Abstract
Microarray-based Comparative Genomic Hybridization (array-CGH) has been applied for a decade to screen for submicroscopic DNA gains and losses in tumor and constitutional DNA samples. This method has become increasingly flexible with the integration of new biological resources generated by genome sequencing projects. In this chapter, we describe alternative strategies for whole genome screening and high resolution breakpoint mapping of copy number changes by array-CGH, as well as tools available for accurate analysis of array-CGH experiments. Although most methods listed here have been designed for microarrays comprising large-insert clones, they can be adapted easily to other types of microarray platforms, such as those constructed from printed or synthesized oligonucleotides.
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Kallioniemi, A., Kallioniemi, O.P., Sudar, D., Rutovitz, D., Gray, J.W., Waldman, F. and Pinkel, D. (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science, 258, 818–821.
du Manoir, S., Speicher, M.R., Joos, S., Schrock, E., Popp, S., Dohner, H., Kovacs, G., Robert-Nicoud, M., Lichter, P. and Cremer, T. (1993) Detection of complete and partial chromosome gains and losses by comparative genomic in situ hybridization. Hum genet, 90, 590–610.
Gebhart, E. and Liehr, T. (2000) Patterns of genomic imbalances in human solid tumors (Review). Int J Oncol, 16, 383–399.
Cheung, V.G., Nowak, N., Jang, W., Kirsch, I.R., Zhao, S., Chen, X.N., Furey, T.S., Kim, U.J., Kuo, W.L., Olivier, M. et al. (2001) Integration of cytogenetic landmarks into the draft sequence of the human genome. Nature, 409, 953–958.
Solinas-Toldo, S., Lampel, S., Stilgenbauer, S., Nickolenko, J., Benner, A., Dohner, H., Cremer, T. and Lichter, P. (1997) Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer, 20, 399–407.
Pinkel, D., Segraves, R., Sudar, D., Clark, S., Poole, I., Kowbel, D., Collins, C., Kuo, W.L., Chen, C., Zhai, Y. et al. (1998) High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet, 20, 207–211.
Dhami, P., Coffey, A.J., Abbs, S., Vermeesch, J.R., Dumanski, J.P., Woodward, K.J., Andrews, R.M., Langford, C. and Vetrie, D. (2005) Exon array CGH: detection of copy-number changes at the resolution of individual exons in the human genome. Am J Hum Genet, 76, 750–762.
Selzer, R.R., Richmond, T.A., Pofahl, N.J., Green, R.D., Eis, P.S., Nair, P., Brothman, A.R. and Stallings, R.L. (2005) Analysis of chromosome breakpoints in neuroblastoma at sub-kilobase resolution using fine-tiling oligonucleotide array CGH. Genes Chromosomes Cancer, 44, 305–319.
Redon, R., Baujat, G., Sanlaville, D., Le Merrer, M., Vekemans, M., Munnich, A., Carter, N.P., Cormier-Daire, V. and Colleaux, L. (2006) Interstitial 9q22.3 microdeletion: clinical and molecular characterisation of a newly recognised overgrowth syndrome. Eur J Hum Genet, 14, 759–767.
Veltman, J.A., Schoenmakers, E.F., Eussen, B.H., Janssen, I., Merkx, G., van Cleef, B., van Ravenswaaij, C.M., Brunner, H.G., Smeets, D. and van Kessel, A.G. (2002) High-throughput analysis of subtelomeric chromosome rearrangements by use of array-based comparative genomic hybridization. Am J Hum Genet, 70, 1269–1276.
Shaw-Smith, C., Redon, R., Rickman, L., Rio, M., Willatt, L., Fiegler, H., Firth, H., Sanlaville, D., Winter, R., Colleaux, L. et al. (2004) Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features. J Med Genet, 41, 241–248.
Fiegler, H., Redon, R., Andrews, D., Scott, C., Andrews, R., Carder, C., Clark, R., Dovey, O., Ellis, P., Feuk, L. et al. (2006) Accurate and reliable high-throughput detection of copy number variation in the human genome. Genome research, 16, 1566–1574.
Price, T.S., Regan, R., Mott, R., Hedman, A., Honey, B., Daniels, R.J., Smith, L., Greenfield, A., Tiganescu, A., Buckle, V. et al. (2005) SW-ARRAY: a dynamic programming solution for the identification of copy-number changes in genomic DNA using array comparative genome hybridization data. Nucl Acids Res, 33, 3455–3464.
Smith, T.F. and Waterman, M.S. (1981) Identification of common molecular subsequences. J Mol Biol, 147, 195–197.
Jong, K., Marchiori, E., Meijer, G., Vaart, A.V. and Ylstra, B. (2004) Breakpoint identification and smoothing of array comparative genomic hybridization data. Bioinformatics (Oxford, England), 20, 3636–3637.
Olshen, A.B., Venkatraman, E.S., Lucito, R. and Wigler, M. (2004) Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics (Oxford, England), 5, 557–572.
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. et al. (2006) Global variation in copy number in the human genome. Nature, 444, 444–454.
McCarroll, S.A. and Altshuler, D.M. (2007) Copy-number variation and association studies of human disease. Nat Genet, 39, S37–42.
Perry, G.H., Dominy, N.J., Claw, K.G., Lee, A.S., Fiegler, H., Redon, R., Werner, J., Villanea, F.A., Mountain, J.L., Misra, R. et al. (2007) Diet and the evolution of human amylase gene copy number variation. Nat Genet, 39, 1256–1260.
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This work was supported by the Wellcome Trust.
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© 2009 Humana Press, a part of Springer Science+Business Media, LLC
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Redon, R., Carter, N.P. (2009). Comparative Genomic Hybridization: Microarray Design and Data Interpretation. In: Dufva, M. (eds) DNA Microarrays for Biomedical Research. Methods in Molecular Biology, vol 529. Humana Press. https://doi.org/10.1007/978-1-59745-538-1_3
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DOI: https://doi.org/10.1007/978-1-59745-538-1_3
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