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Molecular cytogenetic analyses of breakpoints in apparently balanced reciprocal translocations carried by phenotypically normal individuals

Molecular cytogenetic analyses of breakpoints in apparently balanced reciprocal translocations carried by phenotypically normal individuals
Molecular cytogenetic analyses of breakpoints in apparently balanced reciprocal translocations carried by phenotypically normal individuals
To test the hypothesis that translocation breakpoints in normal individuals are simple and do not disrupt genes, we characterised the breakpoints in 13 phenotypically normal individuals incidentally ascertained with an apparently balanced reciprocal translocation. Cases were karyotyped, and the breakpoints were refined by fluorescence in situ hybridisation until breakpoint-spanning clones were identified. 1 Mb array-CGH was performed as a whole genome analysis tool to detect any imbalances in chromatin not directly involved in the breakpoints. Breakpoint-associated imbalances were not found in any of the patients analysed in this study. However, breakpoints which disrupted known genes were identified in two patients, with RYR2 disrupted in one patient and COL13A1 in the other. In a further eight patients, Ensembl mapping data suggested that a gene might be disrupted by a breakpoint. In one further patient, the translocation was shown to be nonreciprocal. This study shows that apparently balanced reciprocal translocations in phenotypically normal patients do not have imbalances at the breakpoints, in contrast to phenotypically abnormal patients where the translocation breakpoints are often associated with cryptic imbalances. However, phenotypically normal individuals, and phenotypically abnormal individuals may have genes disrupted and therefore inactivated by one of the breakpoints. The significance of these disruptions remains to be determined.
apparently balanced translocation, fluorescence in situ hybridisation, array-cgh
1018-4813
1205-1212
Baptista, J.
9f4f967b-773c-4375-93e6-3d8daf773e02
Prigmore, E.
927d327c-f0f6-4e37-88f8-47de5a8e5a82
Gribble, S.M.
01b3b3bd-746f-4815-96ec-b8cb2c772554
Jacobs, P.A.
32993834-5b30-4706-a09b-640baf848c49
Carter, N.P.
d9377125-5da4-45eb-bfbf-4e797d1c048a
Crolla, J.A.
c5f23751-8de9-4a55-9cc5-ca2fb635769c
Baptista, J.
9f4f967b-773c-4375-93e6-3d8daf773e02
Prigmore, E.
927d327c-f0f6-4e37-88f8-47de5a8e5a82
Gribble, S.M.
01b3b3bd-746f-4815-96ec-b8cb2c772554
Jacobs, P.A.
32993834-5b30-4706-a09b-640baf848c49
Carter, N.P.
d9377125-5da4-45eb-bfbf-4e797d1c048a
Crolla, J.A.
c5f23751-8de9-4a55-9cc5-ca2fb635769c

Baptista, J., Prigmore, E., Gribble, S.M., Jacobs, P.A., Carter, N.P. and Crolla, J.A. (2005) Molecular cytogenetic analyses of breakpoints in apparently balanced reciprocal translocations carried by phenotypically normal individuals. European Journal of Human Genetics, 13 (11), 1205-1212. (doi:10.1038/sj.ejhg.5201488).

Record type: Article

Abstract

To test the hypothesis that translocation breakpoints in normal individuals are simple and do not disrupt genes, we characterised the breakpoints in 13 phenotypically normal individuals incidentally ascertained with an apparently balanced reciprocal translocation. Cases were karyotyped, and the breakpoints were refined by fluorescence in situ hybridisation until breakpoint-spanning clones were identified. 1 Mb array-CGH was performed as a whole genome analysis tool to detect any imbalances in chromatin not directly involved in the breakpoints. Breakpoint-associated imbalances were not found in any of the patients analysed in this study. However, breakpoints which disrupted known genes were identified in two patients, with RYR2 disrupted in one patient and COL13A1 in the other. In a further eight patients, Ensembl mapping data suggested that a gene might be disrupted by a breakpoint. In one further patient, the translocation was shown to be nonreciprocal. This study shows that apparently balanced reciprocal translocations in phenotypically normal patients do not have imbalances at the breakpoints, in contrast to phenotypically abnormal patients where the translocation breakpoints are often associated with cryptic imbalances. However, phenotypically normal individuals, and phenotypically abnormal individuals may have genes disrupted and therefore inactivated by one of the breakpoints. The significance of these disruptions remains to be determined.

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Published date: 2005
Keywords: apparently balanced translocation, fluorescence in situ hybridisation, array-cgh

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Local EPrints ID: 24617
URI: http://eprints.soton.ac.uk/id/eprint/24617
ISSN: 1018-4813
PURE UUID: dd85833c-67b0-480f-b9c6-937975e6c20c

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Date deposited: 03 Apr 2006
Last modified: 25 Nov 2019 19:28

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