Background A detailed understanding of genetic variants that affect beef merit helps maximize the efficiency of breeding for improved production merit in beef cattle.To prioritize the putative variants and genes,we ra...Background A detailed understanding of genetic variants that affect beef merit helps maximize the efficiency of breeding for improved production merit in beef cattle.To prioritize the putative variants and genes,we ran a com-prehensive genome-wide association studies(GWAS)analysis for 21 agronomic traits using imputed whole-genome variants in Simmental beef cattle.Then,we applied expression quantitative trait loci(eQTL)mapping between the genotype variants and transcriptome of three tissues(longissimus dorsi muscle,backfat,and liver)in 120 cattle.Results We identified 1,580 association signals for 21 beef agronomic traits using GWAS.We then illuminated 854,498 cis-eQTLs for 6,017 genes and 46,970 trans-eQTLs for 1,903 genes in three tissues and built a synergistic network by integrating transcriptomics with agronomic traits.These cis-eQTLs were preferentially close to the transcription start site and enriched in functional regulatory regions.We observed an average of 43.5%improvement in cis-eQTL discovery using multi-tissue eQTL mapping.Fine-mapping analysis revealed that 111,192,and 194 variants were most likely to be causative to regulate gene expression in backfat,liver,and muscle,respectively.The transcriptome-wide association studies identified 722 genes significantly associated with 11 agronomic traits.Via the colocalization and Mendelian randomization analyses,we found that eQTLs of several genes were associated with the GWAS signals of agronomic traits in three tissues,which included genes,such as NADSYN1,NDUFS3,LTF and KIFC2 in liver,GRAMD1C,TMTC2 and ZNF613 in backfat,as well as TIGAR,NDUFS3 and L3HYPDH in muscle that could serve as the candidate genes for economic traits.Conclusions The extensive atlas of GWAS,eQTL,fine-mapping,and transcriptome-wide association studies aid in the suggestion of potentially functional variants and genes in cattle agronomic traits and will be an invaluable source for genomics and breeding in beef cattle.展开更多
miRNAs are a class of small, single-stranded, non-coding RNAs that perform post-transcriptional repression of target genes by binding to 3＇ untranslated regions. Research has found that miRNAs involved in the regulat...miRNAs are a class of small, single-stranded, non-coding RNAs that perform post-transcriptional repression of target genes by binding to 3＇ untranslated regions. Research has found that miRNAs involved in the regulation of many metabolic processes. Here we uncovered that the beef quality of Angus cattle sharply diversified after acute stress. By performing miRNA microarray analysis, 13 miRNAs were significantly differentially expressed in stressed group compared to control group. Using a bioinformatics method, 135 protein-coding genes were predicted as the targets of significant differentially expressed miRNAs. Gene Ontology （GO） term and Ingenuity Pathway Analysis （IPA） mined that these target genes involved in some important pathways, which may have impact on meat quality and beef tenderness.展开更多
Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by Marek’s disease virus (MDV), an oncogenic and highly contagious α-herpesvirus. MD has been controlled by vaccination but sporadic...Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by Marek’s disease virus (MDV), an oncogenic and highly contagious α-herpesvirus. MD has been controlled by vaccination but sporadic outbreaks of MD still occur in some parts of the world. Efforts to improve vaccine efficacy have continued in both research communities and vaccine industries. We reported the host genetic variation affecting Marek’s disease vaccine-induced immunity in chickens earlier. In this study, we evaluated chicken lines, vaccines, and line by vaccine interaction on the protective efficacy of vaccination against MD. Specific pathogen free chickens from the relatively resistant line 63 and the highly susceptible line 72 were primarily used to evaluate the protection by three kinds of vaccines (rMd5ΔMeq, CVI988/Rispens, and HVT) upon challenge with a very virulent plus strain of MDV, vv+648A. Our data confirmed that both the chicken line and the vaccine significantly affected the protective efficacy of vaccination and showed that a chicken line by vaccine interaction, in most of the trials, also altered vaccine protective efficacy. More interestingly, although the protective index of all vaccine strains was higher in resistant than in susceptible line of chickens, the difference for HVT protection was striking and warrants further study. The findings may have important implications for vaccine development as well as for selective use of particular vaccines in specific lines of chickens to achieve maximum protection at minimized costs.展开更多
Background: Grass-fed and grain-fed Angus cattle differ in the diet regimes. However, the intricate mechanisms of different beef quality and other phenotypes induced by diet differences are still unclear. Diet affects...Background: Grass-fed and grain-fed Angus cattle differ in the diet regimes. However, the intricate mechanisms of different beef quality and other phenotypes induced by diet differences are still unclear. Diet affects mitochondrial function and dynamic behavior in response to changes in energy demand and supply. In this study, we examined the mtDNA copy number, mitochondria-related genes expression, and metabolic biomarkers in grass-fed and grainfed Angus cattle.Results: We found that the grass-fed group had a higher mtDNA copy number than the grain-fed group. Among different tissues, the mtDNA copy number was the highest in the liver than muscle, rumen, and spleen. Based on the transcriptome of the four tissues, a lower expression of mtDNA-encoded genes in the grass-fed group compared to the grain-fed group was discovered. For the mitochondria-related nuclear genes, however, most of them were significantly down-regulated in the muscle of the grass-fed group and up-regulated in the other three tissues. In which, COX6 A2, POLG2, PPIF, DCN, and NDUFA12, involving in ATP synthesis, mitochondrial replication,transcription, and maintenance, might contribute to the alterations of mtDNA copy number and gene expression.Meanwhile, 40 and 23 metabolic biomarkers were identified in the blood and muscle of the grain-fed group compared to a grass-fed group, respectively. Integrated analysis of the altered metabolites and gene expression revealed the high expression level of MDH1 in the grain-fed group might contribute to the mitochondrial NADH oxidation and spermidine metabolism for adapting the deletion mtDNA copy number.Conclusions: Overall, the study may provide further deep insight into the adaptive and regulatory modulations of the mitochondrial function in response to different feeding systems in Angus cattle.展开更多
Background: Marek’s disease(MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. However, the mechanisms of genetic resistance for MD are complex and not fully understood. MD-resi...Background: Marek’s disease(MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. However, the mechanisms of genetic resistance for MD are complex and not fully understood. MD-resistant line 63and MD-susceptible line 72are two highly inbred progenitor lines of White Leghorn. Recombinant Congenic Strains(RCS) were developed from these two lines, which show varied susceptibility to MD.Results: We investigated genetic structure and genomic signatures across the genome, including the line 63and line72, six RCSs, and two reciprocally crossed flocks between the lines 63and 72(F1 63× 72and F1 72× 63) using Affymetrix~? Axiom~? HD 600 K genotyping array. We observed 18 chickens from RCS lines were specifically clustered into resistance sub-groups distributed around line 63. Additionally, homozygosity analysis was employed to explore potential genetic components related to MD resistance, while runs of homozygosity(ROH) are regions of the genome where the identical haplotypes are inherited from each parent. We found several genes including SIK, SOX1, LIG4, SIK1 and TNFSF13B were contained in ROH region identified in resistant group(line 63and RCS), and these genes have been reported that are contribute to immunology and survival. Based on FSTbased population differential analysis, we also identified important genes related to cell death and anti-apoptosis, including AKT1, API5, CDH13, CFDP and USP15,which could be involved in divergent selection during inbreeding process.Conclusions: Our findings offer valuable insights for understanding the genetic mechanism of resistance to MD and the identified genes could be considered as candidate biomarkers in further evaluation.展开更多
Without known analogous sex-determining factors like SRY(sex determining region Y)in mammals,the chicken(Gallus gallus)sex determination mechanism still remains unclear,which highly restricts the biological research o...Without known analogous sex-determining factors like SRY(sex determining region Y)in mammals,the chicken(Gallus gallus)sex determination mechanism still remains unclear,which highly restricts the biological research on chicken development and poultry single-sex reproduction.Here we not only characterized a new female-biased gene UBE2I and identified the expression pattern by qRT-PCR,but also described the functional role of UBE2I in the gonadal development of chicken embryos.Results showed that UBE2I exhibited a female-biased expression pattern in the early stage of PGCs(primordial germ cells)in embryonic gonads and robust expression in ovaries of newborn chickens.Most importantly,we successfully developed an effective method to interfere or overexpress UBE2I in chicken embryos through the intravascular injection.The qRT-PCR analysis showed that the sex-related genes(FOXL2,CYP19A1 and HINTW)in females were upregulated(P<0.05)under the overexpression of UBE2I and the sex-related genes(SOX9,DMRT1 and WT1)in females were downregulated(P<0.05)after interfering UBE2I.Furthermore,the change of UBE2I expression was associated with the level of estradiol and its receptors(AR and ESR),which suggests that UBE2I is necessary to initiate the female-specific development in chickens.In conclusion,this work demonstrates that UBE2I is a crucial sex differentiation-related gene in the embryonic development of chickens,which provides insights for further understanding the mechanism of sex determination in chickens.展开更多
Marek’s disease virus (MDV) challenge induces lymphoma in susceptible chickens. Host genes, especially immune related genes, are activated by the virus. DNA methylation is an epigenetic mechanism that governs gene tr...Marek’s disease virus (MDV) challenge induces lymphoma in susceptible chickens. Host genes, especially immune related genes, are activated by the virus. DNA methylation is an epigenetic mechanism that governs gene transcription. In the present study, we found that expression of signal transducer and activator of transcription 1 (STAT1) was upregulated at 10 days post infection (dpi) in MD susceptible chickens, whereas interleukin 12A (IL12A) was elevated in both resistant and susceptible chickens. However, we did not observe MDV-induced DNA methylation variations at the promoter CpG islands (CGIs) in STAT1 and IL12A. Interestingly, the methylation levels at Chicken Repeat 1 (CR1), the transposable elements (TEs) located upstream of two genes, were different between resistant and susceptible chickens. Furthermore, a mutation was identified in the CR1 element near IL12A. The impact of the point mutation in transcriptional factor binding is to be examined in the near future.展开更多
基金supported by grants from the Central Public-interest Scientific Institution Basal Research Fund(2020-YWF-YB-02)the Young Scientists Fund of the National Natural Science Foundation of China(32202652)+1 种基金China Agriculture Research System of MOF and MARA(CARS-37)the Science and Technology Project of Inner Mongolia Autonomous Region(2020GG0210).
文摘Background A detailed understanding of genetic variants that affect beef merit helps maximize the efficiency of breeding for improved production merit in beef cattle.To prioritize the putative variants and genes,we ran a com-prehensive genome-wide association studies(GWAS)analysis for 21 agronomic traits using imputed whole-genome variants in Simmental beef cattle.Then,we applied expression quantitative trait loci(eQTL)mapping between the genotype variants and transcriptome of three tissues(longissimus dorsi muscle,backfat,and liver)in 120 cattle.Results We identified 1,580 association signals for 21 beef agronomic traits using GWAS.We then illuminated 854,498 cis-eQTLs for 6,017 genes and 46,970 trans-eQTLs for 1,903 genes in three tissues and built a synergistic network by integrating transcriptomics with agronomic traits.These cis-eQTLs were preferentially close to the transcription start site and enriched in functional regulatory regions.We observed an average of 43.5%improvement in cis-eQTL discovery using multi-tissue eQTL mapping.Fine-mapping analysis revealed that 111,192,and 194 variants were most likely to be causative to regulate gene expression in backfat,liver,and muscle,respectively.The transcriptome-wide association studies identified 722 genes significantly associated with 11 agronomic traits.Via the colocalization and Mendelian randomization analyses,we found that eQTLs of several genes were associated with the GWAS signals of agronomic traits in three tissues,which included genes,such as NADSYN1,NDUFS3,LTF and KIFC2 in liver,GRAMD1C,TMTC2 and ZNF613 in backfat,as well as TIGAR,NDUFS3 and L3HYPDH in muscle that could serve as the candidate genes for economic traits.Conclusions The extensive atlas of GWAS,eQTL,fine-mapping,and transcriptome-wide association studies aid in the suggestion of potentially functional variants and genes in cattle agronomic traits and will be an invaluable source for genomics and breeding in beef cattle.
基金supported by Maryland Agricultural Experiment Station and Jorgensen Endowment Funds
文摘miRNAs are a class of small, single-stranded, non-coding RNAs that perform post-transcriptional repression of target genes by binding to 3＇ untranslated regions. Research has found that miRNAs involved in the regulation of many metabolic processes. Here we uncovered that the beef quality of Angus cattle sharply diversified after acute stress. By performing miRNA microarray analysis, 13 miRNAs were significantly differentially expressed in stressed group compared to control group. Using a bioinformatics method, 135 protein-coding genes were predicted as the targets of significant differentially expressed miRNAs. Gene Ontology （GO） term and Ingenuity Pathway Analysis （IPA） mined that these target genes involved in some important pathways, which may have impact on meat quality and beef tenderness.
文摘Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by Marek’s disease virus (MDV), an oncogenic and highly contagious α-herpesvirus. MD has been controlled by vaccination but sporadic outbreaks of MD still occur in some parts of the world. Efforts to improve vaccine efficacy have continued in both research communities and vaccine industries. We reported the host genetic variation affecting Marek’s disease vaccine-induced immunity in chickens earlier. In this study, we evaluated chicken lines, vaccines, and line by vaccine interaction on the protective efficacy of vaccination against MD. Specific pathogen free chickens from the relatively resistant line 63 and the highly susceptible line 72 were primarily used to evaluate the protection by three kinds of vaccines (rMd5ΔMeq, CVI988/Rispens, and HVT) upon challenge with a very virulent plus strain of MDV, vv+648A. Our data confirmed that both the chicken line and the vaccine significantly affected the protective efficacy of vaccination and showed that a chicken line by vaccine interaction, in most of the trials, also altered vaccine protective efficacy. More interestingly, although the protective index of all vaccine strains was higher in resistant than in susceptible line of chickens, the difference for HVT protection was striking and warrants further study. The findings may have important implications for vaccine development as well as for selective use of particular vaccines in specific lines of chickens to achieve maximum protection at minimized costs.
基金supported by Maryland Agricultural Experiment Station(MAES),Jorgensen Endowment Funds。
文摘Background: Grass-fed and grain-fed Angus cattle differ in the diet regimes. However, the intricate mechanisms of different beef quality and other phenotypes induced by diet differences are still unclear. Diet affects mitochondrial function and dynamic behavior in response to changes in energy demand and supply. In this study, we examined the mtDNA copy number, mitochondria-related genes expression, and metabolic biomarkers in grass-fed and grainfed Angus cattle.Results: We found that the grass-fed group had a higher mtDNA copy number than the grain-fed group. Among different tissues, the mtDNA copy number was the highest in the liver than muscle, rumen, and spleen. Based on the transcriptome of the four tissues, a lower expression of mtDNA-encoded genes in the grass-fed group compared to the grain-fed group was discovered. For the mitochondria-related nuclear genes, however, most of them were significantly down-regulated in the muscle of the grass-fed group and up-regulated in the other three tissues. In which, COX6 A2, POLG2, PPIF, DCN, and NDUFA12, involving in ATP synthesis, mitochondrial replication,transcription, and maintenance, might contribute to the alterations of mtDNA copy number and gene expression.Meanwhile, 40 and 23 metabolic biomarkers were identified in the blood and muscle of the grain-fed group compared to a grass-fed group, respectively. Integrated analysis of the altered metabolites and gene expression revealed the high expression level of MDH1 in the grain-fed group might contribute to the mitochondrial NADH oxidation and spermidine metabolism for adapting the deletion mtDNA copy number.Conclusions: Overall, the study may provide further deep insight into the adaptive and regulatory modulations of the mitochondrial function in response to different feeding systems in Angus cattle.
基金supported in part by U.S.Department of Agriculture(USDA)-Nation Research Initiative/National Institute of Food and Agriculture(NRI/NIFA)2008–35204-04660,2010–65205-20588 and 2011–67015-30183
文摘Background: Marek’s disease(MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. However, the mechanisms of genetic resistance for MD are complex and not fully understood. MD-resistant line 63and MD-susceptible line 72are two highly inbred progenitor lines of White Leghorn. Recombinant Congenic Strains(RCS) were developed from these two lines, which show varied susceptibility to MD.Results: We investigated genetic structure and genomic signatures across the genome, including the line 63and line72, six RCSs, and two reciprocally crossed flocks between the lines 63and 72(F1 63× 72and F1 72× 63) using Affymetrix~? Axiom~? HD 600 K genotyping array. We observed 18 chickens from RCS lines were specifically clustered into resistance sub-groups distributed around line 63. Additionally, homozygosity analysis was employed to explore potential genetic components related to MD resistance, while runs of homozygosity(ROH) are regions of the genome where the identical haplotypes are inherited from each parent. We found several genes including SIK, SOX1, LIG4, SIK1 and TNFSF13B were contained in ROH region identified in resistant group(line 63and RCS), and these genes have been reported that are contribute to immunology and survival. Based on FSTbased population differential analysis, we also identified important genes related to cell death and anti-apoptosis, including AKT1, API5, CDH13, CFDP and USP15,which could be involved in divergent selection during inbreeding process.Conclusions: Our findings offer valuable insights for understanding the genetic mechanism of resistance to MD and the identified genes could be considered as candidate biomarkers in further evaluation.
基金funded by the National Natural Science Foundation of China(31772582 and 31972547)the National Key R&D Program of China(2017YFE0108000)+2 种基金the High Level Talents Support Program of Yangzhou University,Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX182376)the Jiangsu Science and Technology Project,China(Youth Fund,BK20180918)the Natural Science Research Project of Jiangsu Higher Education Institutions,China(18KJB230008)。
文摘Without known analogous sex-determining factors like SRY(sex determining region Y)in mammals,the chicken(Gallus gallus)sex determination mechanism still remains unclear,which highly restricts the biological research on chicken development and poultry single-sex reproduction.Here we not only characterized a new female-biased gene UBE2I and identified the expression pattern by qRT-PCR,but also described the functional role of UBE2I in the gonadal development of chicken embryos.Results showed that UBE2I exhibited a female-biased expression pattern in the early stage of PGCs(primordial germ cells)in embryonic gonads and robust expression in ovaries of newborn chickens.Most importantly,we successfully developed an effective method to interfere or overexpress UBE2I in chicken embryos through the intravascular injection.The qRT-PCR analysis showed that the sex-related genes(FOXL2,CYP19A1 and HINTW)in females were upregulated(P<0.05)under the overexpression of UBE2I and the sex-related genes(SOX9,DMRT1 and WT1)in females were downregulated(P<0.05)after interfering UBE2I.Furthermore,the change of UBE2I expression was associated with the level of estradiol and its receptors(AR and ESR),which suggests that UBE2I is necessary to initiate the female-specific development in chickens.In conclusion,this work demonstrates that UBE2I is a crucial sex differentiation-related gene in the embryonic development of chickens,which provides insights for further understanding the mechanism of sex determination in chickens.
文摘Marek’s disease virus (MDV) challenge induces lymphoma in susceptible chickens. Host genes, especially immune related genes, are activated by the virus. DNA methylation is an epigenetic mechanism that governs gene transcription. In the present study, we found that expression of signal transducer and activator of transcription 1 (STAT1) was upregulated at 10 days post infection (dpi) in MD susceptible chickens, whereas interleukin 12A (IL12A) was elevated in both resistant and susceptible chickens. However, we did not observe MDV-induced DNA methylation variations at the promoter CpG islands (CGIs) in STAT1 and IL12A. Interestingly, the methylation levels at Chicken Repeat 1 (CR1), the transposable elements (TEs) located upstream of two genes, were different between resistant and susceptible chickens. Furthermore, a mutation was identified in the CR1 element near IL12A. The impact of the point mutation in transcriptional factor binding is to be examined in the near future.
