Identification of structural variants and selection signatures in cattle
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Data
2021-02-02
Autores
Peripolli, Elisa [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Devido aos impactos causados na produção animal recorrentes das mudanças climáticas, é importante caracterizar o genoma bovino para desvendar os mecanismos genéticos envolvidos na variação fenotípica que foram influenciados pelo ambiente e moldados pela seleção natural. O objetivo deste estudo é descrever os principais efeitos da adaptação e seleção em animais zebuínos e taurinos localmente adaptadas através da identificação de variações estruturais e assinaturas de seleção utilizando dados genotípicos e de sequenciamento de genoma inteiro. No capítulo 2, foram utilizados genótipos imputados (n=735.044 marcadores) de 9,386 animais da raça Nellore e de suas respectivas linhagens a fim de estimar a autozigosidade do genoma baseado nas corridas de homozigose (ROH) por meio do software Plink. Em geral, os coeficientes de endogamia baseados em ROH (FROH) não foram altos, com valores próximos a 2%. As ilhas de autozigosidade foram evidentes em todo o genoma e sua localização não diferiu em grande número dentro das linhagens. Termos enriquecidos (p<0,01) dentro das ilhas de autozigosidade sugeriam uma forte seleção para características relacionadas à resposta imune, podendo explicar uma maior adaptabilidade do gado zebuíno em ambientes severos. O capítulo 3 visou avaliar a autozigosidade de todo o genoma para explorar regiões ricas em ROH que poderiam melhor caracterizar os diferentes tipos biológicos (produtivo ou adaptativo) do gado de corte composto Montana Tropical®. Animais Montana (n=1.436) foram genotipados com o GGP-LD BeadChip (n=30.105 marcadores) e os ROH foram identificados em cada indivíduo usando o software Plink. O número de ilhas de autozigosidade não diferiu consideravelmente entre os tipos biológicos e não foi encontrado nenhum termo enriquecido significativo (p<0,05) compartilhado entre eles. Termos enriquecidos associados à resposta imunológica e homeostase foram descritos para o tipo biológico adaptativo, enquanto aqueles ligados ao sistema imunológico, bem como às funções reprodutivas e produtivas, foram identificados para o tipo biológico produtivo. No capítulo 4, quatro métodos estatísticos foram implementados para detectar regiões genômicas sob pressão seletiva usando dados de sequenciamento de genoma inteiro (12.4 X) de bovinos das raças Gir (GIR, n=13), Caracu Caldeano (CAR, n=12), Crioulo Lageano (CRL, n=12) e Pantaneiro (PAN, n=12). As estatísticas dentro de população (CLR e iHS) e entre populações (FST e XPEHH) foram combinadas separadamente em um único valor por meio do método ‘de-correlated composite of multiple signals’ (DCMS). As regiões de varredura seletiva foram identificadas por meio dos valores do limite superior (1%) da distribuição empírica gerada por cada estatística DCMS. As assinaturas de seleção identificadas forneceram uma percepção abrangente de genes candidatos juntamente com QTLs relacionadas a características produtivas e de adaptação ao ambiente hostil no qual estas raças foram expostas. No capítulo 5, o método de leitura baseada em ‘read-depth’ implementado no software CNVnator foi utilizado para identificar variações no número de cópias (CNVs) utilizando dados de sequenciamento de genoma inteiro (14.07 X) de bovinos das raças CAR (n=12), CRL (n=12) e PAN (n=12). Regiões de CNV (CNVRs) foram identificadas sobrepondo as CNVs individuais dentro de cada raça. A anotação funcional das CNVRs revelou variantes com elevada consequência na sequência proteica abrangendo genes fortemente associados a resiliência ambiental, dentre os quais podemos destacar o BOLA-DQB, BOLA-DQA5, CD1A, β-defensins, PRG3 e ULBP21. A análise de enriquecimento funcional utilizando os genes prospectados nas CNVRs também revelou termos significativos (p<0.01) fortemente associados à imunidade e resistência do gado a ambientes severos. Nossos resultados elucidaram os mecanismos biológicos inerentes as raças bovinas aqui estudadas, fornecendo informações a respeito de genes candidatos e regiões genômicas que abrangem características adaptativas relevantes, bem como informações úteis para futuras abordagens de conservação, estudos de associação ou seleção.
Given the impacts caused by climate change upon livestock production, it is important to characterize the cattle genome to unravel the genetic mechanisms underlying phenotypic variation that were influenced by the environment and shaped by natural selection that allowed them to thrive in distinct ecosystems. Therefore, the objective of this study is to describe the main effects of adaptation and selection in indicine and locally adapted taurine cattle breeds through the identification of structural variants and signatures of selection using genotypic and whole-genome re-sequencing data. In chapter 2, imputed genotypes (n=735,044 markers) were used to assess genome-wide autozygosity based on runs of homozygosity (ROH) in 9,386 Nellore animals and its lineages using the Plink software. Overall, inbreeding coefficients based on ROH (FROH) were not high, with values close to 2%. Autozygosity islands were evident across the genome, and their genomic location did not largely differ within lineages. Enriched terms (p<0.01) within the autozygosity islands suggested a strong selection for immune response-related traits and might explain the greater adaptability of the indicine cattle in harsh environments. Chapter 3 aimed to assess genome-wide autozygosity to explore ROH hotspot regions which could better characterize the different biological types (productive or adaptive) within the composite Montana Tropical® beef cattle. Montana animals (n=1,436) were genotyped with the GGP-LD BeadChip (n=30,105 markers), and ROH were identified in every individual using the Plink software. The number of autozygosity islands did not differ considerably between biological types, and no significant enriched term (p<0.05) was found to be shared between them. Enriched terms associated with the immune response and homeostasis were described for the adaptive biological type, while those linked to the immune system as well as with reproductive and productive functions we identified for the productive biological type. In chapter 4, four statistical methods were implemented to detect genomic regions under selective pressure using whole-genome re-sequencing data from Gir (GIR, n=13), Caracu Caldeano (CAR, n=12), Crioulo Lageano (CRL, n=12), and Pantaneiro (PAN, n=12) cattle breeds. Within-population (CLR and iHS) and cross-population statistics (FST and XPEHH) were combined separately in a single score using the de-correlated composite of multiple signals (DCMS) method, and putative sweep regions were revealed by assessing the top 1% of the empirical distribution generated by each DCMS statistic. The signatures of selection identified herein provided a comprehensive set of putative candidate genes together with QTLs disclosing cattle production traits and adaptation to the challenging environment in which these breeds have been exposed. In chapter 5, the read depth-based method implemented in CNVnator was used for copy number variants (CNV) calling on resequenced data (~14.07 X) from CAR (n=12), CRL (n=12), and PAN (n=12) cattle breeds. CNV regions (CNVRs) were identified by overlapping individual CNVs within each breed. The functional annotation of the CNVRs revealed variants with high consequence on protein sequence harboring relevant genes with functions strongly linked to environmental resilience (i.e., BOLA-DQB, BOLA-DQA5, CD1A, β-defensins, PRG3, and ULBP21). Enrichment analysis based on the gene list retrieved from the viii CNVRs also disclosed over-represented terms (p<0.01) greatly associated with immunity and cattle resistance to harsh environments. Our findings improve the knowledge about the genome biology of such cattle breeds and provide candidate genes and genomic regions encompassing relevant traits as well as useful information for future conservation, association, or selection approaches.
Given the impacts caused by climate change upon livestock production, it is important to characterize the cattle genome to unravel the genetic mechanisms underlying phenotypic variation that were influenced by the environment and shaped by natural selection that allowed them to thrive in distinct ecosystems. Therefore, the objective of this study is to describe the main effects of adaptation and selection in indicine and locally adapted taurine cattle breeds through the identification of structural variants and signatures of selection using genotypic and whole-genome re-sequencing data. In chapter 2, imputed genotypes (n=735,044 markers) were used to assess genome-wide autozygosity based on runs of homozygosity (ROH) in 9,386 Nellore animals and its lineages using the Plink software. Overall, inbreeding coefficients based on ROH (FROH) were not high, with values close to 2%. Autozygosity islands were evident across the genome, and their genomic location did not largely differ within lineages. Enriched terms (p<0.01) within the autozygosity islands suggested a strong selection for immune response-related traits and might explain the greater adaptability of the indicine cattle in harsh environments. Chapter 3 aimed to assess genome-wide autozygosity to explore ROH hotspot regions which could better characterize the different biological types (productive or adaptive) within the composite Montana Tropical® beef cattle. Montana animals (n=1,436) were genotyped with the GGP-LD BeadChip (n=30,105 markers), and ROH were identified in every individual using the Plink software. The number of autozygosity islands did not differ considerably between biological types, and no significant enriched term (p<0.05) was found to be shared between them. Enriched terms associated with the immune response and homeostasis were described for the adaptive biological type, while those linked to the immune system as well as with reproductive and productive functions we identified for the productive biological type. In chapter 4, four statistical methods were implemented to detect genomic regions under selective pressure using whole-genome re-sequencing data from Gir (GIR, n=13), Caracu Caldeano (CAR, n=12), Crioulo Lageano (CRL, n=12), and Pantaneiro (PAN, n=12) cattle breeds. Within-population (CLR and iHS) and cross-population statistics (FST and XPEHH) were combined separately in a single score using the de-correlated composite of multiple signals (DCMS) method, and putative sweep regions were revealed by assessing the top 1% of the empirical distribution generated by each DCMS statistic. The signatures of selection identified herein provided a comprehensive set of putative candidate genes together with QTLs disclosing cattle production traits and adaptation to the challenging environment in which these breeds have been exposed. In chapter 5, the read depth-based method implemented in CNVnator was used for copy number variants (CNV) calling on resequenced data (~14.07 X) from CAR (n=12), CRL (n=12), and PAN (n=12) cattle breeds. CNV regions (CNVRs) were identified by overlapping individual CNVs within each breed. The functional annotation of the CNVRs revealed variants with high consequence on protein sequence harboring relevant genes with functions strongly linked to environmental resilience (i.e., BOLA-DQB, BOLA-DQA5, CD1A, β-defensins, PRG3, and ULBP21). Enrichment analysis based on the gene list retrieved from the viii CNVRs also disclosed over-represented terms (p<0.01) greatly associated with immunity and cattle resistance to harsh environments. Our findings improve the knowledge about the genome biology of such cattle breeds and provide candidate genes and genomic regions encompassing relevant traits as well as useful information for future conservation, association, or selection approaches.
Descrição
Palavras-chave
Adaptação, Recursos genéticos, Sequenciamento de nova geração, Varreduras de seleção, Bos taurus taurus, Bos taurus indicus