Article

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: 13.85). 03/2012; 22(5):899-907. DOI: 10.1101/gr.128991.111
Source: PubMed

ABSTRACT 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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    • "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.
    MGG Molecular & General Genetics 09/2014; 290(1). DOI:10.1007/s00438-014-0923-4 · 2.83 Impact Factor
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    ABSTRACT: Background Secretoglobin 1A1 (SCGB 1A1), also called Clara cell secretory protein, is the most abundantly secreted protein of the airway. The SCGB1A1 gene has been characterized in mammals as a single copy in the genome. However, analysis of the equine genome suggested that horses might have multiple SCGB1A1 gene copies. Non-ciliated lung epithelial cells produce SCGB 1A1 during inhalation of noxious substances to counter airway inflammation. Airway fluid and lung tissue of horses with recurrent airway obstruction (RAO), a chronic inflammatory lung disease affecting mature horses similar to environmentally induced asthma of humans, have reduced total SCGB 1A1 concentration. Herein, we investigated whether horses have distinct expressed SCGB1A1 genes; whether the transcripts are differentially expressed in tissues and in inflammatory lung disease; and whether there is cell specific protein expression in tissues. Results We identified three SCGB1A1 gene copies on equine chromosome 12, contained within a 512-kilobase region. Bioinformatic analysis showed that SCGB1A1 genes differ from each other by 8 to 10 nucleotides, and that they code for different proteins. Transcripts were detected for SCGB1A1 and SCGB1A1A, but not for SCGB1A1P. The SCGB1A1P gene had most inter-individual variability and contained a non-sense mutation in many animals, suggesting that SCGB1A1P has evolved into a pseudogene. Analysis of SCGB1A1 and SCGB1A1A sequences by endpoint-limiting dilution PCR identified a consistent difference affecting 3 bp within exon 2, which served as a gene-specific “signature”. Assessment of gene- and organ-specific expression by semiquantitative RT-PCR of 33 tissues showed strong expression of SCGB1A1 and SCGB1A1A in lung, uterus, Fallopian tube and mammary gland, which correlated with detection of SCGB 1A1 protein by immunohistochemistry. Significantly altered expression of the ratio of SCGB1A1A to SCGB1A1 was detected in RAO-affected animals compared to controls, suggesting different roles for SCGB 1A1 and SCGB 1A1A in this inflammatory condition. Conclusions This is the first report of three SCGB1A1 genes in a mammal. The two expressed genes code for proteins predicted to differ in function. Alterations in the gene expression ratio in RAO suggest cell and tissue specific regulation and functions. These findings may be important for understanding of lung and reproductive conditions.
    BMC Genomics 12/2012; 13(1):712. DOI:10.1186/1471-2164-13-712 · 4.04 Impact Factor
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    BMC Genomics 12/2012; 13(1):733. DOI:10.1186/1471-2164-13-733 · 4.04 Impact Factor
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