Improved structural characterization of chromosomal breakpoints using high resolution custom array-CGH
Article first published online: 4 MAR 2010
© 2010 John Wiley & Sons A/S
Volume 77, Issue 6, pages 552–562, June 2010
How to Cite
Lindstrand, A., Schoumans, J., Gustavsson, P., Hanemaaijer, N., Malmgren, H. and Blennow, E. (2010), Improved structural characterization of chromosomal breakpoints using high resolution custom array-CGH. Clinical Genetics, 77: 552–562. doi: 10.1111/j.1399-0004.2009.01341.x
- Issue published online: 9 MAY 2010
- Article first published online: 4 MAR 2010
- Received 4 September 2009, revised and accepted for publication 15 October 2009
- chromosomal translocation;
- complex chromosomal rearrangement;
- cryptic deletion;
- fluorescence in situ hybridization;
- oligonucleotide array-CGH
Lindstrand A, Schoumans J, Gustavsson P, Hanemaaijer N, Malmgren H, Blennow E. Improved structural characterization of chromosomal breakpoints using high resolution custom array-CGH.
Array-CGH is a powerful tool for the rapid detection of genomic imbalances. By customizing the array it is possible to increase the resolution in a targeted genomic region of interest and determine the structure of the breakpoints with high accuracy, as well as to detect very small imbalances. We have used targeted custom arrays to zoom in on 38 chromosomal breakpoints from 12 different patients carrying both balanced and unbalanced rearrangements. We show that it is possible to characterize unbalanced breakpoints within 17–20,000 bp, depending on the structure of the genome. All of the deletion and duplication breakpoints were further refined and potential underlying molecular mechanisms of formation are discussed. In one of seven carriers of apparently balanced reciprocal translocations we detected a small deletion of 200 bp within the previously FISH-defined breakpoint, and in another patient, a large deletion of 11 Mb was identified on a chromosome not involved in the translocation. Targeted custom oligonucleotide arrays make it possible to perform fine mapping of breakpoints with a resolution within the breakpoint region much higher compared to commercially available array platforms. In addition, identification of small deletions or duplications in apparently balanced rearrangements may contribute to the identification of new disease causing genes.