Nature Communications (Jul 2024)

Multi-omic characterization of allele-specific regulatory variation in hybrid pigs

  • Jianping Quan,
  • Ming Yang,
  • Xingwang Wang,
  • Gengyuan Cai,
  • Rongrong Ding,
  • Zhanwei Zhuang,
  • Shenping Zhou,
  • Suxu Tan,
  • Donglin Ruan,
  • Jiajin Wu,
  • Enqin Zheng,
  • Zebin Zhang,
  • Langqing Liu,
  • Fanming Meng,
  • Jie Wu,
  • Cineng Xu,
  • Yibin Qiu,
  • Shiyuan Wang,
  • Meng Lin,
  • Shaoyun Li,
  • Yong Ye,
  • Fuchen Zhou,
  • Danyang Lin,
  • Xuehua Li,
  • Shaoxiong Deng,
  • Yuling Zhang,
  • Zekai Yao,
  • Xin Gao,
  • Yingshan Yang,
  • Yiyi Liu,
  • Yuexin Zhan,
  • Zhihong Liu,
  • Jiaming Zhang,
  • Fucai Ma,
  • Jifei Yang,
  • Qiaoer Chen,
  • Jisheng Yang,
  • Jian Ye,
  • Linsong Dong,
  • Ting Gu,
  • Sixiu Huang,
  • Zheng Xu,
  • Zicong Li,
  • Jie Yang,
  • Wen Huang,
  • Zhenfang Wu

DOI
https://doi.org/10.1038/s41467-024-49923-5
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 18

Abstract

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Abstract Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.