Transcriptomics

Dataset Information

3

Analysis of copy number changes and complex rearrangements in patients with congenital abnormalities


ABSTRACT: Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyzed the genomes of ten patients with congenital disease that were preselected to carry complex chromosomal rearrangements (CCRs) with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint-junctions indicates that break-repair involves non-homologous or microhomology mediated end-joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred bp and several Mb. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template-switching. Our work provides detailed insight in the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. We analyzed five patient-parent trios with Illumina BeadChip arrays to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients.

ORGANISM(S): Homo sapiens  

SUBMITTER: Wigard Kloosterman   Martin Poot  Ron Hochstenbach  Eberhard Passarge  Björn Menten  Ivo Renkens  Claudia A Ruivenkamp  Arie van Haeringen  Daniela Giardino  Wigard P Kloosterman  Karen Duran  Edwin Cuppen  Thomas Haaf  Ruben van 't Slot  Masoumeh Tavakoli-Yaraki  Kerstin Hansson  Elly F Ippel  Sarah Vergult  Lucia Ballarati  Lidia Larizza  Ellen van Binsbergen  Victor Guryev  Markus J van Roosmalen 

PROVIDER: E-GEOD-37906 | ArrayExpress | 2012-05-10

SECONDARY ACCESSION(S): GSE37906PRJNA165661

REPOSITORIES: GEO, ArrayExpress

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