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

Author

Listed:
  • Xiaoning Zhu

    (China Agricultural University
    State Key Laboratory of Swine and Poultry Breeding Industry
    Aarhus 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
    Guangdong Academy of Agricultural Sciences)

  • Peng Chen

    (Guangdong Academy of Agricultural Sciences)

  • Jiangli Ren

    (China Agricultural University
    China Agricultural University)

  • Ran Song

    (China Agricultural University
    China Agricultural University)

  • Lingzhao Fang

    (Aarhus University)

  • Hao Qu

    (State Key Laboratory of Swine and Poultry Breeding Industry
    Guangdong Academy of Agricultural Sciences)

  • Yuzhe Wang

    (China Agricultural University
    China Agricultural University
    China Agricultural University)

  • Xiaoxiang Hu

    (China Agricultural University
    China Agricultural University
    China Agricultural University)

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.

Suggested Citation

  • Xiaoning Zhu & Chong Li & Chenglong Luo & Zhonghao Bai & Dingming Shu & Peng Chen & Jiangli Ren & Ran Song & Lingzhao Fang & Hao Qu & Yuzhe Wang & Xiaoxiang Hu, 2025. "Mapping the regulatory genetic landscape of complex traits using a chicken advanced intercross line," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60834-x
    DOI: 10.1038/s41467-025-60834-x
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    as
    1. Hui Yang & Jinyuan Wu & Xiaochang Huang & Yunyan Zhou & Yifeng Zhang & Min Liu & Qin Liu & Shanlin Ke & Maozhang He & Hao Fu & Shaoming Fang & Xinwei Xiong & Hui Jiang & Zhe Chen & Zhongzi Wu & Huanfa, 2022. "ABO genotype alters the gut microbiota by regulating GalNAc levels in pigs," Nature, Nature, vol. 606(7913), pages 358-367, June.
    2. Natalia M. Gonzales & Jungkyun Seo & Ana I. Hernandez Cordero & Celine L. St. Pierre & Jennifer S. Gregory & Margaret G. Distler & Mark Abney & Stefan Canzar & Arimantas Lionikas & Abraham A. Palmer, 2018. "Genome wide association analysis in a mouse advanced intercross line," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    3. Alvaro N Barbeira & Milton Pividori & Jiamao Zheng & Heather E Wheeler & Dan L Nicolae & Hae Kyung Im, 2019. "Integrating predicted transcriptome from multiple tissues improves association detection," PLOS Genetics, Public Library of Science, vol. 15(1), pages 1-20, January.
    4. Xiaoquan Wen & Roger Pique-Regi & Francesca Luca, 2017. "Integrating molecular QTL data into genome-wide genetic association analysis: Probabilistic assessment of enrichment and colocalization," PLOS Genetics, Public Library of Science, vol. 13(3), pages 1-25, March.
    5. Zhengkui Zhou & Ming Li & Hong Cheng & Wenlei Fan & Zhengrong Yuan & Qiang Gao & Yaxi Xu & Zhanbao Guo & Yunsheng Zhang & Jian Hu & Hehe Liu & Dapeng Liu & Weihuang Chen & Zhuqing Zheng & Yong Jiang &, 2018. "An intercross population study reveals genes associated with body size and plumage color in ducks," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    6. Loïc Yengo & Sailaja Vedantam & Eirini Marouli & Julia Sidorenko & Eric Bartell & Saori Sakaue & Marielisa Graff & Anders U. Eliasen & Yunxuan Jiang & Sridharan Raghavan & Jenkai Miao & Joshua D. Aria, 2022. "A saturated map of common genetic variants associated with human height," Nature, Nature, vol. 610(7933), pages 704-712, October.
    7. Zhengkui Zhou & Ming Li & Hong Cheng & Wenlei Fan & Zhengrong Yuan & Qiang Gao & Yaxi Xu & Zhanbao Guo & Yunsheng Zhang & Jian Hu & Hehe Liu & Dapeng Liu & Weihuang Chen & Zhuqing Zheng & Yong Jiang &, 2018. "Author Correction: An intercross population study reveals genes associated with body size and plumage color in ducks," Nature Communications, Nature, vol. 9(1), pages 1-1, December.
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