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http://dx.doi.org/10.5713/ajas.2013.13857

Copy Number Deletion Has Little Impact on Gene Expression Levels in Racehorses  

Park, Kyung-Do (Genomic Informatics Center, Hankyong National University)
Kim, Hyeongmin (Department of Agricultural Biotechnology, Animal Biotechnology Major, and Research Institute of Agriculture and Life Science, Seoul National University)
Hwang, Jae Yeon (Department of Agricultural Biotechnology, Animal Biotechnology Major, and Research Institute of Agriculture and Life Science, Seoul National University)
Lee, Chang-Kyu (Department of Agricultural Biotechnology, Animal Biotechnology Major, and Research Institute of Agriculture and Life Science, Seoul National University)
Do, Kyoung-Tag (Genomic Informatics Center, Hankyong National University)
Kim, Heui-Soo (Department of Biological Sciences, College of Natural Sciences, Pusan National University)
Yang, Young-Mok (Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University)
Kwon, Young-Jun (Interdisciplinary Program in Bioinformatics, Seoul National University)
Kim, Jaemin (Interdisciplinary Program in Bioinformatics, Seoul National University)
Kim, Hyeon Jeong (CHO & KIM genomics)
Song, Ki-Duk (Genomic Informatics Center, Hankyong National University)
Oh, Jae-Don (Genomic Informatics Center, Hankyong National University)
Kim, Heebal (Department of Agricultural Biotechnology, Animal Biotechnology Major, and Research Institute of Agriculture and Life Science, Seoul National University)
Cho, Byung-Wook (Department of Animal Science, College of Life Sciences, Pusan National University)
Cho, Seoae (CHO & KIM genomics)
Lee, Hak-Kyo (Genomic Informatics Center, Hankyong National University)
Publication Information
Asian-Australasian Journal of Animal Sciences / v.27, no.9, 2014 , pp. 1345-1354 More about this Journal
Abstract
Copy number variations (CNVs), important genetic factors for study of human diseases, may have as large of an effect on phenotype as do single nucleotide polymorphisms. Indeed, it is widely accepted that CNVs are associated with differential disease susceptibility. However, the relationships between CNVs and gene expression have not been characterized in the horse. In this study, we investigated the effects of copy number deletion in the blood and muscle transcriptomes of Thoroughbred racing horses. We identified a total of 1,246 CNVs of deletion polymorphisms using DNA re-sequencing data from 18 Thoroughbred racing horses. To discover the tendencies between CNV status and gene expression levels, we extracted CNVs of four Thoroughbred racing horses of which RNA sequencing was available. We found that 252 pairs of CNVs and genes were associated in the four horse samples. We did not observe a clear and consistent relationship between the deletion status of CNVs and gene expression levels before and after exercise in blood and muscle. However, we found some pairs of CNVs and associated genes that indicated relationships with gene expression levels: a positive relationship with genes responsible for membrane structure or cytoskeleton and a negative relationship with genes involved in disease. This study will lead to conceptual advances in understanding the relationship between CNVs and global gene expression in the horse.
Keywords
Copy Number Variation; Genome-wide Expression; Horse; Thoroughbred;
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1 Somerville, M. J., C. B. Mervis, E. J. Young, E. J. Seo, M. del Campo, S. Bamforth, E. Peregrine, W. Loo, M. Lilley, and L. A. Perez-Jurado. 2005. Severe expressive-language delay related to duplication of the Williams-Beuren locus. N. Engl. J. Med. 353:1694-1701.   DOI   ScienceOn
2 Subramanian, A., P. Tamayo, V. K. Mootha, S. Mukherjee, B. L. Ebert, M. A. Gillette, A. Paulovich, S. L. Pomeroy, T. R. Golub, E. S. Lander, and J. P. Mesirov. 2005. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA. 102:15545-15550.   DOI   ScienceOn
3 Trapnell, C., B. A. Williams, G. Pertea, A. Mortazavi, G. Kwan, M. J. Van Baren, S. L. Salzberg, B. J. Wold, and L. Pachter. 2010. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28:511-515.   DOI   ScienceOn
4 Xi, R., A. G. Hadjipanayis, L. J. Luquette, T.-M. Kim, E. Lee, J. Zhang, M. D. Johnson, D. M. Muzny, D. A. Wheeler, R. A. Gibbs et al. 2011. Copy number variation detection in whole-genome sequencing data using the Bayesian information criterion. Proc. Natl. Acad. Sci. 108:E1128-E1136.   DOI   ScienceOn
5 Mills, R. E., K. Walter, C. Stewart, R. E. Handsaker, K. Chen, C. Alkan, A. Abyzov, S. C. Yoon, K. Ye, R. K. Cheetham et al. 2011. Mapping copy number variation by population-scale genome sequencing. Nature 470:59-65.   DOI   ScienceOn
6 Orozco, L. D., S. J. Cokus, A. Ghazalpour, L. Ingram-Drake, S. Wang, A. Van Nas, N. Che, J. A. Araujo, M. Pellegrini, and A. J. Lusis. 2009. Copy number variation influences gene expression and metabolic traits in mice. Hum. Mol. Genet. 18:4118-4129.   DOI   ScienceOn
7 Park, K.-D., J. Park, J. Ko, B. C. Kim, H.-S. Kim, K. Ahn, K.-T. Do, H. Choi, H.-M. Kim, S. Song et al. 2012. Whole transcriptome analyses of six thoroughbred horses before and after exercise using RNA-Seq. BMC Genomics 13:473.   DOI   ScienceOn
8 Reich, D. E., S. F. Schaffner, M. J. Daly, G. McVean, J. C. Mullikin, J. M. Higgins, D. J. Richter, E. S. Lander, and D. Altshuler. 2002. Human genome sequence variation and the influence of gene history, mutation and recombination. Nature Genet. 32:135-142.   DOI   ScienceOn
9 Scherer, S. W., C. Lee, E. Birney, D. M. Altshuler, E. E. Eichler, N. P. Carter, M. E. Hurles, and L. Feuk. 2007. Challenges and standards in integrating surveys of structural variation. Nat. Genet. 39:S7-S15.   DOI   ScienceOn
10 Sharp, A. J., Z. Cheng, and E. E. Eichler. 2006. Structural variation of the human genome. Annu. Rev. Genomics Hum. Genet. 7:407-442.   DOI
11 Hosack, D. A., G. Dennis Jr, B. T. Sherman, H. C. Lane, and R. A. Lempicki. 2003. Identifying biological themes within lists of genes with EASE. Genome Biol. 4:R70.   DOI
12 Inagaki, T., S. Suzuki, T. Miyamoto, T. Takeda, K. Yamashita, A. Komatsu, K. Yamauchi, and K. Hashizume. 2003. The retinoic acid-responsive proline-rich protein is identified in promyeloleukemic HL-60 cells. J. Biol. Chem. 278:51685-51692.   DOI   ScienceOn
13 Lee, J. A., R. E. Madrid, K. Sperle, C. M. Ritterson, G. M. Hobson, J. Garbern, J. R. Lupski, and K. Inoue. 2006. Spastic paraplegia type 2 associated with axonal neuropathy and apparent PLP1 position effect. Ann. Neurol. 59:398-403.   DOI   ScienceOn
14 Jaenisch, R. and A. Bird. 2003. Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals. Nat. Genet. 33:245-254.   DOI   ScienceOn
15 Kim, H., T. Lee, W. Park, J. W. Lee, J. Kim, B.-Y. Lee, H. Ahn, S. Moon, S. Cho, K.-T. Do et al. 2013. Peeling back the evolutionary layers of molecular mechanisms responsive to exercise-stress in the skeletal muscle of the racing horse. DNA Res. 20:287-298.   DOI   ScienceOn
16 Langmead, B. and S. L. Salzberg. 2012. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9:357-359.   DOI   ScienceOn
17 Li, H., B. Handsaker, A. Wysoker, T. Fennell, J. Ruan, N. Homer, G. Marth, G. Abecasis, and R. Durbin. 2009. The sequence alignment/map format and SAMtools. Bioinformatics 25:2078-2079.   DOI   ScienceOn
18 McCarroll, S. A. and D. M. Altshuler. 2007. Copy-number variation and association studies of human disease. Nat. Genet. 39:S37-S42.   DOI   ScienceOn
19 McKenna, A., M. Hanna, E. Banks, A. Sivachenko, K. Cibulskis, A. Kernytsky, K. Garimella, D. Altshuler, S. Gabriel, M. Daly, and M. A. DePristo. 2010. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20:1297-1303.   DOI   ScienceOn
20 Doan, R., N. Cohen, J. Harrington, K. Veazy, R. Juras, G. Cothran, M. E. McCue, L. Skow, and S. V. Dindot. 2012. Identification of copy number variants in horses. Genome Res. 22:899-907.   DOI   ScienceOn
21 Henrichsen, C. N., E. Chaignat, and A. Reymond. 2009a. Copy number variants, diseases and gene expression. Hum. Mol. Genet. 18:R1-R8.   DOI   ScienceOn
22 Gonzalez, E., H. Kulkarni, H. Bolivar, A. Mangano, R. Sanchez, G. Catano, R. J. Nibbs, B. I. Freedman, M. P. Quinones, M. J. Bamshad et al. 2005. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307(5714):1434-1440.   DOI   ScienceOn
23 Guryev, V., K. Saar, T. Adamovic, M. Verheul, S. A. A. C. van Heesch, S. Cook, M. Pravenec, T. Aitman, H. Jacob, and J. D. Shull, N. Hubner, and E. Cuppen. 2008. Distribution and functional impact of DNA copy number variation in the rat. Nat. Genet. 40:538-545.   DOI   ScienceOn
24 Handsaker, R. E., J. M. Korn, J. Nemesh, and S. A. McCarroll. 2011. Discovery and genotyping of genome structural polymorphism by sequencing on a population scale. Nat. Genet. 43:269-276.   DOI   ScienceOn
25 Henrichsen, C. N., N. Vinckenbosch, S. Zollner, E. Chaignat, S. Pradervand, F. Schutz, M. Ruedi, H. Kaessmann, and A. Reymond. 2009b. Segmental copy number variation shapes tissue transcriptomes. Nat. Genet. 41:424-429.   DOI   ScienceOn
26 Hollox, E. J., J. A. L. Armour, and J. C. K. Barber. 2003. Extensive normal copy number variation of a $\beta$-defensin antimicrobial-gene cluster. Am. J. Hum. Genet. 73:591-600.   DOI   ScienceOn
27 Hornik, K. The R FAQ [Internet]. ISBN 3-900051-08-9. Available from: http://CRAN.R-project.org/doc/FAQ/R-FAQ.html
28 Aldred, P. M. R., E. J. Hollox, and J. A. L. Armour. 2005. Copy number polymorphism and expression level variation of the human $\alpha  $-defensin genes DEFA1 and DEFA3. Hum. Mol. Genet. 14:2045-2052.   DOI   ScienceOn
29 Alterovitz, G. and M. F. Ramoni. 2010. Knowledge Based Bioinformatics: From Analysis to Interpretation. John Wiley & Sons, Ltd, Chichester, UK.
30 Alkan, C., B. P. Coe, and E. E. Eichler. 2011. Genome structural variation discovery and genotyping. Nat. Rev. Genet. 12:363-376.   DOI   ScienceOn
31 Alvarez, C. E. and J. M. Akey. 2012. Copy number variation in the domestic dog. Mamm. Genome 23:144-163.   DOI   ScienceOn
32 Bolstad, B. preprocessCore: A collection of pre-processing functions. R package version 1.
33 Castano-Rodriguez, N., L. M. Diaz-Gallo, R. Pineda-Tamayo, A. Rojas-Villarraga, and J. M. Anaya. 2008. Meta-analysis of HLA-DRB1 and HLA-DQB1 polymorphisms in Latin American patients with systemic lupus erythematosus. Autoimmun. Rev. 7:322-330.   DOI   ScienceOn
34 Chorzalska, A., A. Lach, T. Borowik, M. Wolny, A. Hryniewicz-Jankowska, A. Kolondra, M. Langner, and A. F. Sikorski. 2010. The effect of the lipid-binding site of the ankyrin-binding domain of erythroid $\beta$-spectrin on the properties of natural membranes and skeletal structures. Cell. Mol. Biol. Lett. 15:406-423.
35 Cobb, J. P., M. N. Mindrinos, C. Miller-Graziano, S. E. Calvano, H. V. Baker, W. Xiao, K. Laudanski, B. H. Brownstein, C. M. Elson, D. L. Hayden et al. 2005. Application of genome-wide expression analysis to human health and disease. Proc. Natl. Acad. Sci. USA. 102:4801-4806.   DOI   ScienceOn
36 Dawson, T. M. and V. L. Dawson. 2010. The role of parkin in familial and sporadic Parkinson's disease. Mov. Disord. 25:S32-S39.   DOI   ScienceOn
37 Dennis Jr, G., B. T. Sherman, D. A. Hosack, J. Yang, W. Gao, H. C. Lane, and R. A. Lempicki. 2003. DAVID: database for annotation, visualization, and integrated discovery. Genome Biol. 4:R60.   DOI
38 Sachidanandam, R., D. Weissman, S. C. Schmidt, J. M. Kakol, L. D. Stein, G. Marth, S. Sherry, J. C. Mullikin, B. J. Mortimore, D. L. Willey et al. 2001. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409:928-933.   DOI   ScienceOn
39 Aitman, T. J., R. Dong, T. J. Vyse, P. J. Norsworthy, M. D. Johnson, J. Smith, J. Mangion, C. Roberton-Lowe, A. J. Marshall, E. Petretto et al. 2006. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 439:851-855.   DOI   ScienceOn
40 Pankratz, N., A. Dumitriu, K. N. Hetrick, M. Sun, J. C. Latourelle, J. B. Wilk, C. Halter, K. F. Doheny, J. F. Gusella, W. C. Nichols et al. 2011. Copy number variation in familial Parkinson disease. PloS one 6:e20988.   DOI
41 Feuk, L., A. R. Carson, and S. W. Scherer. 2006. Structural variation in the human genome. Nat. Rev. Genet. 7:85-97.