title: Significant Role of Segmental Duplications and SIDD Sites in Chromosomal Translocations of Hematological Malignancies: A Multi-parametric Bioinformatic Analysis.
abstract: Recurrent non-random chromosomal translocations are hallmark characteristics of leukemogenesis, and however, molecular mechanisms underlying these rearrangements are less explored. The fundamental question is, why and how chromosomes break and reunite so precisely in the genome. Meticulous understanding of mechanism leading to chromosomal rearrangement can be achieved by characterizing breakpoints. To address this hypothesis, a novel multi-parametric computational approach for characterization of major leukemic translocations within and around breakpoint region was performed. To best of our knowledge, this bioinformatic analysis is unique in finding the presence of segmental duplications (SDs) flanking breakpoints of all major leukemic translocation. Breakpoint islands (BpIs) were analyzed for stress-induced duplex destabilization (SIDD) sites along with other complex genomic architecture and physicochemical properties. Our study distinctly emphasizes on the probable correlative role of SDs, SIDD sites and various genomic features in the occurrence of breakpoints. Further, it also highlights potential features which may be playing a crucial role in causing double-strand breaks, leading to translocation.
authors.affiliation: Department of Microbiology, MVM Science College, Saurashtra University, Near Under Bridge, Kalawad Road, Rajkot, Gujarat, 360007, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Daga
authors.affiliation: BIT Virtual Institute of Bioinformatics (GCRI Node), GSBTM, Gandhinagar, Gujarat, India.|BIT Virtual Institute of Bioinformatics (GCRI Node), Division of Medicinal Chemistry and Pharmacogenomics, The Gujarat Cancer and Research Institute, NCH Campus, Asarwa, Ahmedabad, Gujarat, 380016, India.
authors.forename: Afzal
authors.initials: A
authors.lastname: Ansari
authors.affiliation: Department of Bioinformatics, Maharaja Krishnakumarsinhji Bhavnagar University, Bhavnagar, Gujarat, 364022, India.|Department of Physics, Maharaja Krishnakumarsinhji Bhavnagar University, Bhavnagar, Gujarat, 364022, India.
authors.forename: Medha
authors.initials: M
authors.lastname: Pandya
authors.affiliation: Division of Medicinal Chemistry and Pharmacogenomics, Department of Cancer Biology, The Gujarat Cancer and Research Institute, NCH Campus, Asarwa, Ahmedabad, Gujarat, 380016, India.
authors.forename: Krupa
authors.initials: K
authors.lastname: Shah
authors.affiliation: Division of Medicinal Chemistry and Pharmacogenomics, Department of Cancer Biology, The Gujarat Cancer and Research Institute, NCH Campus, Asarwa, Ahmedabad, Gujarat, 380016, India.
authors.forename: Shanaya
authors.initials: S
authors.lastname: Patel
authors.affiliation: Division of Medicinal Chemistry and Pharmacogenomics, Department of Cancer Biology, The Gujarat Cancer and Research Institute, NCH Campus, Asarwa, Ahmedabad, Gujarat, 380016, India. rakeshmrawal@gmail.com.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Rawal
authors.affiliation: Department of Microbiology, MVM Science College, Saurashtra University, Near Under Bridge, Kalawad Road, Rajkot, Gujarat, 360007, India.
authors.forename: Valentina
authors.initials: V
authors.lastname: Umrania
mesh_terms: D000465:Algorithms; D001482:Base Composition / Q000235:genetics; D019457:Chromosome Breakage; D019295:Computational Biology / Q000379:methods*; D004249:DNA Damage / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D056916:Segmental Duplications, Genomic; D014178:Translocation, Genetic
keywords: Chromosomal breakage; Chromosomal translocations; Cytogenetic abnormalities; Hematological malignancies; Physicochemical parameters; Segmental duplication; Stress-induced duplex destabilization