Mahony Fenn1, Ryan Hedley1, Dr. Melody Caramins2, Dr. Nicole Chia3
1 Western Diagnostic Pathology, 74 McCoy St, Myaree, WA, 6154, Mahony.Fenn@wdp.com.au
2 Genomic Diagnostics, 60 Waterloo Road, Macquarie Park, NSW, 2113
3 Queensland Medical Laboraory, Metroplex on Gateway, 11 Riverview Pl, Murarrie, QLD, 4172
The distal short arm of chromosome 8 is a well described hotspot for chromosomal rearrangement resulting in inversion, duplication and deletion. Until recently these have been detected by conventional chromosome analysis with subjective interpretation of chromosomal bands. The implementation of molecular karyotyping by chromosome microarray has elucidated these rearrangements with respect to the genomic location of the duplicated and deleted segments. Several mechanisms have been described which hypothesise the derivation of these rearrangements. In general these stem from the formation of a dicentric chromosome with a subsequent breakage leading to the classical invdupdel(8p). Parental paracentric inversions within 8p23 and Olfactory receptor (OR) gene clusters (including low copy repeat regions REPP and REPD) have been highlighted as the major triggers involved in the generation of the dicentric chromosome.
The subsequent breakage of the dicentric chromosome will often leave this derivative without a telomere resulting in chromosome instability. Stability is regained by restoration of the telomere. This can be done through telomere healing with the addition of telomeric sequences or by telomere capture whereby telomeres are sourced from another chromosome.
Here we describe 5 case studies of invdupdel(8p) and demonstrate the presence of the dicentric chromosome consistent with the early hypothesis and 2 cases showing telomere capture as the mechanism of telomere repair. This study highlights the value of the information provided by molecular karyotyping for the detection of chromosomal anomalies and additional insight of the mode of derivation.
I am one of the senior scientists at WDP and the 2IC of the Cytogenetics dept at WDP. I have worked in the field of cytogenetics for just over 15 years. Our main areas of interest currently at WDP are fertility, prenatal and paediatrics. We use conventional cytogenetics, FISH, QFPCR and microarray as our main techniques of analysis.