Identification of copy number variants in horses

Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
Genome Research (Impact Factor: 14.63). 03/2012; 22(5):899-907. DOI: 10.1101/gr.128991.111
Source: PubMed


Copy number variants (CNVs) represent a substantial source of genetic variation in mammals. However, the occurrence of CNVs in horses and their subsequent impact on phenotypic variation is unknown. We performed a study to identify CNVs in 16 horses representing 15 distinct breeds (Equus caballus) and an individual gray donkey (Equus asinus) using a whole-exome tiling array and the array comparative genomic hybridization methodology. We identified 2368 CNVs ranging in size from 197 bp to 3.5 Mb. Merging identical CNVs from each animal yielded 775 CNV regions (CNVRs), involving 1707 protein- and RNA-coding genes. The number of CNVs per animal ranged from 55 to 347, with median and mean sizes of CNVs of 5.3 kb and 99.4 kb, respectively. Approximately 6% of the genes investigated were affected by a CNV. Biological process enrichment analysis indicated CNVs primarily affected genes involved in sensory perception, signal transduction, and metabolism. CNVs also were identified in genes regulating blood group antigens, coat color, fecundity, lactation, keratin formation, neuronal homeostasis, and height in other species. Collectively, these data are the first report of copy number variation in horses and suggest that CNVs are common in the horse genome and may modulate biological processes underlying different traits observed among horses and horse breeds.

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    • "CNVRs that overlap with SDs are dominated by vomeronasal receptors and olfactory genes and are enriched for processes such as the sensory perception of taste, immune response, and G-protein coupled receptor signaling pathway (Supplemental Table S2). The association of CNVs with gene families involved in these processes has also been reported in other species and in inbred mouse strains (Perry et al. 2006; Cutler et al. 2007; Guryev et al. 2008; She et al. 2008; Chen et al. 2009, 2012; Doan et al. 2012). Genes in CNVRs that do not overlap with large SDs showed enrichment for terms related to a much broader spectrum of biological processes, such as protein modification, signaling , and ion transport (Supplemental Table S3). "
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    ABSTRACT: Copy number variation represents a major source of genetic divergence, yet the evolutionary dynamics of genic copy number variation in natural populations during differentiation and adaptation remain unclear. We applied a read depth approach to genome resequencing data to detect copy number variants (CNVs) ≥1 kb in wild-caught mice belonging to four populations of Mus musculus domesticus. We complemented the bioinformatics analyses with experimental validation using droplet digital PCR. The specific focus of our analysis is CNVs that include complete genes, as these CNVs could be expected to contribute most directly to evolutionary divergence. In total, 1863 transcription units appear to be completely encompassed within CNVs in at least one individual when compared to the reference assembly. Further, 179 of these CNVs show population-specific copy number differences, and 325 are subject to complete deletion in multiple individuals. Among the most copy-number variable genes are three highly conserved genes that encode the splicing factor CWC22, the spindle protein SFI1, and the Holliday junction recognition protein HJURP. These genes exhibit population-specific expansion patterns that suggest involvement in local adaptations. We found that genes that overlap with large segmental duplications are generally more copy-number variable. These genes encode proteins that are relevant for environmental and behavioral interactions, such as vomeronasal and olfactory receptors, as well as major urinary proteins and several proteins of unknown function. The overall analysis shows that genic CNVs contribute more to population differentiation in mice than in humans and may promote and speed up population divergence. © 2015 Pezer et al.; Published by Cold Spring Harbor Laboratory Press.
    Full-text · Article · Jul 2015 · Genome Research
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    • "In the past decades, animal CNVs have been assessed according to various criteria including phenotypic, biochemical, and molecular parameters. With the development of molecular biology techniques that utilize single-nucleotide polymorphisms (SNPs) (Illumina technologies Inc.), hybridization (Agilent technologies Inc.), and whole genome resequencing, characterization of CNVs has been successively carried out in cattle (Fadista et al. 2010), pig (Fadista et al. 2008), goat (Fontanesi et al. 2010), sheep (Fontanesi et al. 2011), and horse (Doan et al. 2012). In cattle, most of these studies have focused on European breeds such as Black Angus (Stothard et al. 2011) and Holsten (Seroussi et al. 2010), but little information is available on the CNVs of Chinese indigenous breeds, especially in Qinchuan cattle. "
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    ABSTRACT: In recent years, copy number variations (CNVs), which associate with complex traits such as disease and quantitative phenotypes, are increasingly recognized as an important and abundant source of genetic variation and phenotypic diversity. CNVs have been studied in several breeds of cattle with the goal of improving selection methods for commercial use; however, little is known about the extent to which CNVs contribute to genetic variation in Qinchuan cattle. The BovineHD Genotyping BeadChip array was used for analyzing the whole genomic CNVs of Qinchuan cattle breed; we discovered 367 unique CNV events from 6 Qinchuan cattle. Accounting for overlapping regions, a total of 365 autosomal copy number variation regions (CNVRs) (131 losses and 234 gains) were identified with an average number of 60.8 CNV events per individual, which covered 13.13 Mb of the cattle genomic sequence corresponding to 0.4 % of the whole cattle genome. The average and median sizes of CNVRs were 35.07 and 18.56 kb, respectively. The CNVRs map of Qinchuan cattle was first constructed based on the BovineHD Genotyping Beadchip array. Functional analysis indicated that most genes in CNVRs that were significantly enriched are involved in environmental stress. Comparison of CNVRs in ten published studies and the 365 CNVRs identified in our study overlapped 0.7–42.7 %. These findings are the first report of CNVs mapping in Qinchuan cattle and contribute to the greater understanding of CNV genetics in commercial cattle phenotypes.
    Full-text · Article · Sep 2014 · MGG Molecular & General Genetics
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    • "Since the accomplishment of the first human genome CNV map, many reports have been published on the characterization of the genomic architecture of CNVs in domestic species. Low-resolution CNV maps were produced for cattle, dog, pig, goat, sheep, chicken, duck, turkey and horse, showing that these structural polymorphisms comprise a significant part of these genomes [17], [28]–[32]. Based on porcine SNP60 Beadchip and aCGH, Fadista et al. [33], Ramayo-Caldas et al. [29], Wang et al. [34], [35], Chen et al. [36], and Li et al. [37] have identified a large amount of CNVs in pig genome among different breeds, including several Chinese breeds. "
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    ABSTRACT: Copy number variations (CNVs) represent a substantial source of structural variants in mammals and contribute to both normal phenotypic variability and disease susceptibility. Although low-resolution CNV maps are produced in many domestic animals, and several reports have been published about the CNVs of porcine genome, the differences between Chinese and western pigs still remain to be elucidated. In this study, we used Porcine SNP60 BeadChip and PennCNV algorithm to perform a genome-wide CNV detection in 302 individuals from six Chinese indigenous breeds (Tongcheng, Laiwu, Luchuan, Bama, Wuzhishan and Ningxiang pigs), three western breeds (Yorkshire, Landrace and Duroc) and one hybrid (Tongcheng×Duroc). A total of 348 CNV Regions (CNVRs) across genome were identified, covering 150.49 Mb of the pig genome or 6.14% of the autosomal genome sequence. In these CNVRs, 213 CNVRs were found to exist only in the six Chinese indigenous breeds, and 60 CNVRs only in the three western breeds. The characters of CNVs in four Chinese normal size breeds (Luchuan, Tongcheng and Laiwu pigs) and two minipig breeds (Bama and Wuzhishan pigs) were also analyzed in this study. Functional annotation suggested that these CNVRs possess a great variety of molecular function and may play important roles in phenotypic and production traits between Chinese and western breeds. Our results are important complementary to the CNV map in pig genome, which provide new information about the diversity of Chinese and western pig breeds, and facilitate further research on porcine genome CNVs.
    Full-text · Article · Sep 2014 · PLoS ONE
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