Reveal genomic insights into cotton domestication and improvement using gene level functional haplotype-based GWAS

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