MicroRNAs(miRNAs)are key regulators of myocyte development and traits,yet insight into the genetic basis of variation in miRNA expression is still limited.Here,we present a systematic analysis of expression quantitati...MicroRNAs(miRNAs)are key regulators of myocyte development and traits,yet insight into the genetic basis of variation in miRNA expression is still limited.Here,we present a systematic analysis of expression quantitative trait loci(eQTL)for miRNA profiling in longissimus muscle of pigs from an eight-breed crossed heterogeneous population.By integrating the whole-genome sequencing and miRNAomics data,we map 54 cis-and 292 trans-e QTLs at high resolution that are associated with the expression of 54 and 92miRNAs,respectively.Twenty-three trans-acting loci are identified to affect the expression of nine myomi Rs(known muscle-specific miRNAs).MiRNAs in mammalian conserved miRNA clusters are found to be subjected to regulation by shared cis-e QTLs,while the expression of mature miRNA-5p/-3p counterparts is more likely to be regulated by different cis-e QTLs.Fine mapping and bioinformatics analyses pinpoint the peak cis-e SNP of mi R-4331-5p,rs344650810,which is located in its seed region,as a causal variant for the changes in expression and function of this miRNA.Additionally,rs344650810 is significantly(P<0.01)correlated with the density and percentage of type I muscle fibers.Altogether,this study provides a comprehensive atlas of miRNA-e QTLs in porcine skeletal muscle and new insights into regulatory mechanisms of miRNA expression.展开更多
Subcutaneous fat(SCF)and intramuscular fat(IMF)deposition is relevant to health in humans,as well as meat production and quality in pigs.In this study,we generated RNA sequence data for 122 SCF,120 IMF,and 87 longissi...Subcutaneous fat(SCF)and intramuscular fat(IMF)deposition is relevant to health in humans,as well as meat production and quality in pigs.In this study,we generated RNA sequence data for 122 SCF,120 IMF,and 87 longissimus dorsi muscle(LDM)samples using 155 F6 pigs from a specially designed heterogeneous population generated by intercrossing four highly selected European commercial breeds and four indigenous Chinese pig breeds.The phenotypes including waist back fat thickness and intramuscular fat content were also measured in the 155 F6 pigs.We found that the genes in SCF and IMF differed largely in both expression levels and network connectivity,and highlighted network modules that exhibited strongest gain of connectivity in SCF and IMF,containing genes that were associated with the immune process and DNA double-strand repair,respectively.We identified 215 SCF genes related to kinase inhibitor activity,mitochondrial fission,and angiogenesis,and 90 IMF genes related to lipolysis and fat cell differentiation,displayed a tissue-specific association with back fat thickness and IMF content,respectively.We found that cis-expression QTL for trait-associated genes in the two adipose tissues tended to have tissuedependent predictability for the two adipose traits.Alternative splicing of genes was also found to be associated with SCF or IMF deposition,but the association was much less extensive than that based on expression levels.This study provides a better understanding of SCF and IMF gene transcription and network organization and identified critical genes and network modules that displayed tissue-specific associations with subcutaneous and intramuscular fat deposition.These features are helpful for designing breeding programs to genetically improve the two adipose traits in a balanced way.展开更多
Sequencing-based genome-wide association studies(GWAS) have facilitated the identification of causal associations between genetic variants and traits in diverse species. However, it is cost-prohibitive for the majorit...Sequencing-based genome-wide association studies(GWAS) have facilitated the identification of causal associations between genetic variants and traits in diverse species. However, it is cost-prohibitive for the majority of research groups to sequence a large number of samples. Here, we carried out genotype imputation to increase the density of single nucleotide polymorphisms in a large-scale Swine F;population using a reference panel including 117 individuals, followed by a series of GWAS analyses. The imputation accuracies reached 0.89 and 0.86 for allelic concordance and correlation, respectively. A quantitative trait nucleotide(QTN) affecting the chest vertebrate was detected directly, while the investigation of another QTN affecting the residual glucose failed due to the presence of similar haplotypes carrying wild-type and mutant allelesin the reference panel used in this study. A high imputation accuracy was confirmed by Sanger sequencing technology for the most significant loci. Two candidate genes,CPNE5 and MYH3, affecting meat-related traits were proposed. Collectively, we illustrated four scenarios in imputation-based GWAS that may be encountered by researchers, and our results will provide an extensive reference for future genotype imputation-based GWAS analyses in the future.展开更多
Dear Editor,Mitochondria are the center of cellular energy generation and free radical metabolism,with important functions in regulating intracellular calcium levels,cell apoptosis,cell cycle and epigenetic modificati...Dear Editor,Mitochondria are the center of cellular energy generation and free radical metabolism,with important functions in regulating intracellular calcium levels,cell apoptosis,cell cycle and epigenetic modifications.Mitochondrial DNA copy number(mtDNA-CN)is an indicator of mitochondrial biogenesis and has been associated with several diseases,such as cardiovascular disease,depression,chronic kidney disease and aging in humans(Clyde,2022).展开更多
基金supported by the National Natural Science Foundation of China(31790413 and 31872339)。
文摘MicroRNAs(miRNAs)are key regulators of myocyte development and traits,yet insight into the genetic basis of variation in miRNA expression is still limited.Here,we present a systematic analysis of expression quantitative trait loci(eQTL)for miRNA profiling in longissimus muscle of pigs from an eight-breed crossed heterogeneous population.By integrating the whole-genome sequencing and miRNAomics data,we map 54 cis-and 292 trans-e QTLs at high resolution that are associated with the expression of 54 and 92miRNAs,respectively.Twenty-three trans-acting loci are identified to affect the expression of nine myomi Rs(known muscle-specific miRNAs).MiRNAs in mammalian conserved miRNA clusters are found to be subjected to regulation by shared cis-e QTLs,while the expression of mature miRNA-5p/-3p counterparts is more likely to be regulated by different cis-e QTLs.Fine mapping and bioinformatics analyses pinpoint the peak cis-e SNP of mi R-4331-5p,rs344650810,which is located in its seed region,as a causal variant for the changes in expression and function of this miRNA.Additionally,rs344650810 is significantly(P<0.01)correlated with the density and percentage of type I muscle fibers.Altogether,this study provides a comprehensive atlas of miRNA-e QTLs in porcine skeletal muscle and new insights into regulatory mechanisms of miRNA expression.
基金supported by funds from the National Natural Science Foundation of China.
文摘Subcutaneous fat(SCF)and intramuscular fat(IMF)deposition is relevant to health in humans,as well as meat production and quality in pigs.In this study,we generated RNA sequence data for 122 SCF,120 IMF,and 87 longissimus dorsi muscle(LDM)samples using 155 F6 pigs from a specially designed heterogeneous population generated by intercrossing four highly selected European commercial breeds and four indigenous Chinese pig breeds.The phenotypes including waist back fat thickness and intramuscular fat content were also measured in the 155 F6 pigs.We found that the genes in SCF and IMF differed largely in both expression levels and network connectivity,and highlighted network modules that exhibited strongest gain of connectivity in SCF and IMF,containing genes that were associated with the immune process and DNA double-strand repair,respectively.We identified 215 SCF genes related to kinase inhibitor activity,mitochondrial fission,and angiogenesis,and 90 IMF genes related to lipolysis and fat cell differentiation,displayed a tissue-specific association with back fat thickness and IMF content,respectively.We found that cis-expression QTL for trait-associated genes in the two adipose tissues tended to have tissuedependent predictability for the two adipose traits.Alternative splicing of genes was also found to be associated with SCF or IMF deposition,but the association was much less extensive than that based on expression levels.This study provides a better understanding of SCF and IMF gene transcription and network organization and identified critical genes and network modules that displayed tissue-specific associations with subcutaneous and intramuscular fat deposition.These features are helpful for designing breeding programs to genetically improve the two adipose traits in a balanced way.
基金supported by the National Natural Science Foundation of China (31640046 and 31760656)the National Key Research and Development Program of China (2020YFA0509500)
文摘Sequencing-based genome-wide association studies(GWAS) have facilitated the identification of causal associations between genetic variants and traits in diverse species. However, it is cost-prohibitive for the majority of research groups to sequence a large number of samples. Here, we carried out genotype imputation to increase the density of single nucleotide polymorphisms in a large-scale Swine F;population using a reference panel including 117 individuals, followed by a series of GWAS analyses. The imputation accuracies reached 0.89 and 0.86 for allelic concordance and correlation, respectively. A quantitative trait nucleotide(QTN) affecting the chest vertebrate was detected directly, while the investigation of another QTN affecting the residual glucose failed due to the presence of similar haplotypes carrying wild-type and mutant allelesin the reference panel used in this study. A high imputation accuracy was confirmed by Sanger sequencing technology for the most significant loci. Two candidate genes,CPNE5 and MYH3, affecting meat-related traits were proposed. Collectively, we illustrated four scenarios in imputation-based GWAS that may be encountered by researchers, and our results will provide an extensive reference for future genotype imputation-based GWAS analyses in the future.
基金This work was supported by the National Key Research and Development Program of China(2021YFF1000601).
文摘Dear Editor,Mitochondria are the center of cellular energy generation and free radical metabolism,with important functions in regulating intracellular calcium levels,cell apoptosis,cell cycle and epigenetic modifications.Mitochondrial DNA copy number(mtDNA-CN)is an indicator of mitochondrial biogenesis and has been associated with several diseases,such as cardiovascular disease,depression,chronic kidney disease and aging in humans(Clyde,2022).
