Investigação de genes candidatos para características reprodutivas e efeito pleiotrópico para características de produção em bovinos

Abstract

Reproductive disorders are one of the major causes of economic loss in bovine herds. A decrease in reproduction efficiency has been observed in bovine breeds under intensive artificial selection. This may be explained by unidirectional selection, hitchhiking effect or can be a consequence of a pleiotropic effect. In this study, different high throughput methodologies were combined in order to identify candidate genes for bovine reproductive traits. Initially, a Genome-wide association study (GWAS) was developed to identify candidate genomic regions for gonadal hypoplasia and spermatic abnormalities in the Gyr breed. This approach allowed identification of important functional candidate genes for these phenotypes; for example, AR, TUBB and GOPC. Following this approach, a systematic review along with a prioritization analysis were conducted to identify candidate genes for spermatic and testicular traits among taurine and indicine breeds, integrating published GWAS data. The results of this analysis reinforce the genetic heterogeneity of reproductive phenotypes. Testicular traits presented lower variance, when compared to spermatic traits, and, the co-occurrence of specific candidate genes, emerging in more than one GWAS, was larger for testicular traits. Using this systematic review and prioritization analysis approach, regions suggesting specialization in the control of reproductive traits, having a species-specific pattern were identified in taurine chromosomes BTAX, BTA14 and BTA17. In addition, to identify genes potentially able to underlie or regulate pleiotropic effects affecting both production and reproduction traits, a multi-omics and multi-breed approach was developed. RNA-seq and GWAS data for traits related to puberty development in Brangus, Brahman and Tropical Composite females were integrated and compared with a map of the pleiotropic effect across the bovine genome. This approach allowed the identification of candidate genes in regions having a high pleiotropic effect signal shared among studies and high evidence of functional effect. It is important to highlight the strong association observed between the candidate genes and the activity of thyroid hormones; for example, the TG and IYD genes. The results obtained in the present study allow the identification of biological processes shared among reproductive phenotypes; contribute to the knowledge of the genetic architecture and the biological processes related to the regulation of reproductive traits. In addition, the candidate genes identified in the present study can be used to unravel genetic variants associated with reproductive phenotypes. A better understanding of genes and genetic variants underlying pleiotropic effects can be helpful in reducing the reproductive loss associated with genetic selection programs.