A 13.42-kb tandem duplication at the ASIP locus is strongly associated with the depigmentation phenotype of non-classic Swiss markings in goats

BACKGROUND: The pigmentation phenotype diversity is rich in domestic goats, and identification of the genetic loci affecting coat color in goats has long been of interest. Via the detections of selection signatures, a duplication upstream ASIP was previously reported to be a variant affecting the Swiss markings depigmentation phenotype in goats. RESULTS: We conducted a genome-wide association study using whole-genome sequencing (WGS) data to identify the genetic loci and causal variants affecting the pigmentation phenotype in 65 Jintang black (JT) goats (i.e., 48 solid black vs. 17 non-classic Swiss markings). Although a single association peak harboring the ASIP gene at 52,619,845–72,176,538 bp on chromosome 13 was obtained using a linear mixed model approach, all the SNPs and indels in this region were excluded as causal variants for the pigmentation phenotype. We then found that all 17 individuals with non-classic Swiss markings carried a 13,420-bp duplication (CHI13:63,129,198–63,142,617 bp) nearly 101 kb upstream of ASIP, and this variant was strongly associated (P = 1.48 × 10(− 12)) with the coat color in the 65 JT goats. The copy numbers obtained from the WGS data also showed that the duplication was present in all 53 goats from three European breeds with Swiss markings and absent in 45 of 51 non-Swiss markings goats from four other breeds and 21 Bezoars, which was further validated in 314 samples from seven populations based on PCR amplification. The copy numbers of the duplication vary in different goat breeds with Swiss markings, indicating a threshold effect instead of a dose-response effect at the molecular level. Furthermore, breakpoint flanking repeat analysis revealed that the duplication was likely to be a result of the Bov-B-mediated nonallelic homologous recombination. CONCLUSION: We confirmed that a genomic region harboring the ASIP gene is a major locus affecting the coat color phenotype of Swiss markings in goats. Although the molecular genetic mechanisms remain unsolved, the 13,420-bp duplication upstream of ASIP is a necessary but not sufficient condition for this phenotype in goats. Moreover, the variations in the copy number of the duplication across different goat breeds do not lead to phenotypic heterogeneity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-08672-9.