Phenotypic, transcriptomic, and genomic analyses reveal the spatial-temporal patterns and associated genes of coarse hair density in goats

The genetic basis of hair density in animals remains poorly understood. The Dazu black goat, characterized by black coarse hair and white skin, offers a unique model to study coarse hair density (CHD) using micro-camera technology. In this study, we collected 905 skin images, 33 skin transcriptomes, 272 whole-genome sequences, and 182 downloaded transcriptomes. From kid to adult stages, hair shafts thickened and became less dense, while the rapid trunk surface expansion directly reduced CHD. Transcriptome analysis identified 572 differentially expressed genes (DEGs) between high- and low-CHD groups. Genome-wide association study identified 25 significant single nucleotide polymorphisms (P<9.07e-8) and 48 annotated genes, with a pronounced signal peak near GJA1 on chr9_15831585-18621011. Literature review and Venn analysis highlighted six genes (GJA1, GPRC5D, CD1D, CD207, TFAM, and CXCL12) related to “skin” or “hair” biology, and three (GJA1, GPRC5D, and ATP6V1B1) overlapping DEGs. Multiple-tissue transcriptome, immunohistochemistry, and skin single-cell transcriptome analyses showed that GJA1 and GPRC5D were highly and specifically expressed in skin tissue, particularly in hair follicles, with their expression mainly from the hair follicle stem cells and dermal papilla cells, suggesting their significant roles in hair follicle biology. Four public datasets confirmed that the expression of GJA1 and GPRC5D shows a positive correlation with changes in hair follicle density. After comprehensive evaluation, GJA1 and GPRC5D emerged as the strongest candidate genes for influencing CHD. The innovative micro-camera application allowed us to elucidate the spatial-temporal patterns and genes associated with CHD, thereby addressing a significant knowledge gap in animal hair density.