras de animais sobraram para análise. Os genótipos ausentes foram imputados usando estimativas de frequência de alelos de uma distribuição binomial dos dados. SNPs nas interações P < 1 × 10!" foram mapeados individualmente e usados para pesquisar genes candidatos. 602, 3, 13, 23, 13, 215 e 169 genes candidatos foram identificados para a soma de ácidos graxos saturados (AGS), ácidos graxos monoinsaturados (AGMI), ácidos graxos poliinsaturados (AGPI), ômega-3 (OM3), ômega-6 (OM6) e as razões AGS: AGPI e OM3: OM6, respectivamente. Os genes candidatos encontrados estavam associados ao colesterol, diferenciação de células de gordura, processo e regulação metabólica de lipídios, desenvolvimento do músculo esquelético, receptores de lipoproteínas de baixa densidade, eficiência alimentar e resposta inflamatória. A análise de enriquecimento revelou 75 termos significativos (P <0,05), a maioria relacionada à qualidade da carne e termos complementares. O número de interações significativas por característica de ácido graxo variou amplamente. Isso pode indicar que algumas características de ácidos graxos podem exigir quantidades variáveis de redundância genética ou controle para criar ácidos graxos essenciais para o condicionamento físico. A visualização de interações epistáticas significativas revelou muitas regiões de controle regulatório potencial em vários cromossomos. Nossos resultados mostraram interações genéticas substanciais associadas ao perfil lipídico, qualidade da carne, características de carcaça e eficiência alimentar, indicando que as interações gene-gene podem desempenhar 1 papéis muito diferentes no controle da variação fenotípica de caracteres relacionados aos lipídeos em bovinos.
Meat is an important source of amino acids, vitamins, minerals, and fatty acids. Genomic selection has been suggested as an alternative to deal with complex characteristics such as the fatty acid profile of the meat. Epistasis is a non-additive genetic effect and occurs between SNPs (single nucleotide polymorphisms), genes, or QTLs (quantitative trait loci). Approaches to model epistatic effects have also been developed in genomic selection, however, studies that consider the identification of epistatic effects between genomic regions in farm animals are still rare. The variation in the fatty acid composition can be explained by the characterization and identification of epistatic interactions that can be useful for the prediction of phenotypes. Thus, the objective of this study was to identify epistatic interactions for the meat fatty acid (FA) profile traits in Nellore animals. Data from 963 Nellore males from farms that integrate the breeding programs DeltaGen, CRV PAINT, and Nelore Qualitas were used. The FA profile was analyzed in Longissimus thoracis samples using gas chromatography, with a 100 m capillary column. This study aimed to conduct a Genomic Interaction Study to identify gene-gene interactions using the Hilbert-Schmidt Independence Criterion (HSIC) empirical method to test epistasis in fatty acid profile traits. The quality control of the SNP markers consisted of excluding those with an unknown genomic position, located on the sex chromosomes; monomorphic and markers with a minor allelic frequency less than 0.10; SNP that were out of the Hardy-Weinberg balance, call rate below 90%, markers with excess heterozygosity and SNP very correlated. After quality control, 347,393 SNP of 890 animal samples were left. The missing genotypes were imputed using allele frequency estimates from a binomial distribution of the data. SNPs in interactions P < 1 × 10!"were individually mapped and used to search for candidate genes. 602, 3, 13, 23, 13, 215, and 169 candidate genes were identified for the sum of saturated fatty acids (AGS), monounsaturated fatty acids (AGMI), polyunsaturated fatty acids (AGPI), omega- 3 (OM3), omega-6 (OM6), and the AGS: AGPI and OM3: OM6 ratios, respectively. The candidate genes found were associated with cholesterol, differentiation of fat cells, lipid metabolic process and regulation, skeletal muscle development, low-density lipoprotein receptors, food efficiency, and inflammatory response. The enrichment analysis revealed 75 significant terms (P <0.05), most related to the quality of the meat and complementary terms. The number of significant interactions per fatty acid characteristic varied widely. This may indicate that some fatty acid traits may require varying amounts of genetic redundancy or control to create fatty acids essential for fitness. Visualization of significant epistatic interactions revealed many regions of potential regulatory control on several chromosomes. Our results showed substantial genetic interactions associated with lipid profile, meat quality, carcass characteristics, and feed efficiency, indicating that genegene interactions can play very different roles in controlling the phenotypic variation of lipid-related characters in cattle.
Meat is an important source of amino acids, vitamins, minerals, and fatty acids. Genomic selection has been suggested as an alternative to deal with complex characteristics such as the fatty acid profile of the meat. Epistasis is a non-additive genetic effect and occurs between SNPs (single nucleotide polymorphisms), genes, or QTLs (quantitative trait loci). Approaches to model epistatic effects have also been developed in genomic selection, however, studies that consider the identification of epistatic effects between genomic regions in farm animals are still rare. The variation in the fatty acid composition can be explained by the characterization and identification of epistatic interactions that can be useful for the prediction of phenotypes. Thus, the objective of this study was to identify epistatic interactions for the meat fatty acid (FA) profile traits in Nellore animals. Data from 963 Nellore males from farms that integrate the breeding programs DeltaGen, CRV PAINT, and Nelore Qualitas were used. The FA profile was analyzed in Longissimus thoracis samples using gas chromatography, with a 100 m capillary column. This study aimed to conduct a Genomic Interaction Study to identify gene-gene interactions using the Hilbert-Schmidt Independence Criterion (HSIC) empirical method to test epistasis in fatty acid profile traits. The quality control of the SNP markers consisted of excluding those with an unknown genomic position, located on the sex chromosomes; monomorphic and markers with a minor allelic frequency less than 0.10; SNP that were out of the Hardy-Weinberg balance, call rate below 90%, markers with excess heterozygosity and SNP very correlated. After quality control, 347,393 SNP of 890 animal samples were left. The missing genotypes were imputed using allele frequency estimates from a binomial distribution of the data. SNPs in interactions P < 1 × 10!"were individually mapped and used to search for candidate genes. 602, 3, 13, 23, 13, 215, and 169 candidate genes were identified for the sum of saturated fatty acids (AGS), monounsaturated fatty acids (AGMI), polyunsaturated fatty acids (AGPI), omega- 3 (OM3), omega-6 (OM6), and the AGS: AGPI and OM3: OM6 ratios, respectively. The candidate genes found were associated with cholesterol, differentiation of fat cells, lipid metabolic process and regulation, skeletal muscle development, low-density lipoprotein receptors, food efficiency, and inflammatory response. The enrichment analysis revealed 75 significant terms (P <0.05), most related to the quality of the meat and complementary terms. The number of significant interactions per fatty acid characteristic varied widely. This may indicate that some fatty acid traits may require varying amounts of genetic redundancy or control to create fatty acids essential for fitness. Visualization of significant epistatic interactions revealed many regions of potential regulatory control on several chromosomes. Our results showed substantial genetic interactions associated with lipid profile, meat quality, carcass characteristics, and feed efficiency, indicating that genegene interactions can play very different roles in controlling the phenotypic variation of lipid-related characters in cattle.
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Epistasia, GWIS, Àcidos graxos, Nelore, Epistasis, Fatty acids, Nellore