Integrated Aanalysis of Genome and DNA Methylation for Screening Key Genes Related to Pork Quality Traits
[Background]The meat quality traits of pigs are important economic traits.Studying the molecular mechanisms that affect various meat quality traits and discovering key genes can guide genetic improvement of pigs and have significant implications for improving pork quality.Currently,those researches on meat-related mechanisms were mainly based on DNA genomics,while studies on DNA methylation related to meat quality traits,as well as integrated analysis of combining genomics and methylation,are scarce.[Objective]The potential key genes affecting pork meat quality were screened and identified by combined analysis of genome and DNA methylome,so as to provide a reference for the genetic improvement of pork quality.[Method]In this study,28 meat quality traits of the ongissimus dorsi muscle of 140 Large White pigs were examined.Epigenome-wide association analysis(EWAS)and genome-wide association analysis(GWAS)were performed to identify CpG and SNP sites significantly associated with each trait.Subsequently,the conditional association analysis was performed by using SNPs as covariates on the significantly associated sites overlapping between GWAS and EWAS to further identify CpG sites with independent effects.Association analysis was then conducted to identify methylation quantitative trait loci(meQTL)by using the methylation levels of CpG sites as the dependent variable and SNPs as the independent variable.Finally,the cis-methylation quantitative trait loci(cis-meQTL)were used as instrumental variables for Mendelian randomization analysis to infer the causal relationship between cis-meQTL and phenotypes,while potential key genes at the loci were annotated and identified.[Result](1)The significant associated sites were identified in the same genomic regions for the meat quality traits,namely yellowness value at slaughter 45 minutes postmortem(b45min),drip loss(DL),and docosahexaenoic acid(C22:6n-3),by both EWAS and GWAS.(2)After conditional association analysis,seven CpG sites for b45min and one CpG site for DL remained significant,while the three sites for C22:6n-3 were no longer significant after using SNPs as covariates,indicating that the significant associations of the seven CpG sites for b45min and one CpG site for DL identified by EWAS were not influenced by nearby significant SNPs.(3)A total of ten meQTL were identified for the seven CpG sites for b45min and one CpG site for DL,but the majority were trans-meQTL,with only one CpG site(SSC12:44 254 675 bp)identifying a cis-meQTL,suggesting that this site might be regulated by nearby SNPs.(4)Mendelian randomization analysis showed a causal relationship between the CpG site(SSC12:44 254 675 bp)and the b45min phenotype.(5)annotation of the locus revealed that the nearest gene to the CpG site(SSC12:44 254 675 bp)and its cis-meQTL was NOS2,and the CpG site was located within the NOS2 gene.[Conclusion]Based on the integrated analysis of DNA methylation and genomics data,this study proposed that the NOS2 gene might be a key candidate gene for meat color traits.DNA methylation and SNP jointly regulated gene expression,thereby affecting the expression of genes related to meat color traits.
epigenome-wide association study(EWAS)genome-wide association study(GWAS)meat quality traitsDNA methylationmeQTL
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