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Improved structural characterization of chromosomal breakpoints using high resolution custom array‐CGH
Author(s) -
Lindstrand A,
Schoumans J,
Gustavsson P,
Hanemaaijer N,
Malmgren H,
Blennow E
Publication year - 2010
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2009.01341.x
Subject(s) - breakpoint , biology , comparative genomic hybridization , genetics , gene duplication , chromosomal translocation , computational biology , structural variation , genome , chromosome , copy number variation , gene
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.