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Impact of copy number variations burden on coding genome in humans using integrated high resolution arrays

  • AVINASH M. VEERAPPA (a1), KUSUMA LINGAIAH (a1), SANGEETHA VISHWESWARAIAH (a1), MEGHA N. MURTHY (a1), RAVIRAJ V. SURESH (a1), DINESH S. MANJEGOWDA (a2) and NALLUR B. RAMACHANDRA (a1)...

Summary

Copy number variations (CNVs) alter the transcriptional and translational levels of genes by disrupting the coding structure and this burden of CNVs seems to be a significant contributor to phenotypic variations. Therefore it was necessary to assess the complexities of CNV burden on the coding genome. A total of 1715 individuals from 12 populations were used for CNV analysis in the present investigation. Analysis was performed using Affymetrix Genome-Wide Human SNP Array 6·0 chip and CytoScan High-Density arrays. CNVs were more frequently observed in the coding region than in the non-coding region. CNVs were observed vastly more frequently in the coding region than the non-coding region. CNVs were found to be enriched in the regions containing functional genes (83–96%) compared with the regions containing pseudogenes (4–17%). CNVs across the genome of an individual showed multiple hits across many genes, whose proteins interact physically and function under the same pathway. We identified varying numbers of proteins and degrees of interactions within protein complexes of single individual genomes. This study represents the first draft of a population-specific CNV genes map as well as a cross-populational map. The complex relationship of CNVs on genes and their physically interacting partners unravels many complexities involved in phenotype expression. This study identifies four mechanisms contributing to the complexities caused by the presence of multiple CNVs across many genes in the coding part of the genome.

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Corresponding author

* Corresponding author: Nallur B. Ramachandra, Genetics and Genomics Lab, Department of Studies in Zoology, University of Mysore, Manasagangotri, Mysore-06, Karnataka, India. Tel: + 91-821-2419781/2419888. Fax: + 91-821-2516056. E-mail: nallurbr@gmail.com

References

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Abu-Helalah, M., Law, M. R., Bestwick, J. P., Monson, J. P. & Wald, N. J. (2010). A randomized double-blind crossover trial to investigate the efficacy of screening for adult hypothyroidism. Journal of Medical Screening 17, 164169.
Aitman, T. J., Dong, R., Vyse, T. J., Norsworthy, P. J., Johnson, M. D., Smith, J., Mangion, J., Roberton-Lowe, C., Marshall, A. J., Petretto, E., Hodges, M. D., Bhangal, G., Patel, S. G., Sheehan-Rooney, K., Duda, M., Cook, P. R., Evans, D. J., Domin, J., Flint, J., Boyle, J. J., Pusey, C. D. & Cook, H. T. (2006). Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 439, 851855.
Armengol, L., Villatoro, S., González, J. R., Pantano, L., García-Aragonés, M., Rabionet, R., Cáceres, M. & Estivill, X. (2009). Identification of copy number variants defining genomic differences among major human groups. PLoS One 4, e7230.
Azim, M. K., Yang, C., Yan, Z., Choudhary, M. I., Khan, A., Sun, X., Li, R., Asif, H., Sharif, S. & Zhang, Y. (2013). Complete genome sequencing and variant analysis of a Pakistani individual. Journal of Human Genetics 58, 622626.
Beckmann, J. S., Estivill, X. & Antonarakis, S. E. (2007). Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability. Nature Reviews Genetics 8, 639646.
Chen, W., Hayward, C., Wright, A. F., Hicks, A. A., Vitart, V., Knott, S., Wild, S. H., Pramstaller, P. P., Wilson, J. F., Rudan, I. & Porteous, D. J. (2011). Copy number variation across European populations. PLoS One 6, e23087.
Cheung, J., Estivill, X., Khaja, R., MacDonald, J. R., Lau, K., Tsui, L. C. & Scherer, S. W. (2003). Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence. Genome Biology 4, R25.
Fanciulli, M., Norsworthy, P. J., Petretto, E., Dong, R., Harper, L., Kamesh, L., Heward, J. M., Gough, S. C., de Smith, A., Blakemore, A. I., Froguel, P., Owen, C. J., Pearce, S. H., Teixeira, L., Guillevin, L., Graham, D. S., Pusey, C. D., Cook, H. T., Vyse, T. J. & Aitman, T. J. (2007). FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nature Genetics 39, 721723.
Fellermann, K., Stange, D. E., Schaeffeler, E., Schmalzl, H., Wehkamp, J., Bevins, C. L., Reinisch, W., Teml, A., Schwab, M., Lichter, P., Radlwimmer, B. & Stange, E. F. (2006). Chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. American Journal of Human Genetics 79, 439448.
Feuk, L., Carson, A. R. & Scherer, S. W. (2006). Structural variation in the human genome Nature Reviews Genetics 7, 8597.
Gautam, P., Jha, P., Kumar, D., Tyagi, S., Varma, B., Dash, D., Mukhopadhyay, A., Indian Genome Variation Consortium & Mukerji, M. (2012). Spectrum of large copy number variations in 26 diverse Indian populations: potential involvement in phenotypic diversity. Human Genetics 131, 131143.
Girirajan, S. & Eichler, E. E. (2010). Phenotypic variability and genetic susceptibility to genomic disorders. Human Molecular Genetics 15, R176R187.
Girirajan, S., Rosenfeld, J. A., Coe, B. P., Parikh, S., Friedman, N., Goldstein, A., Filipink, R. A., McConnell, J. S., Angle, B., Meschino, W. S., Nezarati, M. M., Asamoah, A., Jackson, K. E., Gowans, G. C., Martin, J. A., Carmany, E. P., Stockton, D. W., Schnur, R. E., Penney, L. S., Martin, D. M., Raskin, S., Leppig, K., Thiese, H., Smith, R., Aberg, E., Niyazov, D. M., Escobar, L. F., El-Khechen, D., Johnson, K. D., Lebel, R. R., Siefkas, K., Ball, S., Shur, N., McGuire, M., Brasington, C. K., Spence, J. E., Martin, L. S., Clericuzio, C., Ballif, B. C., Shaffer, L. G. & Eichler, E. E. (2012). Phenotypic heterogeneity of genomic disorders and rare copy-number variants. New England Journal of Medicine 367, 13211331.
Go, Y. & Niimura, Y. (2008). Similar numbers but different repertoires of olfactory receptor genes in humans and chimpanzees. Molecular Biology and Evolution 25, 18971907.
Gonzalez, E., Kulkarni, H., Bolivar, H., Mangano, A., Sanchez, R., Catano, G., Nibbs, R. J., Freedman, B. I., Quinones, M. P., Bamshad, M. J., Murthy, K. K., Rovin, B. H., Bradley, W., Clark, R. A., Anderson, S. A., O'Connell, R. J., Agan, B. K., Ahuja, S. S., Bologna, R., Sen, L., Dolan, M. J. & Ahuja, S. K. (2005). The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307, 14341440.
Guruharsha, K. G., Rual, J. F., Zhai, B., Mintseris, J., Vaidya, P., Vaidya, N., Beekman, C., Wong, C., Rhee, D. Y., Cenaj, O., McKillip, E., Shah, S., Stapleton, M., Wan, K. H., Yu, C., Parsa, B., Carlson, J. W., Chen, X., Kapadia, B., VijayRaghavan, K., Gygi, S. P., Celniker, S. E., Obar, R. A. & Artavanis-Tsakonas, S. (2011). A protein complex network of Drosophila melanogaster . Cell 147, 690703.
Hollox, E. J., Huffmeier, U., Zeeuwen, P. L., Palla, R., Lascorz, J., Rodijk-Olthuis, D., van de Kerkhof., P. C., Traupe, H., de Jongh, G., den Heijer, M., Reis, A., Armour, J. A. & Schalkwijk, J. (2008). Psoriasis is associated with increased beta-defensin genomic copy number. Nature Genetics 40, 2325.
Kanduri, C., Ukkola-Vuoti, L., Oikkonen, J., Buck, G., Blancher, C., Raijas, P., Karma, K., Lähdesmäki, H. & Järvelä, I. (2013). The genome-wide landscape of copy number variations in the MUSGEN study provides evidence for a founder effect in the isolated Finnish population. European Journal of Human Genetics 21, 14111416.
Kim, H. L., Iwase, M., Igawa, T., Nishioka, T., Kaneko, S., Katsura, Y., Takahata, N. & Satta, Y. (2012). Genomic structure and evolution of multigene families: “flowers” on the human genome. International Journal of Evolutionary Biology 2012, 917678.
Krzywinski, M., Schein, J., Birol, I., Connors, J., Gascoyne, J. & Horsman, D. (2009). Circos: an information aesthetic for comparative genomics. Genome Research 19, 16391645.
Lin, C. H., Li, L. H., Ho, S. F., Chuang, T. P., Wu, J. Y., Chen, Y. T. & Fann, C. S. (2008). A large-scale survey of genetic copy number variations among Han Chinese residing in Taiwan. BMC Genetics 9, 92.
Liu, X., Cheng, R., Ye, X., Verbitsky, M., Kisselev, S., Mejia-Santana, H., Louis, E., Cote, L., Andrews, H., Waters, C., Ford, B., Fahn, S., Marder, K., Lee, J. & Clark, L. (2013). Increased rate of sporadic and recurrent rare genic copy number variants in Parkinson's disease among Ashkenazi Jews. Molecular Genetics and Genomic Medicine 1, 142154.
Lou, H., Li, S., Yang, Y., Kang, L., Zhang, X., Jin, W., Wu, B., Jin, L. & Xu, S. (2011). A map of copy number variations in Chinese populations. PLoS One 6, e27341.
McElroy, J. P., Nelson, M. R., Caillier, S. J. & Oksenberg, J. R. (2009). Copy number variation in African Americans. BMC Genetics 10, 15.
Nguyen, D. Q., Webber, C. & Ponting, C. P. (2006). Bias of selection on human copy-number variants. PLoS Genetics 2, e20.
Niimura, Y. & Nei, M. (2003). Evolution of olfactory receptor genes in the human genome. Proceedings of the National Academy of Sciences of the United States of America 100, 1223512240.
Park, J., Chen, L., Ratnashinge, L., Sellers, T. A., Tanner, J. P., Lee, J. H., Dossett, N., Lang, N., Kadlubar, F. F., Ambrosone, C. B., Zachariah, B., Heysek, R. V., Patterson, S. & Pow-Sang, J. (2006). Deletion polymorphism of UDP-glucuronosyltransferase 2B17 and risk of prostate cancer in African American and Caucasian men. Cancer Epidemiology, Biomarkers and Prevention 15, 14731478.
Redon, R., Ishikawa, S., Fitch, K. R., Feuk, L., Perry, G. H., Andrews, T. D., Fiegler, H., Shapero, M. H., Carson, A. R., Chen, W., Cho, E. K., Dallaire, S., Freeman, J. L., González, J. R., Gratacòs, M., Huang, J., Kalaitzopoulos, D., Komura, D., MacDonald, J. R., Marshall, C. R., Mei, R., Montgomery, L., Nishimura, K., Okamura, K., Shen, F., Somerville, M. J., Tchinda, J., Valsesia, A., Woodwark, C., Yang, F., Zhang, J., Zerjal, T., Zhang, J., Armengol, L., Conrad, D. F., Estivill, X., Tyler-Smith, C., Carter, N. P., Aburatani, H., Lee, C., Jones, K. W., Scherer, S. W. & Hurles, M. E. (2006). Global variation in copy number in the human genome. Nature 444, 444454.
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., Leotta, A., Pai, D., Zhang, R., Lee, Y. H., Hicks, J., Spence, S. J., Lee, A. T., Puura, K., Lehtimäki, T., Ledbetter, D., Gregersen, P. K., Bregman, J., Sutcliffe, J. S., Jobanputra, V., Chung, W., Warburton, D., King, M. C., Skuse, D., Geschwind, D. H., Gilliam, T. C., Ye, K. & Wigler, M. (2007). Strong association of de novo copy number mutations with autism. Science 316, 445449.
Sharp, A. J., Cheng, Z. & Eichler, E. E. (2006). Structural variation of the human genome. Annual Review of Genomics and Human Genetics 7, 407442.
Simonson, T. S., Yang, Y., Huff, C. D., Yun, H., Qin, G., Witherspoon, D. J., Bai, Z., Lorenzo, F. R., Xing, J., Jorde, L. B., Prchal, J. T. & Ge, R. (2010). Genetic evidence for high-altitude adaptation in Tibet. Science 329, 7275.
Sudmant, P. H., Kitzman, J. O., Antonacci, F., Alkan, C., Malig, M., Tsalenko, A., Sampas, N., Bruhn, L., Shendure, J., 1000 Genomes Project & Eichler, E. E. (2010). Diversity of human copy number variation and multicopy genes. Science 330, 641646.
The International HapMap Consortium. (2003). The International HapMap Project. Nature 426, 789796.
Veerappa, A. M., Vishweswaraiah, S., Lingaiah, K., Murthy, M., Manjegowda, D. S., Nayaka, R. & Ramachandra, N. B. (2013 a). Unravelling the complexity of human olfactory receptor repertoire by copy number analysis across population using high resolution arrays. PLoS One 8, e66843.
Veerappa, A. M., Saldanha, M., Padakannaya, P. & Ramachandra, N. B. (2013 b). Family-based genome-wide copy number scan identifies five new genes of dyslexia involved in dendritic spinal plasticity. Journal of Human Genetics 58, 539547.
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., Stray, S. M., Rippey, C. F., Roccanova, P., Makarov, V., Lakshmi, B., Findling, R. L., Sikich, L., Stromberg, T., Merriman, B., Gogtay, N., Butler, P., Eckstrand, K., Noory, L., Gochman, P., Long, R., Chen, Z., Davis, S., Baker, C., Eichler, E. E., Meltzer, P. S., Nelson, S. F., Singleton, A. B., Lee, M. K., Rapoport, J. L., King, M. C. & Sebat, J. (2008). Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320, 539543.
Yang, Y., Chung, E. K., Wu, Y. L., Savelli, S. L., Nagaraja, H. N., Zhou, B., Hebert, M., Jones, K. N., Shu, Y., Kitzmiller, K., Blanchong, C. A., McBride, K. L., Higgins, G. C., Rennebohm, R. M., Rice, R. R., Hackshaw, K. V., Roubey, R. A., Grossman, J. M., Tsao, B. P., Birmingham, D. J., Rovin, B. H., Hebert, L. A. & Yu, C. Y. (2007). Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans. American Journal of Human Genetics 80, 10371054.
Zhang, F., Gu, W., Hurles, M. E. & Lupski, J. R. (2009). Copy number variation in human health, disease, and evolution. Annual Review of Genomics and Human Genetics 10, 451481.
Zhang, Y.-B., Li, X., Zhang, F., Wang, D.-M. & Yu, J. (2012). A preliminary study of copy number variation in Tibetans. PLoS One 7, e41768.

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Impact of copy number variations burden on coding genome in humans using integrated high resolution arrays

  • AVINASH M. VEERAPPA (a1), KUSUMA LINGAIAH (a1), SANGEETHA VISHWESWARAIAH (a1), MEGHA N. MURTHY (a1), RAVIRAJ V. SURESH (a1), DINESH S. MANJEGOWDA (a2) and NALLUR B. RAMACHANDRA (a1)...

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