Deletion of an enhancer in FGF5 is associated with ectopic expression in goat hair follicle s and the cashmere growth phenotype

Research on cashmere growth has a significant effect on the production of cashmere and a profound influence on cashmere goat breeding. Whole-genome sequencing is a powerful platform to rapidly gain novel insights into the identification of genetic mechanisms underlying cashmere fiber growth. Here, we generated whole-genome sequences of 115 domestic goats from China, Nepal and Pakistan, including 51 cashmere goats and 64 non-cashmere goats. We found genetically distinct clusters according to their geographic locations but genetic admixture or introgression may have occurred between the Chinese and Nepalese goats. We identified that the fibroblast growth factor 5 gene (FGF5) shows a strong signature for positive selection in the cashmere goat. The 505-bp indel variant at the FGF5 gene locus appeared to be strongly associated with cashmere growth. Functional validation showed that the insertion variant may serve as an enhancer for transcription factor binding, resulting in increased transcription of the upstream FGF5 gene in non-cashmere goats. Our study provides useful information for the sustainable utilization and improved conservation of goat genetic resources and demonstrates that the indel mutation in the FGF5 gene could potentially serve as a molecular marker of cashmere growth in cashmere goat breeding. Author summaryCashmere goats have been selected for thousands of years and have become economically significant livestock in China and other central Asian countries. The mechanism of cashmere growth is not well understood because most studies have focused on the investigation of candidate genes. Here, we conducted a comprehensive whole-genome analysis for selection signatures in a total of 115 goats from 15 genetically diverse goat breeds. The results revealed a strong selection signature at the FGF5 gene locus associated with the cashmere growth phenotype. A 505-bp indel was located in the downstream region of FGF5 and significantly separated in the cashmere goats versus non-cashmere goats. Functional effect analysis of the indel revealed that it may act as an enhancer by specifically binding transcription factors to mediate quantitative changes in FGF5 mRNA expression. Our study illustrates how a structural mutation of the FGF5 gene has contributed to the cashmere growth phenotype in domestic goats.