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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 () and Xiaoxiang Hu
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Xiaoning Zhu: China Agricultural University
Chong Li: China Agricultural University
Chenglong Luo: Guangdong Academy of Agricultural Sciences
Zhonghao Bai: Aarhus University
Dingming Shu: State Key Laboratory of Swine and Poultry Breeding Industry
Peng Chen: Guangdong Academy of Agricultural Sciences
Jiangli Ren: China Agricultural University
Ran Song: China Agricultural University
Lingzhao Fang: Aarhus University
Hao Qu: State Key Laboratory of Swine and Poultry Breeding Industry
Yuzhe Wang: China Agricultural University
Xiaoxiang Hu: China Agricultural University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60834-x

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