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 thos...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 integrat-ing 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 ob-served 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 invalu-able resource for sheep developmental biology,genetics,genomics,and selective breeding.展开更多
基金supported by grants from the National Key R&D Program of China(Grant No.2021YFF1000702)the National Natural Science Foundation of China(Grant No.32402755)+7 种基金the Technological Innovation Project of Shandong Academy of Agricultural Sciences,China(Grant No.CXGC2023F10)the Project of Seed Industry Revitalization in Jiangsu Province,China(Grant No.JBGS[2021]113)the 2023 Excellent Postdoctoral Program in Jiangsu Province,China(Grant No.2023ZB584)the Australian Research Council's Discovery Projects(Grant Nos.DP200100499 and DP160101056)the Department of Agriculture,Fisheries and Forestry of the Commonwealth of Australia(Grant No.DAFF 1193857-31)the Flling the Research Gap(2013-2016)‘Host Control of Methane Emissions from Sheep,Australia(Grant No.DP160101056)the Institute Strategic Programme grants(Grant Nos.BBS/E/D/10002070 and BB/X010945/1)awarded to the Roslin Institute by the Biotechnology and Biological Sciences Research Council,UKthe high-performance computing platform of Bioinformatics Center,Nanjing Agricultural University,China.We would like to express our deep gratitude to the late Professor Shengli Zhang for his invaluable support and guidance.
文摘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 integrat-ing 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 ob-served 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 invalu-able resource for sheep developmental biology,genetics,genomics,and selective breeding.