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Cited by 27Genomic variations and chromosomal abnormalitiesGenome Rearrangement AlgorithmsChromosomal and Genetic Variations

A recurrent translocation is mediated by homologous recombination between HERV-H elements

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Hermetz, Karen E, Surti, Urvashi, Cody, Jannine D, Rudd, M Katharine·2012·Molecular Cytogenetics
DOI 10.1186/1755-8166-5-6PMC PMC3292815
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Abstract

BACKGROUND: Chromosome rearrangements are caused by many mutational mechanisms; of these, recurrent rearrangements can be particularly informative for teasing apart DNA sequence-specific factors. Some recurrent translocations are mediated by homologous recombination between large blocks of segmental duplications on different chromosomes. Here we describe a recurrent unbalanced translocation casued by recombination between shorter homologous regions on chromosomes 4 and 18 in two unrelated children with intellectual disability. RESULTS: Array CGH resolved the breakpoints of the 6.97-Megabase (Mb) loss of 18q and the 7.30-Mb gain of 4q. Sequencing across the translocation breakpoints revealed that both translocations occurred between 92%-identical human endogenous retrovirus (HERV) elements in the same orientation on chromosomes 4 and 18. In addition, we find sequence variation in the chromosome 4 HERV that makes one allele more like the chromosome 18 HERV. CONCLUSIONS: Homologous recombination between HERVs on the same chromosome is known to cause chromosome deletions, but this is the first report of interchromosomal HERV-HERV recombination leading to a translocation. It is possible that normal sequence variation in substrates of non-allelic homologous recombination (NAHR) affects the alignment of recombining segments and influences the propensity to chromosome rearrangement.

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  • Loss of the eyes absent 1 (EYA1) gene in branchio-oto-renal syndrome and recurrent unbalanced translocations leading to intellectual disability result from recombination between HERV-H copies.

    “Also, loss of the eyes absent 1 (EYA1) gene in branchio-oto-renal syndrome and recurrent unbalanced translocations leading to intellectual disability have been shown to result from recombination between HERV-H copies 23,24.”

    From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [23]

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Research works printed but not linked: 44

  1. Shaffer LG Kashork CD Saleki R Rorem E Sundin K Ballif BC Bejjani BA Targeted genomic microarray analysis for identification of chromosome abnormalities in 1500 consecutive clinical cases J Pediatr 2006 149 98 102 10.1016/j.jpeds.2006.02.006 16860135 · DOI
  2. Cooper GM Coe BP Girirajan S Rosenfeld JA Vu TH Baker C Williams C Stalker H Hamid R Hannig V A copy number variation morbidity map of developmental delay Nat Genet 2011 43 838 846 10.1038/ng.909 21841781 PMC3171215 · DOI · Paper page
  3. Kaminsky EB Kaul V Paschall J Church DM Bunke B Kunig D Moreno-De-Luca D Moreno-De-Luca A Mulle JG Warren ST An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities Genetics in medicine 2011 13 777 784 10.1097/GIM.0b013e31822c79f9 21844811 PMC3661946 · DOI · Paper page
  4. Hastings PJ Lupski JR Rosenberg SM Ira G Mechanisms of change in gene copy number Nat Rev Genet 2009 10 551 564 19597530 PMC2864001
  5. Vissers LE Bhatt SS Janssen IM Xia Z Lalani SR Pfundt R Derwinska K de Vries BB Gilissen C Hoischen A Rare pathogenic microdeletions and tandem duplications are microhomology-mediated and stimulated by local genomic architecture Hum Mol Genet 2009 18 3579 3593 10.1093/hmg/ddp306 19578123 · DOI
  6. Luo Y Hermetz KE Jackson JM Mulle JG Dodd A Tsuchiya KD Ballif BC Shaffer LG Cody JD Ledbetter DH Diverse mutational mechanisms cause pathogenic subtelomeric rearrangements Hum Mol Genet 2011 20 3769 3778 10.1093/hmg/ddr293 21729882 PMC3168286 · DOI
  7. Sharp AJ Hansen S Selzer RR Cheng Z Regan R Hurst JA Stewart H Price SM Blair E Hennekam RC Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome Nat Genet 2006 38 1038 1042 10.1038/ng1862 16906162 · DOI · Paper page
  8. Rudd MK Keene J Bunke B Kaminsky EB Adam MP Mulle JG Ledbetter DH Martin CL Segmental duplications mediate novel, clinically relevant chromosome rearrangements Hum Mol Genet 2009 18 2957 2962 10.1093/hmg/ddp233 19443486 PMC2714723 · DOI
  9. Mefford HC Eichler EE Duplication hotspots, rare genomic disorders, and common disease Curr Opin Genet Dev 2009 19 196 204 10.1016/j.gde.2009.04.003 19477115 PMC2746670 · DOI
  10. Lupski JR Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits Trends Genet 1998 14 417 422 10.1016/S0168-9525(98)01555-8 9820031 · DOI · Paper page
  11. Stankiewicz P Lupski JR Genome architecture, rearrangements and genomic disorders Trends Genet 2002 18 74 82 10.1016/S0168-9525(02)02592-1 11818139 · DOI
  12. Giglio S Calvari V Gregato G Gimelli G Camanini S Giorda R Ragusa A Guerneri S Selicorni A Stumm M Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation Am J Hum Genet 2002 71 276 285 10.1086/341610 12058347 PMC379160 · DOI
  13. van der Maarel SM Deidda G Lemmers RJ van Overveld PG van der Wielen M Hewitt JE Sandkuijl L Bakker B van Ommen GJ Padberg GW Frants RR De novo facioscapulohumeral muscular dystrophy: frequent somatic mosaicism, sex-dependent phenotype, and the role of mitotic transchromosomal repeat interaction between chromosomes 4 and 10 Am J Hum Genet 2000 66 26 35 10.1086/302730 10631134 PMC1288331 · DOI
  14. South ST Whitby H Maxwell T Aston E Brothman AR Carey JC Co-occurrence of 4p16.3 deletions with both paternal and maternal duplications of 11p15: modification of the Wolf-Hirschhorn syndrome phenotype by genetic alterations predicted to result in either a Beckwith-Wiedemann or Russell-Silver phenotype Am J Med Genet A 2008 146A 2691 2697 10.1002/ajmg.a.32516 18798325 · DOI
  15. Ou Z Stankiewicz P Xia Z Breman AM Dawson B Wiszniewska J Szafranski P Cooper ML Rao M Shao L Observation and prediction of recurrent human translocations mediated by NAHR between nonhomologous chromosomes Genome Res 2011 21 33 46 10.1101/gr.111609.110 21205869 PMC3012924 · DOI
  16. Kurahashi H Shaikh TH Hu P Roe BA Emanuel BS Budarf ML Regions of genomic instability on 22q11 and 11q23 as the etiology for the recurrent constitutional t(11;22) Hum Mol Genet 2000 9 1665 1670 10.1093/hmg/9.11.1665 10861293 · DOI
  17. Sheridan MB Kato T Haldeman-Englert C Jalali GR Milunsky JM Zou Y Klaes R Gimelli G Gimelli S Gemmill RM A palindrome-mediated recurrent translocation with 3:1 meiotic nondisjunction: the t(8;22)(q24.13;q11.21) Am J Hum Genet 2010 87 209 218 10.1016/j.ajhg.2010.07.002 20673865 PMC2917714 · DOI
  18. Gajecka M Gentles AJ Tsai A Chitayat D Mackay KL Glotzbach CD Lieber MR Shaffer LG Unexpected complexity at breakpoint junctions in phenotypically normal individuals and mechanisms involved in generating balanced translocations t(1;22)(p36;q13) Genome Res 2008 18 1733 1742 10.1101/gr.077453.108 18765821 PMC2577863 · DOI
  19. Higgins AW Alkuraya FS Bosco AF Brown KK Bruns GA Donovan DJ Eisenman R Fan Y Farra CG Ferguson HL Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project Am J Hum Genet 2008 82 712 722 10.1016/j.ajhg.2008.01.011 18319076 PMC2427206 · DOI
  20. Chen W Kalscheuer V Tzschach A Menzel C Ullmann R Schulz MH Erdogan F Li N Kijas Z Arkesteijn G Mapping translocation breakpoints by next-generation sequencing Genome Res 2008 18 1143 1149 10.1101/gr.076166.108 18326688 PMC2493403 · DOI
  21. Batzer MA Deininger PL Alu repeats and human genomic diversity Nat Rev Genet 2002 3 370 379 10.1038/nrg798 11988762 · DOI
  22. Abeysinghe SS Chuzhanova N Krawczak M Ball EV Cooper DN Translocation and gross deletion breakpoints in human inherited disease and cancer I: Nucleotide composition and recombination-associated motifs Human mutation 2003 22 229 244 10.1002/humu.10254 12938088 · DOI
  23. Rouyer F Simmler MC Page DC Weissenbach J A sex chromosome rearrangement in a human XX male caused by Alu-Alu recombination Cell 1987 51 417 425 10.1016/0092-8674(87)90637-4 2822256 · DOI
  24. Lehrman MA Schneider WJ Sudhof TC Brown MS Goldstein JL Russell DW Mutation in LDL receptor: Alu-Alu recombination deletes exons encoding transmembrane and cytoplasmic domains Science 1985 227 140 146 10.1126/science.3155573 3155573 PMC4449727 · DOI
  25. Pousi B Hautala T Heikkinen J Pajunen L Kivirikko KI Myllyla R Alu-Alu recombination results in a duplication of seven exons in the lysyl hydroxylase gene in a patient with the type VI variant of Ehlers-Danlos syndrome Am J Hum Genet 1994 55 899 906 7977351 PMC1918329
  26. Kamp C Hirschmann P Voss H Huellen K Vogt PH Two long homologous retroviral sequence blocks in proximal Yq11 cause AZFa microdeletions as a result of intrachromosomal recombination events Hum Mol Genet 2000 9 2563 2572 10.1093/hmg/9.17.2563 11030762 · DOI · Paper page
  27. Blanco P Shlumukova M Sargent CA Jobling MA Affara N Hurles ME Divergent outcomes of intrachromosomal recombination on the human Y chromosome: male infertility and recurrent polymorphism J Med Genet 2000 37 752 758 10.1136/jmg.37.10.752 11015452 PMC1757162 · DOI
  28. Lander ES Linton LM Birren B Nusbaum C Zody MC Baldwin J Devon K Dewar K Doyle M FitzHugh W Initial sequencing and analysis of the human genome Nature 2001 409 860 921 10.1038/35057062 11237011 · DOI · Paper page
  29. Paces J Pavlicek A Paces V HERVd: database of human endogenous retroviruses Nucleic Acids Res 2002 30 205 206 10.1093/nar/30.1.205 11752294 PMC99133 · DOI
  30. Patience C Wilkinson DA Weiss RA Our retroviral heritage Trends Genet 1997 13 116 120 10.1016/S0168-9525(97)01057-3 9066271 · DOI
  31. Turner G Barbulescu M Su M Jensen-Seaman MI Kidd KK Lenz J Insertional polymorphisms of full-length endogenous retroviruses in humans Curr Biol 2001 11 1531 1535 10.1016/S0960-9822(01)00455-9 11591322 · DOI · Paper page
  32. Bannert N Kurth R Retroelements and the human genome: new perspectives on an old relation Proc Natl Acad Sci USA 2004 101 Suppl 2 14572 14579 15310846 PMC521986
  33. Hughes JF Coffin JM Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution Nat Genet 2001 29 487 489 10.1038/ng775 11704760 · DOI
  34. Hughes JF Coffin JM Human endogenous retroviral elements as indicators of ectopic recombination events in the primate genome Genetics 2005 171 1183 1194 10.1534/genetics.105.043976 16157677 PMC1456821 · DOI · Paper page
  35. Gunn SR Mohammed M Reveles XT Viskochil DH Palumbos JC Johnson-Pais TL Hale DE Lancaster JL Hardies LJ Boespflug-Tanguy O Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalanced translocation between chromosomes 4q and 18q Am J Med Genet A 2003 120A 127 135 10.1002/ajmg.a.20026 12794705 · DOI
  36. Horbinski C Carter EM Heard PL Sathanoori M Hu J Vockley J Gunn S Hale DE Surti U Cody JD Molecular and clinical characterization of a recurrent cryptic unbalanced t(4q;18q) resulting in an 18q deletion and 4q duplication Am J Med Genet A 2008 PMC2584776 18932219
  37. Hirose Y Takamatsu M Harada F Presence of env genes in members of the RTVL-H family of human endogenous retrovirus-like elements Virology 1993 192 52 61 10.1006/viro.1993.1007 8517031 · DOI
  38. Naylor JA Buck D Green P Williamson H Bentley D Giannelli F Investigation of the factor VIII intron 22 repeated region (int22h) and the associated inversion junctions Hum Mol Genet 1995 4 1217 1224 10.1093/hmg/4.7.1217 8528212 · DOI
  39. Reiter LT Murakami T Koeuth T Gibbs RA Lupski JR The human COX10 gene is disrupted during homologous recombination between the 24 kb proximal and distal CMT1A-REPs Hum Mol Genet 1997 6 1595 1603 10.1093/hmg/6.9.1595 9285799 · DOI
  40. Inoue K Lupski JR Molecular mechanisms for genomic disorders Annu Rev Genomics Hum Genet 2002 3 199 242 10.1146/annurev.genom.3.032802.120023 12142364 · DOI
  41. Kidd JM Graves T Newman TL Fulton R Hayden HS Malig M Kallicki J Kaul R Wilson RK Eichler EE A human genome structural variation sequencing resource reveals insights into mutational mechanisms Cell 2010 143 837 847 10.1016/j.cell.2010.10.027 21111241 PMC3026629 · DOI
  42. Conrad DF Bird C Blackburne B Lindsay S Mamanova L Lee C Turner DJ Hurles ME Mutation spectrum revealed by breakpoint sequencing of human germline CNVs Nat Genet 2010 42 385 391 10.1038/ng.564 20364136 PMC3428939 · DOI
  43. Kent WJ BLAT--the BLAST-like alignment tool Genome Res 2002 12 656 664 11932250 PMC187518
  44. Benson G Tandem repeats finder: a program to analyze DNA sequences Nucleic Acids Res 1999 27 573 580 10.1093/nar/27.2.573 9862982 PMC148217 · DOI · Paper page

Cited by

Sorted by citations

Authors
Hermetz, K. E., Surti, U., Cody, J. D., & Rudd, M. K.
Affiliations
  • Emory University (US)
  • University of Pittsburgh (US)
  • The University of Texas at San Antonio Health Science Center (US)
Corresponding author
Rudd, M Katharine
ORCID
Venue
Molecular Cytogenetics
Publisher
Springer Science and Business Media LLC
Published
2012-01-19
Volume
5
Issue
1
Pages
6-6
ISSN
1755-8166 (ISSN-L)
DOI
10.1186/1755-8166-5-6
PMC
PMC3292815
OpenAlex
W2115368313
Cited by
27
References
3
Citations by year
2025: 4 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2019: 2 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 2
FWCI
2.51
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Cytogenetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Institute of Mental Health (R01MH092902)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
recurrent translocations, homologous recombination, HERV-H, human endogenous retroviruses, non-allelic homologous recombination, interchromosomal recombination, chromosome 4, chromosome 18, 18q deletion, intellectual disability, sequence variation, chromosomal rearrangements

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