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

Authors: GUO, JIAZHONG - Sichuan Agricultural University; SUN, XUELIANG - Sichuan Agricultural University; MAO, AYI - Sichuan Agricultural University; LIU, HAIFENG - Sichuan Agricultural University; ZHAN, SIYUAN - Sichuan Agricultural University; LI, LI - Sichuan Agricultural University; ZHONG, TAO - Sichuan Agricultural University; WANG, LINJIE - Sichuan Agricultural University; CAO, JIAXUE - Sichuan Agricultural University; Liu, Ge - George; ZHENG, HONGPING - Sichuan Agricultural University

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/27/2022
Publication Date: 6/13/2022
Citation: Guo, J., Sun, X., Mao, A., Liu, H., Zhan, S., Li, L., Zhong, T., Wang, L., Cao, J., Liu, G., Zheng, H. 2022. A 13.42-kb tandem duplication at the ASIP locus is strongly associated with the pigmentation phenotype of Swiss markings in goats. BMC Genomics. 23:437. https://doi.org/10.1186/s12864-022-08672-9.
DOI: https://doi.org/10.1186/s12864-022-08672-9

Interpretive Summary: There is a long-term interest in the coat color phenotype in livestock. We did SNP- and CNV-based association studies and found that the duplications near the ASIP gene are major loci affecting the coat color phenotypes in the goat. These results fill our knowledge gaps and provide the foundation for incorporating CNV into the future goat breeding program. Farmers, scientists, and policy planners who need to improve animal health and production based on genome-enable animal selection will benefit from this study.

Technical Abstract: 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 great interest. However, it is still challenging to pinpoint the underlying genetic causal variants. Results: In this study, we conducted a genome-wide association study using whole-genome sequencing (WGS) data to identify the genetic loci and causal variants affecting the Swiss marking pigmentation phenotype in 65 Jintang black (JT) goats (i.e., 48 animals with solid black vs. 17 goats with 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 Swiss markings. We then found that all 17 individuals with 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 x 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 most 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. Interestingly, 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: 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 sufficient to cause this phenotype in goats. In addition, the variations in the copy number of the duplication across different goat breeds do not lead to phenotypic heterogeneity.