Genome-wide Target Enrichment-aided Chip Design: a 66\u2009K SNP Chip for Cashmere Goat

Xun Xu,Bin Liu,Qiwu Xu,Yang Dong,Wei Chen,Dongming Fang,Xiaowen Wang,Zhiying Wang,Qianjun Zhao,Yaolei Zhang,Yixing Fan,Xuguang Qiao ,Jian Wang,Jiang Huai-Zhi ,Ruijun Wang,Xin Liu,Ran Di,Ting Yang,Yanjun Zhang,Rui Su,Wen Wang,Jiang Chen,Danqing Mao,Tao Zhong,Yu Jiang,Yan Wang ,Wenting Wan,Xiaokai Li,Zhihong Liu,Huanming Yang,Duoyuan Chen,Xiaoli Chen,Shiyang He,Jinquan Li,Wenguang Zhang

doi:10.1038/s41598-017-09285-z

Abstract

Compared with the commercially available single nucleotide polymorphism (SNP) chip based on the Bead Chip technology, the solution hybrid selection (SHS)-based target enrichment SNP chip is not only design-flexible, but also cost-effective for genotype sequencing. In this study, we propose to design an animal SNP chip using the SHS-based target enrichment strategy for the first time. As an update to the international collaboration on goat research, a 66 K SNP chip for cashmere goat was created from the whole-genome sequencing data of 73 individuals. Verification of this 66 K SNP chip with the whole-genome sequencing data of 436 cashmere goats showed that the SNP call rates was between 95.3% and 99.8%. The average sequencing depth for target SNPs were 40X. The capture regions were shown to be 200 bp that flank target SNPs. This chip was further tested in a genome-wide association analysis of cashmere fineness (fiber diameter). Several top hit loci were found marginally associated with signaling pathways involved in hair growth. These results demonstrate that the 66 K SNP chip is a useful tool in the genomic analyses of cashmere goats. The successful chip design shows that the SHS-based target enrichment strategy could be applied to SNP chip design in other species.

Highlights

The first-generation animal breeding strategies for important quantitative traits relied heavily on keeping meticulous documentation of animal phenotypes and breeding values over several generations[1]
Another strategy known as genome-wide association (GWA) analysis was proposed, which believed that specific single nucleotide polymorphism (SNP) markers could be in genetic linkage disequilibrium with a causative mutation affecting animal traits[10]
Even though current commercial SNP chips based on the Bead Chip technology for different domestic animals have been successful[22,23,24,25,26,27], we propose to design an animal SNP chip using the solution hybrid selection (SHS)-based target enrichment strategy for the first time

Summary

Introduction

The first-generation animal breeding strategies for important quantitative traits relied heavily on keeping meticulous documentation of animal phenotypes and breeding values over several generations[1]. The MAS program used a small number of DNA markers to trace limited numbers of QTLs8 This disadvantage lead to the development of genomic selection (GS), which aimed to use simultaneously all available genome-wide dense SNP markers to predict breeding values[9]. Another strategy known as genome-wide association (GWA) analysis was proposed, which believed that specific SNP markers could be in genetic linkage disequilibrium with a causative mutation affecting animal traits[10]. No special SNP chip is designed for cashmere goat till

Methods

Results

Conclusion