Predominance of constitutional chromosomal rearrangements in human chromosomal fragile sites

Abstract

Chromosomal fragile sites (CFSs) are loci or regions susceptible to spontaneous or induced occurrence of gaps, breaks and rearrangements. In this work, we studied the data of 4535 patients stored at DECI-PHER (Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources). We mapped fragile sites to chromosomal bands and divided the 23 chromosomes into fragile and non-fragile sites. The frequency of rearrangements at the chromosomal location of clones found to be deleted or duplicated in the array/CGH analysis, provided by DE-CIPHER, was compared in Chromosomal Fragile Sites vs. non-Fragile Sites of the human genome. The POSSUM Web was used to complement this study. The results indicated 1) a predominance of rearrangements in CFSs, 2) the absence of statistically significant difference between the frequency of rearrangements in common CFSs vs. rare CFSs, 3) a predominance of deletions over duplications in CFSs. These results on constitutional chromosomal rearrangements are evocative of the findings previously reported by others relatively to cancer supporting the current line of evidence and suggesting that a common mechanism can underlie the generation of constitutional and somatic rearrangements. The combination of insights obtained from our results and their interrelationships can indicate strategies by which the mechanisms can be targeted with preventive medical interventions.

Integration of HIV in the Human Genome: Which Sites Are Preferential? A Genetic and Statistical Assessment

“…A list of FSs was obtained from Mrasek et al [ 6 ] and completed with FSs from Lukusa and Fryns [ 8 ]. Two consecutive bands associated with FSs were grouped to form a fragile region (FR) and a region between two FRs was considered a NFR [ 35 , 36 ]. The Y chromosome was not considered because it does not have well defined FSs; there is only a possibility of existing one FS [ 37 ].…”