STRUCTURAL CHROMOSOMAL REARRANGEMENTS AND THEIR IMPLICATIONS IN DEVELOPMENTAL AND GENETIC DISORDERS

Abstract

Background: The structural rearrangements of chromosomes such as translocations, inversion, deletions, and duplications are major causes of developmental and genetic disorders. These changes may cause disruptions of the gene activity, chromosomal arrangement and control systems with a broad spectrum of clinical phenotypes.

Objective: This paper will compare the clinical and detection sensitivity of structural chromosomal rearrangements with both traditional cytogenetic and newer molecular technology.

Methodology: G-banding, fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and next-generation sequencing (NGS) were used to analyze 180 samples (clinical and research). Methodologies were compared in terms of the detection rates and rearrangement types.

Findings: G-banding was found to detect structural abnormalities in 46% of cases, giving way to better rates of 58 and 71 with FISH and aCGH respectively. NGS showed the best detection rate at 84% with detection of rearrangements (both balanced and complex) and microdeletions and cryptic translocations that could not be detected using conventional methods.

Conclusion: The new sophisticated genomic methods are very useful in identifying and characterizing structural chromosomal rearrangements. The combination of various methods enhances the accuracy of the diagnosis and offers more explanations on the molecular mechanisms of developmental and genetic disease.