Structural variation-driven FADS2P1 expression modulates hair trait diversity through unsaturated fatty acid...

Through natural and artificial selection, goats develop distinct hair phenotypes driven by genomic variations, such as structural variations (SVs). The fatty acid desaturase (FADS) family plays an important role in hair follicle (HF) growth, yet its molecular mechanisms remain unclear. In this study, we construct a goat graph-based pangenome containing 99,792 non-redundant presence-absence variations (PAVs) from 16 goat breeds. Using this pangenome, we identify 15,866 allelic variants of PAVs with distinct dominant frequencies (dPAVs) from the resequencing data of 300 goats. Among them, 1290 dPAVs regulate the expression of 772 corresponding genes in cashmere goats (CGs) with different hair types over 12 months. We identify an expanded FADS2P1 gene family with two intact copies and one truncated copy within segmental duplications. An intron deletion in the truncated FADS2P1 copy shows population-specific distribution patterns among goats with cashmere traits. All FADS2P1 copies are significantly upregulated in short-hair CGs, and their expression levels are negatively correlated with oleic acid (OA) levels. Functional validation in FADS2P1 knock-in mice indicates a slower hair growth rate and reduced HF numbers. These findings demonstrate that SV-driven FADS2P1 expression regulates HF development and growth through OA metabolism, providing insights into how PAVs influence complex phenotypes.