Integrated analysis of genome-wide association studies and 3D epigenomic characteristics reveal the BMP2 gene regulating loin muscle depth in Yorkshire pigs

Yuanxin Miao; Yunxia Zhao; Siqi Wan; Quanshun Mei; Heng Wang; Chuanke Fu; Xinyun Li; Shuhong Zhao; Xuewen Xu; Tao Xiang

doi:10.1371/journal.pgen.1010820

Integrated analysis of genome-wide association studies and 3D epigenomic characteristics reveal the BMP2 gene regulating loin muscle depth in Yorkshire pigs

PLoS Genet. 2023 Jun 20;19(6):e1010820. doi: 10.1371/journal.pgen.1010820. eCollection 2023 Jun.

Authors

Yuanxin Miao^{1

2}, Yunxia Zhao¹, Siqi Wan¹, Quanshun Mei¹, Heng Wang¹, Chuanke Fu¹, Xinyun Li^{1

3}, Shuhong Zhao^{1

3}, Xuewen Xu¹, Tao Xiang¹

Affiliations

¹ Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China.
² Research Institute of Agricultural Biotechnology, Jingchu University of Technology, Jingmen 448000, China.
³ Hubei Hongshan laboratory, Huazhong Agricultural University, Wuhan 430070, China.

Abstract

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.

Copyright: © 2023 Miao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Meta-Analysis

MeSH terms

Animals
Epigenomics*
Genome-Wide Association Study* / methods
Muscles
Phenotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci / genetics
Swine / genetics

Grants and funding

TX acknowledges funding from the National Key Research and Development Program of China (No. 2021YFF1000601 & 2022YFD1301900), Major Science and Technology Projects in Hubei Province (No.2020ABA016); SZ acknowledges funding from the China Agriculture Research System of MOF and MARA (CARS-35); YM acknowledges funding from Natural Science Foundation in Hubei Province (No. 2022CFB021), the Scientific Research Program Key Project of Hubei Provincial Department of education (D20214301), the Natural Science Foundation of Jingmen City (2022YFZD051), and the research fund from Jingchu University of Technology (ZD202102, 2022ZD005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.