Copyright © 2008 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 82, Issue 4, 927-936, 28 March 2008
doi:10.1016/j.ajhg.2008.02.012
Article
Breakpoint Mapping and Array CGH in Translocations: Comparison of a Phenotypically Normal and an Abnormal Cohort
Julia Baptista1, 2, Catherine Mercer3, Elena Prigmore4, Susan M. Gribble4, Nigel P. Carter4, Viv Maloney5, N. Simon Thomas1, 2, Patricia A. Jacobs1, 2 and John A. Crolla1, 2, 
, 
1 Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire, UK
2 Division of Human Genetics, School of Medicine, University of Southampton, Southampton, UK
3 Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
4 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
5 National Genetics Reference Laboratory (Wessex), Salisbury Hospital NHS Trust, Salisbury, Wiltshire, UK
Corresponding authorAbstract
We report the analyses of breakpoints in 31 phenotypically normal and 14 abnormal carriers of balanced translocations. Our study assesses the differences between balanced translocations in normal carriers and those in abnormal carriers, focusing on the presence of genomic imbalances at the breakpoints or elsewhere in the genome, presence of cryptic chromosome rearrangements, and gene disruption. Our hypothesis is that all four features will be associated with phenotypic abnormalities and absent or much less frequent in a normal population. In the normal cohort, we identified neither genomic imbalances at the breakpoints or elsewhere in the genome nor cryptic chromosome rearrangements. In contrast, we identified candidate disease-causing imbalances in 4/14 abnormal patients. These were three breakpoint associated deletions and three deletions unrelated to the breakpoints. All six de novo deletions originated on the paternally inherited chromosome. Additional complexity was also present in one of these cases. Gene disruption by the breakpoints was present in 16/31 phenotypically normal individuals and in 5/14 phenotypically abnormal patients. Our results show that translocations in phenotypically abnormal patients are molecularly distinct from those in normal individuals: the former are more likely to be associated with genomic imbalances at the breakpoints or elsewhere and with chromosomal complexity, whereas the frequency of gene disruption is similar in both normal and abnormal translocation carriers.
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