Asian-Australasian Journal of Animal Sciences

Asian Australasian Association of Animal Production Societies (아세아태평양축산학회)
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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)
  • Received : 2013.12.30
  • Accepted : 2014.05.12
  • Published : 2014.09.01
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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.

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References

  1. 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. https://doi.org/10.1038/nature04489
  2. 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. https://doi.org/10.1093/hmg/ddi209
  3. Alkan, C., B. P. Coe, and E. E. Eichler. 2011. Genome structural variation discovery and genotyping. Nat. Rev. Genet. 12:363-376. https://doi.org/10.1038/nrg2958
  4. Alterovitz, G. and M. F. Ramoni. 2010. Knowledge Based Bioinformatics: From Analysis to Interpretation. John Wiley & Sons, Ltd, Chichester, UK.
  5. Alvarez, C. E. and J. M. Akey. 2012. Copy number variation in the domestic dog. Mamm. Genome 23:144-163. https://doi.org/10.1007/s00335-011-9369-8
  6. Bolstad, B. preprocessCore: A collection of pre-processing functions. R package version 1.
  7. 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. https://doi.org/10.1016/j.autrev.2007.12.002
  8. 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.
  9. 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. https://doi.org/10.1073/pnas.0409768102
  10. Dawson, T. M. and V. L. Dawson. 2010. The role of parkin in familial and sporadic Parkinson's disease. Mov. Disord. 25:S32-S39. https://doi.org/10.1002/mds.22798
  11. 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. https://doi.org/10.1186/gb-2003-4-9-r60
  12. 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. https://doi.org/10.1101/gr.128991.111
  13. Feuk, L., A. R. Carson, and S. W. Scherer. 2006. Structural variation in the human genome. Nat. Rev. Genet. 7:85-97.
  14. 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. https://doi.org/10.1126/science.1101160
  15. 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. https://doi.org/10.1038/ng.141
  16. 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. https://doi.org/10.1038/ng.768
  17. Henrichsen, C. N., E. Chaignat, and A. Reymond. 2009a. Copy number variants, diseases and gene expression. Hum. Mol. Genet. 18:R1-R8. https://doi.org/10.1093/hmg/ddp011
  18. 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. https://doi.org/10.1038/ng.345
  19. 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. https://doi.org/10.1086/378157
  20. Hornik, K. The R FAQ [Internet]. ISBN 3-900051-08-9. Available from: http://CRAN.R-project.org/doc/FAQ/R-FAQ.html
  21. 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. https://doi.org/10.1186/gb-2003-4-10-r70
  22. 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. https://doi.org/10.1074/jbc.M308016200
  23. Jaenisch, R. and A. Bird. 2003. Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals. Nat. Genet. 33:245-254. https://doi.org/10.1038/ng1089
  24. 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. https://doi.org/10.1093/dnares/dst010
  25. Langmead, B. and S. L. Salzberg. 2012. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9:357-359. https://doi.org/10.1038/nmeth.1923
  26. 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. https://doi.org/10.1002/ana.20732
  27. 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. https://doi.org/10.1093/bioinformatics/btp352
  28. McCarroll, S. A. and D. M. Altshuler. 2007. Copy-number variation and association studies of human disease. Nat. Genet. 39:S37-S42. https://doi.org/10.1038/ng2080
  29. 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. https://doi.org/10.1101/gr.107524.110
  30. 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. https://doi.org/10.1038/nature09708
  31. 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. https://doi.org/10.1093/hmg/ddp360
  32. 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. https://doi.org/10.1371/journal.pone.0020988
  33. 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. https://doi.org/10.1186/1471-2164-13-473
  34. 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. https://doi.org/10.1038/ng947
  35. 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. https://doi.org/10.1038/35057149
  36. 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. https://doi.org/10.1038/ng2093
  37. Sharp, A. J., Z. Cheng, and E. E. Eichler. 2006. Structural variation of the human genome. Annu. Rev. Genomics Hum. Genet. 7:407-442. https://doi.org/10.1146/annurev.genom.7.080505.115618
  38. 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. https://doi.org/10.1056/NEJMoa051962
  39. 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. https://doi.org/10.1073/pnas.0506580102
  40. 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. https://doi.org/10.1038/nbt.1621
  41. 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. https://doi.org/10.1073/pnas.1110574108

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