Complex Reorganization and Predominant Non-Homologous Repair Following Chromosomal Breakage in Karyotypically Balanced Germline Rearrangements and Transgenic Integration

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Complex Reorganization and Predominant Non-Homologous Repair Following Chromosomal Breakage in Karyotypically Balanced Germline Rearrangements and Transgenic Integration

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Title: Complex Reorganization and Predominant Non-Homologous Repair Following Chromosomal Breakage in Karyotypically Balanced Germline Rearrangements and Transgenic Integration
Author: Chiang, Colby; Jacobsen, Jessie C.; Ernst, Carl; Hanscom, Carrie; Heilbut, Adrian; Blumenthal, Ian; Mills, Ryan E.; Kirby, Andrew; Rudiger, Skye R.; McLaughlan, Clive J.; Bawden, C. Simon; Reid, Suzanne J.; Faull, Richard L. M.; Snell, Russell G.; Hall, Ira M.; Ohsumi, Toshiro K.; Shen, Yiping; Borowsky, Mark L; Daly, Mark Joseph; Lee, Charles; Morton, Cynthia Casson; MacDonald, Marcy Elizabeth; Gusella, James Francis; Talkowski, Michael Edward; Lindgren, Amelia M.

Note: Order does not necessarily reflect citation order of authors.

Citation: Chiang, Colby, Jessie C. Jacobsen, Carl Ernst, Carrie Hanscom, Adrian Heilbut, Ian Blumenthal, Ryan E. Mills et al. 2012. Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nature Genetics 44(4): 390-397.
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Abstract: We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically-interpreted translocations and inversions. We confirm that the recently described phenomenon of “chromothripsis” (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline where it can resolve to a karyotypically balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign CNVs. We compared these results to experimentally-generated DNA breakage-repair by sequencing seven transgenic animals, and revealed extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion is the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations.
Published Version: doi:10.1038/ng.2202
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340016/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10579135
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