Yahui Gao

Characterization of genetic regulatory variants acting on livestock gene expression is essential for interpreting the molecular mechanisms underlying traits of economic value and for increasing the rate of genetic gain through artificial selection. Here we build a Cattle Genotype–Tissue Expression atlas (CattleGTEx) as part of the pilot phase of the Farm animal GTEx (FarmGTEx) project for the research community based on 7,180 publicly available RNA-sequencing (RNA-seq) samples. We describe the transcriptomic landscape of more than 100 tissues/cell types and report hundreds of thousands of genetic associations with gene expression and alternative splicing for 23 distinct tissues. We evaluate the tissue-sharing patterns of these genetic regulatory effects, and functionally annotate them using multiomics data. Finally, we link gene expression in different tissues to 43 economically important traits using both transcriptome-wide association and colocalization analyses to decipher the molecular regulatory mechanisms underpinning such agronomic traits in cattle. The cattle Genotype–Tissue Expression atlas of expression and splicing QTLs is generated from 7,180 uniformly re-processed RNA-seq samples. Integration with GWAS identifies candidate genes and variants associated with economically important traits.

Abstract The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.

By uniformly analyzing 723 RNA-seq data from 91 tissues and cell types, we built a comprehensive gene atlas and studied tissue specificity of genes in cattle. We demonstrated that tissue-specific genes significantly reflected the tissue-relevant biology, showing distinct promoter methylation and evolution patterns (e.g., brain-specific genes evolve slowest, whereas testis-specific genes evolve fastest). Through integrative analyses of those tissue-specific genes with large-scale genome-wide association studies, we detected relevant tissues/cell types and candidate genes for 45 economically important traits in cattle, including blood/immune system (e.g., CCDC88C ) for male fertility, brain (e.g., TRIM46 and RAB6A ) for milk production, and multiple growth-related tissues (e.g., FGF6 and CCND2 ) for body conformation. We validated these findings by using epigenomic data across major somatic tissues and sperm. Collectively, our findings provided novel insights into the genetic and biological mechanisms underlying complex traits in cattle, and our transcriptome atlas can serve as a primary source for biological interpretation, functional validation, studies of adaptive evolution, and genomic improvement in livestock.

Previous studies have shown that our understanding of species diversity within Diaporthe (syn. Phomopsis) is limited. In this study, 49 strains obtained from different countries were subjected to DNA sequence analysis. Based on these results, eight new species names are introduced for lineages represented by multiple strains and distinct morphology. Twelve Phomopsis species previously described from China were subjected to DNA sequence analysis, and confirmed to belong to Diaporthe. The genus Diaporthe is shown to be paraphyletic based on multi-locus (LSU, ITS and TEF1) phylogenetic analysis. Several morphologically distinct genera, namely Mazzantia, Ophiodiaporthe, Pustulomyces, Phaeocytostroma, and Stenocarpella, are embedded within Diaporthe s. lat., indicating divergent morphological evolution. However, splitting Diaporthe into many smaller genera to achieve monophyly is still premature, and further collections and phylogenetic datasets need to be obtained to address this situation.

Indigenous Chinese cattle combine taurine and indicine origins and occupy a broad range of different environments. By 50 K SNP genotyping we found a discontinuous distribution of taurine and indicine cattle ancestries with extremes of less than 10% indicine cattle in the north and more than 90% in the far south and southwest China. Model-based clustering and f4-statistics indicate introgression of both banteng and gayal into southern Chinese cattle while the sporadic yak influence in cattle in or near Tibetan area validate earlier findings of mitochondrial DNA analysis. Geographic patterns of taurine and indicine mitochondrial and Y-chromosomal DNA diversity largely agree with the autosomal cline. The geographic distribution of the genomic admixture of different bovine species is proposed to be the combined effect of prehistoric immigrations, gene flow, major rivers acting as genetic barriers, local breeding objectives and environmental adaptation. Whole-genome scan for genetic differentiation and association analyses with both environmental and morphological covariables are remarkably consistent with previous studies and identify a number of genes implicated in adaptation, which include TNFRSF19, RFX4, SP4 and several coat color genes. We propose indigenous Chinese cattle as a unique and informative resource for gene-level studies of climate adaptation in mammals.