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
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. Complex traits present challenges for gene mapping and molecular characterization. Here, the authors develop a 16-generation intercross line of chickens to explore the genetic architecture of complex traits in chicken.