Genome-wide patterns of copy number variation in the diversified chicken genomes using next-generation sequencing.

Guoqiang Yi,Ning Yang,Yiyuan Yan,Lujiang Qu,Jianfeng Liu,Guiyun Xu

doi:10.1186/1471-2164-15-962

Abstract

BackgroundCopy number variation (CNV) is important and widespread in the genome, and is a major cause of disease and phenotypic diversity. Herein, we performed a genome-wide CNV analysis in 12 diversified chicken genomes based on whole genome sequencing.ResultsA total of 8,840 CNV regions (CNVRs) covering 98.2 Mb and representing 9.4% of the chicken genome were identified, ranging in size from 1.1 to 268.8 kb with an average of 11.1 kb. Sequencing-based predictions were confirmed at a high validation rate by two independent approaches, including array comparative genomic hybridization (aCGH) and quantitative PCR (qPCR). The Pearson’s correlation coefficients between sequencing and aCGH results ranged from 0.435 to 0.755, and qPCR experiments revealed a positive validation rate of 91.71% and a false negative rate of 22.43%. In total, 2,214 (25.0%) predicted CNVRs span 2,216 (36.4%) RefSeq genes associated with specific biological functions. Besides two previously reported copy number variable genes EDN3 and PRLR, we also found some promising genes with potential in phenotypic variation. Two genes, FZD6 and LIMS1, related to disease susceptibility/resistance are covered by CNVRs. The highly duplicated SOCS2 may lead to higher bone mineral density. Entire or partial duplication of some genes like POPDC3 may have great economic importance in poultry breeding.ConclusionsOur results based on extensive genetic diversity provide a more refined chicken CNV map and genome-wide gene copy number estimates, and warrant future CNV association studies for important traits in chickens.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-962) contains supplementary material, which is available to authorized users.

Highlights

Copy number variation (CNV) is important and widespread in the genome, and is a major cause of disease and phenotypic diversity
After sequence alignment and removing potential PCR duplicates, the sequencing depth varied from 8.2× (CS) to 12.4× (WR), which was sufficient for CNV detection, and the average coverage with respect to the chicken reference genome sequence was 97.2% (Table 1)
In this study, we performed genome-wide CNV detection and estimated the absolute copy number of the corresponding genetic locus based on whole genome sequencing data of 12 chickens abundant in genetic diversity, and constructed the highest-resolution individualized chicken CNV map so far

Summary

Introduction

Copy number variation (CNV) is important and widespread in the genome, and is a major cause of disease and phenotypic diversity. Copy number variations (CNVs) are defined as gains or losses of DNA fragments of 50 bp or longer in length in comparison with reference genome [1,2]. CNVs contribute significantly to both disease susceptibility/resistance and normal phenotypic variability in humans [3,4,5] and animals [6,7,8,9]. CNVs are found to alone capture 18 to 30% of the total detected genetic variation in gene expression in humans and animals, and may contribute to a fraction of the missing heritability [17,18]. Identification of CNVs is essential in whole genome fine-mapping of CNVs and association studies for important phenotypes

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