Inverted genomic segments and complex triplication rearrangements are mediated by inverted repeats in the human genome
Claudia M B Carvalho, Melissa B Ramocki, Davut Pehlivan, Luis M Franco, Claudia Gonzaga-Jauregui, Ping Fang, Alanna McCall, Eniko Karman Pivnick, Stacy Hines-Dowell, Laurie H Seaver, Linda Friehling, Sansan Lee, Rosemarie Smith, Daniela Del Gaudio, Marjorie Withers, Pengfei Liu, Sau Wai Cheung, John W Belmont, Huda Y Zoghbi, P J Hastings, James R Lupski, Claudia M B Carvalho, Melissa B Ramocki, Davut Pehlivan, Luis M Franco, Claudia Gonzaga-Jauregui, Ping Fang, Alanna McCall, Eniko Karman Pivnick, Stacy Hines-Dowell, Laurie H Seaver, Linda Friehling, Sansan Lee, Rosemarie Smith, Daniela Del Gaudio, Marjorie Withers, Pengfei Liu, Sau Wai Cheung, John W Belmont, Huda Y Zoghbi, P J Hastings, James R Lupski
Abstract
We identified complex genomic rearrangements consisting of intermixed duplications and triplications of genomic segments at the MECP2 and PLP1 loci. These complex rearrangements were characterized by a triplicated segment embedded within a duplication in 11 unrelated subjects. Notably, only two breakpoint junctions were generated during each rearrangement formation. All the complex rearrangement products share a common genomic organization, duplication-inverted triplication-duplication (DUP-TRP/INV-DUP), in which the triplicated segment is inverted and located between directly oriented duplicated genomic segments. We provide evidence that the DUP-TRP/INV-DUP structures are mediated by inverted repeats that can be separated by >300 kb, a genomic architecture that apparently leads to susceptibility to such complex rearrangements. A similar inverted repeat-mediated mechanism may underlie structural variation in many other regions of the human genome. We propose a mechanism that involves both homology-driven events, via inverted repeats, and microhomologous or nonhomologous events.
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References
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Source: PubMed