Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Segmental duplications: an 'expanding' role in genomic instability and disease

Nature Reviews Genetics volume 2, pages 791–800 (2001)Cite this article

Key Points

  • Segmental duplications are a class of repetitive DNA element in the human genome.

  • Segmental duplications have various sizes and organizational configurations.

  • The different copies of a segmental duplication can share 96–99% nucleotide sequence identity with each other.

  • Segmental duplications have been implicated in the aetiology of chromosomal rearrangements that are associated with several genomic disorders.

  • The chromosomal rearrangements include deletions, interstitial duplications, inversions, supernumerary marker chromosomes and translocations.

  • The genomic disorders include DiGeorge and velocardiofacial syndromes, cat eye syndrome, Prader–Willi and Angelman syndromes, Williams–Beuren syndrome and many more.

  • Many models are proposed to explain the mechanisms involved in segmental-duplication-mediated rearrangements.

  • All of these models are based on misalignment between non-allelic segmental duplications, followed by recombination.

  • Segmental duplications represent an under-appreciated source of genetic change in the human genome.

Abstract

The knowledge that specific genetic diseases are caused by recurrent chromosomal aberrations has indicated that genomic instability might be directly related to the structure of the regions involved. The sequencing of the human genome has directed significant attention towards understanding the molecular basis of such recombination 'hot spots'. Segmental duplications have emerged as a significant factor in the aetiology of disorders that are caused by abnormal gene dosage. These observations bring us closer to understanding the mechanisms and consequences of genomic rearrangement.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Chromosomal rearrangements mediated by segmental duplications.
Figure 2: Chromosomes 15 and 22: deletions and inverted duplication chromosomes.
Figure 3: Models for formation of deletions and duplications.
Figure 4: Models for formation of cat eye syndrome or inv dup (15) marker chromosomes.
Figure 5: Model for translocations in 22q11.

Similar content being viewed by others

References

  1. Mazzarella, R. & Schlessinger, D. Pathological consequences of sequence duplications in the human genome. Genome Res. 8, 1007–1021 (1998).

    CAS  PubMed  Google Scholar 

  2. Lupski, J. R. Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet. 14, 417–422 (1998).

    CAS  PubMed  Google Scholar 

  3. Ji, Y., Eichler, E. E., Schwartz, S. & Nicholls, R. D. Structure of chromosomal duplicons and their role in mediating human genomic disorders. Genome Res. 10, 597–610 (2000).References 1–3 are excellent early reviews that discuss segmental duplications in the human genome and their involvement in genomic disorders.

    CAS  PubMed  Google Scholar 

  4. IHGSC (International Human Genome Sequencing Consortium). Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).Landmark paper that reports the draft sequence of the human genome and also presents a comprehensive analysis of repetitive and duplicated DNA in the entire human genome.

  5. Shaikh, T. H., Kurahashi, H. & Emanuel, B. S. Evolutionarily conserved duplications in 22q11 mediate deletions, duplications, translocations and genomic instability. Genet. Med. 3, 6–13 (2001).

    CAS  PubMed  Google Scholar 

  6. Eichler, E. E. et al. Duplication of a gene rich cluster between 16p11.1 and Xq28: a novel pericentromeric-directed mechanism for paralogous genome evolution. Hum. Mol. Genet. 5, 899–912 (1996).

    CAS  PubMed  Google Scholar 

  7. Eichler, E. E. et al. Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity. Hum. Mol. Genet. 6, 991–1002 (1997).

    CAS  PubMed  Google Scholar 

  8. Regnier, V. et al. Emergence and scattering of multiple neurofibromatosis (NF-1)-related sequences during hominoid evolution suggest a process of pericentromeric interchromosomal transposition. Hum. Mol. Genet. 6, 9–16 (1997).References 7 and 8 were among the earliest papers to recognize the pericentromeric plasticity of chromosomes in higher primates.

    CAS  PubMed  Google Scholar 

  9. Trask, B. et al. Members of the olfactory receptor gene family are contained in large blocks of DNA duplicated polymorphically near the ends of human chromosomes. Hum. Mol. Genet. 7, 13–26 (1998).

    CAS  PubMed  Google Scholar 

  10. Trask, B. J. et al. Large multi-chromosomal duplications encompass many members of the olfactory receptor gene family in the human genome. Hum. Mol. Genet. 7, 2007–2020 (1998).

    CAS  PubMed  Google Scholar 

  11. Purandare, S. M. & Patel, P. I. Recombination hot spots and human disease. Genome Res. 7, 773–786 (1997).

    CAS  PubMed  Google Scholar 

  12. Shaffer, L. G. & Lupski, J. R. Molecular mechanisms for constitutional chromosomal rearrangements in humans. Annu. Rev. Genet. 34, 297–329 (2000).

    CAS  PubMed  Google Scholar 

  13. Chance, P. F. et al. Two autosomal dominant neuropathies result from reciprocal DNA duplication/deletion of a region on chromosome 17. Hum. Mol. Genet. 3, 223–228 (1994).

    CAS  PubMed  Google Scholar 

  14. Lupski, J. R. Charcot–Marie–Tooth disease: lessons in genetic mechanisms. Mol. Med. 4, 3–11 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Dorschner, M. O., Sybert, V. P., Weaver, M., Pletcher, B. A. & Stephens, K. NF1 microdeletion breakpoints are clustered at flanking repetitive sequences. Hum. Mol. Genet. 9, 35–46 (2000).

    CAS  PubMed  Google Scholar 

  16. Christian, S. L., Fantes, J. A., Mewborn, S. K., Huang, B. & Ledbetter, D. H. Large genomic duplicons map to sites of instability in Prader–Willi/Angelman syndrome chromosome region (15q11–q13). Hum. Mol. Genet. 8, 1025–1037 (1999).

    CAS  PubMed  Google Scholar 

  17. Amos-Landgraf, J. M. et al. Chromosome breakage in the Prader–Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints. Am. J. Hum. Genet. 65, 370–386 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Perez-Jurado, L. A. et al. A duplicated gene in the breakpoint regions of the 7q11.23 Williams–Beuren syndrome deletion encodes the initiator binding protein TFII-I and BAP-135, a phosphorylation target of BTK. Hum. Mol. Genet. 7, 325–334 (1998).

    CAS  PubMed  Google Scholar 

  19. Peoples, R. et al. A physical map, including a BAC/PAC clone contig, of the Williams–Beuren syndrome –deletion region at 7q11.23. Am. J. Hum. Genet. 66, 47–68 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Chen, K. S. et al. Homologous recombination of a flanking repeat gene cluster is a mechanism for a common contiguous gene deletion syndrome. Nature Genet. 17, 154–163 (1997).

    CAS  PubMed  Google Scholar 

  21. Potocki, L. et al. Molecular mechanism for duplication 17p11.2 – the homologous recombination reciprocal of the Smith–Magenis microdeletion. Nature Genet. 24, 84–87 (2000).

    CAS  PubMed  Google Scholar 

  22. McTaggart, K. E. et al. Cat eye syndrome chromosome breakpoint clustering: identification of two intervals also associated with 22q11 deletion syndrome breakpoints. Cytogenet. Cell Genet. 81, 222–228 (1998).

    CAS  PubMed  Google Scholar 

  23. Edelmann, L., Pandita, R. K. & Morrow, B. E. Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. Am. J. Hum. Genet. 64, 1076–1086 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Edelmann, L. et al. A common molecular basis for rearrangement disorders on chromosome 22q11. Hum. Mol. Genet. 8, 1157–1167 (1999).

    CAS  PubMed  Google Scholar 

  25. Shaikh, T. H. et al. Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis. Hum. Mol. Genet. 9, 489–501 (2000).

    CAS  PubMed  Google Scholar 

  26. Dunham, I. et al. The DNA sequence of human chromosome 22. Nature 402, 489–495 (1999).References 25 and 26 present a detailed, sequence-based analysis of segmental duplications on 22q11.

    CAS  PubMed  Google Scholar 

  27. Emanuel, B. S. et al. in Etiology and Morphogenesis of Congenital Heart Disease (eds Clark, E., Nakazawa, M. & Takao, A.) 335–339 (Futura Publishing Co., Inc., Armonk, New York, 1999).

    Google Scholar 

  28. Shaikh, T. H., Budarf, M. L., Celle, L., Zackai, E. H. & Emanuel, B. S. Clustered 11q23 and 22q11 breakpoints and 3:1 meiotic malsegregation in multiple unrelated t(11;22) families. Am. J. Hum. Genet. 65, 1595–1607 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Edelmann, L. et al. A common breakpoint on 11q23 in carriers of the constitutional t(11;22) translocation. Am. J. Hum. Genet. 65, 1608–1616 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Kurahashi, H. et al. Regions of genomic instability on 22q11 and 11q23 as the etiology for the recurrent constitutional t(11;22). Hum. Mol. Genet. 9, 1665–1670 (2000).

    CAS  PubMed  Google Scholar 

  31. Kurahashi, H. et al. Tightly clustered 11q23 and 22q11 breakpoints permit PCR-based detection of the recurrent constitutional t(11;22). Am. J. Hum. Genet. 67, 763–768 (2000).References 30 and 31 present extensive research in mapping the breakpoints of the constitutional t(11; 22). Reference 30 was the first to show that the t(11; 22) breakpoints localize to palindromic (A+T)-rich repeats. Reference 31 describes identical sequences of t(11; 22) breakpoints in several, unrelated translocation carriers.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Reiter, L. T., Murakami, T., Koeuth, T., Gibbs, R. A. & Lupski, J. R. The human COX10 gene is disrupted during homologous recombination between the 24 kb proximal and distal CMT1A-REPs. Hum. Mol. Genet. 6, 1595–1603 (1997).

    CAS  PubMed  Google Scholar 

  33. Reiter, L. T. et al. Human meiotic recombination products revealed by sequencing a hotspot for homologous strand exchange in multiple HNPP deletion patients. Am. J. Hum. Genet. 62, 1023–1033 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Inoue, K. et al. The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes. Genome Res. 11, 1018–1033 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Yen, P. H. et al. Frequent deletions of the human X chromosome distal short arm result from recombination between low copy repetitive elements. Cell 61, 603–610 (1990).

    CAS  PubMed  Google Scholar 

  36. Li, X. M., Yen, P. H. & Shapiro, L. J. Characterization of a low copy repetitive element S232 involved in the generation of frequent deletions of the distal short arm of the human X chromosome. Nucleic Acids Res. 20, 1117–1122 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Lahn, B. T. & Page, D. C. A human sex-chromosomal gene family expressed in male germ cells and encoding variably charged proteins. Hum. Mol. Genet. 9, 311–319 (2000).

    CAS  PubMed  Google Scholar 

  38. Small, K., Iber, J. & Warren, S. T. Emerin deletion reveals common X-chromosome inversion mediated by inverted repeats. Nature Genet. 16, 96–99 (1997).

    CAS  PubMed  Google Scholar 

  39. Naylor, J. A. et al. Investigation of the factor VIII intron 22 repeated region (int22h) and the associated inversion junctions. Hum. Mol. Genet. 4, 1217–1224 (1995).

    CAS  PubMed  Google Scholar 

  40. Naylor, J. A. et al. A novel DNA inversion causing severe hemophilia A. Blood 87, 3255–3261 (1996).

    CAS  PubMed  Google Scholar 

  41. Kehrer-Sawatzki, H., Schwickardt, T., Assum, G., Rocchi, M. & Krone, W. A third neurofibromatosis type 1 (NF1) pseudogene at chromosome 15q11.2. Hum. Genet. 100, 595–600 (1997).

    CAS  PubMed  Google Scholar 

  42. Edelmann, L. et al. AT-rich palindromes mediate the constitutional t(11;22) translocation. Am. J. Hum. Genet. 68, 1–13 (2001).

    CAS  PubMed  Google Scholar 

  43. Ji, Y. et al. The ancestral gene for transcribed, low-copy repeats in the Prader–Willi/Angelman region encodes a large protein implicated in protein trafficking, which is deficient in mice with neuromuscular and spermiogenic abnormalities. Hum. Mol. Genet. 8, 533–542 (1999).

    CAS  PubMed  Google Scholar 

  44. Ji, Y. et al. Structure of the highly conserved HERC2 gene and of multiple partially duplicated paralogs in human. Genome Res. 10, 319–329 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Pujana, M. A. et al. Additional complexity on human chromosome 15q: identification of a set of newly recognized duplicons (LCR15) on 15q11–q13, 15q24, and 15q26. Genome Res. 11, 98–111 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Valero, M. C., de Luis, O., Cruces, J. & Perez Jurado, L. A. Fine-scale comparative mapping of the human 7q11.23 region and the orthologous region on mouse chromosome 5G: the low-copy repeats that flank the Williams–Beuren syndrome deletion arose at breakpoint sites of an evolutionary inversion. Genomics 69, 1–13 (2000).

    CAS  PubMed  Google Scholar 

  47. Kiyosawa, H. & Chance, P. F. Primate origin of the CMT1A-REP repeat and analysis of a putative transposon-associated recombinational hot spot. Hum. Mol. Genet. 8, 745–753 (1996).

    Google Scholar 

  48. Reiter, L. T. et al. A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element. Nature Genet. 12, 288–297 (1996).This paper identifies a recombination hot spot in the CMT1A-REP. This report was the first to indicate that there might be recombinogenic hot spots in large segmental duplications.

    CAS  PubMed  Google Scholar 

  49. Lopez-Correa, C. et al. Recombination hotspot in NF1 microdeletion patients. Hum. Mol. Genet. 10, 1387–1392 (2001).

    CAS  PubMed  Google Scholar 

  50. Zimonjic, D., Kelley, M., Rubin, J., Aaronson, S. & Popescu, N. Fluorescence in situ hybridization analysis of keratinocyte growth factor gene amplification and dispersion in evolution of great apes and humans. Proc. Natl Acad. Sci. USA 94, 11461–11465 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Keller, M. P., Seifried, B. A. & Chance, P. F. Molecular evolution of the CMT1A-REP region: a human and chimpanzee-specific repeat. Mol. Biol. Evol. 16, 1019–1026 (1999).

    CAS  PubMed  Google Scholar 

  52. Botta, A., Lindsay, E. A., Jurecic, V. & Baldini, A. Comparative mapping of the DiGeorge syndrome region in mouse shows inconsistent gene order and differential degree of gene conversion. Mamm. Genome 8, 890–895 (1997).

    CAS  PubMed  Google Scholar 

  53. Puech, A. et al. Comparative mapping of the human 22q11 chromosomal region and the orthologous region in mice reveals complex changes in gene organization. Proc. Natl Acad. Sci. USA 94, 14608–14613 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Sutherland, H. F., Kim, U.-J. & Scambler, P. J. Cloning and comparative mapping of the DiGeorge syndrome critical region in the mouse. Genomics 52, 37–43 (1998).

    CAS  PubMed  Google Scholar 

  55. Lund, J. et al. Sequence-ready physical map of the mouse chromosome 16 region with conserved synteny to the human velocardiofacial syndrome region on 22q11.2. Mamm. Genome 10, 438–443 (1999).

    CAS  PubMed  Google Scholar 

  56. Bonifas, J. M., Morley, B. J., Oakey, R. E., Kan, Y. W. & Epstein, E. H. Jr Cloning of a cDNA for steroid sulfatase: frequent occurrence of gene deletions in patients with recessive X chromosome-linked ichthyosis. Proc. Natl Acad. Sci. USA 84, 9248–9251 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Conary, J. T. et al. Genetic heterogeneity of steroid sulfatase deficiency revealed with cDNA for human steroid sulfatase. Biochem. Biophys. Res. Commun. 144, 1010–1017 (1987).

    CAS  PubMed  Google Scholar 

  58. Ballabio, A. & Andria, G. Deletions and translocations involving the distal short arm of the human X chromosome: review and hypotheses. Hum. Mol. Genet. 1, 221–227 (1992).

    CAS  PubMed  Google Scholar 

  59. Ewart, A. K. et al. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nature Genet. 5, 11–16 (1993).

    CAS  PubMed  Google Scholar 

  60. Dutly, F. & Schinzel, A. Unequal interchromosomal rearrangements may result in elastin gene deletions causing the Williams–Beuren syndrome. Hum. Mol. Genet. 5, 1893–1898 (1996).

    CAS  PubMed  Google Scholar 

  61. Urbán, Z. et al. 7q11.23 deletions in Williams syndrome arise as a consequence of unequal meiotic crossover. Am. J. Hum. Genet. 59, 958–962 (1996).

    PubMed  PubMed Central  Google Scholar 

  62. Baumer, A. et al. High level of unequal meiotic crossovers at the origin of the 22q11.2 and 7q11.23 deletions. Hum. Mol. Genet. 7, 887–894 (1998).

    CAS  PubMed  Google Scholar 

  63. Perez Jurado, L. A., Peoples, R., Kaplan, P., Hamel, B. C. & Francke, U. Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth. Am. J. Hum. Genet. 59, 781–792 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Robinson, W. P. et al. Delineation of 7q11.2 deletions associated with Williams–Beuren syndrome and mapping of a repetitive sequence to within and to either side of the common deletion. Genomics 34, 17–23 (1996).

    CAS  PubMed  Google Scholar 

  65. Carrozzo, R. et al. Inter- and intrachromosomal rearrangements are both involved in the origin of 15q11–q13 deletions in Prader–Willi syndrome. Am. J. Hum. Genet. 61, 228–231 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Robinson, W. P. et al. The mechanisms involved in formation of deletions and duplications of 15q11–q13. J. Med. Genet. 35, 130–136 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Pentao, L., Wise, C. A., Chinault A. C., Patel, P. I. & Lupski, J. R. Charcot–Marie–Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unit. Nature Genet. 2, 292–300 (1992).

    CAS  PubMed  Google Scholar 

  68. Lupski, J. R. et al. Gene dosage is a mechanism for Charcot–Marie–Tooth disease type 1A. Nature Genet. 1, 29–33 (1992).

    CAS  PubMed  Google Scholar 

  69. Krawczak, M. & Cooper, D. N. Gene deletions causing human genetic disease: mechanisms of mutagenesis and the role of the local DNA environment. Hum. Genet. 86, 425–441 (1991).

    CAS  PubMed  Google Scholar 

  70. Lakich, D., Kazazian, H. H., Antonarakis, S. E. & Gitschier, J. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nature Genet. 5, 236–241 (1993).

    CAS  PubMed  Google Scholar 

  71. Rossiter, J. P. et al. Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells. Hum. Mol. Genet. 3, 1035–1039 (1994).

    CAS  PubMed  Google Scholar 

  72. Blennow, E. et al. Fifty probands with extra structurally abnormal chromosomes characterized by fluorescence in situ hybridization. Am. J. Med. Genet. 55, 85–94 (1995).

    CAS  PubMed  Google Scholar 

  73. Cheng, E. Y. & Gartler, S. M. A fluorescent in situ hybridization analysis of X chromosome pairing in early human female meiosis. Hum. Genet. 94, 389–394 (1994).

    CAS  PubMed  Google Scholar 

  74. Huang, B. et al. Refined molecular characterization of the breakpoints in small inv dup(15) chromosomes. Hum. Genet. 99, 11–17 (1997).

    CAS  PubMed  Google Scholar 

  75. Wandstrat, A. E., Leana-Cox, J., Jenkins, L. & Schwartz, S. Molecular cytogenetic evidence for a common breakpoint in the largest inverted duplications of chromosome 15. Am. J. Hum. Genet. 62, 925–936 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Wandstrat, A. E. & Schwartz, S. Isolation and molecular analysis of inv dup(15) and construction of a physical map of a common breakpoint in order to elucidate their mechanism of formation. Chromosoma 109, 498–505 (2000).

    CAS  PubMed  Google Scholar 

  77. Christian, S. L. et al. Molecular characterization of two proximal deletion breakpoint regions in both Prader–Willi and Angelman syndrome patients. Am. J. Hum. Genet. 57, 40–48 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Footz, T. K. et al. Analysis of the cat eye syndrome critical region in humans and the region of conserved synteny in mice: a search for candidate genes at or near the human chromosome 22 pericentromere. Genome Res. 11, 1053–1070 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Page, S. L., Shin, J. C., Han, J. Y., Choo, K. H. & Shaffer, L. G. Breakpoint diversity illustrates distinct mechanisms for Robertsonian translocation formation. Hum. Mol. Genet. 5, 1279–1288 (1996).

    CAS  PubMed  Google Scholar 

  80. De La Chapelle, A., Herva, R., Koivisto, M. & Aula, P. A deletion in chromosome 22 can cause DiGeorge syndrome. Hum. Genet. 57, 253–256 (1981).

    CAS  PubMed  Google Scholar 

  81. Li, M. et al. Clustering of DiGeorge/velocardiofacial-associated translocations suggestive of a translocation 'hot spot'. Am. J. Hum. Genet. 57, A119 (1995).

    Google Scholar 

  82. Rhodes, C. H. et al. Molecular studies of an ependymoma-associated constitutional t(1;22)(p22;q11.2). Cytogenet. Cell Genet. 78, 247–252 (1997).

    CAS  PubMed  Google Scholar 

  83. Lopes, J. et al. Sex-dependent rearrangements resulting in CMT1A and HNPP. Nature Genet. 17, 136–137 (1997).

    CAS  PubMed  Google Scholar 

  84. Palau, F. et al. Origin of the de novo duplication in Charcot–Marie–Tooth disease type 1A: unequal nonsister chromatid exchange during spermatogenesis. Hum. Mol. Genet. 2, 2031–2035 (1993).

    CAS  PubMed  Google Scholar 

  85. Lopes, J. et al. Fine mapping of de novo CMT1A and HNPP rearrangements within CMT1A-REPs evidences two distinct sex-dependent mechanisms and candidate sequences involved in recombination. Hum. Mol. Genet. 7, 141–148 (1998).

    CAS  PubMed  Google Scholar 

  86. Saitta, S. C. et al. The 22q11.2 deletion: parental origin and meiotic mechanism. Am. J. Hum. Genet. 67, S163 (2000).

  87. Bondeson, M. L. et al. Inversion of the IDS gene resulting from recombination with IDS-related sequences is a common cause of the Hunter syndrome. Hum. Mol. Genet. 4, 615–621 (1995).

    CAS  PubMed  Google Scholar 

  88. Consevage, M. W. et al. Association of a mosaic chromosomal 22q11 deletion with hypoplastic left heart syndrome. Am. J. Cardiol. 77, 1023–1025 (1996).

    CAS  PubMed  Google Scholar 

  89. Kasprzak, L. et al. Deletion of 22q11 in two brothers with different phenotype. Am. J. Med. Genet. 75, 288–291 (1998).

    CAS  PubMed  Google Scholar 

  90. Anguiano, A. et al. Report of a case with manifestations of DiGeorge/velocardiofacial syndrome (VCFS) and microdeletion 22q11.2 mosaicism. Am. J. Hum. Genet. 67, S142 (2000).

    Google Scholar 

  91. Spinner, N. B. & Emanuel, B. S. in Principles and Practice of Medical Genetics Vol. 1 (eds Rimoin, D. L., Conner, J. M., Pyeritz, R. E. & Emery, A. E. H.) 999–1025 (Churchill Livingstone, 1996).

    Google Scholar 

Download references

Acknowledgements

The authors acknowledge support for their efforts from the National Institutes of Health. B.S.E. gratefully acknowledges the support provided by the Charles E. H. Upham chair in Pediatrics. T.H.S. is partially supported by funds from the Florence R. C. Murray Foundation.

Author information

Authors and Affiliations

  1. Division of Human Genetics and Molecular Biology, 1002 Abramson Research Center, The Children's Hospital of Philadelphia, 3516 Civic Center Blvd, Philadelphia, 19104, Pennsylvania, USA

    Beverly S. Emanuel & Tamim H. Shaikh

  2. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA

    Beverly S. Emanuel

Authors
  1. Beverly S. Emanuel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tamim H. Shaikh
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

DATABASES

LocusLink 

ELN

emerin

HERC2

IDS

NF1

PMP22

STS

 OMIM 

Angelman syndrome

cat eye syndrome

Charcot–Marie–Tooth disease type 1A

DiGeorge syndrome

Emery–Dreifuss muscular dystrophy

haemophilia A

hereditary neuropathy with liability to pressure palsies

Hunter syndrome

neurofibromatosis type 1

Prader–Willi syndrome

Smith–Magenis syndrome

velocardiofacial syndrome

Williams–Beuren syndrome

Glossary

IMPRINTING

A genetic mechanism by which genes are selectively expressed from the maternal or paternal homologue of a chromosome.

UNIPARENTAL DISOMY

A condition whereby an individual or embryo carries two chromosomes inherited from the same parent.

STENOSIS

The blocking of a blood vessel that can be cleared by mechanical disruption.

CONSTITUTIONAL TRANSLOCATION

A rearrangement between two chromosomes that occurs in the parental germ line or very early in embryonic development, such that every cell in the body contains the translocated chromosomes.

ICHTHYOSIS

A genetic disorder that causes the patient to have scaly skin.

CONSERVED SYNTENY

The occurrence of genomic collinearity between homologous genes in different organisms.

HAPLOTYPE

An experimentally determined profile of genetic markers present on a single chromosome of any given individual.

PULSED-FIELD GEL ELECTROPHORESIS

An electrophoretic technique used to separate large fragments of DNA (>20 kb and up to 10 Mb) on an agarose gel by periodically changing the orientation of the electric field applied to the gel.

BISATELLITED

A chromosome that contains two copies of the satellited acrocentric short arm, often as a result of an inverted duplication. It is usually present as a supernumerary marker chromosome in a cell.

ACROCENTRIC

This refers to a chromosome the centromere of which lies very close to one end, such that one arm of the chromosome is much larger than the other.

ACENTRIC

A chromosome or chromosomal fragment that lacks a centromere.

PARACENTRIC INVERSION

An inversion of a chromosomal segment that does not contain the centromere.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Emanuel, B., Shaikh, T. Segmental duplications: an 'expanding' role in genomic instability and disease. Nat Rev Genet 2, 791–800 (2001). https://doi.org/10.1038/35093500

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35093500

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing