A multi-tissue developmental gene expression atlas towards understanding the biological basis of phenotypes in sheep

Abstract

Sheep (Ovis aries) represents one of the most important livestock species for animal protein and wool production worldwide. However, little is known about the genetic and biological basis of ovine phenotypes, particularly for those of high economic value and environmental impact. Here, by generating and integrating 1,413 RNA-seq samples from 51 distinct tissues across 14 developmental time points, representing early prenatal, late prenatal, neonate, lamb, juvenile, adult, and elderly stages, we built a high-resolution developmental Gene Expression Atlas (dGEA) in sheep. We observed dynamic patterns of gene expression and regulatory networks across tissues and developmental stages. When harnessing this resource for interpreting genomic associations of 48 monogenetic and 12 complex traits in sheep, we found that genes upregulated at prenatal developmental stages played more important roles in shaping these phenotypes than those upregulated at postnatal stages. For instance, genetic associations of crimp number, mean staple length (MSL), and individual birth weight were significantly enriched in the prenatal rather than postnatal skin and immune tissues. By comprehensively integrating fine-mapping results and the sheep dGEA, we identified several key genes associated with complex traits in sheep, such as SOX9 (associated with MSL), GNRHR (associated with litter size at birth), and PRKDC (associated with live weight). These results provide novel insights into the gene regulatory and developmental architecture underlying ovine phenotypes. The dGEA (https://sheepdgea.njau.edu.cn/) will serve as an invaluable resource for sheep developmental biology, genetics, genomics, and selective breeding.