Background Backfat thickness(BFT)is a vital economic trait in pigs,reflecting subcutaneous fat levels that affect meat quality and production efficiency.As a complex trait shaped by multiple genetic factors,BFT has be...Background Backfat thickness(BFT)is a vital economic trait in pigs,reflecting subcutaneous fat levels that affect meat quality and production efficiency.As a complex trait shaped by multiple genetic factors,BFT has been studied using genome-wide association studies(GWAS)and linkage analyses to locate fat-related quantitative trait loci(QTLs),but pinpointing causal variants and genes is hindered by linkage disequilibrium and limited regulatory data.This study aimed to dissect the QTLs affecting BFT on Sus scrofa chromosome 1(SSC1),elucidating regulatory variants,effector genes,and the cell types involved.Results Using whole-genome genotyping data from 3,578 pigs and phenotypic data for five BFT traits,we identified a 630.6 kb QTL on SSC1 significantly associated with these traits via GWAS and fine-mapping,pinpointing 34 candidate causal variants.Using deep convolutional neural networks to predict regulatory activity from sequence data integrated with detailed pig epigenetic profiles,we identified five SNPs potentially affecting enhancer activity in specific tissues.Notably,rs342950505(SSC1:161,123,588)influences weak enhancer activity across multiple tissues,including the brain.High-throughput chromosome conformation capture(Hi-C)analysis identified that rs342950505 interacts with eight genes.Chromatin state annotations confirmed enhancer activity at this QTL in the cerebellum.Leveraging these insights,single-cell ATAC-seq revealed a chromatin accessibility peak encompassing rs342950505 that regulates PMAIP1 expression in inhibitory neurons via enhancer-mediated mechanisms,with an adjacent peak modulating CCBE1 expression in neuroblasts and granule cells.Transcriptome-wide association studies(TWAS)confirmed PMAIP1's role in the hypothalamus,and Mendelian randomization(MR)validated PMAIP1 and CCBE1 as key brain expression quantitative trait locus(eQTL)effectors.We propose that the variant rs342950505,located within a regulatory peak,modulates PMAIP1 expression in inhibitory neurons,potentially influencing energy homeostasis via hypothalamic regulation.Similarly,CCBE1 may contribute to this process.Conclusions Our results,through systematic dissection of pleiotropic BFT-associated loci,provide a framework to elucidate regulatory mechanisms of complex traits,offering insights into polygenic control through lipid metabolism and neural signaling pathways.展开更多
Background： Fatness traits in animals are important for their growth, meat quality, reproductive performance, and immunity. The liver is the principal organ of the regulation of lipid metabolism, and this study used ...Background： Fatness traits in animals are important for their growth, meat quality, reproductive performance, and immunity. The liver is the principal organ of the regulation of lipid metabolism, and this study used massive parallelized high-throughput sequencing technologies to determine the porcine liver tissue transcriptome architecture of two full-sibling Songliao black pigs harboring extremely different phenotypes of backfat thickness. Results： The total number of reads produced for each sample was in the region of 53 million, and 8,226 novel transcripts were detected. Approximately 92 genes were differentially regulated in the liver tissue, while 31 spliced transcripts and 33 primary transcripts showed significantly differential expression between pigs with higher and lower backfat thickness. Genes that were differentially expressed were involved in the metabolism of various substances, smal molecule biochemistry, and molecular transport. Conclusions： Genes involved in the regulation of iipids could play an important role in lipid and fatty acid metabolism in the liver. These results could help us understand how liver metabolism affects the backfat thickness of pigs.展开更多
Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effec...Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits.The present study seeks to answer these questions through in vitro and in vivo investigations.Results Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows.In cells treated with melatonin,the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity.Furthermore,we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice.Notably,melatonin treatment caused a significant reduction in the deposition of endometrial collagen,an increase in the number of glands,and repair of the pinopode structure,ultimately improving endometrial receptivity,promoting embryo implantation,and increasing the number of litter size of mice.Conclusions Collectively,the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.展开更多
基金supported by the China Postdoctoral Science Foundation[Grant Number BX20240146 and 2024M761230]Key Project of Research and Development Plan in Jiangxi Province[Grant Number 20243BCC31001].
文摘Background Backfat thickness(BFT)is a vital economic trait in pigs,reflecting subcutaneous fat levels that affect meat quality and production efficiency.As a complex trait shaped by multiple genetic factors,BFT has been studied using genome-wide association studies(GWAS)and linkage analyses to locate fat-related quantitative trait loci(QTLs),but pinpointing causal variants and genes is hindered by linkage disequilibrium and limited regulatory data.This study aimed to dissect the QTLs affecting BFT on Sus scrofa chromosome 1(SSC1),elucidating regulatory variants,effector genes,and the cell types involved.Results Using whole-genome genotyping data from 3,578 pigs and phenotypic data for five BFT traits,we identified a 630.6 kb QTL on SSC1 significantly associated with these traits via GWAS and fine-mapping,pinpointing 34 candidate causal variants.Using deep convolutional neural networks to predict regulatory activity from sequence data integrated with detailed pig epigenetic profiles,we identified five SNPs potentially affecting enhancer activity in specific tissues.Notably,rs342950505(SSC1:161,123,588)influences weak enhancer activity across multiple tissues,including the brain.High-throughput chromosome conformation capture(Hi-C)analysis identified that rs342950505 interacts with eight genes.Chromatin state annotations confirmed enhancer activity at this QTL in the cerebellum.Leveraging these insights,single-cell ATAC-seq revealed a chromatin accessibility peak encompassing rs342950505 that regulates PMAIP1 expression in inhibitory neurons via enhancer-mediated mechanisms,with an adjacent peak modulating CCBE1 expression in neuroblasts and granule cells.Transcriptome-wide association studies(TWAS)confirmed PMAIP1's role in the hypothalamus,and Mendelian randomization(MR)validated PMAIP1 and CCBE1 as key brain expression quantitative trait locus(eQTL)effectors.We propose that the variant rs342950505,located within a regulatory peak,modulates PMAIP1 expression in inhibitory neurons,potentially influencing energy homeostasis via hypothalamic regulation.Similarly,CCBE1 may contribute to this process.Conclusions Our results,through systematic dissection of pleiotropic BFT-associated loci,provide a framework to elucidate regulatory mechanisms of complex traits,offering insights into polygenic control through lipid metabolism and neural signaling pathways.
基金financially supported by the innovation research team for modern agricultural industry and technology in Beijing
文摘Background： Fatness traits in animals are important for their growth, meat quality, reproductive performance, and immunity. The liver is the principal organ of the regulation of lipid metabolism, and this study used massive parallelized high-throughput sequencing technologies to determine the porcine liver tissue transcriptome architecture of two full-sibling Songliao black pigs harboring extremely different phenotypes of backfat thickness. Results： The total number of reads produced for each sample was in the region of 53 million, and 8,226 novel transcripts were detected. Approximately 92 genes were differentially regulated in the liver tissue, while 31 spliced transcripts and 33 primary transcripts showed significantly differential expression between pigs with higher and lower backfat thickness. Genes that were differentially expressed were involved in the metabolism of various substances, smal molecule biochemistry, and molecular transport. Conclusions： Genes involved in the regulation of iipids could play an important role in lipid and fatty acid metabolism in the liver. These results could help us understand how liver metabolism affects the backfat thickness of pigs.
基金supported by the China Agriculture Research System(CARS-35-PIG)the National Natural Science Foundation of China(32272847,U22A20516)+1 种基金the National Key Research and Development Program of China(No.2021YFF1000602)the Key Research and Development Program of Shaanxi Province(No.2022ZDLNY01–04)。
文摘Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits.The present study seeks to answer these questions through in vitro and in vivo investigations.Results Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows.In cells treated with melatonin,the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity.Furthermore,we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice.Notably,melatonin treatment caused a significant reduction in the deposition of endometrial collagen,an increase in the number of glands,and repair of the pinopode structure,ultimately improving endometrial receptivity,promoting embryo implantation,and increasing the number of litter size of mice.Conclusions Collectively,the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.
