Multi-strategy genome-wide association studies identify the DCAF16-NCAPG region as a susceptibility locus for average daily gain in cattle

Wengang Zhang,Xue Gao,Lupei Zhang,Yan Chen,Junya Li,Yong Guo,Hemin Ni,Huijiang Gao,Bo Zhu,Lingyang Xu

doi:10.1038/srep38073

Abstract

Average daily gain (ADG) is the most economically important trait in beef cattle industry. Using genome-wide association study (GWAS) approaches, previous studies have identified several causal variants within the PLAG1, NCAPG and LCORL genes for ADG in cattle. Multi-strategy GWASs were implemented in this study to improve detection and to explore the causal genes and regions. In this study, we conducted GWASs based on the genotypes of 1,173 Simmental cattle. In the SNP-based GWAS, the most significant SNPs (rs109303784 and rs110058857, P = 1.78 × 10−7) were identified in the NCAPG intron on BTA6 and explained 4.01% of the phenotypic variance, and the independent and significant SNP (rs110406669, P = 5.18 × 10−6) explained 3.32% of the phenotypic variance. Similarly, in the haplotype-based GWAS, the most significant haplotype block, Hap-6-N1416 (P = 2.56 × 10−8), spanned 12.7 kb on BTA6 and explained 4.85% of the phenotypic variance. Also, in the gene-based GWAS, seven significant genes were obtained which included DCAF16 and NCAPG. Moreover, analysis of the transcript levels confirmed that transcripts abundance of NCAPG (P = 0.046) and DCAF16 (P = 0.046) were significantly correlated with the ADG trait. Overall, our results from the multi-strategy GWASs revealed the DCAF16-NCAPG region to be a susceptibility locus for ADG in cattle.

Highlights

With the recent emergence of genome-wide association studies (GWASs)[1], major advances have been made in the understanding and practice of functional gene discovery and quantitative trait locus (QTL) mapping[2,3,4]
In the Single Nucleotide Polymorphism (SNP)-based association, we identified 40 distinct SNPs (Supplementary Table S2) that exceeded the suggested significance thresholds (P < 10−6), 38 of which were located within BTA6 (Fig. 1a)
We focused on the intersection of candidate SNPs identified by the three GWASs methods with the highest average daily gain (ADG) trait-associated accuracy, which included 28 significant SNPs located at 38.6–39.0 Mb on BTA6

Summary

Introduction

With the recent emergence of genome-wide association studies (GWASs)[1], major advances have been made in the understanding and practice of functional gene discovery and quantitative trait locus (QTL) mapping[2,3,4]. The Single Nucleotide Polymorphism (SNP)-based GWAS has been useful for identifying causal variants[5], this strategy has its limitations. This approach overlooks the interaction between SNPs within a gene, misses weak signals that aggregate within related SNP sets, and incurs a severe penalty for multiple testing[6]. To increase the statistical power and limit the false discovery rate (FDR) associated with GWAS analyses, GWASs have been improved using haplotype-based[7,8,9,10] and gene-based[11,12,13,14] strategies to assess complex and quantitative traits in human and domestic animals. Identification of the promising candidate genes for further studies will greatly dissect the molecular mechanisms underlying ADG trait in cattle and has the practical in breeding program for the improvement of carcass weight in breeding program

Methods

Results

Conclusion