부산대학교 도서관

Background: The lack of integrated analysis of genome-wide association studies (GWAS) and 3D epigenomics restricts a deep understanding of the genetic mechanisms of meat-related traits. With the application of techniques as ChIP-seq and Hi-C, the annotations of cis-regulatory elements in the pig genome have been established, which offers a new opportunity to elucidate the genetic mechanisms and identify major genetic variants and candidate genes that are significantly associated with important economic traits. Among these traits, loin muscle depth (LMD) is an important one as it impacts the lean meat content. In this study, we integrated cis-regulatory elements and genome-wide association studies (GWAS) to identify candidate genes and genetic variants regulating LMD. Results: Five single nucleotide polymorphisms (SNPs) located on porcine chromosome 17 were significantly associated with LMD in Yorkshire pigs. A 10 kb quantitative trait locus (QTL) was identified as a candidate functional genomic region through the integration of linkage disequilibrium and linkage analysis (LDLA) and high-throughput chromosome conformation capture (Hi-C) analysis. The BMP2 gene was identified as a candidate gene for LMD based on the integrated results of GWAS, Hi-C meta-analysis, and cis-regulatory element data. The identified QTL region was further verified through target region sequencing. Furthermore, through using dual-luciferase assays and electrophoretic mobility shift assays (EMSA), two SNPs, including SNP rs321846600, located in the enhancer region, and SNP rs1111440035, located in the promoter region, were identified as candidate SNPs that may be functionally related to the LMD. Conclusions: Based on the results of GWAS, Hi-C, and cis-regulatory elements, the BMP2 gene was identified as an important candidate gene regulating variation in LMD. The SNPs rs321846600 and rs1111440035 were identified as candidate SNPs that are functionally related to the LMD of Yorkshire pigs. Our results shed light on the advantages of integrating GWAS with 3D epigenomics in identifying candidate genes for quantitative traits. This study is a pioneering work for the identification of candidate genes and related genetic variants regulating one key production trait (LMD) in pigs by integrating genome-wide association studies and 3D epigenomics. Author summary: The loin muscle depth (LMD) is positively correlated with lean meat content and can therefore be used to estimate the lean meat content of pigs. The loin muscle depth is a quantitative trait that is influenced by whole-genome distributed polygenes. To identify the possible candidate genes and mutations impacting the LMD, we used genome-wide association study (GWAS), which is commonly used to identify candidate genomic regions associated with complex growth traits, to mapping the genomic regions. As over 90% of the identified variants have been localized to non-coding regions of the pig genome and their functions in phenotype regulation are poorly understood, we further combined 3D epigenomics to understand the mechanism of genetic variants regulating LMD. In combination with different types of data and analyses, we identified a 10 kb quantitative trait locus (QTL) on chromosome 17 that was significantly associated with LMD. We identified the BMP2 gene as a major candidate gene, and SNP rs1111440035 and rs321846600 were identified as likely candidate mutations affecting the LMD. Our study is unique in its attempt to identify candidate genetic variants by integrating GWAS and 3D epigenomics in pigs. [ABSTRACT FROM AUTHOR]