Nature Communications (Jul 2025)

Mapping the regulatory genetic landscape of complex traits using a chicken advanced intercross line

  • Xiaoning Zhu,
  • Chong Li,
  • Chenglong Luo,
  • Zhonghao Bai,
  • Dingming Shu,
  • Peng Chen,
  • Jiangli Ren,
  • Ran Song,
  • Lingzhao Fang,
  • Hao Qu,
  • Yuzhe Wang,
  • Xiaoxiang Hu

DOI
https://doi.org/10.1038/s41467-025-60834-x
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 15

Abstract

Read online

Abstract Complex traits exhibit a highly polygenic architecture that complicates gene mapping and molecular characterization. As a model organism for birds, chickens possess high-quality reference panels, functional annotations, and molecular quantitative trait locus maps. However, the genetic mechanisms underlying growth traits have not been systematically analyzed. Here, we develop a 16-generation advanced intercross line of chickens to enhance informative recombination and identify 154 single-gene quantitative trait loci. We use multiple co-localization methods to establish a network landscape of tissue-specific regulatory mutations and functional gene relationships. We leverage gene-clustering and restoration quantitative trait loci within the omnigenic model framework to elucidate the genetic regulation system of growth traits. Cross-species comparisons show the conserved functions of growth-related genes and divergent features of regulatory mechanisms in mammals and birds.