Genome-wide identification of copy number variation using high-density single-nucleotide polymorphism array in Japanese Black cattle.

Shinji Sasaki,Toshio Watanabe,Yoshikazu Sugimoto,Shota Nishimura

doi:10.1186/s12863-016-0335-z

Abstract

BackgroundCopy number variation (CNV) is an important source of genetic variability associated with phenotypic variation and disease susceptibility. Comprehensive genome-wide CNV maps provide valuable information for genetic and functional studies. To identify CNV in Japanese Black cattle, we performed a genome-wide autosomal screen using genomic data from 1,481 animals analyzed with the Illumina Bovine High-Density (HD) BeadChip Array (735,293 single-nucleotide polymorphisms (SNPs) with an average marker interval of 3.4 kb on the autosomes).ResultsWe identified a total of 861 CNV regions (CNVRs) across all autosomes, which covered 43.65 Mb of the UMD3.1 genome assembly and corresponded to 1.74 % of the 29 bovine autosomes. Overall, 35 % of the CNVRs were present at a frequency of > 1 % in 1,481 animals. The estimated lengths of CNVRs ranged from 1.1 kb to 1.4 Mb, with an average of 50.7 kb. The average number of CNVR events per animal was 35. Comparisons with previously reported cattle CNV showed that 72 % of the CNVR calls detected in this study were within or overlapped with known CNVRs. Experimentally, three CNVRs were validated using quantitative PCR, and one CNVR was validated using PCR with flanking primers for the deleted region. Out of the 861 CNVRs, 390 contained 717 Ensembl-annotated genes significantly enriched for stimulus response, cellular defense response, and immune response in the Gene Ontology (GO) database. To associate genes contained in CNVRs with phenotypes, we converted 560 bovine Ensembl gene IDs to their 438 orthologous associated mouse gene IDs, and 195 of these mouse orthologous genes were categorized into 1,627 phenotypes in the Mouse Genome Informatics (MGI) database.ConclusionsWe identified 861 CNVRs in 1,481 Japanese Black cattle using the Illumina BovineHD BeadChip Array. The genes contained in CNVRs were characterized using GO analysis and the mouse orthologous genes were characterized using the MGI database. The comprehensive genome-wide CNVRs map will facilitate identification of genetic variation and disease-susceptibility alleles in Japanese Black cattle.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0335-z) contains supplementary material, which is available to authorized users.

Highlights

Copy number variation (CNV) is an important source of genetic variability associated with phenotypic variation and disease susceptibility
Since singleton CNVs were only detected in one animal, they were considered false positives compared to CNV region (CNVR) [41] and excluded from subsequent analyses
To further test the CNV calls derived from the PennCNV analysis with Illumina BovineHD BeadChip Array, we examined a region of Claudin 16 gene (CLDN16) on chromosome 1

Summary

Introduction

Copy number variation (CNV) is an important source of genetic variability associated with phenotypic variation and disease susceptibility. Several studies have identified CNVs in cattle using three platforms: single-nucleotide polymorphism (SNP) arrays [2,3,4,5,6,7,8,9], comparative genomic. Stranger et al. Sasaki et al BMC Genetics (2016) 17:26 estimated that CNVs were responsible for 17.7 % of genetic variation in gene expression of human lymphoblastoid cell lines [17], and two studies on rodents showed that CNVs result in genome-wide expression changes in various tissues [18, 19], suggesting that CNVs alter gene dosage and are associated with phenotypic variance and disease susceptibility. CNVs have been shown to contribute to phenotypic diversity and disease susceptibility in other species (for review, see [16, 27])

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