Skip to main content
SpringerLink
Log in

Structural Variation and Its Effect on Expression

  • Protocol
  • First Online:
Genomic Structural Variants

Part of the book series: Methods in Molecular Biology ((MIMB,volume 838))

Abstract

Structural variation, whether it is caused by copy number variants or present in a balanced form, such as reciprocal translocations and inversions, can have a profound and dramatic effect on the expression of genes mapping within and close to the rearrangement, as well as affecting others genome wide. These effects can be caused by altering the copy number of one or more genes or regulatory elements (dosage effect) or from physical disruption of links between regulatory elements and their associated gene or genes, resulting in perturbation of expression. Similarly, large-scale structural variants can result in genome-wide expression changes by altering the positions that chromosomes occupy within the nucleus, potentially disrupting not only local cis interactions, but also trans interactions that occur throughout the genome. Structural variation is, therefore, a significant factor in the study of gene expression and is discussed here in more detail.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Adams, D.J., Dermitzakis, E.T., Cox, T., Smith, J., Davies, R., Banerjee, R., Bonfield, J., Mullikin, J.C., Chung, Y.J., Rogers, J., and Bradley, A. (2005) Complex haplotypes, copy number polymorphisms and coding variation in two recently divergent mouse strains Nat.Genet. 37, 532–536

    CAS  Google Scholar 

  2. Egan, C.M., Sridhar, S., Wigler, M., and Hall, I.M. (2007) Recurrent DNA copy number variation in the laboratory mouse Nat.Genet. 39, 1384–1389

    CAS  Google Scholar 

  3. Henrichsen, C.N., Vinckenbosch, N., Zollner, S., Chaignat, E., Pradervand, S., Schutz, F., Ruedi, M., Kaessmann, H., and Reymond, A. (2009) Segmental copy number variation shapes tissue transcriptomes Nat.Genet. 41, 424–429

    CAS  Google Scholar 

  4. Henrichsen, C.N., Chaignat, E., and Reymond, A. (2009) Copy number variants, diseases and gene expression Hum.Mol.Genet. 18, R1–R8

    CAS  Google Scholar 

  5. Guryev, V., Saar, K., Adamovic, T., Verheul, M., van Heesch, S.A., Cook, S., Pravenec, M., Aitman, T., Jacob, H., Shull, J.D., Hubner, N., and Cuppen, E. (2008) Distribution and functional impact of DNA copy number variation in the rat Nat.Genet. 40, 538–545

    CAS  Google Scholar 

  6. Dopman, E.B. and Hartl, D.L. (2007) A portrait of copy-number polymorphism in Drosophila melanogaster Proc.Natl.Acad.Sci.USA 104, 19920–19925

    Article  CAS  Google Scholar 

  7. Emerson, J.J., Cardoso-Moreira, M., Borevitz, J.O., and Long, M. (2008) Natural selection shapes genome-wide patterns of copy-number polymorphism in Drosophila melanogaster Science 320, 1629–1631

    CAS  Google Scholar 

  8. 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., Gonzalez, J.R., Gratacos, 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., and Hurles, M.E. (2006) Global variation in copy number in the human genome Nature 444, 444–454

    CAS  Google Scholar 

  9. Tuzun, E., Sharp, A.J., Bailey, J.A., Kaul, R., Morrison, V.A., Pertz, L.M., Haugen, E., Hayden, H., Albertson, D., Pinkel, D., Olson, M.V., and Eichler, E.E. (2005) Fine-scale structural variation of the human genome Nat.Genet. 37, 727–732

    CAS  Google Scholar 

  10. Sharp, A.J., Locke, D.P., McGrath, S.D., Cheng, Z., Bailey, J.A., Vallente, R.U., Pertz, L.M., Clark, R.A., Schwartz, S., Segraves, R., Oseroff, V.V., Albertson, D.G., Pinkel, D., and Eichler, E.E. (2005) Segmental duplications and copy-number variation in the human genome Am.J.Hum.Genet. 77, 78–88

    Article  CAS  Google Scholar 

  11. Perry, G.H., Tchinda, J., McGrath, S.D., Zhang, J., Picker, S.R., Caceres, A.M., Iafrate, A.J., Tyler-Smith, C., Scherer, S.W., Eichler, E.E., Stone, A.C., and Lee, C. (2006) Hotspots for copy number variation in chimpanzees and humans Proc.Natl.Acad.Sci. USA 103, 8006–8011

    Article  CAS  Google Scholar 

  12. Kehrer-Sawatzki, H. and Cooper, D.N. (2007) Structural divergence between the human and chimpanzee genomes Hum.Genet. 120, 759–778

    CAS  Google Scholar 

  13. Lee, A.S., Gutierrez-Arcelus, M., Perry, G.H., Vallender, E.J., Johnson, W.E., Miller, G.M., Korbel, J.O., and Lee, C. (2008) Analysis of copy number variation in the rhesus macaque genome identifies candidate loci for evolutionary and human disease studies Hum.Mol.Genet. 17, 1127–1136

    CAS  Google Scholar 

  14. Chen, W.K., Swartz, J.D., Rush, L.J., and Alvarez, C.E. (2009) Mapping DNA structural variation in dogs Genome Res. 19, 500–509

    CAS  Google Scholar 

  15. Nicholas, T.J., Cheng, Z., Ventura, M., Mealey, K., Eichler, E.E., and Akey, J.M. (2009) The genomic architecture of segmental duplications and associated copy number variants in dogs Genome Res. 19, 491–499

    CAS  Google Scholar 

  16. Liu, G.E., Hou, Y., Zhu, B., Cardone, M.F., Jiang, L., Cellamare, A., Mitra, A., Alexander, L.J., Coutinho, L.L., Dell′aquila, M.E., Gasbarre, L.C., Lacalandra, G., Li, R.W., Matukumalli, L.K., Nonneman, D., Regitano, L.C., Smith, T.P., Song, J., Sonstegard, T.S., Van Tassell, C.P., Ventura, M., Eichler, E.E., McDaneld, T.G., and Keele, J.W. (2010) Analysis of copy number variations among diverse cattle breeds Genome Res.

    Google Scholar 

  17. Conrad, D.F., Pinto, D., Redon, R., Feuk, L., Gokcumen, O., Zhang, Y., Aerts, J., Andrews, T.D., Barnes, C., Campbell, P., Fitzgerald, T., Hu, M., Ihm, C.H., Kristiansson, K., Macarthur, D.G., MacDonald, J.R., Onyiah, I., Pang, A.W., Robson, S., Stirrups, K., Valsesia, A., Walter, K., Wei, J., Tyler-Smith, C., Carter, N.P., Lee, C., Scherer, S.W., and Hurles, M.E. (2010) Origins and functional impact of copy number variation in the human genome Nature 464, 704–712

    CAS  Google Scholar 

  18. Ogilvie, C.M., Braude, P., and Scriven, P.N. (2001) Successful pregnancy outcomes after preimplantation genetic diagnosis (PGD) for carriers of chromosome translocations Hum.Fertil.(Camb.) 4, 168–171

    Article  CAS  Google Scholar 

  19. Warburton, D. (1991) De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints Am.J.Hum.Genet 49, 995–1013

    CAS  Google Scholar 

  20. Lupski, J.R., Oca-Luna, R.M., Slaugenhaupt, S., Pentao, L., Guzzetta, V., Trask, B.J., Saucedo-Cardenas, O., Barker, D.F., Killian, J.M., Garcia, C.A., Chakravarti, A., and Patel, P.I. (1991) DNA duplication associated with Charcot-Marie-Tooth disease type 1A Cell 66, 219–232

    Article  PubMed  CAS  Google Scholar 

  21. Balikova, I., Lehesjoki, A.E., de Ravel, T.J., Thienpont, B., Chandler, K.E., Clayton-Smith, J., Traskelin, A.L., Fryns, J.P., and Vermeesch, J.R. (2009) Deletions in the VPS13B (COH1) gene as a cause of Cohen syndrome Hum.Mutat. 30, E845–E854

    Article  CAS  Google Scholar 

  22. Breckpot, J., Takiyama, Y., Thienpont, B., Van Vooren, S., Vermeesch, J.R., Ortibus, E., and Devriendt, K. (2008) A novel genomic disorder: a deletion of the SACS gene leading to spastic ataxia of Charlevoix-Saguenay Eur.J.Hum.Genet. 16, 1050–1054

    Article  CAS  Google Scholar 

  23. Lesnik Oberstein, S.A., Kriek, M., White, S.J., Kalf, M.E., Szuhai, K., den Dunnen, J.T., Breuning, M.H., and Hennekam, R.C. (2006) Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase Am.J.Hum.Genet. 79, 562–566

    Article  Google Scholar 

  24. Watkins-Chow, D.E. and Pavan, W.J. (2008) Genomic copy number and expression variation within the C57BL/6J inbred mouse strain Genome Res. 18, 60–66

    Article  PubMed  CAS  Google Scholar 

  25. Dathe, K., Kjaer, K.W., Brehm, A., Meinecke, P., Nurnberg, P., Neto, J.C., Brunoni, D., Tommerup, N., Ott, C.E., Klopocki, E., Seemann, P., and Mundlos, S. (2009) Duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2 Am.J.Hum.Genet. 84, 483–492

    Article  CAS  Google Scholar 

  26. Weterman, M.A., van Ruissen, F., de Wissel, M., Bordewijk, L., Samijn, J.P., van der Pol, W.L., Meggouh, F., and Baas, F. (2010) Copy number variation upstream of PMP22 in Charcot-Marie-Tooth disease Eur.J.Hum.Genet. 18, 421–428

    Article  CAS  Google Scholar 

  27. Lee, J.A., Madrid, R.E., Sperle, K., Ritterson, C.M., Hobson, G.M., Garbern, J., Lupski, J.R., and Inoue, K. (2006) Spastic paraplegia type 2 associated with axonal neuropathy and apparent PLP1 position effect Ann.Neurol. 59, 398–403

    CAS  Google Scholar 

  28. Brown, K.K., Reiss, J.A., Crow, K., Ferguson, H.L., Kelly, C., Fritzsch, B., and Morton, C.C. (2010) Deletion of an enhancer near DLX5 and DLX6 in a family with hearing loss, craniofacial defects, and an inv(7)(q21.3q35) Hum.Genet. 127, 19–31

    CAS  Google Scholar 

  29. Hogart, A., Leung, K.N., Wang, N.J., Wu, D.J., Driscoll, J., Vallero, R.O., Schanen, N.C., and LaSalle, J.M. (2009) Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number J.Med.Genet. 46, 86–93

    Article  CAS  Google Scholar 

  30. Carelle-Calmels, N., Saugier-Veber, P., Girard-Lemaire, F., Rudolf, G., Doray, B., Guerin, E., Kuhn, P., Arrive, M., Gilch, C., Schmitt, E., Fehrenbach, S., Schnebelen, A., Frebourg, T., and Flori, E. (2009) Genetic compensation in a human genomic disorder N.Engl.J.Med. 360, 1211–1216

    Google Scholar 

  31. Orozco, L.D., Cokus, S.J., Ghazalpour, A., Ingram-Drake, L., Wang, S., van Nas, A., Che, N., Araujo, J.A., Pellegrini, M., and Lusis, A.J. (2009) Copy number variation influences gene expression and metabolic traits in mice Hum.Mol.Genet. 18, 4118–4129

    CAS  Google Scholar 

  32. Iborra, F.J., Pombo, A., Jackson, D.A., and Cook, P.R. (1996) Active RNA polymerases are localized within discrete transcription “factories” in human nuclei J.Cell Sci. 109 ( Pt 6), 1427–1436

    CAS  Google Scholar 

  33. Osborne, C.S., Chakalova, L., Brown, K.E., Carter, D., Horton, A., Debrand, E., Goyenechea, B., Mitchell, J.A., Lopes, S., Reik, W., and Fraser, P. (2004) Active genes dynamically colocalize to shared sites of ongoing transcription Nat.Genet. 36, 1065–1071

    CAS  Google Scholar 

  34. Sexton, T., Umlauf, D., Kurukuti, S., and Fraser, P. (2007) The role of transcription factories in large-scale structure and dynamics of interphase chromatin Semin.Cell Dev.Biol. 18, 691–697

    Article  CAS  Google Scholar 

  35. Merla, G., Howald, C., Henrichsen, C.N., Lyle, R., Wyss, C., Zabot, M.T., Antonarakis, S.E., and Reymond, A. (2006) Submicroscopic deletion in patients with Williams-Beuren syndrome influences expression levels of the nonhemizygous flanking genes Am.J.Hum.Genet. 79, 332–341

    Article  CAS  Google Scholar 

  36. Stranger, B.E., Forrest, M.S., Dunning, M., Ingle, C.E., Beazley, C., Thorne, N., Redon, R., Bird, C.P., de Grassi, A., Lee, C., Tyler-Smith, C., Carter, N., Scherer, S.W., Tavare, S., Deloukas, P., Hurles, M.E., and Dermitzakis, E.T. (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes Science 315, 848–853

    CAS  Google Scholar 

  37. Molina, J., Carmona-Mora, P., Chrast, J., Krall, P.M., Canales, C.P., Lupski, J.R., Reymond, A., and Walz, K. (2008) Abnormal social behaviors and altered gene expression rates in a mouse model for Potocki-Lupski syndrome Hum.Mol.Genet. 17, 2486–2495

    CAS  Google Scholar 

  38. Gabellini, D., Green, M.R., and Tupler, R. (2002) Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle Cell 110, 339–348

    CAS  Google Scholar 

  39. Gabellini, D., D’Antona, G., Moggio, M., Prelle, A., Zecca, C., Adami, R., Angeletti, B., Ciscato, P., Pellegrino, M.A., Bottinelli, R., Green, M.R., and Tupler, R. (2006) Facioscapulohumeral muscular dystrophy in mice overexpressing FRG1 Nature 439, 973–977

    Google Scholar 

  40. Muncke, N., Wogatzky, B.S., Breuning, M., Sistermans, E.A., Endris, V., Ross, M., Vetrie, D., Catsman-Berrevoets, C.E., and Rappold, G. (2004) Position effect on PLP1 may cause a subset of Pelizaeus-Merzbacher disease symptoms J.Med.Genet 41, e121

    Article  CAS  Google Scholar 

  41. Lee, J.A. and Lupski, J.R. (2006) Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders Neuron 52, 103–121

    CAS  Google Scholar 

  42. Fraser, P. and Bickmore, W. (2007) Nuclear organization of the genome and the potential for gene regulation Nature 447, 413–417

    CAS  Google Scholar 

  43. Heard, E. and Bickmore, W. (2007) The ins and outs of gene regulation and chromosome territory organisation Curr.Opin.Cell Biol. 19, 311–316

    Article  CAS  Google Scholar 

  44. Denoeud, F., Kapranov, P., Ucla, C., Frankish, A., Castelo, R., Drenkow, J., Lagarde, J., Alioto, T., Manzano, C., Chrast, J., Dike, S., Wyss, C., Henrichsen, C.N., Holroyd, N., Dickson, M.C., Taylor, R., Hance, Z., Foissac, S., Myers, R.M., Rogers, J., Hubbard, T., Harrow, J., Guigo, R., Gingeras, T.R., Antonarakis, S.E., and Reymond, A. (2007) Prominent use of distal 5′ transcription start sites and discovery of a large number of additional exons in ENCODE regions Genome Res. 17, 746–759

    Article  PubMed  CAS  Google Scholar 

  45. Birney, E., Stamatoyannopoulos, J.A., Dutta, A., Guigo, R., Gingeras, T.R., Margulies, E.H., Weng, Z., Snyder, M., Dermitzakis, E.T., Thurman, R.E., Kuehn, M.S., Taylor, C.M., Neph, S., Koch, C.M., Asthana, S., Malhotra, A., Adzhubei, I., Greenbaum, J.A., Andrews, R.M., Flicek, P., Boyle, P.J., Cao, H., Carter, N.P., Clelland, G.K., Davis, S., Day, N., Dhami, P., Dillon, S.C., Dorschner, M.O., Fiegler, H., Giresi, P.G., Goldy, J., Hawrylycz, M., Haydock, A., Humbert, R., James, K.D., Johnson, B.E., Johnson, E.M., Frum, T.T., Rosenzweig, E.R., Karnani, N., Lee, K., Lefebvre, G.C., Navas, P.A., Neri, F., Parker, S.C., Sabo, P.J., Sandstrom, R., Shafer, A., Vetrie, D., Weaver, M., Wilcox, S., Yu, M., Collins, F.S., Dekker, J., Lieb, J.D., Tullius, T.D., Crawford, G.E., Sunyaev, S., Noble, W.S., Dunham, I., Denoeud, F., Reymond, A., Kapranov, P., Rozowsky, J., Zheng, D., Castelo, R., Frankish, A., Harrow, J., Ghosh, S., Sandelin, A., Hofacker, I.L., Baertsch, R., Keefe, D., Dike, S., Cheng, J., Hirsch, H.A., Sekinger, E.A., Lagarde, J., Abril, J.F., Shahab, A., Flamm, C., Fried, C., Hackermuller, J., Hertel, J., Lindemeyer, M., Missal, K., Tanzer, A., Washietl, S., Korbel, J., Emanuelsson, O., Pedersen, J.S., Holroyd, N., Taylor, R., Swarbreck, D., Matthews, N., Dickson, M.C., Thomas, D.J., Weirauch, M.T., Gilbert, J., Drenkow, J., Bell, I., Zhao, X., Srinivasan, K.G., Sung, W.K., Ooi, H.S., Chiu, K.P., Foissac, S., Alioto, T., Brent, M., Pachter, L., Tress, M.L., Valencia, A., Choo, S.W., Choo, C.Y., Ucla, C., Manzano, C., Wyss, C., Cheung, E., Clark, T.G., Brown, J.B., Ganesh, M., Patel, S., Tammana, H., Chrast, J., Henrichsen, C.N., Kai, C., Kawai, J., Nagalakshmi, U., Wu, J., Lian, Z., Lian, J., Newburger, P., Zhang, X., Bickel, P., Mattick, J.S., Carninci, P., Hayashizaki, Y., Weissman, S., Hubbard, T., Myers, R.M., Rogers, J., Stadler, P.F., Lowe, T.M., Wei, C.L., Ruan, Y., Struhl, K., Gerstein, M., Antonarakis, S.E., Fu, Y., Green, E.D., Karaoz, U., Siepel, A., Taylor, J., Liefer, L.A., Wetterstrand, K.A., Good, P.J., Feingold, E.A., Guyer, M.S., Cooper, G.M., Asimenos, G., Dewey, C.N., Hou, M., Nikolaev, S., Montoya-Burgos, J.I., Loytynoja, A., Whelan, S., Pardi, F., Massingham, T., Huang, H., Zhang, N.R., Holmes, I., Mullikin, J.C., Ureta-Vidal, A., Paten, B., Seringhaus, M., Church, D., Rosenbloom, K., Kent, W.J., Stone, E.A., Batzoglou, S., Goldman, N., Hardison, R.C., Haussler, D., Miller, W., Sidow, A., Trinklein, N.D., Zhang, Z.D., Barrera, L., Stuart, R., King, D.C., Ameur, A., Enroth, S., Bieda, M.C., Kim, J., Bhinge, A.A., Jiang, N., Liu, J., Yao, F., Vega, V.B., Lee, C.W., Ng, P., Shahab, A., Yang, A., Moqtaderi, Z., Zhu, Z., Xu, X., Squazzo, S., Oberley, M.J., Inman, D., Singer, M.A., Richmond, T.A., Munn, K.J., Rada-Iglesias, A., Wallerman, O., Komorowski, J., Fowler, J.C., Couttet, P., Bruce, A.W., Dovey, O.M., Ellis, P.D., Langford, C.F., Nix, D.A., Euskirchen, G., Hartman, S., Urban, A.E., Kraus, P., Van Calcar, S., Heintzman, N., Kim, T.H., Wang, K., Qu, C., Hon, G., Luna, R., Glass, C.K., Rosenfeld, M.G., Aldred, S.F., Cooper, S.J., Halees, A., Lin, J.M., Shulha, H.P., Zhang, X., Xu, M., Haidar, J.N., Yu, Y., Ruan, Y., Iyer, V.R., Green, R.D., Wadelius, C., Farnham, P.J., Ren, B., Harte, R.A., Hinrichs, A.S., Trumbower, H., and Clawson, H. (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project Nature 447, 799–816

    Google Scholar 

  46. Reymond, A., Henrichsen, C.N., Harewood, L., and Merla, G. (2007) Side effects of genome structural changes Curr.Opin.Genet.Dev. 17, 381–386

    Article  CAS  Google Scholar 

  47. Cahan, P., Li, Y., Izumi, M., and Graubert, T.A. (2009) The impact of copy number variation on local gene expression in mouse hematopoietic stem and progenitor cells Nat.Genet. 41, 430–437

    CAS  Google Scholar 

  48. Lindenbaum, R.H., Clarke, G., Patel, C., Moncrieff, M., and Hughes, J.T. (1979) Muscular dystrophy in an X; 1 translocation female suggests that Duchenne locus is on X chromosome short arm J.Med.Genet 16, 389–392

    Article  CAS  Google Scholar 

  49. Verellen-Dumoulin, C., Freund, M., De Meyer, R., Laterre, C., Frederic, J., Thompson, M.W., Markovic, V.D., and Worton, R.G. (1984) Expression of an X-linked muscular dystrophy in a female due to translocation involving Xp21 and non-random inactivation of the normal X chromosome Hum.Genet 67, 115–119

    CAS  Google Scholar 

  50. Ray, P.N., Belfall, B., Duff, C., Logan, C., Kean, V., Thompson, M.W., Sylvester, J.E., Gorski, J.L., Schmickel, R.D., and Worton, R.G. (1985) Cloning of the breakpoint of an X;21 translocation associated with Duchenne muscular dystrophy Nature 318, 672–675

    Article  PubMed  CAS  Google Scholar 

  51. Cremers, F.P., Brunsmann, F., Berger, W., van Kerkhoff, E.P., van de Pol, T.J., Wieringa, B., Pawlowitzki, I.H., and Ropers, H.H. (1990) Cloning of the breakpoints of a deletion associated with choroidermia Hum.Genet 86, 61–64

    CAS  Google Scholar 

  52. Attree, O., Olivos, I.M., Okabe, I., Bailey, L.C., Nelson, D.L., Lewis, R.A., McInnes, R.R., and Nussbaum, R.L. (1992) The Lowe’s oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase Nature 358, 239–242

    Article  PubMed  CAS  Google Scholar 

  53. Gleeson, J.G., Allen, K.M., Fox, J.W., Lamperti, E.D., Berkovic, S., Scheffer, I., Cooper, E.C., Dobyns, W.B., Minnerath, S.R., Ross, M.E., and Walsh, C.A. (1998) Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein Cell 92, 63–72

    Article  PubMed  CAS  Google Scholar 

  54. Collin, G.B., Marshall, J.D., Ikeda, A., So, W.V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C.F., Sicolo, N., Martin, M., Nishina, P.M., and Naggert, J.K. (2002) Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome Nat.Genet 31, 74–78

    CAS  Google Scholar 

  55. Hearn, T., Renforth, G.L., Spalluto, C., Hanley, N.A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J.F., Russell-Eggitt, I., Bonneau, D., Walker, M., and Wilson, D.I. (2002) Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome Nat.Genet 31, 79–83

    CAS  Google Scholar 

  56. Kleinjan, D.J. and van Heyningen, V. (1998) Position effect in human genetic disease Hum.Mol.Genet 7, 1611–1618

    CAS  Google Scholar 

  57. Kleinjan, D.J. and Coutinho, P. (2009) Cis-ruption mechanisms: disruption of cis-regulatory control as a cause of human genetic disease Brief.Funct.Genomic.Proteomic. 8, 317–332

    Article  CAS  Google Scholar 

  58. Lauderdale, J.D., Wilensky, J.S., Oliver, E.R., Walton, D.S., and Glaser, T. (2000) 3′ deletions cause aniridia by preventing PAX6 gene expression Proc.Natl.Acad.Sci. USA 97, 13755–13759

    Article  CAS  Google Scholar 

  59. Benko, S., Fantes, J.A., Amiel, J., Kleinjan, D.J., Thomas, S., Ramsay, J., Jamshidi, N., Essafi, A., Heaney, S., Gordon, C.T., McBride, D., Golzio, C., Fisher, M., Perry, P., Abadie, V., Ayuso, C., Holder-Espinasse, M., Kilpatrick, N., Lees, M.M., Picard, A., Temple, I.K., Thomas, P., Vazquez, M.P., Vekemans, M., Crollius, H.R., Hastie, N.D., Munnich, A., Etchevers, H.C., Pelet, A., Farlie, P.G., FitzPatrick, D.R., and Lyonnet, S. (2009) Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence Nat.Genet. 41, 359–364

    CAS  Google Scholar 

  60. Gordon, C.T., Tan, T.Y., Benko, S., FitzPatrick, D., Lyonnet, S., and Farlie, P.G. (2009) Long-range regulation at the SOX9 locus in development and disease J.Med.Genet. 46, 649–656

    Article  CAS  Google Scholar 

  61. Leipoldt, M., Erdel, M., Bien-Willner, G.A., Smyk, M., Theurl, M., Yatsenko, S.A., Lupski, J.R., Lane, A.H., Shanske, A.L., Stankiewicz, P., and Scherer, G. (2007) Two novel translocation breakpoints upstream of SOX9 define borders of the proximal and distal breakpoint cluster region in campomelic dysplasia Clin.Genet. 71, 67–75

    CAS  Google Scholar 

  62. Velagaleti, G.V., Bien-Willner, G.A., Northup, J.K., Lockhart, L.H., Hawkins, J.C., Jalal, S.M., Withers, M., Lupski, J.R., and Stankiewicz, P. (2005) Position effects due to chromosome breakpoints that map approximately 900 Kb upstream and approximately 1.3 Mb downstream of SOX9 in two patients with campomelic dysplasia Am.J.Hum.Genet 76, 652–662

    CAS  Google Scholar 

  63. Demura, M., Martin, R.M., Shozu, M., Sebastian, S., Takayama, K., Hsu, W.T., Schultz, R.A., Neely, K., Bryant, M., Mendonca, B.B., Hanaki, K., Kanzaki, S., Rhoads, D.B., Misra, M., and Bulun, S.E. (2007) Regional rearrangements in chromosome 15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene Hum.Mol.Genet. 16, 2529–2541

    CAS  Google Scholar 

  64. Shozu, M., Sebastian, S., Takayama, K., Hsu, W.T., Schultz, R.A., Neely, K., Bryant, M., and Bulun, S.E. (2003) Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene N.Engl.J.Med. 348, 1855–1865

    Google Scholar 

  65. Lieberman-Aiden, E., van Berkum, N.L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B.R., Sabo, P.J., Dorschner, M.O., Sandstrom, R., Bernstein, B., Bender, M.A., Groudine, M., Gnirke, A., Stamatoyannopoulos, J., Mirny, L.A., Lander, E.S., and Dekker, J. (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome Science 326, 289–293

    CAS  Google Scholar 

  66. Mitchell, J.A. and Fraser, P. (2008) Transcription factories are nuclear subcompartments that remain in the absence of transcription Genes Dev. 22, 20–25

    CAS  Google Scholar 

  67. Simonis, M., Klous, P., Splinter, E., Moshkin, Y., Willemsen, R., de Wit, E., van Steensel, B., and de Laat, W. (2006) Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4 C) Nat.Genet. 38, 1348–1354

    CAS  Google Scholar 

  68. Croft, J.A., Bridger, J.M., Boyle, S., Perry, P., Teague, P., and Bickmore, W.A. (1999) Differences in the localization and morphology of chromosomes in the human nucleus J.Cell Biol. 145, 1119–1131

    Article  CAS  Google Scholar 

  69. Boyle, S., Gilchrist, S., Bridger, J.M., Mahy, N.L., Ellis, J.A., and Bickmore, W.A. (2001) The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells Hum.Mol.Genet 10, 211–219

    CAS  Google Scholar 

  70. Taslerova, R., Kozubek, S., Lukasova, E., Jirsova, P., Bartova, E., and Kozubek, M. (2003) Arrangement of chromosome 11 and 22 territories, EWSR1 and FLI1 genes, and other genetic elements of these chromosomes in human lymphocytes and Ewing sarcoma cells Hum.Genet. 112, 143–155

    CAS  Google Scholar 

  71. Taslerova, R., Kozubek, S., Bartova, E., Gajdus-kova, P., Kodet, R., and Kozubek, M. (2006) Localization of genetic elements of intact and derivative chromosome 11 and 22 territories in nuclei of Ewing sarcoma cells J.Struct.Biol. 155, 493–504

    Article  CAS  Google Scholar 

  72. Finlan, L.E., Sproul, D., Thomson, I., Boyle, S., Kerr, E., Perry, P., Ylstra, B., Chubb, J.R., and Bickmore, W.A. (2008) Recruitment to the nuclear periphery can alter expression of genes in human cells PLoS.Genet. 4, e1000039

    Google Scholar 

  73. Reddy, K.S., Rajangam, S., and Thomas, I.M. (1999) Structural chromosomal anomaly in mental retardation Indian J.Pediatr. 66, 937–940

    CAS  Google Scholar 

  74. Deniaud, E. and Bickmore, W.A. (2009) Trans-cription and the nuclear periphery: edge of darkness? Curr.Opin.Genet.Dev. 19, 187–191

    Article  PubMed  CAS  Google Scholar 

  75. Williams, R.R., Azuara, V., Perry, P., Sauer, S., Dvorkina, M., Jorgensen, H., Roix, J., McQueen, P., Misteli, T., Merkenschlager, M., and Fisher, A.G. (2006) Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus J.Cell Sci. 119, 132–140

    Article  CAS  Google Scholar 

  76. Szczerbal, I., Foster, H.A., and Bridger, J.M. (2009) The spatial repositioning of adipogenesis genes is correlated with their expression status in a porcine mesenchymal stem cell adipogenesis model system Chromosoma 118, 647–663

    CAS  Google Scholar 

  77. Harewood, L., Schutz, F., Boyle, S., Perry, P., Delorenzi, M., Bickmore, W.A., and Reymond, A. (2010) The effect of translocation-induced nuclear reorganization on gene expression Genome Res.

    Google Scholar 

  78. Brown, J.M., Green, J., das Neves, R.P., Wallace, H.A., Smith, A.J., Hughes, J., Gray, N., Taylor, S., Wood, W.G., Higgs, D.R., Iborra, F.J., and Buckle, V.J. (2008) Association between active genes occurs at nuclear speckles and is modulated by chromatin environment J.Cell Biol. 182, 1083–1097

    Google Scholar 

  79. Misteli, T. (2004) Spatial positioning; a new dimension in genome function Cell 119, 153–156

    Article  PubMed  CAS  Google Scholar 

  80. Osborne, C.S., Chakalova, L., Mitchell, J.A., Horton, A., Wood, A.L., Bolland, D.J., Corcoran, A.E., and Fraser, P. (2007) Myc dynamically and preferentially relocates to a transcription factory occupied by Igh PLoS.Biol. 5, e192

    Google Scholar 

  81. Branco, M.R. and Pombo, A. (2006) Interming-ling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations PLoS.Biol. 4, e138

    Google Scholar 

  82. Goetze, S., Mateos-Langerak, J., Gierman, H.J., de Leeuw, W., Giromus, O., Indemans, M.H., Koster, J., Ondrej, V., Versteeg, R., and van Driel, R. (2007) The three-dimensional structure of human interphase chromosomes is related to the transcriptome map Mol.Cell Biol. 27, 4475–4487

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

    Louise Harewood, Evelyne Chaignat & Alexandre Reymond

Authors
  1. Louise Harewood
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evelyne Chaignat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexandre Reymond
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexandre Reymond .

Editor information

Editors and Affiliations

  1. Dept. Immunology, Genetics & Pathology, Uppsala University, Dag Hammarskjölds väg 20, Uppsala, 751 85, Sweden

    Lars Feuk

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Harewood, L., Chaignat, E., Reymond, A. (2012). Structural Variation and Its Effect on Expression. In: Feuk, L. (eds) Genomic Structural Variants. Methods in Molecular Biology, vol 838. Springer, New York, NY. https://doi.org/10.1007/978-1-61779-507-7_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-507-7_8

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-61779-506-0

  • Online ISBN: 978-1-61779-507-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation