Identification of regulatory elements and association analysis of genetic variants with growth traits of goat ADAMTS15 gene

ADAM metallopeptidase with thrombospondin type 1 motif 15 ( ADAMTS15 ) is a member of the ADAMTS family of metalloproteinases and participates in tissue remodeling through the hydrolysis of hyaluronic acid in the extracellular matrix. Studies have shown that ADAMTS15 is expressed during murine myogenesis and is involved in the regulation of myoblast fusion; however, its expression regulatory mechanisms in goat remain largely unknown. In this study, we first characterized the expression profile of ADAMTS15 in Anhui White goats tissues, and in longissimus dorsi muscle at different developmental stages. Subsequently, we systematically identified the promoter and enhancer activity regions of the ADAMTS15 gene using dual-luciferase reporter assays, and characterized the features of the regulatory sequences. On this basis, genetic variants in the promoter and enhancer activity regions, and ADAMTS15 gene were screened by Sanger sequencing, and their associations with growth traits of Anhui White goats were analyzed. The results showed that ADAMTS15 was expressed in goat muscle and its expression in embryonic muscle tissues was significantly higher than that in postnatal stages, exhibiting a progressive decline during development. The promoter activity region was mapped to − 678 to − 385 bp upstream of the transcription start site, overlapping with a CpG island; DNA methylation analysis showed that all 14 CpG sites within this CpG island remained unmethylated in longissimus dorsi muscle from 75-day-old fetuses, 1-day-old newborns, and 10-month-old adult goats. The enhancer active fragments were identified as E2, E4, E6, E7, and E8. Genetic variant analysis revealed that Promoter-SNP2 and Promoter-SNP5 in the promoter region were significantly associated with body weight and cannon circumference, respectively. The Enhancer-SNP1 was significantly associated with chest circumference and cannon circumference. In the genic region, SNP2 was significantly associated with body weight, while SNP3 showed significant associations with all six growth traits. Further functional analysis showed that Promoter-SNP2 genotypes significantly affected promoter activity, while Enhancer-SNP1 genotypes significantly affected enhancer activity. This study provides an important foundation for understanding the transcriptional regulatory mechanisms of ADAMTS15 in goat muscle development, and the identified genetic variants may serve as potential molecular markers for goat molecular breeding.