1932

Abstract

Chromosomal abnormalities, including microdeletions and microduplications, have long been associated with abnormal developmental outcomes. Early discoveries relied on a common clinical presentation and the ability to detect chromosomal abnormalities by standard karyotype analysis or specific assays such as fluorescence in situ hybridization. Over the past decade, the development of novel genomic technologies has allowed more comprehensive, unbiased discovery of microdeletions and microduplications throughout the human genome. The ability to quickly interrogate large cohorts using chromosome microarrays and, more recently, next-generation sequencing has led to the rapid discovery of novel microdeletions and microduplications associated with disease, including very rare but clinically significant rearrangements. In addition, the observation that some microdeletions are associated with risk for several neurodevelopmental disorders contributes to our understanding of shared genetic susceptibility for such disorders. Here, we review current knowledge of microdeletion/duplication syndromes, with a particular focus on recurrent rearrangement syndromes.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genom-091212-153408
2014-08-31
2024-06-20
Loading full text...

Full text loading...

/deliver/fulltext/genom/15/1/annurev-genom-091212-153408.html?itemId=/content/journals/10.1146/annurev-genom-091212-153408&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 1000 Genomes Proj. Consort 2010. A map of human genome variation from population-scale sequencing. Nature 467:1061–73 [Google Scholar]
  2. 2. 1000 Genomes Proj. Consort 2012. An integrated map of genetic variation from 1,092 human genomes. Nature 491:56–65 [Google Scholar]
  3. Albers CA, Paul DS, Schulze H, Freson K, Stephens JC. 3.  et al. 2012. Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome. Nat. Genet. 44:435–39 [Google Scholar]
  4. Amos-Landgraf JM, Ji Y, Gottlieb W, Depinet T, Wandstrat AE. 4.  et al. 1999. Chromosome breakage in the Prader-Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints. Am. J. Hum. Genet. 65:370–86 [Google Scholar]
  5. Andrieux J, Dubourg C, Rio M, Attie-Bitach T, Delaby E. 5.  et al. 2009. Genotype-phenotype correlation in four 15q24 deleted patients identified by array-CGH. Am. J. Med. Genet. A 149A:2813–19 [Google Scholar]
  6. Antonacci F, Kidd JM, Marques-Bonet T, Teague B, Ventura M. 6.  et al. 2010. A large and complex structural polymorphism at 16p12.1 underlies microdeletion disease risk. Nat. Genet. 42:745–50 [Google Scholar]
  7. Antonacci F, Kidd JM, Marques-Bonet T, Ventura M, Siswara P. 7.  et al. 2009. Characterization of six human disease-associated inversion polymorphisms. Hum. Mol. Genet. 18:2555–66 [Google Scholar]
  8. Aradhya S, Woffendin H, Jakins T, Bardaro T, Esposito T. 8.  et al. 2001. A recurrent deletion in the ubiquitously expressed NEMO (IKK-γ) gene accounts for the vast majority of incontinentia pigmenti mutations. Hum. Mol. Genet. 10:2171–79 [Google Scholar]
  9. Bailey JA, Gu Z, Clark RA, Reinert K, Samonte RV. 9.  et al. 2002. Recent segmental duplications in the human genome. Science 297:1003–7 [Google Scholar]
  10. Balciuniene J, Feng N, Iyadurai K, Hirsch B, Charnas L. 10.  et al. 2007. Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated with cognitive and behavioral abnormalities. Am. J. Hum. Genet. 80:938–47 [Google Scholar]
  11. Bassett AS, Marshall CR, Lionel AC, Chow EW, Scherer SW. 11.  et al. 2008. Copy number variations and risk for schizophrenia in 22q11.2 deletion syndrome. Hum. Mol. Genet. 17:4045–53 [Google Scholar]
  12. Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C. 12.  et al. 2010. PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 327:836–40 [Google Scholar]
  13. Bearden CE, Jawad AF, Lynch DR, Sokol S, Kanes SJ. 13.  et al. 2004. Effects of a functional COMT polymorphism on prefrontal cognitive function in patients with 22q11.2 deletion syndrome. Am. J. Psychiatry 161:1700–2 [Google Scholar]
  14. Ben-Shachar S, Lanpher B, German JR, Qasaymeh M, Potocki L. 14.  et al. 2009. Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J. Med. Genet. 46:382–88 [Google Scholar]
  15. Béna F, Gimelli S, Migliavacca E, Brun-Druc N, Buiting K. 15.  et al. 2010. A recurrent 14q32.2 microdeletion mediated by expanded TGG repeats. Hum. Med. Genet. 19:1967–73 [Google Scholar]
  16. Berg IL, Neumann R, Lam KW, Sarbajna S, Odenthal-Hesse L. 16.  et al. 2010. PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans. Nat. Genet. 42:859–63 [Google Scholar]
  17. Bochukova EG, Huang N, Keogh J, Henning E, Purmann C. 17.  et al. 2010. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature 463:666–70 [Google Scholar]
  18. Boettger LM, Handsaker RE, Zody MC, McCarroll SA. 18.  2012. Structural haplotypes and recent evolution of the human 17q21.31 region. Nat. Genet. 44:881–85 [Google Scholar]
  19. Bondeson ML, Dahl N, Malmgren H, Kleijer WJ, Tönnesen T, Carlberg BM. 19.  et al. 1995. Inversion of the IDS gene resulting from recombination with IDS-related sequences is a common cause of the Hunter syndrome. Hum. Med. Genet. 4:615–21 [Google Scholar]
  20. Borel C, Cheung F, Stewart H, Koolen DA, Phillips C. 20.  et al. 2012. Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders and chromosomal non-disjunction. Hum. Genet. 131:1519–24 [Google Scholar]
  21. Breckpot J, Thienpont B, Bauters M, Tranchevent LC, Gewillig M. 21.  et al. 2012. Congenital heart defects in a novel recurrent 22q11.2 deletion harboring the genes CRKL and MAPK1. Am. J. Med. Genet. A 158A:574–80 [Google Scholar]
  22. Brunetti-Pierri N, Berg JS, Scaglia F, Belmont J, Bacino CA. 22.  et al. 2008. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nat. Genet. 40:1466–71 [Google Scholar]
  23. Burrow AA, Williams LE, Pierce LC, Wang YH. 23.  2009. Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites. BMC Genomics 10:59 [Google Scholar]
  24. Butler MG, Meaney FJ, Palmer CG. 24.  1986. Clinical and cytogenetic survey of 39 individuals with Prader-Labhart-Willi syndrome. Am. J. Med. Genet. 23:793–809 [Google Scholar]
  25. Carvalho CM, Pehlivan D, Ramocki MB, Fang P, Alleva B. 25.  et al. 2013. Replicative mechanisms for CNV formation are error prone. Nat. Genet. 45:1319–26 [Google Scholar]
  26. Chance PF. 26.  2006. Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy. Neuromol. Med. 8:159–74 [Google Scholar]
  27. Chance PF, Alderson MK, Leppig KA, Lensch MW, Matsunami N. 27.  et al. 1993. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell 72:143–51 [Google Scholar]
  28. Chen C, Kolodner RD. 28.  1999. Gross chromosomal rearrangements in Saccharomyces cerevisiae replication and recombination defective mutants. Nat. Genet. 23:81–85 [Google Scholar]
  29. Chen KS, Manian P, Koeuth T, Potocki L, Zhao Q. 29.  et al. 1997. Homologous recombination of a flanking repeat gene cluster is a mechanism for a common contiguous gene deletion syndrome. Nat. Genet. 17:154–63 [Google Scholar]
  30. Christian SL, Brune CW, Sudi J, Kumar RA, Liu S. 30.  et al. 2008. Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biol. Psychiatry 63:1111–17 [Google Scholar]
  31. Ciccone R, Mattina T, Giorda R, Bonaglia MC, Rocchi M. 31.  et al. 2006. Inversion polymorphisms and non-contiguous terminal deletions: the cause and the (unpredicted) effect of our genome architecture. J. Med. Genet. 43:e19 [Google Scholar]
  32. Conrad DF, Bird C, Blackburne B, Lindsay S, Mamanova L. 32.  et al. 2010. Mutation spectrum revealed by breakpoint sequencing of human germline CNVs. Nat. Genet. 42:385–91 [Google Scholar]
  33. Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH. 33.  et al. 2011. A copy number variation morbidity map of developmental delay. Nat. Genet. 43:838–46 [Google Scholar]
  34. Cooper GM, Mefford HC. 34.  2011. Detection of copy number variation using SNP genotyping. Methods Mol. Biol. 767:243–52 [Google Scholar]
  35. Coulter ME, Miller DT, Harris DJ, Hawley P, Picker J. 35.  et al. 2011. Chromosomal microarray testing influences medical management. Genet. Med. 13:770–76 [Google Scholar]
  36. Cuscó I, Corominas R, Bayés M, Flores R, Rivera-Brugués N. 36.  et al. 2008. Copy number variation at the 7q11.23 segmental duplications is a susceptibility factor for the Williams-Beuren syndrome deletion. Genome Res. 18:683–94 [Google Scholar]
  37. Dathe K, Kjaer KW, Brehm A, Meinecke P, Nürnberg P. 37.  et al. 2009. Duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2. Am. J. Hum. Genet. 84:483–92 [Google Scholar]
  38. de Cid R, Riveira-Munoz E, Zeeuwen PLJM, Robarge J, Liao W. 38.  et al. 2009. Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat. Genet. 41:211–15 [Google Scholar]
  39. de Kovel CG, Trucks H, Helbig I, Mefford HC, Baker C. 39.  et al. 2010. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain 133:23–32 [Google Scholar]
  40. de Ligt J, Boone PM, Pfundt R, Vissers LE, Richmond T. 40.  et al. 2013. Detection of clinically relevant copy number variants with whole-exome sequencing. Hum. Mutat. 34:1439–48 [Google Scholar]
  41. de Vries BB, Pfundt R, Leisink M, Koolen DA, Vissers LE. 41.  et al. 2005. Diagnostic genome profiling in mental retardation. Am. J. Hum. Genet. 77:606–16 [Google Scholar]
  42. Dharmadhikari AV, Kang SH, Szafranski P, Person RE, Sampath S. 42.  et al. 2012. Small rare recurrent deletions and reciprocal duplications in 2q21.1, including brain-specific ARHGEF4 and GPR148. Hum. Med. Genet. 21:3345–55 [Google Scholar]
  43. Dibbens LM, Mullen S, Helbig I, Mefford HC, Bayly MA. 43.  et al. 2009. Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance. Hum. Mol. Genet. 18:3626–31 [Google Scholar]
  44. Dorschner MO, Sybert VP, Weaver M, Pletcher BA, Stephens K. 44.  et al. 2000. NF1 microdeletion breakpoints are clustered at flanking repetitive sequences. Hum. Med. Genet. 9:35–46 [Google Scholar]
  45. Edelmann L, Pandita RK, Spiteri E, Funke B, Goldberg R. 45.  et al. 1999. A common molecular basis for rearrangement disorders on chromosome 22q11. Hum. Mol. Genet. 8:1157–67 [Google Scholar]
  46. Edelmann L, Spiteri E, Koren K, Pulijaal V, Bialer MG. 46.  et al. 2001. AT-rich palindromes mediate the constitutional t(11;22) translocation. Am. J. Hum. Genet. 68:1–13 [Google Scholar]
  47. El-Hattab AW, Fang P, Jin W, Hughes JR, Gibson JB. 47.  et al. 2011. Int22h-1/int22h-2-mediated Xq28 rearrangements: intellectual disability associated with duplications and in utero male lethality with deletions. J. Med. Genet. 48:840–50 [Google Scholar]
  48. El-Hattab AW, Smolarek TA, Walker ME, Schorry EK, Immken LL. 48.  et al. 2009. Redefined genomic architecture in 15q24 directed by patient deletion/duplication breakpoint mapping.. Hum. Genet. 126:589–602 [Google Scholar]
  49. El-Hattab AW, Zhang F, Maxim R, Christensen KM, Ward JC. 49.  et al. 2010. Deletion and duplication of 15q24: molecular mechanisms and potential modification by additional copy number variants. Genet. Med. 12:573–86 [Google Scholar]
  50. Elia J, Gai X, Xie HM, Perin JC, Geiger E. 50.  et al. 2010. Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. Mol. Psychiatry 15:637–46 [Google Scholar]
  51. Elinati E, Kuentz P, Redin C, Jaber S, Vanden Meerschaut F. 51.  et al. 2012. Globozoospermia is mainly due to DPY19L2 deletion via non-allelic homologous recombination involving two recombination hotspots. Hum. Med. Genet. 21:3695–702 [Google Scholar]
  52. 52. ENCODE Proj. Consort 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74 [Google Scholar]
  53. Engreitz JM, Agarwala V, Mirny LA. 53.  2012. Three-dimensional genome architecture influences partner selection for chromosomal translocations in human disease. PLoS ONE 7:e44196 [Google Scholar]
  54. Erdogan F, Larsen LA, Zhang L, Tumer Z, Tommerup N. 54.  et al. 2008. High frequency of submicroscopic genomic aberrations detected by tiling path array comparative genome hybridisation in patients with isolated congenital heart disease. J. Med. Genet. 45:704–9 [Google Scholar]
  55. Fisher J, Upadhyaya M. 55.  1997. Molecular genetics of facioscapulohumeral muscular dystrophy (FSHD). Neuromuscul. Disord. 7:55–62 [Google Scholar]
  56. Fromer M, Moran JL, Chambert K, Banks E, Bergen SE. 56.  et al. 2012. Discovery and statistical genotyping of copy-number variation from whole-exome sequencing depth. Am. J. Hum. Genet. 91:597–60 [Google Scholar]
  57. Gimelli G, Pujana MA, Patricelli MG, Russo S, Giardino D. 57.  et al. 2003. Genomic inversions of human chromosome 15q11-q13 in mothers of Angelman syndrome patients with class II (BP2/3) deletions. Hum. Med. Genet. 12:849–58 [Google Scholar]
  58. Girirajan S, Dennis MY, Baker C, Malig M, Coe BP. 58.  et al. 2013. Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. Am. J. Hum. Genet. 92:221–37 [Google Scholar]
  59. Girirajan S, Rosenfeld JA, Coe BP, Parikh S, Friedman N. 59.  et al. 2012. Phenotypic heterogeneity of genomic disorders and rare copy-number variants. N. Engl. J. Med. 367:1321–31 [Google Scholar]
  60. Girirajan S, Rosenfeld JA, Cooper GM, Antonacci F, Siswara P. 60.  et al. 2010. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat. Genet. 42:203–9 [Google Scholar]
  61. Glessner JT, Wang K, Cai G, Korvatska O, Kim CE. 61.  et al. 2009. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 459:569–73 [Google Scholar]
  62. Goldlust IS, Hermetz KE, Catalano LM, Barfield RT, Cozad R. 62.  et al. 2013. Mouse model implicates GNB3 duplication in a childhood obesity syndrome. Proc. Natl. Acad. Sci. USA 110:14990–94 [Google Scholar]
  63. Harvard C, Strong E, Mercier E, Colnaghi R, Alcantara D. 63.  et al. 2011. Understanding the impact of 1q21.1 copy number variant. Orphanet J. Rare Dis. 6:54 [Google Scholar]
  64. Hastings PJ, Lupski JR, Rosenberg SM, Ira G. 64.  2009. Mechanisms of change in gene copy number. Nat. Rev. Genet. 10:551–64 [Google Scholar]
  65. Heinzen EL, Radtke RA, Urban TJ, Cavalleri GL, Depondt C. 65.  et al. 2010. Rare deletions at 16p13.11 predispose to a diverse spectrum of sporadic epilepsy syndromes. Am. J. Hum. Genet. 86:707–18 [Google Scholar]
  66. Helbig I, Mefford HC, Sharp AJ, Guipponi M, Fichera M. 66.  et al. 2009. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat. Genet. 41:160–62 [Google Scholar]
  67. Hormozdiari F, Hajirasouliha I, McPherson A, Eichler EE, Sahinalp SC. 67.  et al. 2011. Simultaneous structural variation discovery among multiple paired-end sequenced genomes. Genome Res. 21:2203–12 [Google Scholar]
  68. Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK. 68.  et al. 2004. Detection of large-scale variation in the human genome. Nat. Genet. 36:949–51 [Google Scholar]
  69. Ingason A, Rujescu D, Cichon S, Sigurdsson E, Sigmundsson T. 69.  et al. 2011. Copy number variations of chromosome 16p13.1 region associated with schizophrenia. Mol. Psychiatry 16:17–25 [Google Scholar]
  70. 70. Int. Schizophr. Consort 2008. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455:237–41 [Google Scholar]
  71. Itsara A, Cooper GM, Baker C, Girirajan S, Li J. 71.  et al. 2009. Population analysis of large copy number variants and hotspots of human genetic disease. Am. J. Hum. Genet. 84:148–61 [Google Scholar]
  72. Itsara A, Vissers LE, Steinberg KM, Meyer KJ, Zody MC. 72.  et al. 2012. Resolving the breakpoints of the 17q21.31 microdeletion syndrome with next-generation sequencing. Am. J. Hum. Genet. 90:599–613 [Google Scholar]
  73. Jehee FS, Krepischi-Santos AC, Rocha KM, Cavalcanti DP, Kim CA. 73.  et al. 2008. High frequency of submicroscopic chromosomal imbalances in patients with syndromic craniosynostosis detected by a combined approach of microsatellite segregation analysis, multiplex ligation-dependent probe amplification and array-based comparative genome hybridisation. J. Med. Genet. 45:447–50 [Google Scholar]
  74. Jensen TJ, Dzakula Z, Deciu C, van den Boom D, Ehrich M. 74.  et al. 2012. Detection of microdeletion 22q11.2 in a fetus by next-generation sequencing of maternal plasma. Clin. Chem. 58:1148–51 [Google Scholar]
  75. Jiang Z, Tang H, Ventura M, Cardone MF, Marques-Bonet T. 75.  et al. 2007. Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution. Nat. Genet. 39:1361–68 [Google Scholar]
  76. Johnson ME, Viggiano L, Bailey JA, Abdul-Rauf M, Goodwin G. 76.  et al. 2001. Positive selection of a gene family during the emergence of humans and African apes. Nature 413:514–19 [Google Scholar]
  77. Juyal RC, Kuwano A, Kondo I, Zara F, Baldini A. 77.  et al. 1996. Mosaicism for del(17)(p11.2p11.2) underlying the Smith-Magenis syndrome. Am. J. Med. Genet. 66:193–96 [Google Scholar]
  78. Kidd JM, Cooper GM, Donahue WF, Hayden HS, Sampas N. 78.  et al. 2008. Mapping and sequencing of structural variation from eight human genomes. Nature 453:56–64 [Google Scholar]
  79. Kidd JM, Graves T, Newman TL, Fulton R, Hayden HS. 79.  et al. 2010. A human genome structural variation sequencing resource reveals insights into mutational mechanisms. Cell 143:837–47 [Google Scholar]
  80. Kidd JM, Sampas N, Antonacci F, Graves T, Fulton R. 80.  et al. 2010. Characterization of missing human genome sequences and copy-number polymorphic insertions. Nat. Methods 7:365–71 [Google Scholar]
  81. Kiezun A, Pulit SL, Francioli LC, van Dijk F, Swertz M. 81.  et al. 2013. Deleterious alleles in the human genome are on average younger than neutral alleles of the same frequency. PLoS Genet. 9:e1003301 [Google Scholar]
  82. Kirov G, Grozeva D, Norton N, Ivanov D, Mantripragada KK. 82.  et al. 2009. Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. Hum. Med. Genet. 18:1497–503 [Google Scholar]
  83. Kirov G, Pocklington AJ, Holmans P, Ivanov D, Ikeda M. 83.  et al. 2012. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol. Psychiatry 17:142–53 [Google Scholar]
  84. Kitzman JO, Mackenzie AP, Adey A, Hiatt JB, Patwardhan RP. 84.  et al. 2011. Haplotype-resolved genome sequencing of a Gujarati Indian individual. Nat. Biotechnol. 29:59–63 [Google Scholar]
  85. Kitzman JO, Snyder MW, Ventura M, Lewis AP, Qiu R. 85.  et al. 2012. Noninvasive whole-genome sequencing of a human fetus. Sci. Transl. Med. 4:137ra76 [Google Scholar]
  86. Klopocki E, Graul-Neumann LM, Grieben U, Tönnies H, Ropers HH. 86.  et al. 2008. A further case of the recurrent 15q24 microdeletion syndrome, detected by array CGH. Eur. J. Pediatr. 167:903–8 [Google Scholar]
  87. Klopocki E, Schulze H, Strauss G, Ott CE, Hall J. 87.  et al. 2007. Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome. Am. J. Hum. Genet. 80:232–40 [Google Scholar]
  88. Koolen DA, Sharp AJ, Hurst JA, Firth HV, Knight SJ. 88.  et al. 2008. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. J. Med. Genet. 45:710–20 [Google Scholar]
  89. Koren A, Polak P, Nemesh J, Michaelson JJ, Sebat J. 89.  et al. 2012. Differential relationship of DNA replication timing to different forms of human mutation and variation. Am. J. Hum. Genet. 91:1033–40 [Google Scholar]
  90. Krumm N, O'Roak BJ, Karakoc E, Mohajeri K, Nelson B. 90.  et al. 2013. Transmission disequilibrium of small CNVs in simplex autism. Am. J. Hum. Genet. 93:595–606 [Google Scholar]
  91. Krumm N, Sudmant PH, Ko A, O'Roak BJ, Malig M. 91.  et al. 2012. Copy number variation detection and genotyping from exome sequence data. Genome Res. 22:1525–32 [Google Scholar]
  92. Kumar RA, KaraMohamed S, Sudi J, Conrad DF, Brune C. 92.  et al. 2008. Recurrent 16p11.2 microdeletions in autism. Hum. Mol. Genet. 17:628–38 [Google Scholar]
  93. Kurahashi H, Emanuel BS. 93.  2001. Long AT-rich palindromes and the constitutional t(11;22) breakpoint. Hum. Med. Genet. 10:2605–17 [Google Scholar]
  94. Kurahashi H, Shaikh T, Takata M, Toda T, Emanuel BS. 94.  et al. 2003. The constitutional t(17;22): another translocation mediated by palindromic AT-rich repeats. Am. J. Hum. Genet. 72:733–38 [Google Scholar]
  95. Lakich D, Kazazian HH Jr, Antonarakis SE, Gitschier J. 95.  1993. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nat. Genet. 5:236–41 [Google Scholar]
  96. Lako M, Ramsden S, Campbell RD, Strachan T. 96.  1999. Mutation screening in British 21-hydroxylase deficiency families and development of novel microsatellite based approaches to prenatal diagnosis. J. Med. Genet. 36:119–24 [Google Scholar]
  97. Levy D, Ronemus M, Yamrom B, Lee YH, Leotta A. 97.  et al. 2011. Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron 70:886–97 [Google Scholar]
  98. Li J, Lupat R, Amarasinghe KC, Thompson ER, Doyle MA. 98.  et al. 2012. CONTRA: copy number analysis for targeted resequencing. Bioinformatics 28:1307–13 [Google Scholar]
  99. Liehr T, Rautenstrauss B, Grehl H, Bathke KD, Ekici A. 99.  et al. 1996. Mosaicism for the Charcot-Marie-Tooth disease type 1A duplication suggests somatic reversion. Hum. Genet. 98:22–28 [Google Scholar]
  100. Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S. 100.  et al. 1992. A chimaeric 11β-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 355:262–65 [Google Scholar]
  101. Lindsay SJ, Khajavi M, Lupski JR, Hurles ME. 101.  2006. A chromosomal rearrangement hotspot can be identified from population genetic variation and is coincident with a hotspot for allelic recombination. Am. J. Hum. Genet. 79:890–902 [Google Scholar]
  102. Liu P, Lacaria M, Zhang F, Withers M, Hastings PJ. 102.  et al. 2011. Frequency of nonallelic homologous recombination is correlated with length of homology: evidence that ectopic synapsis precedes ectopic crossing-over. Am. J. Hum. Genet. 89:580–88 [Google Scholar]
  103. Locke DP, Sharp AJ, McCarroll SA, McGrath SD, Newman TL. 103.  et al. 2006. Linkage disequilibrium and heritability of copy-number polymorphisms within duplicated regions of the human genome. Am. J. Hum. Genet. 79:275–90 [Google Scholar]
  104. Lupski JR. 104.  1998. Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet. 14:417–22 [Google Scholar]
  105. Lupski JR, de Oca-Luna RM, Slaugenhaupt S, Pentao L, Guzzetta V. 105.  et al. 1991. DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell 66:219–32 [Google Scholar]
  106. Magoulas PL, El-Hattab AW. 106.  2012. Chromosome 15q24 microdeletion syndrome. Orphanet J. Rare Dis. 7:2 [Google Scholar]
  107. Marques-Bonet T, Kidd JM, Ventura M, Graves TA, Cheng Z. 107.  et al. 2009. A burst of segmental duplications in the genome of the African great ape ancestor. Nature 457:877–81 [Google Scholar]
  108. Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L. 108.  et al. 2008. Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet. 82:477–88 [Google Scholar]
  109. McDonald-McGinn DM, Fahiminiya S, Revil T, Nowakowska BA, Suhl J. 109.  et al. 2013. Hemizygous mutations in SNAP29 unmask autosomal recessive conditions and contribute to atypical findings in patients with 22q11.2DS. J. Med. Genet. 50:80–90 [Google Scholar]
  110. McTaggart KE, Budarf ML, Driscoll DA, Emanuel BS, Ferreira P. 110.  et al. 1998. Cat eye syndrome chromosome breakpoint clustering: identification of two intervals also associated with 22q11 deletion syndrome breakpoints. Cytogenet. Cell Genet. 81:222–28 [Google Scholar]
  111. Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullmann R. 111.  et al. 2007. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am. J. Hum. Genet. 81:1057–69 [Google Scholar]
  112. Mefford HC, Cooper GM, Zerr T, Smith JD, Baker C. 112.  et al. 2009. A method for rapid, targeted CNV genotyping identifies rare variants associated with neurocognitive disease. Genome Res. 19:1579–85 [Google Scholar]
  113. Mefford HC, Eichler EE. 113.  2009. Duplication hotspots, rare genomic disorders, and common disease. Curr. Opin. Genet. Dev. 19:196–204 [Google Scholar]
  114. Mefford HC, Muhle H, Ostertag P, von Spiczak S, Buysse K. 114.  et al. 2010. Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. PLoS Genet. 6:e1000962 [Google Scholar]
  115. Mefford HC, Rosenfeld JA, Shur N, Slavotinek AM, Cox VA. 115.  et al. 2012. Further clinical and molecular delineation of the 15q24 microdeletion syndrome. J. Med. Genet. 49:110–18 [Google Scholar]
  116. Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z. 116.  et al. 2008. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N. Engl. J. Med. 359:1685–99 [Google Scholar]
  117. Mefford HC, Yendle SC, Hsu C, Cook J, Geraghty E. 117.  et al. 2011. Rare copy number variants are an important cause of epileptic encephalopathies. Ann. Neurol. 70:974–85 [Google Scholar]
  118. Menko FH, Kneepkens CM, de Leeuw N, Peeters EA, Van Maldergem L. 118.  et al. 2008. Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes. Clin. Genet. 74:145–54 [Google Scholar]
  119. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR. 119.  et al. 2010. Consensus statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am. J. Hum. Genet. 86:749–64 [Google Scholar]
  120. Miller DT, Shen Y, Weiss LA, Korn J, Anselm I. 120.  et al. 2009. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J. Med. Genet. 46:242–48 [Google Scholar]
  121. Mills RE, Walter K, Stewart C, Handsaker RE, Chen K. 121.  et al. 2011. Mapping copy number variation by population-scale genome sequencing. Nature 470:59–65 [Google Scholar]
  122. Molina O, Blanco J, Vidal F. 122.  2010. Deletions and duplications of the 15q11-q13 region in spermatozoa from Prader-Willi syndrome fathers. Mol. Hum. Reprod. 16:320–28 [Google Scholar]
  123. Moreno-De-Luca D, Mulle JG, Kaminsky EB, Sanders SJ, Myers SM. 123.  et al. 2010. Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am. J. Hum. Genet. 87:618–30 [Google Scholar]
  124. Moreno-De-Luca D, Sanders SJ, Willsey AJ, Mulle JG, Lowe JK. 124.  et al. 2013. Using large clinical data sets to infer pathogenicity for rare copy number variants in autism cohorts. Mol. Psychiatry 18:1090–95 [Google Scholar]
  125. Nakashima S, Watanabe Y, Okada J, Ono H, Nagata E. 125.  et al. 2013. Critical role of Yp inversion in PRKX/PRKY-mediated Xp;Yp translocation in a patient with 45,X testicular disorder of sex development. Endocr. J. 60:1329–34 [Google Scholar]
  126. Nathans J, Piantanida TP, Eddy RL, Shows TB, Hogness DS. 126.  et al. 1986. Molecular genetics of inherited variation in human color vision. Science 232:203–10 [Google Scholar]
  127. Need AC, Ge D, Weale ME, Maia J, Feng S. 127.  et al. 2009. A genome-wide investigation of SNPs and CNVs in schizophrenia. PLoS Genet. 5:e1000373 [Google Scholar]
  128. O'Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N. 128.  et al. 2012. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 485:246–50 [Google Scholar]
  129. Ou Z, Stankiewicz P, Xia Z, Breman AM, Dawson B. 129.  et al. 2011. Observation and prediction of recurrent human translocations mediated by NAHR between nonhomologous chromosomes. Genome Res. 21:33–46 [Google Scholar]
  130. Palumbo O, Palumbo P, Palladino T, Stallone R, Miroballo M. 130.  et al. 2012. An emerging phenotype of interstitial 15q25.2 microdeletions: clinical report and review. Am. J. Med. Genet. A 158A:3182–89 [Google Scholar]
  131. Pérez Jurado LA, Peoples R, Kaplan P, Hamel BC, Francke U. 131.  et al. 1996. Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth. Am. J. Hum. Genet. 59:781–92 [Google Scholar]
  132. Peters D, Chu T, Yatsenko SA, Hendrix N, Hogge WA. 132.  et al. 2011. Noninvasive prenatal diagnosis of a fetal microdeletion syndrome. N. Engl. J. Med. 365:1847–48 [Google Scholar]
  133. Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D. 133.  et al. 2010. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466:368–72 [Google Scholar]
  134. Plagnol V, Curtis J, Epstein M, Mok KY, Stebbings E. 134.  et al. 2012. A robust model for read count data in exome sequencing experiments and implications for copy number variant calling. Bioinformatics 28:2747–54 [Google Scholar]
  135. Popesco MC, MacLaren EJ, Hopkins J, Dumas L, Cox M. 135.  et al. 2006. Human lineage-specific amplification, selection, and neuronal expression of DUF1220 domains. Science 313:1304–7 [Google Scholar]
  136. Poultney CS, Goldberg AP, Drapeau E, Kou Y, Harony-Nicolas H. 136.  et al. 2013. Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder. Am. J. Hum. Genet. 93:607–19 [Google Scholar]
  137. Prado-Martinez J, Sudmant PH, Kidd JM, Li H, Kelley JL. 137.  et al. 2013. Great ape genetic diversity and population history. Nature 499:471–75 [Google Scholar]
  138. Putnam CD, Hayes TK, Kolodner RD. 138.  2009. Specific pathways prevent duplication-mediated genome rearrangements. Nature 460:984–89 [Google Scholar]
  139. Ramocki MB, Bartnik M, Szafranski P, Kołodziejska KE, Xia Z. 139.  et al. 2010. Recurrent distal 7q11.23 deletion including HIP1 and YWHAG identified in patients with intellectual disabilities, epilepsy, and neurobehavioral problems. Am. J. Hum. Genet. 87:857–65 [Google Scholar]
  140. Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH. 140.  et al. 2006. Global variation in copy number in the human genome. Nature 444:444–54 [Google Scholar]
  141. Richards AA, Santos LJ, Nichols HA, Crider BP, Elder FF. 141.  et al. 2008. Cryptic chromosomal abnormalities identified in children with congenital heart disease. Pediatr. Res. 64:358–63 [Google Scholar]
  142. Riggs ER, Wain KE, Riethmaier D, Smith-Packard B, Faucett WA. 142.  et al. 2013. Chromosomal microarray impacts clinical management. Clin. Genet. 85:147–53 [Google Scholar]
  143. Rosenfeld JA, Mason CE, Smith TM. 143.  2012. Limitations of the human reference genome for personalized genomics. PLoS ONE 7e40294 [Google Scholar]
  144. Rudd MK, Keene J, Bunke B, Kaminsky EB, Adam MP. 144.  et al. 2009. Segmental duplications mediate novel, clinically relevant chromosome rearrangements. Hum. Med. Genet. 18:2957–62 [Google Scholar]
  145. Sagoo G, Butterworth A, Sanderson S, Shaw-Smith C, Higgins J. 145.  et al. 2009. Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects. Genet. Med. 11:139–46 [Google Scholar]
  146. Sanders SJ, Ercan-Sencicek AG, Hus V, Luo R, Murtha MT. 146.  et al. 2011. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70:863–85 [Google Scholar]
  147. Sathirapongsasuti JF, Lee H, Horst BA, Brunner G, Cochran AJ. 147.  et al. 2011. Exome sequencing-based copy-number variation and loss of heterozygosity detection: ExomeCNV. Bioinformatics 27:2648–54 [Google Scholar]
  148. Saunier S, Calado J, Benessy F, Silbermann F, Heilig R. 148.  et al. 2000. Characterization of the NPHP1 locus: mutational mechanism involved in deletions in familial juvenile nephronophthisis. Am. J. Hum. Genet. 66:778–89 [Google Scholar]
  149. Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B. 149.  et al. 2010. Complete Khoisan and Bantu genomes from southern Africa. Nature 463:943–47 [Google Scholar]
  150. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C. 150.  et al. 2007. Strong association of de novo copy number mutations with autism. Science 316:445–49 [Google Scholar]
  151. Sebat J, Lakshmi B, Troge J, Alexander J, Young J. 151.  et al. 2004. Large-scale copy number polymorphism in the human genome. Science 305:525–28 [Google Scholar]
  152. Shaffer LG, Kashork CD, Saleki R, Rorem E, Sundin K. 152.  et al. 2006. Targeted genomic microarray analysis for identification of chromosome abnormalities in 1500 consecutive clinical cases. J. Pediatr. 149:98–102 [Google Scholar]
  153. Shaikh TH, Kurahashi H, Saitta SC, O'Hare AM, Hu P. 153.  et al. 2000. Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis. Hum. Med. Genet. 9:489–501 [Google Scholar]
  154. Sharp AJ. 154.  2009. Emerging themes and new challenges in defining the role of structural variation in human disease. Hum. Mutat. 30:135–44 [Google Scholar]
  155. Sharp AJ, Hansen S, Selzer RR, Cheng Z, Regan R. 155.  et al. 2006. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nat. Genet. 38:1038–42 [Google Scholar]
  156. Sharp AJ, Locke DP, McGrath SD, Cheng Z, Bailey JA. 156.  et al. 2005. Segmental duplications and copy-number variation in the human genome. Am. J. Hum. Genet. 77:78–88 [Google Scholar]
  157. Sharp AJ, Mefford HC, Li K, Baker C, Skinner C. 157.  et al. 2008. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat. Genet. 40:322–28 [Google Scholar]
  158. Sharp AJ, Selzer RR, Veltman JA, Gimelli S, Gimelli G. 158.  et al. 2007. Characterization of a recurrent 15q24 microdeletion syndrome. Hum. Mol. Genet. 16:567–72 [Google Scholar]
  159. Shaw-Smith C, Pittman AM, Willatt L, Martin H, Rickman L. 159.  et al. 2006. Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability. Nat. Genet. 38:1032–37 [Google Scholar]
  160. Shirakawa T, Fujisawa M, Kanzaki M, Okada H, Arakawa S. 160.  et al. 1997. Y chromosome (Yq11) microdeletions in idiopathic azoospermia. Int. J. Urol. 4:198–201 [Google Scholar]
  161. Shoichet SA, Waibel S, Endruhn S, Sperfeld AD, Vorwerk B. 161.  et al. 2009. Identification of candidate genes for sporadic amyotrophic lateral sclerosis by array comparative genomic hybridization. Amyotroph. Lateral Scler. 10:162–69 [Google Scholar]
  162. Smith S, Hwang JY, Banerjee S, Majeed A, Gupta A. 162.  et al. 2004. Mutator genes for suppression of gross chromosomal rearrangements identified by a genome-wide screening in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 101:9039–44 [Google Scholar]
  163. Sparrow DB, Chapman G, Smith AJ, Mattar MZ, Major JA. 163.  et al. 2012. A mechanism for gene-environment interaction in the etiology of congenital scoliosis. Cell 149:295–306 [Google Scholar]
  164. Srinivasan A, Bianchi DW, Huang H, Sehnert AJ, Rava RP. 164.  et al. 2013. Noninvasive detection of fetal subchromosome abnormalities via deep sequencing of maternal plasma. Am. J. Hum. Genet. 92:167–76 [Google Scholar]
  165. Stankiewicz P, Kulkarni S, Dharmadhikari AV, Sampath S, Bhatt SS. 165.  et al. 2012. Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats. Hum. Mutat. 33:165–79 [Google Scholar]
  166. Stankiewicz P, Lupski JR. 166.  2002. Genome architecture, rearrangements and genomic disorders. Trends Genet. 18:74–82 [Google Scholar]
  167. Stefansson H, Helgason A, Thorleifsson G, Steinthorsdottir V, Masson G. 167.  et al. 2005. A common inversion under selection in Europeans. Nat. Genet. 37:129–37 [Google Scholar]
  168. Stefansson H, Rujescu D, Cichon S, Pietilainen OP, Ingason A. 168.  et al. 2008. Large recurrent microdeletions associated with schizophrenia. Nature 455:232–36 [Google Scholar]
  169. Steinberg KM, Antonacci F, Sudmant PH, Kidd JM, Campbell CD. 169.  et al. 2012. Structural diversity and African origin of the 17q21.31 inversion polymorphism. Nat. Genet. 44:872–80 [Google Scholar]
  170. Stone JL, O'Donovan MC, Gurling H, Kirov GK, Blackwood DH. 170.  et al. 2008. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455:237–41 [Google Scholar]
  171. Sudmant PH, Huddleston J, Catacchio CR, Malig M, Hillier LW. 171.  et al. 2013. Evolution and diversity of copy number variation in the great ape lineage. Genome Res. 23:1373–82 [Google Scholar]
  172. Sudmant PH, Kitzman JO, Antonacci F, Alkan C, Malig M. 172.  et al. 2010. Diversity of human copy number variation and multicopy genes. Science 330:641–46 [Google Scholar]
  173. Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J. 173.  et al. 2007. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat. Genet. 39:319–28 [Google Scholar]
  174. Tatton-Brown K, Douglas J, Coleman K, Baujat G, Chandler K. 174.  et al. 2005. Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome. J. Med. Genet. 42:307–13 [Google Scholar]
  175. Turner DJ, Miretti M, Rajan D, Fiegler H, Carter NP. 175.  et al. 2008. Germline rates of de novo meiotic deletions and duplications causing several genomic disorders. Nat. Genet. 40:90–95 [Google Scholar]
  176. Tuzun E, Sharp AJ, Bailey JA, Kaul R, Morrison VA. 176.  et al. 2005. Fine-scale structural variation of the human genome. Nat. Genet. 37:727–32 [Google Scholar]
  177. van Bon BW, Mefford HC, Menten B, Koolen DA, Sharp AJ. 177.  et al. 2009. Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome. J. Med. Genet. 46:511–23 [Google Scholar]
  178. van der Zwaag B, Staal WG, Hochstenbach R, Poot M, Spierenburg HA. 178.  et al. 2010. A co-segregating microduplication of chromosome 15q11.2 pinpoints two risk genes for autism spectrum disorder. Am. J. Med. Genet. B 153B:960–66 [Google Scholar]
  179. Van Esch H, Backx L, Pijkels E, Fryns JP. 179.  2009. Congenital diaphragmatic hernia is part of the new 15q24 microdeletion syndrome. Eur. J. Med. Genet. 52:153–56 [Google Scholar]
  180. Van Esch H, Hollanders K, Badisco L, Melotte C, Van Hummelen P. 180.  et al. 2005. Deletion of VCX-A due to NAHR plays a major role in the occurrence of mental retardation in patients with X-linked ichthyosis. Hum. Med. Genet. 14:1795–803 [Google Scholar]
  181. Vassos E, Collier DA, Holden S, Patch C, Rujescu D. 181.  et al. 2010. Penetrance for copy number variants associated with schizophrenia. Hum. Med. Genet. 19:3477–81 [Google Scholar]
  182. Veltman JA, Fridlyand J, Pejavar S, Olshen AB, Korkola JE. 182.  et al. 2003. Array-based comparative genomic hybridization for genome-wide screening of DNA copy number in bladder tumors. Cancer Res. 63:2872–80 [Google Scholar]
  183. Vissers LE, de Vries BB, Veltman JA. 183.  2010. Genomic microarrays in mental retardation: from copy number variation to gene, from research to diagnosis. J. Med. Genet. 47:289–97 [Google Scholar]
  184. Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB. 184.  et al. 2008. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320:539–43 [Google Scholar]
  185. Wang J, Wang W, Li R, Li Y, Tian G. 185.  et al. 2008. The diploid genome sequence of an Asian individual. Nature 456:60–65 [Google Scholar]
  186. Wat MJ, Enciso VB, Wiszniewski W, Resnick T, Bader P. 186.  et al. 2010. Recurrent microdeletions of 15q25.2 are associated with increased risk of congenital diaphragmatic hernia, cognitive deficits and possibly Diamond–Blackfan anaemia. J. Med. Genet. 47:777–81 [Google Scholar]
  187. Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT. 187.  et al. 2008. Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med. 358:667–75 [Google Scholar]
  188. Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L. 188.  et al. 2008. The complete genome of an individual by massively parallel DNA sequencing. Nature 452:872–76 [Google Scholar]
  189. Willatt L, Cox J, Barber J, Cabanas ED, Collins A. 189.  et al. 2005. 3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome. Am. J. Hum. Genet. 77:154–60 [Google Scholar]
  190. Williams NM, Zaharieva I, Martin A, Langley K, Mantripragada K. 190.  et al. 2010. Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet 376:1401–8 [Google Scholar]
  191. Winokur ST, Bengtsson U, Feddersen J, Mathews KD, Weiffenbach B. 191.  et al. 1994. The DNA rearrangement associated with facioscapulohumeral muscular dystrophy involves a heterochromatin-associated repetitive element: implications for a role of chromatin structure in the pathogenesis of the disease. Chromosome Res. 2:225–34 [Google Scholar]
  192. Xi R, Hadjipanayis AG, Luquette LJ, Kim TM, Lee E. 192.  et al. 2011. Copy number variation detection in whole-genome sequencing data using the Bayesian information criterion. Proc. Natl. Acad. Sci. USA 108:E1128–36 [Google Scholar]
  193. Yoon S, Xuan Z, Makarov V, Ye K, Sebat J. 193.  et al. 2009. Sensitive and accurate detection of copy number variants using read depth of coverage. Genome Res. 19:1586–92 [Google Scholar]
  194. Zhang F, Khajavi M, Connolly AM, Towne CF, Batish SD. 194.  et al. 2009. The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans. Nat. Genet. 41:849–53 [Google Scholar]
  195. Zhang Y, McCord RP, Ho YJ, Lajoie BR, Hildebrand DG. 195.  et al. 2012. Spatial organization of the mouse genome and its role in recurrent chromosomal translocations. Cell 148:908–21 [Google Scholar]
  196. Zhu M, Need AC, Han Y, Ge D, Maia JM. 196.  et al. 2012. Using ERDS to infer copy-number variants in high-coverage genomes. Am. J. Hum. Genet. 91:408–21 [Google Scholar]
  197. Zimran A, Sorge J, Gross E, Kubitz M, West C. 197.  et al. 1990. A glucocerebrosidase fusion gene in Gaucher disease. Implications for the molecular anatomy, pathogenesis, and diagnosis of this disorder. J. Clin. Investig. 85:219–22 [Google Scholar]
  198. Zody MC, Jiang Z, Fung HC, Antonacci F, Hillier LW. 198.  et al. 2008. Evolutionary toggling of the MAPT 17q21.31 inversion region. Nat. Genet. 40:1076–83 [Google Scholar]
  199. Zori RT, Lupski JR, Heju Z, Greenberg F, Killian JM. 199.  et al. 1993. Clinical, cytogenetic, and molecular evidence for an infant with Smith-Magenis syndrome born from a mother having a mosaic 17p11.2p12 deletion. Am. J. Med. Genet. 47:504–11 [Google Scholar]
/content/journals/10.1146/annurev-genom-091212-153408
Loading
/content/journals/10.1146/annurev-genom-091212-153408
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error