A complex rearrangement involving simultaneous translocation and inversion is associated with a change in chromatin compaction

• Published in: Chromosoma 2002-09, Vol.111 (3), p.170-175
• Main Authors: Callen, D F, Eyre, H, McDonnell, S, Schuffenhauer, S, Bhalla, K
• Format: Article
• Language: English
• Subjects: Chromatin - metabolism; Chromosome Banding; Chromosome Inversion; Chromosomes; DNA Probes - metabolism; Humans; Intellectual Disability - genetics; Male; Translocation, Genetic
• ISSN: 0009-5915; 1432-0886
• DOI: 10.1007/s00412-002-0203-7

Detailed fluorescence in situ hybridisation analysis of a previously described translocation revealed it to be a more complex rearrangement consisting of both a translocation and a paracentric inversion with an apparent coincident breakpoint at 16p13.3, t(14;16)(p32;p13.3) inv16(p13.3p12.1). This unusual three-breakpoint rearrangement was not obvious from examination of G-banding. Such rearrangements may be undiagnosed in cytogenetic studies. The presence of an interstitial deletion of 16p was unlikely as the rearranged chromosome contained probes distributed along the short arm of chromosome 16. Fluorescence in situ hybridisation studies suggested that the inverted segment was smaller in size than that on the normal chromosome. Measurements of distances between probes on metaphase chromosomes confirmed that there was differential compaction of the inverted portion on 16p. The inverted region was significantly reduced in size by 21% compared with the same region on the normal chromosome 16. The size reduction across the region was non-uniform, with one region showing a 55% increase in compaction. The change in compaction was also associated with a change in the lateral position of a probe on the chromatids. The finding that a single chromosome breakpoint can change the compaction of chromatin over an extensive region has implications for models of the structure of metaphase chromosomes. Possible explanations are either a localized severe disruption of DNA packaging over relatively short distances (hundreds of kilobases) or a more generalized change that extends over many megabases. These results raise the important possibility that chromosome breaks may result in a more global change in DNA compaction across large segments of a chromosome.