A Developmental Gene Expression Atlas Reveals Novel Biological Basis of Complex Phenotypes in Sheep

Abstract Sheep (Ovis aries) represent one of the most important livestock species for global animal protein and wool production. However, little is known about the genetic and biological basis of ovine phenotypes, particularly those with high economic value and environmental impact. Here, by integrating 1413 RNA sequencing (RNA-seq) samples from 51 distinct tissues across 14 developmental time points, representing early-prenatal, late-prenatal, neonatal, lamb, juvenile, adult, and elderly stages, we constructed 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. Leveraging this resource to interpret genetic associations for 48 monogenic 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 birthweight were significantly enriched in the prenatal rather than postnatal skin and immune tissues. By comprehensively integrating genome-wide association study (GWAS) fine-mapping results with the sheep dGEA, we identified several candidate genes for complex traits in sheep, such as SOX9 for MSL, GNRHR for litter size at birth, and PRKDC for live weight. These results provide novel insights into the developmental and molecular architecture of ovine phenotypes. The dGEA (https://sheepdgea.njau.edu.cn/) will serve as an invaluable resource for sheep developmental biology, genetics, genomics, and selective breeding.