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104 reviewsGenome-wide association studies (GWAS) are widely used to detect associations between genetic variants and phenotypes. However, few studies havethoroughly analyzed genes, the fundamental and most crucial functional units.Here, we develop an innovative strategy to translate genomic variants intogene-level functional haplotypes (FHs), effectively reducing the interferencefrom complex genome structure and linkage disequilibrium (LD) present inthe conventional genetic mapping framework. Using refined mixed linearmodels, gene-level FH is regressed with 20 cotton agronomic traits across 245sets of phenotypic values in 3,724 accessions, directly identifying 532 quantitative trait genes (QTGs) with significant breeding potential. The biologicalfunction of a superior fiber quality QTG encoding ferulic acid 5-hydroxylase 1 isexperimentally validated. Thereafter, we systematically analyze the geneticbasis of cotton domestication and improvement at the gene level. This reportprovides genomic insight into the genetic dissection and efficient mapping offunctional genes in plants.
