The search for genetic functional variants of feed efficiency in Nelore cattle

Author(s)

Gabriela Ribeiro

• Document type: Master's Dissertation
• Press: Pirassununga.
• Institution: Universidade de São Paulo (USP). Faculdade de Zootecnica e Engenharia de Alimentos (FZE/BT)
• Defense date: 2021-04-05

Examining board members

Heidge Fukumasu; Luiz Lehmann Coutinho; Polyana Cristine Tizioto

• Advisor: Heidge Fukumasu; Aline Silva Mello Cesar

Abstract

Feed efficiency (FE) in animal protein production systems is a feature of great importance, since more efficient animals reflect directly on better productivity and sustainability indexes of the production chains. However, the evaluation of this characteristic is complex, slow and costly, which justifies the search for more effective approaches to identify animals regarding FE. A possible strategy is the identification of molecular markers that allow the selection of animals with better or worse FE. Approaches based on studies of broad genome association (GWAS) have generated a lot of information, however in most cases the markers found are not responsible for the phenotypic (causal) effects, which makes the analysis of the results speculative using genes present in large chromosomal windows. Another problem of these studies is that the analyzes are performed from the DNA of any cell, losing the possibility of understanding the functional and tissue-specific importance of the causal variants in a given phenotype. Thus, this work is organized in chapters, where the first one analyzed data generated from RNA-seq from liver biopsy samples from animals of high and low FE, with the objective of identifying functional variants that regulate genes and biological pathways related to the studied phenotype. It was possible to identify 256 variants (247 SNPs and 9 INDELs (insertions and deletions)) distributed in 190 genes that regulate important pathways of innate immunity, which leads to the conclusion that the immune system is one of the main pathways that regulate animal efficiency, be it directly or indirectly. Among the main findings are 4 homozygous variants for highly efficient animals (HFE) in the CFH and CFH5 genes, which are responsible for the phagocytosis of microbes and damaged cells that induce infection, changes in these variants can lead to changes in biological pathways related to immunities, causing economic losses. In the second chapter, data analysis was performed using RNA-seq from several organs (adrenal, hypothalamus, pituitary, liver, muscle), to identify functional variants that can be central regulators, their biological interactions with the efficiency characteristic and finally to validate the results in an independent population. With this research it was possible to identify 169 variants expressed in common in the five tissues, and these variants are mainly related to MHC class I. A total of 144, 252, 413, 416 and 340 potential functional variants (PFVs) were also identified. in the liver, muscle, hypothalamus, pituitary and adrenal, which were adjacent to 223, 422, 694, 697 and 554 SNP markers presented in BovineHD (Illumina), respectively. To perform the validation and genomic predictions for the validation set, the SNP markers adjacent to the PFV were differentially weighted based on the results obtained with ssGWAS using the training set. Through the obtained data and the applied methodology, it was possible to verify that the precision of the prediction increased from 31.03% to 40%, when adding the data of the differently weighted PFVs in the prediction matrix. Through the genomic data obtained and using the methodology of identification of PFVs and validation by ssGWAS, it was possible to develop a consistent pipeline that can be used to improve the breeding programs. (AU)

• FAPESP's process: 19/01234-1 - Identification of functional variants of the type SNP, indels and isoforms of alternative splicing associated with feed efficiency in Nelore cattle
• Grantee: Gabriela Ribeiro
• Support Opportunities: Scholarships in Brazil - Master