Background:A large number of pig breeds are distributed around the world,their features and characteristics vary among breeds,and they are valuable resources.Understanding the underlying genetic mechanisms that explai...Background:A large number of pig breeds are distributed around the world,their features and characteristics vary among breeds,and they are valuable resources.Understanding the underlying genetic mechanisms that explain across-breed variation can help breeders develop improved pig breeds.Results:In this study,we performed GWAS using a standard mixed linear model with three types of genome variants(SNP,InDel,and CNV)that were identified from public,whole-genome,sequencing data sets.We used 469 pigs of 57 breeds,and we identified and analyzed approximately 19 million SNPs,1.8 million InDels,and 18,016 CNVs.We defined six biological phenotypes by the characteristics of breed features to identify the associated genome variants and candidate genes,which included coat color,ear shape,gradient zone,body weight,body length,and body height.A total of 37 candidate genes was identified,which included 27 that were reported previously(e.g.,PLAG1 for body weight),but the other 10 were newly detected candidate genes(e.g.,ADAMTS9 for coat color).Conclusion:Our study indicated that using GWAS across a modest number of breeds with high density genome variants provided efficient mapping of complex traits.展开更多
Exercise intervention at the early stage of type 2 diabetes mellitus(T2DM)can aid in the maintenance of blood glucose homeostasis and prevent the development of macrovascular and microvascular complications.However,th...Exercise intervention at the early stage of type 2 diabetes mellitus(T2DM)can aid in the maintenance of blood glucose homeostasis and prevent the development of macrovascular and microvascular complications.However,the exercise-regulated pathways that prevent the development of T2DM remain largely unclear.In this study,two forms of exercise intervention,treadmill training and voluntary wheel running,were conducted for high-fat diet(HFD)-induced obese mice.We observed that both forms of exercise intervention alleviated HFD-induced insulin resistance and glucose intolerance.Skeletal muscle is recognized as the primary site for postprandial glucose uptake and for responsive alteration beyond exercise training.Metabolomic profiling of the plasma and skeletal muscle in Chow,HFD,and HFD-exercise groups revealed robust alterations in metabolic pathways by exercise intervention in both cases.Overlapping analysis identified nine metabolites,including beta-alanine,leucine,valine,and tryptophan,which were reversed by exercise treatment in both the plasma and skeletal muscle.Transcriptomic analysis of gene expression profiles in the skeletal muscle revealed several key pathways involved in the beneficial effects of exercise on metabolic homeostasis.In addition,integrative transcriptomic and metabolomic analyses uncovered strong correlations between the concentrations of bioactive metabolites and the expression levels of genes involved in energy metabolism,insulin sensitivity,and immune response in the skeletal muscle.This work established two models of exercise intervention in obese mice and provided mechanistic insights into the beneficial effects of exercise intervention on systemic energy homeostasis.展开更多
Along with the develoipment of high-throughput sequencing technologies,both sample size and SNP number are increasing rapidly in genome-wide association studies(GWAS),and the associated computation is more challenging...Along with the develoipment of high-throughput sequencing technologies,both sample size and SNP number are increasing rapidly in genome-wide association studies(GWAS),and the associated computation is more challenging than ever.Here,we present a memory-efficient,visualization-enhanced,and parallel-accelerated R package called“r MVP”to address the need for improved GWAS computation.r MVP can 1)effectively process large GWAS data,2)rapidly evaluate population structure,3)efficiently estimate variance components by Efficient Mixed-Model Association e Xpedited(EMMAX),Factored Spectrally Transformed Linear Mixed Models(Fa ST-LMM),and Haseman-Elston(HE)regression algorithms,4)implement parallel-accelerated association tests of markers using general linear model(GLM),mixed linear model(MLM),and fixed and random model circulating probability unification(Farm CPU)methods,5)compute fast with a globally efficient design in the GWAS processes,and 6)generate various visualizations of GWASrelated information.Accelerated by block matrix multiplication strategy and multiple threads,the association test methods embedded in r MVP are significantly faster than PLINK,GEMMA,and Farm CPU_pkg.r MVP is freely available at https://github.com/xiaolei-lab/r MVP.展开更多
基金supported by the Key Project of National Natural Science Foundation of China(31790414)the National Natural Science Foundation of China(31702087,31902156,31730089)+1 种基金Fundamental Research Funds for the Central Universities(2662020DKPY007,2662017QD016)the National Swine Industry Technology System(CARS-35).
文摘Background:A large number of pig breeds are distributed around the world,their features and characteristics vary among breeds,and they are valuable resources.Understanding the underlying genetic mechanisms that explain across-breed variation can help breeders develop improved pig breeds.Results:In this study,we performed GWAS using a standard mixed linear model with three types of genome variants(SNP,InDel,and CNV)that were identified from public,whole-genome,sequencing data sets.We used 469 pigs of 57 breeds,and we identified and analyzed approximately 19 million SNPs,1.8 million InDels,and 18,016 CNVs.We defined six biological phenotypes by the characteristics of breed features to identify the associated genome variants and candidate genes,which included coat color,ear shape,gradient zone,body weight,body length,and body height.A total of 37 candidate genes was identified,which included 27 that were reported previously(e.g.,PLAG1 for body weight),but the other 10 were newly detected candidate genes(e.g.,ADAMTS9 for coat color).Conclusion:Our study indicated that using GWAS across a modest number of breeds with high density genome variants provided efficient mapping of complex traits.
基金supported by grants from the National Key Research and Development Program of China(2018YFA0800403 and 2021YFC2701903)the Training Program of the Major Research Plan of the National Natural Science Foundation of China(91857110)+5 种基金the National Natural Science Foundation of China(81670740,82100904,and 32000817)the National Natural Science Fund for Excellent Young Scholars of China(81722012)Zhejiang Provincial Natural Science Foundation of China(LZ21H070001 and LQ21C110001)the Innovative Institute of Basic Medical Sciences of Zhejiang University,the Fundamental Research Funds for the Central Universities,the Construction Fund of Medical Key Disciplines of Hangzhou,Hangzhou Science and Technology Bureau(20150733Q13 and ZD20200129)the Construction Fund of Key Medical Disciplines of Hangzhou(OO20200055)the K.C.Wong Education Foundation.
文摘Exercise intervention at the early stage of type 2 diabetes mellitus(T2DM)can aid in the maintenance of blood glucose homeostasis and prevent the development of macrovascular and microvascular complications.However,the exercise-regulated pathways that prevent the development of T2DM remain largely unclear.In this study,two forms of exercise intervention,treadmill training and voluntary wheel running,were conducted for high-fat diet(HFD)-induced obese mice.We observed that both forms of exercise intervention alleviated HFD-induced insulin resistance and glucose intolerance.Skeletal muscle is recognized as the primary site for postprandial glucose uptake and for responsive alteration beyond exercise training.Metabolomic profiling of the plasma and skeletal muscle in Chow,HFD,and HFD-exercise groups revealed robust alterations in metabolic pathways by exercise intervention in both cases.Overlapping analysis identified nine metabolites,including beta-alanine,leucine,valine,and tryptophan,which were reversed by exercise treatment in both the plasma and skeletal muscle.Transcriptomic analysis of gene expression profiles in the skeletal muscle revealed several key pathways involved in the beneficial effects of exercise on metabolic homeostasis.In addition,integrative transcriptomic and metabolomic analyses uncovered strong correlations between the concentrations of bioactive metabolites and the expression levels of genes involved in energy metabolism,insulin sensitivity,and immune response in the skeletal muscle.This work established two models of exercise intervention in obese mice and provided mechanistic insights into the beneficial effects of exercise intervention on systemic energy homeostasis.
基金supported by the National Natural Science Foundation of China(Grant Nos.31730089,31672391,31702087,and 31701144)the National Key R&D Program of China(Grant No.2016YFD0101900)+2 种基金the Fundamental Research Funds for the Central Universities,China(Grant Nos.2662020DKPY007 and 2662019PY011)the National Science Foundation,USA(Grant No.DBI 1661348)the National Swine System Industry Technology System,China(Grant No.CARS-35)。
文摘Along with the develoipment of high-throughput sequencing technologies,both sample size and SNP number are increasing rapidly in genome-wide association studies(GWAS),and the associated computation is more challenging than ever.Here,we present a memory-efficient,visualization-enhanced,and parallel-accelerated R package called“r MVP”to address the need for improved GWAS computation.r MVP can 1)effectively process large GWAS data,2)rapidly evaluate population structure,3)efficiently estimate variance components by Efficient Mixed-Model Association e Xpedited(EMMAX),Factored Spectrally Transformed Linear Mixed Models(Fa ST-LMM),and Haseman-Elston(HE)regression algorithms,4)implement parallel-accelerated association tests of markers using general linear model(GLM),mixed linear model(MLM),and fixed and random model circulating probability unification(Farm CPU)methods,5)compute fast with a globally efficient design in the GWAS processes,and 6)generate various visualizations of GWASrelated information.Accelerated by block matrix multiplication strategy and multiple threads,the association test methods embedded in r MVP are significantly faster than PLINK,GEMMA,and Farm CPU_pkg.r MVP is freely available at https://github.com/xiaolei-lab/r MVP.