FarmGTEx: understanding regulatory variants in farm animal species

Complex traits are often regulated by multiple genetic and environmental factors. Genome-wide association studies (GWAS) have uncovered many loci that contribute to a wide range of complex traits in both livestock and humans. However, the molecular mechanisms underlying these loci are largely unknown, partially due to 1) the high Linkage Disequilibrium (LD) among causal variants and nearby markers, and 2) the lack of detailed functional annotations of these associations. These factors hinder the discovery of causal variants/genes, the biological interpretation, functional follow-ups, and the further improvement of genomic prediction for complex trait phenotypes. It has been well proposed that genomic variants often locate in non-coding regions and affect complex traits via changes in intermediate molecular phenotypes (e.g., gene expression). Thus, systematic characterization of the regulatory landscape of the transcriptome of livestock is essential for interpreting the molecular mechanisms underlying complex traits of economic value. Given a wealth of publicly available RNA-sequencing (RNA-seq) data in livestock and inspired by the GTEx project in humans, Farm animal Genotype–Tissue Expression (FarmGTEx) project has been established to build the reference resource for regulatory variant discovery and molecular phenotype prediction in farmed species. This resource will facilitate the translation o genetic findings between species.

The overall aim of this PhD is to fully develop the public FarmGTEx resource for studying the genetic regulation of the transcriptome and other molecular phenotypes across tissues in farmed animals: 1) build genotype imputation reference panel for each species, 2) QTL mapping for different molecular phenotypes mainly derived from RNA-Seq, 3) benchmark and develop new integrative genomics methods to decipher the molecular mechanisms underlying GWAS signals, 4) understanding the evolutionary conservation of regulatory events across different species.