Genome-wide association study reveals 14 new SNPs and confirms two structural variants highly associated with the horned/ polled phenotype in goats

Authors: GUO, JIAZHONG - Sichuan Agricultural University; RUI, JIANG - Sichuan Agricultural University; MAO, AYI - Sichuan Agricultural University; Liu, Ge - George; 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; CHEN, YU - Collaborator; ZHANG, GUOJUN - Collaborator; ZHENG, HONGPING - Sichuan Agricultural University

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/14/2021
Publication Date: 10/28/2021
Citation: Guo, J., Rui, J., Mao, A., Liu, G., Zhan, S., Li, L., Zhong, T., Wang, L., Cao, J., Chen, Y., Zhang, G., Zheng, H. 2021. Genome-wide association study reveals 14 new SNPs and confirms two structural variants highly associated with the horned/polled phenotype in goats. BMC Genomics. 22:769. https://doi.org/10.1186/s12864-021-08089-w.
DOI: https://doi.org/10.1186/s12864-021-08089-w

Interpretive Summary: There is a long-term interest in the horned/polled phenotype in livestock. We did SNP- and CNV-based association studies and found that one deletion and one duplication spanning two genes KCNJ15 and ERG are major loci affecting the polled phenotypes in goat. These results fill our knowledge gaps and provide the foundation for incorporating CNV into the future goat breeding program. Farmers, scientist, and policy planners who need improve animal health and production based on genome-enable animal selection will benefit from this study.

Technical Abstract: Background: There is a long-term interest to investigate the genetic basis of the horned/polled phenotype in domestic goats. Here, we report genome-wide association studies (GWAS) to detect the genetic loci affecting the polled phenotype in goats. Results: We obtained a total of 13,980,209 biallelic SNPs, using the genotyping-by-sequencing data from 45 Jintang Black (JT) goats, which included 32 female and nine male goats, and four individuals with the polled intersex syndrome (PIS). Using a mixed model-based GWAS, we identified two association signals, which were located on 150,334,857–150,817,260 bp (P = 5.15×10-119) and 128,286,704–131,306,537 bp (P = 2.74×10-15) on chromosome 1. The genotype distributions of the 14 most significantly associated SNPs were completely correlated with horn status in goats, based on the whole-genome sequencing (WGS) data from JT and two other Chinese horned breeds. However, variant annotation suggested that none of the detected SNPs within the associated regions were plausible causal mutations. Via additional read-depth analyses and visual inspections of WGS data, we found a 10.1-kb deletion (chr1:g. 129424781_129434939del) and a 480-kb duplication (chr1:150,334,286–150,818,098 bp) encompassing two genes KCNJ15 and ERG in the associated regions of polled and PIS-affected goats. Notably, the 10.1-kb deletion served as the insertion site for the 480-kb duplication, as validated by PCR and Sanger sequencing. Our WGS genotyping showed that all horned goats were homozygous for the reference alleles without either the structural variants (SVs), whereas the PIS-affected goats were homozygous for both the SVs. We also demonstrated that horned, polled, and PIS-affected individuals among 333 goats from JT and three other Chinese horned breeds can be accurately classified via PCR amplification and agarose gel electrophoresis of two fragments in both SVs. Conclusion: Our results revealed that two genomic regions on chromosome 1 are major loci affecting the polled phenotypes in goats. We provided a diagnostic PCR to accurately classify horned, polled, and PIS-affected goats, which enable a reliable genetic test for the early-in-life prediction of horn status in goats.