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LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV

(2018) HUMAN MUTATION. 39(12). p.1916-1925
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Abstract
Transposable elements modify human genome by inserting into new loci or by mediating homology-, microhomology-, or homeology-driven DNA recombination or repair, resulting in genomic structural variation. Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. Eighty-five percent of 45 ACDMPV-causative CNV deletions, of which junctions have been sequenced, had at least one of their two breakpoints located in a retrotransposon, with more than half of them being Alu elements. We describe a novel similar to 35 kb-large genomic instability hotspot at 16q24.1, involving two evolutionarily young LINE-1 (L1) elements, L1PA2 and L1PA3, flanking AluY, two AluSx, AluSx1, and AluJr elements. The occurrence of L1s at this location coincided with the branching out of the Homo-Pan-Gorilla clade, and was preceded by the insertion of AluSx, AluSx1, and AluJr. Our data show that, in addition to mediating recurrent CNVs, L1 and Alu retrotransposons can predispose the human genome to formation of variably sized CNVs, both of clinical and evolutionary relevance. Nonetheless, epigenetic or other genomic features of this locus might also contribute to its increased instability.
Keywords
DNA repair, genome instability, nonrecurrent structural variants, ALVEOLAR-CAPILLARY DYSPLASIA, ALLELIC HOMOLOGOUS RECOMBINATION, COPY-NUMBER VARIANTS, STRUCTURAL VARIATION, SOMATIC RETROTRANSPOSITION, TRANSPOSABLE ELEMENTS, EVOLUTIONARY DYNAMICS, FOXF1 ENHANCER, 3' UTR, REVEALS

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Citation

Please use this url to cite or link to this publication:

Chicago
Szafranski, Przemyslaw, Ewelina Kośmider, Qian Liu, Justyna A Karolak, Lauren Currie, Sandhya Parkash, Stephen G Kahler, et al. 2018. “LINE- and Alu-containing Genomic Instability Hotspot at 16q24.1 Associated with Recurrent and Nonrecurrent CNV Deletions Causative for ACDMPV.” Human Mutation 39 (12): 1916–1925.
APA
Szafranski, P., Kośmider, E., Liu, Q., Karolak, J. A., Currie, L., Parkash, S., Kahler, S. G., et al. (2018). LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV. HUMAN MUTATION, 39(12), 1916–1925.
Vancouver
1.
Szafranski P, Kośmider E, Liu Q, Karolak JA, Currie L, Parkash S, et al. LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV. HUMAN MUTATION. 2018;39(12):1916–25.
MLA
Szafranski, Przemyslaw et al. “LINE- and Alu-containing Genomic Instability Hotspot at 16q24.1 Associated with Recurrent and Nonrecurrent CNV Deletions Causative for ACDMPV.” HUMAN MUTATION 39.12 (2018): 1916–1925. Print.
@article{8600984,
  abstract     = {Transposable elements modify human genome by inserting into new loci or by mediating homology-, microhomology-, or homeology-driven DNA recombination or repair, resulting in genomic structural variation. Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. Eighty-five percent of 45 ACDMPV-causative CNV deletions, of which junctions have been sequenced, had at least one of their two breakpoints located in a retrotransposon, with more than half of them being Alu elements. We describe a novel similar to 35 kb-large genomic instability hotspot at 16q24.1, involving two evolutionarily young LINE-1 (L1) elements, L1PA2 and L1PA3, flanking AluY, two AluSx, AluSx1, and AluJr elements. The occurrence of L1s at this location coincided with the branching out of the Homo-Pan-Gorilla clade, and was preceded by the insertion of AluSx, AluSx1, and AluJr. Our data show that, in addition to mediating recurrent CNVs, L1 and Alu retrotransposons can predispose the human genome to formation of variably sized CNVs, both of clinical and evolutionary relevance. Nonetheless, epigenetic or other genomic features of this locus might also contribute to its increased instability.},
  author       = {Szafranski, Przemyslaw and Ko\'{s}mider, Ewelina and Liu, Qian and Karolak, Justyna A and Currie, Lauren and Parkash, Sandhya and Kahler, Stephen G and Roeder, Elizabeth and Littlejohn, Rebecca O and DeNapoli, Thomas S and Shardonofsky, Felix R and Henderson, Cody and Powers, George and Poisson, Virginie and B{\'e}rub{\'e}, Denis and Oligny, Luc and Michaud, Jacques L and Janssens, Sandra and De Coen, Kris and Van Dorpe, Jo and Dheedene, Annelies and Harting, Matthew T and Weaver, Matthew D and Khan, Amir M and Tatevian, Nina and Wambach, Jennifer and Gibbs, Kathleen A and Popek, Edwina and Gambin, Anna and Stankiewicz, Pawe\unmatched{0142}},
  issn         = {1059-7794},
  journal      = {HUMAN MUTATION},
  language     = {eng},
  number       = {12},
  pages        = {1916--1925},
  title        = {LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV},
  url          = {http://dx.doi.org/10.1002/humu.23608},
  volume       = {39},
  year         = {2018},
}

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