Genes candidatos funcionais para eficiência alimentar: Revisão sistemática e análise funcional de resultados do GWAS

Abstract

The economic importance of improving genetically feed efficiency (FE) has been recognized for over 40 years. Functional analysis can be relevant to reveal the action and interaction of all genes and improve the understanding of the genetic mechanisms evolved in the phenotypic expression of FE. The objective was to carry out a systematic review using data from GWAS that evaluated FE in species of productive interest and to identify candidate genes relevant to FE shared among the different species. In addition, to reinforce the importance of systematic reviews in the discovery of markers associated with FE that can be useful to validate findings of studies in a specific population. The search for articles for a systematic review was carried out on the Pubmed and Google Scholar platforms, using 180 keyword models and the papers were selected based on the eligibility criteria. To recover the positional candidate genes associated with the markers and / or window, the assembly of the current genome of each species was considered. The identification of the chosen candidate genes was carried out using the approaches where the genes were prioritized by the principle of “guilt by association” and meta-analysis (GUILDify and ToppGene software, respectively). 22 articles were selected in the systematic review that described the information of 1.886 markers. The gene annotation process resulted in 3.227 positional candidate genes annotated, simultaneously, for all species (660 cattle, 870 chickens, 1,662 pigs and 35 sheep). A relevant point is that 172 positional candidate genes were shared by at least two different species and were used to identify whether any of these genes would be prioritized as a functional candidate gene. The top 100 ranked genes obtained in the GUILDify analysis were used to build a trained list of genes. The ToppGene analysis resulted in 122 significant genes and 17 genes were automatically prioritized because they were already on the trained list. In this way, 139 functional candidate genes for FE were identified. Five genes shared between the species of productive interest were prioritized as functional candidate genes: SOX17, PENK, GRM5, CTNND1, KRAS, therefore, they should be considered relevant genes for EA. The list of functional candidate genes found in this study, is composed of some genes that play crucial roles in biological processes associated with immune response, these results corroborate that food efficiency is related to the immune response. In addition, our results show that the regulatory genetic mechanisms involved in the phenotypic expression of feed efficiency, in fact, are affected by genes whose functions are involved in the rate of growth of animals. The discovery of functional candidate genes shared between different species, may bring new considerations to the current knowledge of the genetic architecture of EA, since the markers associated with these genes can be attributed with higher weights in genomic selection and validated in populations specific information.