Whole-genome sequencing reveals complex structural variations at a major locus linked to pigmented spot sizes in Tianfu goats

Authors: GUO, JIAZHONG - Sichuan Agricultural University; HUANG, QINGSI - Sichuan Agricultural University; XIANG, QIUNAN - Sichuan Agricultural University; WU, GUO - Sichuan Agricultural University; BIAN, PEIPEI - Northwest A&f University; WANG, XIHONG - Northwest A&f University; LI, LI - Sichuan Agricultural University; Liu, Ge; ZHANG, HONGPING - Sichuan Agricultural University

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/26/2025
Publication Date: 9/29/2025
Citation: Guo, J., Huang, Q., Xiang, Q., Wu, G., Bian, P., Wang, X., Li, L., Liu, G., Zhang, H. 2025. Whole-genome sequencing reveals complex structural variations at a major locus linked to pigmented spot sizes in Tianfu goats. BMC Genomics. https://doi.org/10.1186/s12864-025-12055-1.
DOI: https://doi.org/10.1186/s12864-025-12055-1

Interpretive Summary: Coat color is one of the most noticeable traits and is often used to tell breeds and individual animals apart. In this study, we found key genetic areas that affect the size of pigmented spots in Tianfu goats, with a major region on chromosome 17 that contains a duplicated piece of DNA. These findings enhance our understanding of goat coat color genetics, potentially aiding in selective breeding for desired pigmentation traits. This study will be valuable for farmers, scientists, and policymakers focused on enhancing animal health and production through genome-enabled selection.

Technical Abstract: Background Coat color is one of the most easily recognizable appearance traits used to discriminate livestock breeds and individuals. This study investigated the genetic loci and candidate genes affecting pigmented spots in Tianfu (TF) goats. Results The pigmented spot scores in 96 TF goats ranged from 0.5 to 3.95. Whole-genome sequencing identified 15,132,314 bi-allelic autosomal SNPs in these animals. Linear mixed-model analyses identified a major locus near the ENDRA gene on chromosome 17 and a second strong association signal on chromosome 4. Annotation of short variants within the major locus revealed no apparent causal mutations. However, analysis of structural variations (SVs) using short-read data identified three duplication and one deletion SV events in TF goats. These findings were validated using PacBio HiFi sequencing data from Boer goats, one of the parental breeds of TF goats. Distribution analysis of the four SVs across two other goat breeds and Bezoars supported the relevance of three duplications to pigmentation traits. Among them, a 9579-bp tandem duplication exhibited the strongest phenotypic association, as demonstrated by a univariate model in which this duplication explained 31.38% of the phenotypic variation. In silico analysis revealed that this duplication contains putative binding sites for pigmentation-related transcription factors, including MITF and POU6F2. Furthermore, this tandem duplication, combined with the lead SNP on chromosome 14, accounted for 50.71% of the phenotypic variation. Conclusion A genomic region harboring complex SVs near ENDRA on chromosome 17 represents a major locus affecting pigmented spot sizes in TF goats. The most likely causal mutation was refined to a 9758-bp duplicated segment, which warrants further functional analysis. A second strong association signal on chromosome 4 also requires further investigation with larger sample sizes to confirm its role. These findings advance our understanding of the genetic mechanisms underlying pigmentation in goats and provide valuable insights for selective breeding programs aimed at optimizing coat color patterns for economic and conservation purposes.